The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases
The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding
The helix-turn-helix (HTH) motif in the cytoplasmic domain of the N-terminus is involved in the formation of spirals to maintain the rigid rod shape. As this protein is anchored in the cytoplasmic membrane, the HTH motif may contribute to protein-protein interactions to form the RodZ helix, which is localized beneath the cytoplasmic membrane. The C-terminal domain may be critical for determination of the rod shape by probably interacting with enzymes required for synthesis of the peptidoglycan layer, including PBPs in the periplasm
The coiled coil domain mediates homo- and hetero-oligomerization
The MATH/TRAF domain binds to receptor cytoplasmic domains
The RING-type zinc finger domain is essential for E3 ubiquitin-protein ligase activity. It is not essential for the stabilization of BIRC2, or for the ubiquitination of RIPK1 in response to TNFR1 signaling
The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements
Consists of 3 domains; the N-terminus binds the ribosome, the middle domain has PPIase activity, while the C-terminus has intrinsic chaperone activity on its own
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin
Seems to contain an N-terminal exonuclease domain and a C-terminal UvrC-like endonuclease domain
The beta-hairpin motif is involved in DNA binding
The acidic-tail domain of UBC2 mediates interaction with UBR1 and UBR2, and thus is important for polyubiquitination of histones. This domain is also important for sporulation
Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains (By similarity). Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3)
PAZ domain is absent, but Ago is capable of binding small RNAs in the same way as the other Argonaute proteins
Does not bind DNA by a helix-turn-helix motif
The cysteine framework is X (CC-CX[hydroxyPro]C)
The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain
The PH domain binds phospholipids. Binds preferentially phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for phosphatidylinositol-4,5-bisphosphate (By similarity)
The N-terminal region displays a ubiquitin-type fold and mediates interaction with membranes containing negatively charged phosphatidylinositol phosphate via a surface enriched in positively charged residues
The cysteine framework is VI/VII (C-C-CC-C-C)
The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis
The first ATP-binding region binds ATP with low affinity whereas the second ATP-binding region binds ATP with high affinity
TPR repeats 1-7 mediate homodimerization, while the C-terminal TPR repeats bind to CDC26, burying its hydrophobic N-terminus
Lacks alpha-helical transmembrane segments, suggesting that it resides in the membrane via beta-sheet conformations similar to those predicted for other outer membrane proteins and porin
The SMP-LTD domain is a barrel-like domain that can bind various types of glycerophospholipids in its interior and mediate their transfer between two adjacent bilayers
Lacks the C-terminal regulatory region which is replaced by HisZ
The beta chain mediates most of the interactions with both subunits of hemoglobin, while the alpha chain forms the homodimeric interface
The C-terminus is required for mitochondrial or peroxisomal localization, while the N-terminus is necessary for mitochondrial or peroxisomal fission
The Ig-like domain is required for the anti-apoptotic ability
Probably exists in a closed and an open conformation due to interaction of the C-terminal coiled-coil domain with an N-terminal region including the calponin-homology (CH) and the LIM zinc-binding domain. The conformational change is regulated by RAB13 (By similarity)
Consists of three domains: the N-terminal catalytic domain, the editing domain and the C-terminal anticodon-binding domain
The N-terminus (1-10) forms an essential portion of the targeting information
The acidic N-terminal part may favor interaction with the basic domain of transcription factors
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF7, the motif is inactive
The C-terminal lobe folds into an immunoglobulin-like domain and mediates cell adhesion properties
The N-terminal domain interacts with the head of the 30S subunit; the C-terminal domain interacts with the body and contacts protein S4. The interaction surface between S4 and S5 is involved in control of translational fidelity
Transport is mediated via a series of conformation changes, switching between a conformation where the substrate-binding cavity is accessible from the outside, and a another conformation where it is accessible from the cytoplasm
The PRC barrel domain binds ribosomal protein uS19
The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage
The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate
The structure of NLP effectors is remarkably conserved with a high level of conservation of a central hepta-peptide motif GHRHDWE
The DVD domain (residues 338-361) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation (By similarity)
The D domain (residues 30-46) contains a conserved docking site and is required for the binding to MAPK substrates
The macro domain specifically binds poly-ADP-ribose (PubMed:34887560). Binds poly-ADP-ribose with much higher affinity compared to vertebrate macroH2A1.1 orthologs (PubMed:34887560)
Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis
The J domain is necessary and sufficient to stimulate DnaK ATPase activity. Zinc center 1 plays an important role in the autonomous, DnaK-independent chaperone activity of DnaJ. Zinc center 2 is essential for interaction with DnaK and for DnaJ activity
The TIR domain mediates the interaction with TRAF6 and MYD88
The mature N-terminus is involved in the interaction with XIAP
The PDZ domain mediates interaction with MXI2
The leader sequence region and some other sequence particularities suggest that TcpA may represent a novel class of pilin, and imply the existence of a novel signal peptidase
N-terminal loop binds to the intracellular vestibule of the transporter, arresting the transporter in an inhibited state
The EGF-like domains 10 and 11 are required for binding the ligands JAG1 and DLL1
Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CSalpha/beta)
The myosin motor domain displays actin-stimulated ATPase activity and generates a mechanochemical force
The tail domain participates in molecular interactions that specify the role of the motor domain (By similarity). It is composed of several tail homology (TH) domains, namely a putative phospholipid-binding myosin tail domain (also named TH1), an Ala- and Pro-rich domain (TH2), followed by an SH3 domain and a C-terminal acidic domain (TH3)
Has a two-domain beta-structure, folded into four very similar Greek key motifs
The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1
The C-terminal di-lysine motif confers endoplasmic reticulum localization
The DHHC domain is required for palmitoyltransferase activity
Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity (By similarity)
The interaction with glycans occurs through a binding site in the globular lectin domain
The zinc binding sites are localized to the N-domain
The LRR (leucine-rich repeat) domain forms a slightly curved solenoid and may mediate interaction with target proteins
Contains the canonical two aspartate-rich DDxxD motifs, designated as FARM (the first aspartate-rich motif) and SARM (the second aspartate-rich motif). The primary role of the FARM and SARM is the chelation of the divalent magnesium ion cofactors that assist substrate binding and catalysis, but it may also play a role in determining product chain length
Has a modular structure: an endo-beta-1,4-glucanase catalytic module at the N-terminus, a linker rich in serines and threonines, and a C-terminal carbohydrate-binding module (CBM). The genes for catalytic modules and CBMs seem to have evolved separately and have been linked by gene fusion
The N-terminal domain determines nucleotide recognition and specific binding, while the C-terminal domain determines the specific binding to the target protein
The last Arg residue of the ACP-binding site is essential for the weak association between ACP/AcpP and FabH
Contains a large N-terminal NADP-binding domain, and a smaller C-terminal substrate-binding domain
This S-layer protein is composed of two distinct structural domains: a larger mass trypsin-resistant N-terminal, containing the binding region for extracellular matrix proteins, and a smaller C-terminal domain with intermediate resistance to trypsin
The DNA polymerase activity domain resides in the N-terminal half of the protein, while the C-terminus is necessary for maintenance of the complex
The CysA-type zinc finger is required for PCNA-binding
The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes
Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2 (PubMed:9872744). The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling (PubMed:9844003)
The clip domain consists of 35-55 residues which are 'knitted' together usually by 3 conserved disulfide bonds forming a clip-like compact structure (By similarity). The clip domain is necessary for regulating the zymogen activation (PubMed:16362048)
Comprises of two domains. The C-terminal domain contains the binding site for glutamine and catalyzes the hydrolysis of this substrate to glutamate and ammonia. The N-terminal domain is anticipated to bind ATP and cobyrinate and catalyzes the ultimate synthesis of the diamide product. The ammonia produced via the glutaminase domain is probably translocated to the adjacent domain via a molecular tunnel, where it reacts with an activated intermediate
The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles
Glu-105 is involved in sensing abasic sites in single-stranded DNA (ssDNA) (PubMed:31504793). His-160 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group (PubMed:31235915)
A Gly-cisPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of L-amino acids
Contains an N-terminal PE domain and a C-terminal catalytic domain, which are connected by a linker region (PubMed:17938218). The PE domain is involved in aggregation and activity regulation (PubMed:26270534). It is also required for ESX-5-dependent secretion (PubMed:21471225). After transport, the PE domain is removed by proteolytic cleavage (PubMed:21471225)
The N-terminal domain does not have lytic activity and probably modulates enzymatic activity. The C-terminal domain is the catalytic active domain
The tau/MAP repeat binds to tubulin
The cysteine framework is V (CC-CC)
The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for the catalytic activity, presumably through binding to Mg(2+)
The tetrapeptide (A-A-P-[AV]) repeats found throughout the protein are also present in many proteins constituting the protective envelope of other species
Each protomer consists of 9 transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site: acyl-CoA enters the active site through the cytosolic tunnel, whereas cholesterol enters from the side through the transmembrane tunnel
The transmembrane domain (TMD) is essential for the interaction with ATP6AP2
Can be divided into 3 domains: the weakly conserved A domain, the highly conserved B domain thought to be involved in subunit interaction and DNA binding, and the Glu-rich C domain
The NR LBD domain and the nuclear receptor DNA binding domain are sufficient for binding to the NGFI-B response element (NBRE) 5'-AAAGGTCA-3'
Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines
The FYVE domain is important for binding to the endosomal membrane
Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal coiled-coil region mediating homodimerization
Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs
The R3H domain recognizes phosphorylated 5'-ends of single-stranded nucleic acids which promotes binding of nucleic acids and stimulates ATPase activity
The TPR 1 repeat interacts with the C-terminal of HSC70. The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8 and 9 repeats (also called TPR2B domain) interact with HSP90 (By similarity)
Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds (CS-alpha/beta)
The PTS EIIA type-3 domain is phosphorylated by phospho-HPr on a histidyl residue. Then, it transfers the phosphoryl group to the PTS EIIB type-3 domain
Its cytoplasmic domain associates with the cytoplasmic domains of TOM20 and TOM70. Its intermembrane space domain provides a trans binding site for presequences and the single membrane anchor is required for a stable interaction between the GIP complex proteins
The KSSR motif is part of a protein interaction pocket that mediates interaction with cellular and viral proteins
The RNA-binding region is not essential for long-term memory
The RNA-binding region is essential for long-term memory
The N-terminal Gln/His-rich domain is necessary and sufficient for long-term memory and is required for formation of amyloid-like oligomers with isoform B (PubMed:17965711, PubMed:23083740). Binds transition metals (PubMed:28763009). Might bind lipid membranes (PubMed:28700922)
The N-terminal Gln/His-rich domain is both dispensable and insufficient for long-term memory and for formation of amyloid-like oligomers with isoform A
Has three domains with a flexible linker between the domains II and III and assumes an 'L' shape. Domain III is highly mobile and contacts RuvB
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme
Has the canonical translocation RxLR motif, but lacks the canonical EER motif, which characterizes most oomycete effectors identified so far
The cysteine framework is I (CC-C-C). Alpha3/5 pattern
The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3
Interaction with the C-terminus of CFTR could be mediated through independent binding of 1, 3 and 4 domains
The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1
The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1
The PDZ 1 domain interacts with BCR
The first C2 domain mediates Ca(2+)-dependent phospholipid binding
The second C2 domain mediates interaction with Stonin 2. The second C2 domain mediates phospholipid and inositol polyphosphate binding in a calcium-independent manner
The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins
Consists of a C-terminal hydrophilic region and a predominantly hydrophobic remainder
The chaperone-containing TCP1 (CCT) domain is essential for the interaction with the scaffold protein vac14/SPBC25H2.03
The conserved cysteine-rich (CCR) domain contacts intramolecularly the C-terminus, including the kinase domain, and this interaction negatively regulates PI(3) 5-kinase activity
RRM 1 and RRM 2 bind cooperatively to AU-rich sequences in target mRNAs. RRM 3 binds to poly-A mRNA sequences
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required
The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity
The protein kinase domain is predicted to be catalytically inactive
The VLRF1 domain mediates binding to the 60S ribosomal subunit
May contain a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane
Contains a C-terminal catalytic domain, and an N-terminal region which modulates catalytic activity
Subfamily I proteins are distinguished by three conserved motifs: the CxxC motif localized near the N-terminus, the GNFE motif localized about 40 residues from the C-terminus, and the KC motif localized about 25 residues from the C-terminus (Probable). In the crystal structures of the subfamily I proteins, the side chains of the cysteines in the CxxC and KC motifs face each other across the rim of the putative substrate-binding cleft, and the GNFE motif lies deep in the cleft close to the metal-binding aspartate and asparagine (Probable). the 3 conserved cysteines in motifs CxxC and KC play a key role in the interaction with the Fe-containing chromophore, which is not directly involved in catalysis (Probable)
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9-containing vesicles, thereby enabling growth into autophagosomes
The PTS EIIA type-2 domain is phosphorylated by phospho-HPr on a histidyl residue. Then, it transfers the phosphoryl group to the PTS EIIB type-2 domain
In contrast to classical PTS systems, the fructose-specific PTS has no requirement for HPr; FruB combines a IIA domain with two HPr domains
Contains 2 adjacent but distinct nuclear receptor interaction domains (NID+L and NID-L) to which nuclear receptors bind differentially in the presence and absence of ligand respectively
The cysteine framework is IX (C-C-C-C-C-C)
The Clp repeat (R) domain probably functions as a substrate-discriminating domain, recruiting aggregated proteins to the ClpB hexamer and/or stabilizing bound proteins. The NBD2 domain is responsible for oligomerization, whereas the NBD1 domain stabilizes the hexamer probably in an ATP-dependent manner. The movement of the coiled-coil domain is essential for ClpB ability to rescue proteins from an aggregated state, probably by pulling apart large aggregated proteins, which are bound between the coiled-coils motifs of adjacent ClpB subunits in the functional hexamer (By similarity)
Possesses an unusual extended V-shaped dimeric structure with each monomer consisting of three distinct domains arranged along a curved 'spinal' alpha-helix. The N-terminal catalytic domain specifically recognizes the glutamate moiety of the substrate. The second domain is the NADPH-binding domain, and the third C-terminal domain is responsible for dimerization
The conserved DXD motif is involved in enzyme activity
The F-box is necessary for the interaction with ASK proteins
This protein is mostly composed of repetitive C-G-P motifs
The IMD domain is predicted to have a helical structure. It may induce actin bundling and filopodia formation (By similarity)
The NH2-terminal transmembrane domaine (TMD) is involved in the recognition of substrates, and undergoes a conformational change upon ATP binding to the COOH-terminal nucleotide binding domain (NBD)
The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation
The N- and C-terminal flexible termini are involved in oligomerization and in the binding of non-native substrate proteins, and are essential for chaperone activity
The N-terminus contains an autoinhibitory calmodulin-binding domain, which binds calmodulin in a calcium-dependent fashion
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC2, forming a V-shaped heterodimer
D-BOX motif functions as a recognition motif for the ubiquitination machinery
Repression activity depends on the C-terminal DNA-binding zinc fingers and on the N-terminal repression domain
Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation
PLN and SLN both have a single transmembrane helix; both occupy a similar binding site that is situated between the ATP2A2 transmembrane helices
The 2 conserved active-site motifs D(D/E)XX(D/E) and NSE are required for coordinating the divalent metal ions that stabilize the PPi moiety of the substrate
The N-terminal unstructured half of Pup provides a signal required to initiate unfolding and degradation by the proteasome but is not needed for pupylation, while the C-terminal helical half of Pup interacts with ARC to target proteins to the proteasome
The short lumenal loops between transmembrane domains 1 and 2 and between transmembrane domains 3 and 4 may impart a wedge-like configuration, thus deforming membranes
The TIR domain mediates NAD(+) hydrolase (NADase) activity. The cyclic nucleotide binds in the C-terminal bacterial STING region
Dileucine motif seems to be involved in protein-protein interactions
In HlyB the peptidase C39 domain, the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
The sonic hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain
The first IBR-type zinc finger is the most crucial for interaction with UBE2L3, UBE2L6 and UCKL1
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain
The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity
The N-terminal half of the protein mediates transcription repression
The transmembrane helix undergoes a conformation change and unravels partially when bound to PSEN1, facilitating cleavage by PSEN1
The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells
The GFLD subdomain binds Cu(2+) ions; this promotes homodimerization
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The YENPXY site is also involved in clathrin-mediated endocytosis
The C-terminal region can bind zinc ions; this favors dimerization and formation of higher oligomers
The OX-2 motif shows some similarity to a region in the N-terminus of CD200/MOX2
The PUB domain mediates the interaction with VCP
The ZP domain is required for localization at the apical cell membrane, secretion and excretory tube and vulval lumen expansion
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis. Some bacteria have evolved a zinc-coordinating structure that stabilizes the LID domain
Both zinc fingers are required to induce development (PubMed:2108321)
C2 domain is a calcium-binding fold, and the binding induces conformational changes, promoting the protein association with membranes. These conformational changes occure at micromolar Ca(2+) concentrations. Exhibits three Ca(2+)-binding sites. Binds also PIP2
The N-terminal domain probably binds unfolded/aggregated proteins; the C-terminal domain interacts with ClpC
The N-terminal region contains the highly conserved SGGXDS motif, predicted to be a P-loop motif involved in ATP binding
The N-terminal and the C-terminal halves of the protein can associate with each other, thereby hindering interactions with ZYX
The RING fingers are required for ubiquitin ligase activity
The YDG domain mediates the interaction with histone H3
The IMP cyclohydrolase activity resides in the N-terminal region
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain
The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions. Also recognizes and binds histones that are butyrylated
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA)
The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family
The cysteine framework is III (CC-C-C-CC). Classified in the M-1 branch, since 1 residue stands between the fourth and the fifth cysteine residues
Disordered regions undergo liquid-liquid phase separation (LLPS) for the formation of membraneless compartments that store maternal mRNAs in oocytes
The 3CxxC-type mediates binding to the 3'-UTR of mRNAs
This protein is considered an atypical serine/threonine kinase, because it lacks the conventional structural elements necessary for the substrate recognition as well as a lysine residue that in all other serine/threonine kinases participates in the catalytic event. TP53RK has protein kinase activity in vitro, but in the context of the EKC/KEOPS complex, the catalytic subunit OSGEP switches the activity of TP53RK from kinase into ATPase (By similarity)
The part of the protein spanning the actin filament-binding domain together with the DH domain and the first PH domain is necessary and sufficient for microspike formation. Activation of MAPK8 requires the presence of all domains with the exception of the actin filament-binding domain
The DOCKER domain is necessary and sufficient for the GEF activity
The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex
Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains (By similarity). The first ABC transporter nucleotide-binding domain has no ATPase activity by itself (PubMed:14685259, PubMed:15619636)
The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, NHERF1/EBP50 complex
The disordered R region mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation
The first PHD-type zinc finger domain recognizes and binds H3-K9Me3
Both the JmjC domain and the JmjN domain are required for enzymatic activity
The PTS EIIA type-4 domain is phosphorylated by phospho-HPr on a histidyl residue. Then, it transfers the phosphoryl group to the PTS EIIB type-4 domain
The PTS EIIB type-4 domain is phosphorylated by phospho-EIIA on a histidyl residue. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the PTS EIIC type-4 domain
The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane
The L/FRRG motif is essential for the cytoplasm to vacuole transport (Cvt) pathway, for the recruitment of ATG8 and ATG16 to the PAS in nutrient-rich medium, and for its recruitment to and dissociation from the PAS under starvation conditions
Dimerization mediated by the LisH domain may be required to activate dynein
The head region is responsible for both junction and actin filament-based distribution
The myosin motor domain binds ADP and ATP but has no intrinsic ATPase activity. Mediates ADP-dependent binding to actin (By similarity)
The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for the catalytic activity in the class I active site, presumably through binding to Mg(2+)
The PID domain specifically binds to the Asn-Pro-Xaa-Tyr(P) motif found in many tyrosine-phosphorylated proteins
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins
The N-terminal seven-bladed beta-propeller is formed by WD40-like repeats, and projects inward from the polyhedral outer clathrin coat. It constitutes a major protein-protein interaction node
IleRS has two distinct active sites: one for aminoacylation and one for editing. The misactivated valine is translocated from the active site to the editing site, which sterically excludes the correctly activated isoleucine. The single editing site contains two valyl binding pockets, one specific for each substrate (Val-AMP or Val-tRNA(Ile))
Consists of two domains: the transglutaminase substrate domain (cementoin moiety) and the elastase inhibitor domain. The transglutaminase substrate domain serves as an anchor to localize elafin covalently to specific sites on extracellular matrix proteins
Has four distinct domains: an N-terminal nucleotidyltransferase (NT) domain responsible for UTase activity, a central HD domain that encodes UR activity, and two C-terminal ACT domains that seem to have a role in glutamine sensing
The C-terminal propeptide is required for normal protein folding and secretion; it maintains the aerolysin precursor in its soluble form and prevents premature heptamerization and pore formation
The activation loop within the kinase domain is the target of phosphorylation/activation by upstream protein kinases. The PPI motif mediates the interaction with the ABI (abscisic acid-insensitive) phosphatases (By similarity)
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors
The PNT domain acts as a transcriptional activator
2 residues (Tyr-66 and Arg-69) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The TIR domain mediates interaction with NOX4
In MsbA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases leading to down-regulation of cell activation
The cytoplasmic domain controls FRC elongation but is dispensable for contraction (By similarity). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (PubMed:25486435)
The MREC motif may be critical for tubulin autoregulation
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. The transmembrane domain is essential for translocation to the mitochondria upon induction of apoptosis (By similarity)
The indian hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain
The N-terminal D domain mediates homodimerization
The RxLR-dEER motif acts to carry the protein into the host cell cytoplasm through binding to cell surface phosphatidylinositol-3-phosphate
The PH 1 domain mediates the oligomerization in a calcium dependent manner
The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity)
The SU domain binds calmodulin in a calcium-dependent manner
Composed of three domains: the N-terminal N domain, which is responsible for interactions with the ribosome, the central G domain, which binds GTP, and the C-terminal M domain, which binds the RNA and the signal sequence of the RNC
The NAB conserved domain 1 (NCD1) interacts with EGR1 inhibitory domain and mediates multimerization
The NAB conserved domain 2 (NCD2) is necessary for transcriptional repression
The winged helix domain is involved in binding to DNA in the preinitiation complex
The hinge domain, which separates the large intramolecular coiled coil regions, allows the homodimerization, forming a V-shaped homodimer
The DDXXD motif is important for the catalytic activity, presumably through binding to Mg(2+)
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities. This domain is also involved in CAND1-, cullins- and RBX1-binding
The C-terminus is required for IGF-binding and growth inhibition
The LCPYTRL domain (18-24) is critical for trafficking from the trans-Golgi network to the prevacuolar compartment and from the prevacuolar compartment to the central vacuole (PubMed:21899678). The PRRRRP domain (36-41) is involved in sorting to the vacuole (PubMed:23737500). At least two Arg are needed for correct delivery and the presence of two neighboring Pro seems to contribute to the sorting efficiency (PubMed:23737500)
The cysteine framework is XIV (C-C-C-C)
The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for interaction with BY55 and BTLA
Has 3 domains, the large (RuvB-L) and small ATPase (RuvB-S) domains and the C-terminal head (RuvB-H) domain. The head domain binds DNA, while the ATPase domains jointly bind ATP, ADP or are empty depending on the state of the subunit in the translocation cycle. During a single DNA translocation step the structure of each domain remains the same, but their relative positions change
The N-terminal region is involved in phosphatidylethanolamine-binding and is required for atg8-PE conjugation (By similarity)
The flexible region (FR) is required for atg7-binding (By similarity)
The handle region (HR) contains the atg8 interaction motif (AIM) and mediates binding to atg8. It is crucial for the cytoplasm-to-vacuole targeting pathway (By similarity)
The C-terminal contains many C-X-P repeats
The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. The TIR domain alone is active and (slowly) produces 2'cADPR (PubMed:36048923)
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases
In the dimer, the N-terminal domains are swapped between the two monomers, such that residues of both chains contribute to the active site
In the CSD domain, Trp-65 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring
The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding
The GH10 domain binds to xylan
Both substrate-binding domains (SBD1 and SBD2) are involved in the substrate recognition, and are sufficient to confer the substrate specificity
The PDZ domains may also mediate association to membranes by binding to EPB41 and ADGRA2 together with the L27 domain that binds CASK and DLG2
The L27 domain may regulate DLG1 self-association. The N-terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization (By similarity)
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF12, the motif is inactive
The Walker A ATP-binding motif also binds Pi and PPi
The cytoplasmic metal binding domain (MBD) is located between transmembrane 2 (TM2) and transmembrane 3 (TM3)
ValRS has two distinct active sites: one for aminoacylation and one for editing. The misactivated threonine is translocated from the active site to the editing site
The C-terminal coiled-coil domain is crucial for aminoacylation activity
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (374-404) inactivates kinase activity under calcium-free conditions
The intermediate domain (ID) is required for the phosphorylation and activation of IRAK
The 7 WD repeats mediate protein-protein interactions with binding partners
The PX domain binds phosphatidylinositol 3-phosphate which is necessary for peripheral membrane localization to the perivacuolar punctate structures
The two metal binding sites M1 and M2 that are halfway through the membrane form a binuclear metal center. M1 is essential to Zn(2+) transport, while the other, M2 appears to have an auxiliary role presumably by acting as an additional transport site that can modulate the properties of the primary transport site. The binuclear metal center plays a key role in Zn(2+) sensing
The cysteine framework is XV (C-C-CC-C-C-C-C)
Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain
Forms a 10-stranded antiparallel beta-barrel structure able to accommodate a hydrophobic ligand in its interior. In fact, this fold hosts the heme group, which is located in a wide surface cleft
There are two conserved domains in the globular part of the protein: the N-terminal domain (domain A) contains the conserved DXD motif and is possibly involved in catalysis and substrate binding. The C-terminal domain (domain B) contains the QXXRW motif and is present only in processive glycosyl transferases. It could be involved in the processivity function of the enzyme, possibly required for holding the growing glycan chain in the active site
Forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior
The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus
The Ig-like C2-type domains 2 and 3 contribute to formation of the complex with BDKRB2 and in regulation of its activity
The LRR region is both necessary and sufficient for the interaction with NTNG1
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity
A pair of annexin repeats may form one binding site for calcium and phospholipid
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding
The box 1 motif is required for JAK interaction and/or activation
Composed of four peptidoglycan binding (LysM) domains and a C-terminal lysostaphin-like (LytM) peptidase domain. The LysM domains are the major mediators of the localization to the division site, probably via direct interaction with peptidoglycans. The LytM region is dispensable for localization, but is essential for function
The BTB/POZ domain mediates the interaction with some component of ubiquitin ligase complexes
The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme
The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides
The enzyme uses its core to engage the disordered anionic tails of alpha- and beta-tubulin and the flexible c-MTBD (cationic microtubule binding domain) region to bind the microtubule and position itself for beta-tail modification. The c-MTBD region is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on alpha-tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding
Rho-GAP domain is able to regulate RhoGTPase activity, actin cytoskeleton and cell spreading. However N-terminally BAR domain plays an autoinhibitory role
The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP
The N-terminal and C-terminal lobes of CALM bind to the C-terminus of KCNQ1 in a clamp-like conformation. Binding of CALM C-terminus to KCNQ1 is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to KCNQ1 is calcium-dependent and regulates electrophysiological activity of the channel
Avian ovomucoid consists of three homologous, tandem Kazal family inhibitory domains
The coiled-coil domains may be important for tubulin-gamma-binding and hence for centrosomal localization
The FFAT 2 motif is required for interaction with VAPA and regulation of the endoplasmic reticulum targeting of ORP3. The FFAT 1 motif may contribute to VAPA binding
The PH domain binds phosphoinositides, with a preference for PI(3,4)P2 and PI(3,4,5)P3. The PH domain mediates targeting to the plasma membrane
The SAM domain mediates interaction with EF1A1, and functions as an autoinhibitory regulator of RhoGAP Activity
The polybasic cluster is required for activation and mediates binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) containing membranes
The leucine-zipper domain is essential for its localization in the caveolae
The N-terminal domain probably functions as a substrate-discriminating domain, recruiting aggregated proteins to the ClpB hexamer and/or stabilizing bound proteins. The NBD2 domain is responsible for oligomerization, whereas the NBD1 domain stabilizes the hexamer probably in an ATP-dependent manner. The movement of the coiled-coil domain is essential for ClpB ability to rescue proteins from an aggregated state, probably by pulling apart large aggregated proteins, which are bound between the coiled-coils motifs of adjacent ClpB subunits in the functional hexamer (By similarity)
Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue
The Gly-Xaa-Gly-Xaa-Gly (GXGXG) motif binds the adenosyl part of S-adenosyl-L-methionine
The carnosine-binding region forms hydrophobic and hydrogen bonds with carnosine, defining a flipping orientation of the imidazole ring so that N1 is present next to S-adenosyl-L-methionine for methylation
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position
The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded (By similarity)
The EIIA type-4 domain is phosphorylated by phospho-HPr on a histidyl residue. Then, it transfers the phosphoryl group to the EIIB type-4 domain
Binds to EPS15 (a clathrin coat-associated protein) via a C-terminal domain containing three Asn-Pro-Phe (NPF) repeats
The C-terminal proline-rich region mediates binding to a variety of SH3 domain-containing proteins including AMPH, SH3GL1, SH3GL2, SH3GL3 and GRB2
The zinc finger domains (C2H2-type and C2HC-type zinc fingers) bind DNA and mediate recruitment to double-strand break sites. They show strong preference for DNA with 5'- or 3'-single-stranded overhangs, while they do not bind blunt-ended double-stranded DNA or poly(ADP-ribose) (PAR) polymers
The N-terminal alpha-helix of peptide ECE1-III allows insertion of the toxin into host epithelial cells membranes
The two conserved Cys that bind zinc constitute the zinc-hook, which separates the large intramolecular coiled coil regions. The 2 Cys residues coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another Rad50 molecule, thereby forming a V-shaped homodimer
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes
Consists of 4 functional domains: (1) the N-terminal GT44 domain (glucosyltransferase, also named GTD), which mediates glucosylation of host small GTPases, (2) an autoprocessing region that catalyzes autoprocessing to release the N-terminal GT44 domain in the host cytosol, (3) the translocation region that forms a pore to promote translocation of the GT44 and peptidase C80 domains across the endosomal membrane and (4) the receptor-binding (CROPS) region that mediates binding to host cells and contribute to entry into cells
The receptor-binding (CROPS) region is dynamic and can have open and closed conformations depending of the pH: has an open conformation at endosomal pH and a closed conformation at neutral pH
The cell wall-binding repeats bind carbohydrates, probably contributing to entry into cells
The four-helical bundle region mediates binding to phospholipids, such as phosphatidylserine and phosphatidic acid. This promotes localization to the inner face of the cell membrane close to small GTPases
The zinc finger domain is required for E3 ligase activity
SH3 domains 1 and 2 are required for its localization to the cell membrane of dense bodies
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids. The pore-forming region H5 is enclosed by the transmembrane segments S5 and S6 in the Shaker-type (1P/6TM) and contains the GYGD signature motif which seems to be involved in potassium selectivity (By similarity)
The KHA domain (rich in hydrophobic and acidic residues) present in the C-terminal part is likely to be important for tetramerization
The N-terminal non-catalytic domain is assumed to mediate recognition of proteins with partial folding defects
The extracellular regions of the homodimer interact in a side-by-side fashion while facing opposite directions. Each extracellular region consists of three domains, LB1 (ligand-binding 1), LB2 and CR (cysteine-rich). The two lobe-shaped domains LB1 and LB2 form a venus flytrap module. In the inactive configuration, the venus flytrap modules of both protomers are in the open conformation associated with the resting state (open-open) and the interdomain cleft is empty. In addition, each protomer contains three anions, which reinforce the inactive conformation, and one calcium ion. In the active configuration, both protomers of extracellular regions have the closed conformation associated with agonist-binding (closed-closed). The ligand-binding cleft of each protomer is solely occupied by an aromatic amino-acid. Calcium is bound at four novel sites, including one at the homodimer interface. Agonist-binding induces large conformational changes within the extracellular region homodimer: first, the venus flytrap module of each protomer undergoes domain closure. Second, the LB2 regions of the two protomers approach each other, resulting in an expansion of the homodimer interactions involving LB2 domains. Third, the CR regions of the two subunits interact to form a large homodimer interface that is unique to the active state. The CR regions are brought into close contact by the motion involving LB2 since the two domains are rigidly associated within each subunit
The transactivation inhibitory domain (TID) can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA*-type isoforms
The L/FRRG motif is essential for the cytoplasm to vacuole transport (Cvt) pathway, for the recruitment of atg8 and atg16 to the PAS in nutrient-rich medium, and for its recruitment to and dissociation from the PAS under starvation conditions
The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3
The first GAF domain protects the heme moiety from auto-oxidation, contributing to the full-length protein's very long half-life (more than 36 hours in buffers without transition metals) (PubMed:19463006). The isolated ATP-binding subdomain (residues 454-578) crystallized in a closed form that is unable to bind ATP, suggesting that ATP-binding requires conformational changes in this loop region; in this closed conformation it binds a zinc atom (PubMed:23486471). The isolated histidine kinase core (HKC, residues 386-578) both autophosphorylates and phosphorylates the isolated histidine acceptor subdomain (residues 386-452) (PubMed:23486471). The relative arrangements of the 2 subdomains of the HKC may control not only kinase activity but exposure of the ATP binding site (PubMed:23486471)
The F/D-rich region (45-62) is necessary but not sufficient for SMAP1 function
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs)
The N-terminal domain (1-233) has a regulatory function and inhibits phosphatase activity
The conserved PP2C phosphatase domain (271-833) is interrupted by an insertion of approximately 200 amino acids
The transmembrane domain (TM) is the major site of interaction with SLC51A. The extracellular-membrane interface is absolutely required for transport activity. The intracellular-membrane interface is necessary for establishing the correct membrane orientation that is essential for the heterodimer Ost-alpha/Ost-beta complex formation and transport activity at the cell membrane surface (By similarity)
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage (By similarity)
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain
Histidine-containing phosphotransfer domain (HPt) contains an active histidine that mediates the phosphotransfer
The N-terminus (targeting peptide) is probably responsible for targeting to the encapsulin nanocompartment
There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding
The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity
The GAR domain modulates the binding strength to each cytoskeletal network
Consists of two domains, an N-terminal nucleotide-binding domain and a C-terminal dimerization domain
Has 3 domains; the N-terminal domain has 3 short repeats and binds RuBisCO. The central region has 5 longer repeats. The C-terminal domain has 1 repeat (compared to orthologs) and a highly conserved C-terminal peptide. The C-repeat serves as the encapsulation signal for the alpha-carboxysome, and is able to target foreign proteins to this organelle
The nitrogen atoms of the two glycine residues in the GGXR motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage
Binds DNA via its HMG boxes. When bound to the mitochondrial light strand promoter, bends DNA into a U-turn shape, each HMG box bending the DNA by 90 degrees (By similarity)
Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import
The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity)
The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity)
The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH)
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors
The C-terminal region (residues 87 to 760) consists of seven imperfect tandem repeats, including one W-Y motif (WY1) and six L-W-Y motifs (LWY2 to LWY7) (By similarity). WY1 forms a 3 alpha-helix fold with one hydrophobic core and each L-W-Y motif forms a highly conserved fold consisting of 5 alpha-helices (By similarity). The units contribute differently to the virulence since WY1, LWY2 and LWY6 are important for the ability to suppress the biogenesis of small RNA in host and virulence activity of the pathogen, whereas LWY3, LWY4, LWY5 and LWY7 are dispensable for PSR2 function (By similarity). WY1 and LWY2 are sufficient for association with DRB4, suppress gene silencing and promote infection (By similarity). These units may function as basic building blocks of Phytophthora effectors to enable virulence activity and accelerate the evolution of novel functions (By similarity)
The cysteine framework is C-C
Consists of three main regions, an N-terminal coiled-coil domain that binds to protein Pup and functions as a docking station, an interdomain involved in ARC hexamerization, and a C-terminal ATPase domain of the AAA type
The Rho-GAP domain mediates the GTPase activator activity toward CDC42
The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain
Tne N-terminal domain is necessary and sufficient for basal body localization and ciliogenesis
Contains various tandem pentapeptide repeats in the C-terminal region. The pentapeptide motif is required to efficiently recruit kinesin-1. No position is completely conserved in these repeats, whose consensus sequence is A-[DN]-[FLM]-X-X. The C-terminal 38 amino acid residues are required for peripheral localization of PipB2 and redistribution of lysosomal-associated membrane protein (LAMP). The N-terminal 225 amino acid residues are sufficient for type III translocation and association with Sifs and SCVs, but not accumulation in peripheral vesicles (By similarity)
The phosphatase catalytic core motif (or RXNCXDCLDRTN motif) from the SAC domain is found in metal-independent protein phosphatases and inositol polyphosphate phosphatases
The Ubiquitin-like domain mediates interaction with proteasomes
The structure of NLP effectors is remarkably conserved with a high level of conservation of a central region containing the conserved undecapeptide motif AIMYAWYFPKD and heptapeptide motif GHRHDWE
The monomer structure is formed from three repeating units (RUs) that share the same structure as one another. The monomer and the active site possess nearly threefold rotational symmetry, to the extent that the active site possesses three potential Ser-Lys catalytic dyads, but one of the 3 active site surfaces varies in composition suggesting it is involved in confering substrate specificity
The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons
Structures show 2 discontinuous REC (recognition, residues 15-386, 658-784) and NUC (nuclease, residues 1-14, 387-658 and 785-1129) lobes composed of several domains each; the boundaries given correspond to Lui et al., but Yang et al., differ only by a few residues in most cases (PubMed:27984729, PubMed:27989439). The crRNA (or single guide, sgRNA) binds in a central channel between the 2 lobes (PubMed:27984729, PubMed:27989439). PAM recognition is sequence specific and occurs mostly via interaction with the REC1 (helical-1) and WED-II (OBD-II) domains (PubMed:27984729). The sgRNA-target DNA heteroduplex binds primarily to the REC lobe in a sequence-independent manner (PubMed:27984729)
There is conflicting information regarding the regions required for centrosomal localization. One study shows that the region 1601-1682 is necessary and sufficient for targeting to the centrosome (PubMed:12927815). Another study shows that a separate region, 1291-1575, is important for centrosomal localization (PubMed:15190203). However, a third study shows that the coiled-coil region (373-1885) is not sufficient for centrosomal localization and instead localizes to cytoplasmic speckles (By similarity). The observed differences might be due to oligomerization of the longer coiled-coil domain-containing sequence, which would mask the shorter centrosomal targeting sequences (By similarity)
The N-terminal domain is important for targeting to the mother centriole, although it is not sufficient by itself for centrosomal localization
The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro
The N-terminal part of the protein is required for the interaction with AUR1. Two regions (220-463 and 684-758) seem involved in the targeting to the microtubule cytoskeleton
One-module-bearing peptide synthase with a C-terminal epimerization domain. Each module incorporates one amino acid into the peptide product and can be further subdivided into domains responsible for substrate adenylation, thiolation, condensation (not for the initiation module), and epimerization (optional), and N methylation (optional) (By similarity)
The doublecortin domains, which mediate interaction with microtubules, are required for regulation of microtubule polymerization and function in photoreceptor differentiation
The N-terminal domain is necessary for dimerization
Contains an N-terminal zinc-binding domain, a central core domain that contains the primase activity, and a C-terminal DnaB-binding domain
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (By similarity)
The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-ter of the protein (By similarity)
The proline-rich region is required for endoplasmic reticulum localization
The WRKY domain is required to bind DNA
The TAFH domain mediates interaction with transcription regulators
Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure
Dimerization, activity and interactions with CcmM requires all but the last 60 amino acids of the protein (PubMed:17993516). The C-terminal tail (about 55 residues) inhibits CA activity about 10-fold; it might attenuate activity before encapsulation in the carboxysome (PubMed:27729545)
Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles
Has a putative N-terminal zinc-finger, a middle region with homology to RecA with ATPase motifs including the RadA KNRFG motif, while the C-terminus is homologous to Lon protease
The PH domain mediates interactions with ubiquitin and DSK2A
The DBINO region is involved in binding to DNA
The coiled-coil domain mediates trimerization
The L27 domain mediates interaction with CASK and is involved in the formation of multimeric complexes and the association of LIN7 to membranes
The PDZ domain regulates endocytosis and recycling of the receptor at the membrane
The kinase interacting site is required for proper delivery of ERBB2 to the basolateral membrane
Is homologous throughout its length with the C-terminal 3 domains of the pentafunctional AROM protein. The function of the 2 C-terminal domains may be to act as a molecular sensor that detects the presence of quinate pathway intermediates as a prerequisite for the presumed conformational changes necessary for the control of transcription regulation (By similarity)
Contains two DNA recognition domains, each specifying recognition of one of the two defined components of the target sequence
The LSM14 domain and the RGG repeats are required for accumulation in P-bodies, and the region containing the FDF motif is responsible for cytoplasmic retention
Exists in a closed inactive form by an intramolecular interaction between the N- and the C-terminal domains. The proline-rich motif is critical both for PI3K-AKT activity inhibition and MAP3K5 activation. The PH and C2 domains are necessary for the binding to phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its tumor-suppressive function (By similarity). The C2 and GAP domains constitutively bind to MAP3K5 and facilitate the release of 14-3-3 proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY motif, are crucial for its cell membrane localization and neuronal migration function. The PH domain is necessary but not sufficient to activate the JNK signaling pathway through ERN1
The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex (By similarity)
The cysteine framework is IV (CC-C-C-C-C)
The coiled coil domain may be involved in oligomerization
The PRONE (plant-specific Rop nucleotide exchanger) domain is responsible for the GEF activity
The GAF 1 domain functions as a dimerization domain
The GAF 2 domains binds cGMP, which acts as an allosteric activator
The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested
The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues
A conserved motif [AVN[ED]CD] within the disintegrin-like domain could be involved in the binding to the integrin receptor
Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family
A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes
The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (By similarity)
The C-terminus plays a role in its oligomerization
The CHEK1-binding domain (CKBD) contains 2 potential CHEK1-binding motifs (CKB motifs). Phosphorylation sites within CKB motif 1 and CKB motif 2 are required for interaction with CHEK1
Transmembrane domains are required for enzymatic activity
The minimal CTE binding domain consists of an RNP-type RNA binding domain (RBD) and leucine-rich repeats
The nucleoporin binding domain consists of a NTF2 domain (also called NTF2-like domain) and a TAP-C domain (also called UBA-like domain). It has 2 nucleoporin-FG-repeats binding sites (one in the NTF2 and the other in the TAP-C domain) which contribute to nucleoporin association and act synergistically to export cellular mRNAs
The NTF2 domain is functional only in the presence of NXT1 and is essential for the export of mRNA from the nucleus. It inhibits RNA binding activity through an intramolecular interaction with the N-terminal RNA binding domain (RBD); the inhibition is removed by an association with the TREX complex, specifically involving ALYREF/THOC4 and THOC5
The TAP-C domain mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF1 to the nuclear rim. The conserved loop 594-NWD-596 of the TAP-C domain has a critical role in the interaction with nucleoporins
The leucine-rich repeats are essential for the export of mRNA from the nucleus
The RNA-binding domain is a non-canonical RNP-type domain
The C-terminal short (CTS) helix is essential for catalytic activity. It may be accommodated as a transmembrane helix in the thinned membrane environment of the complex, similarly to the signal peptide in the complex substrates
The Calx-beta domain binds calcium with high affinity and undergo a major conformational shift upon binding
A C-terminal internalization signal (YGTL) appears to allow the targeting of plasma membrane proteins to endosomes
The RRM domain mediates interaction with U1 RNA
The WWE domain mediates non-covalent poly(ADP-ribose)-binding
CETN2-binding regions contains a conserved Trp residue in their C-terminal ends, which seems critical for interaction with CETN2
IQ domain mediates interaction with calmodulin
The N0 region interacts in the periplasm with GspC (PubMed:21931548). The S domain interacts with pilotin AspS2 (PubMed:29632366). The N0, N1, N2 and N3 domains are periplasmic, while the secretin and S domains form a channel that is partially inserted in the outer membrane. The cap gate extends out on the extracellular side of the channel partially closing the channel. The secretin domain forms a double beta-barrel structure; the outer barrel has an outer diameter of about 110 Angstroms while the inner barrel forms the central gate with a small pore in the closed state (By similarity)
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes
The Asp-Xaa-Asp-Asp (DXDD) motif is important for the catalytic activity in the class II active site relevant for the cyclization of GGPP. The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for the catalytic activity in the class I active site, presumably through binding to Mg(2+)
The intra-membrane loop at the C-terminus acts as a calcium pore, mediating calcium leak from the ER into the cytosol
The polyhistidine repeat may act as a targeting signal to nuclear speckles
Contains an N-terminal soluble domain that is likely periplasmic and interacts with LptA, and a C-terminal transmembrane domain, which is predicted to be a beta-barrel and interacts with LptE. Residues 529-538 play a key role in interaction with LptE
Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity)
The coiled-coil domain mediates a strong homo/multidimerization activity essential for core assembly of PML-NBs
Binds arsenic via the RING-type zinc finger
The Sumo interaction motif (SIM) is required for efficient ubiquitination, recruitment of proteasome components within PML-NBs and PML degradation in response to arsenic trioxide
The ATG8 interacting motif (AIM) is required for the interaction with ATG8CL (PubMed:26765567, PubMed:29932422). The AIM motif is required for JOKA2 function as host autophagy cargo receptor (PubMed:26765567, PubMed:29932422)
The SUI1 domain may be involved in RNA binding
The epimerase and isomerase activities are contained in the N-terminal region while the dehydrogenase activity is in the C-terminal region
The 7 WD repeats are necessary and sufficient to support interaction with the RPA complex
The protein kinase domain is predicted to be catalytically inactive. The domain is sufficient for KSR1 and KSR1-mediated MAP2K1 and MAP2K2 membrane localization. The domain is required but not sufficient for MAP kinase-mediated inhibition of ELK1 phosphorylation (PubMed:10409742)
The N-terminal region mediates interaction with BRAF (PubMed:23250398). Also mediates membrane localization (PubMed:23250398)
The C-terminus is required for mitochondrial localization, while the N-terminus is necessary for mitochondrial fission
The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain
The first fibronectin type-III domain mediates a specific interaction with Hh protein, in vitro. The second fibronectin type-III domain is additionally required for in vivo signaling activity (By similarity)
The jas domain (135-160) is required for interaction with COI1
The histidine box domains may contain the active site and/or be involved in metal ion binding
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position
The UBA domain is required for the stability of EGD1
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Unlike other voltage-gated ion channels it lacks the pore domain (By similarity)
The C-terminal coiled coil region mediates homodimerization. It is essential for normal subcellular localization (By similarity)
The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization
The cytoplasmic C-terminal domain contains a functional dilysine-retrieval motif, which is involved in the retrograde Golgi-to-ER transport of the protein
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins. Required for proteolytic activation and delipidation of ATG8 proteins
Consists of three domains: the N-terminal catalytic domain, the anticodon-binding domain and the C-terminal extension. The C-terminal extension binds a zinc ion, which probably plays a non-essential structural role in stabilizing the fold of C-terminal domain
The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B
The F-box is necessary for the interaction with ASK proteins (By similarity). Interacts with ASK4
Contains an N-terminal PQQ binding domain and a C-terminal disorganized low-complexity (LC) hydrophilic region
Has a helix-hairpin-helix (HhH) structural motif conserved among proteins that bind non-specifically to DNA
LEM domain proteins bind centrally on the BAF dimer
Comprises two domains: an N-terminal domain containing the nucleotidyltransferase activity and a C-terminal HD domain associated with both phosphodiesterase and phosphatase activities
The DIX-like oligomerization domain is required for polymerization, edge localization and biological activity
Has 3 domains; the N-terminal domain has 4 short repeats and binds RuBisCO. The central region has 6 longer repeats (Probable) (PubMed:32123388). The C-terminal domain has 3 repeats and a highly conserved C-terminal peptide (Probable). The 3 C-repeats serve as the encapsulation signal for the alpha-carboxysome (Cb), and are able to target foreign proteins to this organelle. Proteins can be targeted to the Cb by a single C-repeat, however more repeats yields more efficient targeting. The C-terminal peptide (CTP) is not required for cargo targeting and is probably on the outside of the Cb (PubMed:33116131, PubMed:25826651)
PTB domain mediates receptor interaction
The glycine-rich (GR) domain is necessary and sufficient for cell-to-cell movement and to interefere with zucchini yellow mosaic virus (ZYMV) infection
N-terminal part of the protein is one of the crucial determinant to confer RNA chaperone activity during cold adaptation process
Consists of three domains: the N-terminal catalytic domain, the anticodon-binding domain and the C-terminal extension
The Beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity
Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move
Contains two amphipathic alpha helix regions separated by a region of less-defined helicity and greater flexibility
The twin Cx9C motifs are involved in the recognition by the mitochondrial disulfide relay system
The N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet
The tail domain is a globular cargo-binding domain
The C-terminal half of the protein is important for interaction with RBX1
Contains various tandem pentapeptide repeats in the C-terminal region. The pentapeptide motif is required to efficiently recruit kinesin-1. No position is completely conserved in these repeats, whose consensus sequence is A-[DN]-[FLM]-X-X. The C-terminal 38 amino acid residues, specifically, the C-terminal motif LFNEF, are required for peripheral localization of PipB2 and redistribution of lysosomal-associated membrane protein (LAMP). The N-terminal 225 amino acid residues are sufficient for type III translocation and association with Sifs and SCVs, but not accumulation in peripheral vesicles
The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The N-terminus of the protein extends into the stroma where it is involved with adhesion of granal membranes and post-translational modifications; both are believed to mediate the distribution of excitation energy between photosystems I and II
The L18 domain (188-205) is required for the transit complex formation with CAO/cpSRP43 and the targeting to the thylakoid
The T14 domain (211-224) is required for the interaction with LTD and the translocation across the envelope
The CFEM domain is involved in heme-binding and contains 8 cysteines and is found in proteins from several pathogenic fungi, including both human and plant pathogens (By similarity). The CFEM domain adopts a novel helical-basket fold that consists of six alpha-helices, and is uniquely stabilized by four disulfide bonds formed by its 8 signature cysteines (By similarity)
Contains two cysteine rich domains (CRD), referred to as the N- and C-terminal CRD's, n-CRD and c-CRD, respectively. A nuclear export signal is embedded in the c-CRD, with which the nuclear export proteins interact only in the absence of disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or between the c-CRD and the n-CRD
The RING finger domain is required for ubiquitin ligase activity and autoubiquitination
The EIIB domain is phosphorylated by phospho-EIIA on a cysteinyl or histidyl residue, depending on the transported sugar. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the EIIC domain
The EIIC domain forms the PTS system translocation channel and contains the specific substrate-binding site
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by His and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins
Contains a pseudo-FCL region, a large solvent-exposed peptide region containing an alpha helix and loop anchored on each end via ligation of two cysteine thiolates to a [4Fe-4S](2+) cluster. This region is involved in DNA binding and catalysis, particularly in duplex DNA contexts
The CRAL-TRIO domain is required for targeting to the membrane and for binding PtdIns(3,5)P2
The cytoplasmic domain controls FRC elongation but is dispensable for contraction (By similarity). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (By similarity)
Contains G-L-F-G repeats
Has a modular structure: a carbohydrate-binding module (CBM) at the N-terminus, a linker rich in serines, and a C-terminal endo-1,4-mannanase catalytic module. The genes for catalytic modules and CBMs seem to have evolved separately and have been linked by gene fusion
The SPOR domain binds septal peptidoglycans and is required to target DamX to the septal ring
In contrast to classical PTS systems, the fructose-specific PTS has no requirement for HPr; FruB combines a IIA domain with a HPr domain
The F5/8 type C domain binds to different types of collagen, including collagens I, III, and V
The CUE domain is required for interaction with the ER quality control machinery and misfolded substrates, ubiquitination, lipid clustering and interaction with AMFR but is not required for localization to lipid droplets
Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the transient carboxylation of the biotin covalently attached to the C-terminal biotinyl-binding/biotin carboxyl carrier (BCC) domain
In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases
The Asp-Xaa-Asp-Asp (DXDD) motif is important for the catalytic activity, presumably through binding to Mg(2+)
The bHLH is essential for interaction with NKX2-2
The SET domain is split between the S-sequence (residues 1-49) and the core SET domain (residues 181-258), however the two segments still come together to form a conserved SET domain fold
Has six binding sites that are non-equivalent, and owing to minor differences in amino-acid composition they exhibit a marked difference in specific ligand recognition (By similarity)
The TOG regions are composed of HEAT-type repeats that assemble into a solenoid structure. They mediate interaction with microtubules
Has 2 forms, fold switches to a thioredoxin-like fold (KaiB(fs)) when bound to KaiC
Interaction between the motor domain and the tail leads to an inactive, monomeric conformation. Phospholipid binding via the PH domains leads to the formation of the active, dimeric form of the protein and strongly increases actin-dependent ATPase activity and motor activity (By similarity)
Interacts with membranes containing phosphatidylinositol-3,4,5-trisphosphate via the PH domains
IQ 3 domain mediates high-affinity calcium-dependent binding to CALM3/CLP
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (By similarity). It can refold after extension suggesting an in vivo force-dependent function (By similarity). An anti-parallel coiled coil is located C-terminal to the SAH domain and mediates dimerization (PubMed:23012428)
Forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior. Can bind at least two ligands per molecule, however, the stoichiometry is debated
Has 3 domains, the large (RuvB-L, also called N) and small ATPase (RuvB-S, also called C) domains and the C-terminal head (RuvB-H, also called M) domain (PubMed:11171970). The head domain binds DNA, while the ATPase domains jointly bind ATP, ADP or are empty depending on the state of the subunit in the translocation cycle. During a single DNA translocation step the structure of each domain remains the same, but their relative positions change. Domains M and C are flexible; they change conformations whenn bound to whole RuvA and only domain III of RuvA; domain C probably binds Holliday junction DNA (PubMed:12408833)
The central Gln-rich region (Q domain) is involved in binding to PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). The C-terminal GOLD domain is essential for giantin binding. The GOLD domain is also involved in homodimerization (PubMed:23572552)
(Microbial infection) The GOLD domain is involved in binding to the picornaviral protein 3A
BOA5 is composed of an enoyl reductase (ER) domain and presumably acts in concert with the polyketide synthase BOA6 that misses an ER domain
Contains a conserved N-terminal oligomerization domain (NTD) that is involved in oligomerization and is essential for proper subapical membrane localization
The second PDZ domain mediates interaction with membranes containing phosphoinositol lipids
The C-terminal domain is necessary for retention within intracellular membranes
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). SidN has the following architecture: A-T-C-A-T-C-A-T-C-T-C-T-C (PubMed:23658520)
Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain
The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors
Exists in at least two conformations. When in the closed, 'inactive' conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an 'active' conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion
The N-terminal globular head (Vh) comprises of subdomains D1-D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. An intramolecular interaction between Vh and Vt masks the F-actin-binding domain located in Vt. The binding of talin and alpha-actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin-binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly
The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins
The C-terminal domain (CTD) helps bind DNA
The tight homopentamer forms a pore with an opening of about 5 Angstroms in diameter which opens into a wider tunnel at the base of the truncated pyramid. The pore is positively charged
Both FN1 and one of the kringle domains are required for binding to fibrin
Both FN1 and EGF-like domains are important for binding to LRP1
The FN1 domain mediates binding to annexin A2
The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site
The histidine box domains are involved in binding the catalytic metal ions
The SPX domain has high affinity for inositol polyphosphates, such as myo-inositol hexakisphosphate and 5-diphospho-myo-inositol pentakisphosphate (5-InsP7). Its affinity for inorganic phosphate is tow to three orders of magnitude lower
The kinase domain is required for chemotaxis activity
The FACS motif is required for catalytic activity and substrate specificity
Composed of a long N-terminal alpha-helix and a core region rich in beta-sheet structures. Before the pore formation, the alpha-helix binds the lipid membrane, partitions into the lipid-water interface and stabilizes the monomeric molecule on the membrane. Finally, it traverses the bilayer, thus forming the transmembrane pore
The BIR2 domain is required for vascular development
The OAR motif may negatively regulate DNA-binding and therefore transcriptional activity. It is found in the C-terminal transactivation domain that stimulates transcription
The N-terminal domain contains the HPr binding site, the central domain the pyrophosphate/phosphate carrier histidine, and the C-terminal domain the pyruvate binding site
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior
The LRR repeats probably act as specificity determinant of pathogen recognition
Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction
The AGC-kinase C-terminal mediates interaction with THEM4
The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2)
The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a nudix box and low sequence similarity with nudix hydrolase domains. The N-terminus and the C-terminus part associate together via the NPAY binding motif and adopt a lose conformation that is disrupted by ITGB1BP1, but not by RAP1A
Contains 4 ANK repeats that precede the FERM domain
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. FG repeat types and their physico-chemical environment change across the NPC from the nucleoplasmic to the cytoplasmic side
The RRM Nup35-type domain might be involved in the control of mitosis
Contains a N-terminal zinc-binding domain and a C-terminal NGN-binding domain
The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding (By similarity)
The second C2 domain/C2B is required for the inhibitory role in both clathrin-mediated and bulk endocytosis. The transmembrane domain and the first C2 domain/C2A are critical for the inhibitory role in clathrin-mediated endocytosis or bulk endocytosis, respectively
Unlike in other synaptotagmin family members, the first C2 domain/C2A does not bind Ca(2+) neither mediates Ca(2+)-dependent phospholipid binding. An aspartate-to-serine substitution in this domain inactivates Ca(2+)/phospho-lipid binding
A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure
The hydrophobic-rich region (HR-A/B) corresponds to the oligomerization domain
The PPC domain mediates interactions between AHL proteins
The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme (By similarity)
The C-terminal region binds to collagen
The di-lysine motif may confer endoplasmic reticulum localization
The second albumin domain forms a deep binding pocket that contains palmitoleic acid (in vitro) (PubMed:29153507). Palmitoleic acid is most likely not the physiological ligand. Instead, this pocket may accomodate the covalently bound lipid moiety of Wnt family members (Probable)
The normal, monomeric form has a mainly alpha-helical structure. The disease-associated, protease-resistant form forms amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization
Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization
The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules
The SH3 domain mediates homodimerization
The xRRM domain binds the 3' end of 7SK snRNA (7SK RNA) at the top of stem-loop 4
SAHS-c1, SAHS-c2 and SAHS-c3 are 3 highly conserved regions within the SAHS protein family (PubMed:22937162)
The C-terminal domain (CTD) is probably responsible for hetero- and homodimerization (By similarity). The CTD assumes a V-shaped, dimeric metallo-chaperone-like fold and binds 1 Fe cation per subunit (By similarity)
Possesses a transit-like peptide, but it is proposed that this peptide is not removed and that therefore the enzyme stays in the cytoplasm instead of going to the chloroplast
The homeodomain differs form the typical one by having namely 4 instead of 3 extra amino acids inserted in the loop between helix 1 and helix 2
The acidic domain is probably involved in the interaction with histones
The cathelin-like domain (CLD), which is the propeptide part, does not seem to exhibit auto-inhibitory function, as it does not inhibit the antibacterial activity of antibacterial peptide LL-37
Undergoes conformational change in the presence of lipid A, transitioning from a random coil to an alpha-helical structure
Residues 17-29 of LL-37 represent the active core of the antimicrobial peptide. Forms ribbon-like fibrils and exhibits antibacterial activity against Gram-positive M.luteus (By similarity). Also exhibits antibacterial activity against Gram-negative E.coli and P.fluorescens (By similarity)
The C2H2-type zinc finger 1 has a major repressor function and is required for CTNNB1 binding
Glutathione binding may promote conformational change, from inactive to active form
N-terminal non-catalytic domain is assumed to mediate recognition of proteins with partial folding defects
The conserved DDXXD and NSE/DTE motifs are important for the catalytic activity, presumably through binding to Mg(2+)
Sushi domains 3 and 4 are the most important for interaction with C3b and C4b
The C-terminal ANK repeats prevent the assembly of the supra-tetrameric filaments
A highly mobile activation loop at the dimer-dimer interface is important for enzyme activity
Consists of an N-terminal domain, which is sufficient for the localization to the septal ring and is required for cell division, followed by a linker domain, and a C-terminal domain, which forms the translocation motor involved in chromosome segregation. The C-terminal domain can be further subdivided into alpha, beta and gamma subdomains. The alpha and beta subdomains multimerise to produce a hexameric ring, contain the nucleotide binding motif and form the DNA pump. The gamma subdomain is a regulatory subdomain that controls translocation of DNA by recognition of KOPS motifs and interacts with XerD recombinase (By similarity)
The PIP-box mediates the interaction with PCNA, while the RanBP2-type zinc finger mediates binding to 'Lys-63'-linked polyubiquitin
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-ter of the protein
The cysteine framework is XII (C-C-C-C-CC-C-C)
The GLUE domain (GRAM-like ubiquitin-binding in EAP45) mediates binding to ubiquitin and phosphoinosides
The cysteine framework is I (CC-C-C). Alpha4/7 pattern
The N-terminal domain has the RNA-binding Sm fold. It harbors the endoribonuclease activity
The C-terminal UBZ-type zinc fingers function as ubiquitin-binding domains
Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with ppk26/pan3
The RING finger mediates E3 ubiquitin ligase activity
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity
The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity
The C1 domain does not bind the diacylglycerol (DAG)
The C-helix is required for assembling the Ca(2+)-free homohexamer. It also plays a key role in mitochondrial calcium uptake, probably by mediating interaction with MICU2
The EF-hand domains have high affinity for calcium and act as sensors of calcium levels
The Tyr-Pro-Ile-Thr-Pro (YPITP) motif is important for the turnover of the reaction, presumably through its flexibility and mobility
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF3, the motif is inactive
The amino-acid kinase (AAK) domain mediates binding of the allosteric activator L-arginine
Divided into an N-terminal domain (TMD0) comprising four transmembrane helices and the following core domain (coreABCB9). TMD0 is required for lysosomal localization and LAMP1, LAMP2 and YIF1B interaction. The core domain is required for homodimerization and peptide transport activity
Consists of two distinct domains; an N-terminal heme-containing oxygen-binding domain and a C-terminal reductase domain with binding sites for FAD and NAD(P)H
The WW domain may play a role as a transcriptional activator directly or via association with the transcription machinery. The WW domain mediates interaction with WBP11, ATN1, SF3B1 and the C-terminal domain of the RNA polymerase II large subunit
Except for the WW domain, the protein is intrinsically disordered
The RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer
Sbi-I and sbi-II domains provide protection only when anchored to the cell surface, whereas only the secreted sbi-III and sbi-IV domains are biologically active
The N-terminus domain is necessary for S/G2 nuclear foci localization (PubMed:23149945)
(Microbial infection) VTT domain is required for flavivirus infection
The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding
The cysteine framework is XI (C-C-CC-CC-C-C)
The GXXXX[G/A/S] motif at the C-terminal part of the transmembrane region mediates interaction with MCU and is required to activate the calcium-conducting pore in the uniporter complex
The poly-Asp region at the C-terminus mediates interaction with the polybasic region of MICU1
The J domain is essential for co-chaperone activity and mediates the heterodimerization with the J-like domain of PAM16
The leucine-zipper is required for dimerization and transcriptional repression
The di-leucine motif mediates lysosomal localization
Splicing of the SAC1 domain does not alter the catalytic activity of synaptojanin 1
The WW domain recognizes the proline, glycine and methionine-rich (PGM) motif present in the splicing factors, as well as the Arg/Gly-rich-flanked Pro-rich domains found in several WW domain-binding proteins
The RING-type zinc finger domain is required for E3 ligase activity
The RGS domain interacts avidly with Galpha and mediates the acceleration of Galpha-mediated GTP hydrolysis
The N-terminus is required for dimer formation, association with RFXANK and RFXAP, assembly of the RFX complex, and for binding of this complex to its X box target site in the MHC-II promoter. The C-terminus mediates cooperative binding between the RFX complex and NF-Y
The PxLPxI/L motif mediates interaction with ankyrin repeats of RFXANK
LysM domains are thought to be involved in peptidoglycan binding
The RRM domain mediates both interaction with RNA and with KMT2A (via the third PHD-type zinc-finger), but has much higher affinity for the KMT2A PHD-type zinc-finger
The transmembrane domain is necessary for interaction with KCNMA1
Contains an N-terminal dimerization domain. The C-terminal region contains the S-adenosyl-L-methionine binding site
The SH3 domain mediates interaction with SMN1
Interaction with the C-terminus of CFTR could be mediated through independent binding of PDZ 1, 3 and 4 domains
The histidyl-tRNA synthetase-like region and protein kinase domains are necessary for eIF-2-alpha kinase activity and eIF-2-alpha-mediated translational control. The histidyl-tRNA synthetase-like domain is necessary for binding to uncharged tRNAs. Kinase domain 1 is a degenerate kinase domain
Riboflavin is stacked with one or more Trp residues in the binding pocket of RibU
The central region (136-221) reveals a striking structural homology with the core domain of GAR1
The CKK domain binds microtubules
The FYVE domain is involved in the binding to phosphatidylinositol 3-phosphate (PtdIns(3)P) which is required for the association to endosomal membranes
Both IUM domains are necessary for efficient binding to ubiquitin
The L-X-X-L-L repeats may be implicated in binding to nuclear receptors
The HSR domain is required for localization on tubular structures (N-terminal part) and for homodimerization
Interacts via the first PHD domain with the N-terminus of histone H3 that is not methylated at 'Lys-4'. Disruption of the first PHD domain has been shown to lead to reduced transcriptional activity and to localization of the protein mainly in the cytoplasm in small granules. While the PHD zinc fingers are necessary for the transactivation capacity of the protein, other regions also modulate this function
Forms a U-shaped beta-half-barrel with a large hydrophobic cavity which is large enough to hold a single phthiocerol dimycocerosate (PDIM) molecule
The cysteine framework is III (CC-C-C-CC). Classified in the M-3 branch, since 3 residues stand between the fourth and the fifth cysteine residues
Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell. This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin. The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane. Each cadherin domain binds three calcium ions
Each zinc finger-like domain binds a zinc ion and is involved in both ssDNA and dsDNA binding, as is the OB-fold domain
The N-terminal domain mediates homodimerization
The kinase domain is involved in SPSB1 binding
The beta-propeller Sema domain mediates binding to HGF
Contains an N-terminal helix-turn-helix DNA-binding domain, an intermediate oligomerization domain and a C-terminal transmembrane domain
Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain (PubMed:6425296). Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein (By similarity)
The C-terminus (approximately residues 1003-1170) is required for interaction with M(2)S(1) and with Escherichia phage T7 Ocr protein
The VIMAG motif is necessary for the function of the protein
Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands
Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B
In an autoinhibited form the C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. An ADP-mediated interaction between the NBD and the WHD also contributes to the autoinhibition
Both the conserved triple repeat of the QXXK/R motif and the hydrophobic region are essential for its activity. The hydrophobic region contributes to the endoplasmic reticulum membrane localization
The PDZ domain in the N-terminal part of the neuronal isoform participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes in muscles. Mediates interaction with VAC14 (By similarity)
Has protease activity
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (PubMed:28252640, PubMed:29649119). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol. The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (PubMed:28252640)
Contains 5 SPKK motifs which may interact with the minor groove of A/T-rich DNA sites. Phosphorylation of this motif may regulate DNA binding. This motif is reiterated in both termini of histone H1 and in the C-terminus of plant H2A, but its presence in the N-terminus seems to be unique to sea urchin histones H2B
The active site is situated at the inner surface of a pore formed by the four subunits
The PX domain binds phosphatidylinositol 3-phosphate (PtdIns(3)P) which is necessary for peripheral membrane localization
The C-terminal region contains a putative helix-turn-helix (HTH) motif, suggesting that this region may bind DNA
Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors
The C-terminal RNA-binding region of CA is sufficient for all its nucleocapsid-like chaperone activities
The EI N-terminal domain contains the HPr binding site, the central domain the pyrophosphate/phosphate carrier histidine, and the C-terminal domain the pyruvate binding site
The GAF domain is an important site of signal perception in prokaryotes and eukaryotes
The cysteine framework is I (CC-C-C). Alpha4/4 pattern
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage
Its C-terminal part seems to contain many membrane-spanning sided beta-sheets, that have the potential to adopt a transmembrane beta-barrel type structure
The NC80 domain (486-565) contains a major active site responsible for the signal transduction processes regulating both hypocotyl inhibition and floral promotion. The C-terminal tail (564-612) is not required for physiological activity of the protein
Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (374-404) inactivates kinase activity under calcium-free conditions (By similarity)
The UBZ2-type zinc finger binds both 'Lys-48'- and 'Lys-63'-linked polyubiquitin with preference for 'Lys-63'-linked polyubiquitin
This protein has four EF-hand domains, three of which may be functional calcium-binding sites
The C-terminal domain binds DNA and the N-terminal domain is involved in dimerization. Both domains are essential for normal function (By similarity)
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC4, forming a V-shaped heterodimer
The PH domain binds phosphoinositides with a broad specificity. It may compete with the PH domain of some other proteins, thereby interfering with their binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity)
The SBP-type zinc finger is required for the binding to DNA
The C2 domain is required for the repression
The leucine-rich repeats (LRRs) are important for potentiation of Wnt7 signaling
The two calmodulin-binding domains appear to act in concert to bind a single molecule of calmodulin and are pseudosubstrate/autoinhibitory domains
The autoinhibitory domain prevents access to the catalytic site
The autoinhibitory segment prevents access to the substrate binding site
Possible isomerization of Pro-309 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA
Consists of a six-stranded anti-parallel beta-barrel core structure with an unstructured N-terminus in apo-form and a C-terminal alpha helix. In the holo-form the C-terminal helix is displaced by the ligand, thereby opening one side of the beta-barrel as a binding site, and the N-terminus containing the RXXXR motif wraps around the ligand and in turn ties the C-terminal helix in a loose conformation. The structural rearrangement upon ligand binding creates a significant change in surface charge distribution
The binding of calmodulin to the C-terminus might interfere with cyclic nucleotide binding and thus channel activation
Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif essential for phosphatidate phosphatase activity
The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida
The complementarity-determining region CDR1 confers specificity to the metabolite antigen
The complementarity-determining region CDR2 confers specificity to the metabolite antigen
The complementarity-determining region CDR3 confers specificity to the metabolite antigen
The connecting peptide (CP) domain contributes to the TR-CD3 assembly and signal transduction
The TM domain mediates the interaction with the CD3 subunits
Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is an head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane (PubMed:27161523). Each cadherin domain binds three calcium ions (PubMed:27161523)
Contains an N-terminal extension, a central body region and a C-terminal tail (PubMed:25784551). The C-terminal tail, which inhibits the protease active site, and the N-terminal extension are both critical for binding and folding of ASP (PubMed:25784551)
Composed of consecutive beta sandwich domains, a coiled-coil domain and a C-terminal transmembrane helix
The Ubiquitin-like domain is required for the interaction with RNF31
The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and 'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin chains. Also binds monoubiquitin (By similarity)
The NEAT domain is responsible for binding Fe(3+) and Fe(2+) heme and fibrinogen. The NEAT domain is an inhibitor of apolactoferrin activity, while the C-domain confers resistance to bovine lactoferricin (By similarity)
The LID domain closes over the active site upon ATP binding
Has three domain each corresponding to an enzymatic activity, namely in N- to C-terminal order: ligase, kinase and cyclic phosphodiesterase (CPDase)
The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm
RII-binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer
The PAL motif is required for normal active site conformation
The coiled coil domain is required for homodimerization
The region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1
The HXXXXD motif is essential for acyltransferase activity
Contains an N-terminal DNA-binding domain and a C-terminal sugar-binding domain
The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases
The BTB (POZ) domain mediates dimerization and interaction with CUL3
The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as MACROH2A1 and BMI1
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. FG repeat types and their physico-chemical environment change across the NPC from the nucleoplasmic to the cytoplasmic side: SXFG/PXFG repeats are especially abundant in NUPs on the cytoplasmic side
OdhA is a fusion protein with two major domains exhibiting structural features of an E1 and E2 protein, and a short sequence stretch of E1 localized at the N-terminus, which is connected by a linker region to the rest of the protein. Deletion of individual parts of odhA show that all parts of odhA are required for a functional tricarboxylic acid cycle in C.glutamicum; the ODH activity is in fact completely abolished in each of these mutants, and the PDH activity is significantly reduced, which could indicate that the overall structure of the supercomplex is disturbed
Has a discontinuous central core of beta sheets stabilized by a disulfide bond that is flanked by 2 structural domain repeats on each side; the protein forms an elongated 'S'-shaped structure (PubMed:26396239, PubMed:26841765, PubMed:26922638). Repeat A2 (approximately residues 265-323) is farthest from the cell inner membrane and is quite mobile, swinging on 2 inter-repeat loops (A, residues 234-264 and B, 324-341) (PubMed:26841765)
Phosphatidylinositol 4,5-bisphosphate binding to the cytoplasmic side of the channel triggers a conformation change leading to channel opening
The L27 domain (also called Maguk recruitment domain) is required for interaction with PALS1 and CRB3, and PALS1 localization to tight junctions
The PDZ domain 6 mediates interaction with the C-terminus of TJP3 and is crucial for localization to the tight junctions (By similarity). The PDZ domain 8 interacts with CLDN1 but is not required for proper localization (By similarity)
Myosin tail domain binds directly to anionic phospholipid membranes; myosins I could therefore move actin relative to membranes and vice versa. TH.2 and SH3 bind tightly to F-actin; this together with the nucleotide-sensitive site in the head, allows single molecules of myosin I to cross-link actin filaments
C2H2-type zinc fingers 3 interacts with DNA-binding site G-clusterinc fingers. C2H2-type zinc fingers 6 and 7 interact with DNA-binding site core sequence
Undergoes conformational changes upon the binding of S-adenosyl-L-methionine and the metal ion
The N-terminal and the C-terminal half of the protein have a very similar 3D-structure, suggesting they arose from duplication. Requires a bound zinc ion for normal folding and solubility
Consists of a typical ABC-ATPase domain, comprising two subdomains, connected by a linker region to a C-terminal domain of unknown function
the 9aaTAD motifs are transactivation domains present in a large number of yeast and animal transcription factors
Consists of an N-terminal domain, which is sufficient for the localization to the septal ring and is required for cell division, followed by a linker domain, and a C-terminal domain, which forms the translocation motor involved in chromosome segregation. The C-terminal domain can be further subdivided into alpha, beta and gamma subdomains. The alpha and beta subdomains form the DNA pump, and the gamma subdomain is a regulatory subdomain (By similarity)
Folds into a two seven-bladed beta-propeller structure which is required for elongator complex assembly
Contains large globular domains required for ATP hydrolysis at each terminus and a third globular domain forming a flexible SMC hinge near the middle of the molecule. These domains are separated by coiled-coil structures
Consists of a single catalytic domain, but remodels its active-site architecture via a large structural change to exhibit dual activities
The cytosolic domain interacts with ECF sigma factor SigD
The extracellular domain assumes a distinct boomerang shape when not bound to IZUMO1R/JUNO (By similarity). Interaction with IZUMO1R/JUNO triggers a conformation change, so that the IZUMO1 extracellular domain assumes an upright conformation (By similarity)
The cytoplasmic C-terminus region is not essential for fertilization (PubMed:27624483). It is however required for protein stability (PubMed:27624483)
Contains the consensus sequence Cys-X(5)-Arg characteristic of Mg-independent phosphatases
It is thought that substrate reaches the active site through the seven-bladed beta propeller channel, while products exit via the six-bladed beta propeller channel
The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum
AC 1 and AC 2 (clusters of acidic amino acids) contain sorting information. AC 1 directs TGN localization and interacts with the TGN sorting protein PACS-1 (By similarity)
The 5 Arg-Ser-Xaa-Ser-Xaa-Xaa (RSXSXX) motifs may constitute binding sites for the 14-3-3 protein
Contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins
The C-terminal SM 1 domain is both necessary for the binding to the Sm-binding site of U7 snRNA and U7 snRNP assembly (By similarity). The N-terminal domain is essential for histone pre-mRNA cleavage (By similarity). Amino acids 63-82 are sufficient to interact with ZNF473 (By similarity)
The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance its ability to phosphorylate the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II)
The N-terminus is involved in the initial binding to heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity). The N-terminus masks the TSP type-1 (TSR) domain which maintains the sporozoites in a migratory state, enabling them to complete their journey to the salivary gland in the mosquito vector and then to the host liver. The unmasking of the TSP type-1 (TSR) domain when the sporozoite interacts with the host hepatocyte also protects sporozoites from host antibodies (By similarity)
The TSP type-1 (TSR) domain is required for sporozoite development and invasion. CSP has two conformational states, an adhesive conformation in which the TSP type-1 (TSR) domain is exposed and a nonadhesive conformation in which the TSR is masked by the N-terminus. TSR-exposed conformation occurs during sporozoite development in the oocyst in the mosquito vector and during host hepatocyte invasion. TSR-masked conformation occurs during sporozoite migration through the hemolymph to salivary glands in the mosquito vector and in the host dermis
The GPI-anchor is essential for cell membrane localization and for sporozoite formation inside the oocyst
Contains 2 SPKK motifs which may interact with the minor groove of A/T-rich DNA sites. Phosphorylation of this motif may regulate DNA binding. This motif is reiterated in both termini of histone H1 and in the N-terminus of sea urchin histones H2B, but its presence in the C-terminus seems to be unique to plant H2A
The RRM domains mediate RNA-binding
The QLQ domain and WRC domain may be involved in protein-protein interaction and DNA-binding, respectively
The GTPase domain may regulate the interaction with UGO1 since FZO1 lacking the GTPase domain binds 5-fold higher amount of UGO1 than full-length FZO1. The coiled-coil heptad repeat domains HRN, HR1 and HR2 are required for the oligomerization and function in mitochondrial fusion
The ADD domain predominantly interacts with histone H3 trimethylated at 'Lys-10'(H3K9me3) (and to a lesser extent H3 mono- or dimethylated at 'Lys-10') and simultanously to histone H3 unmethylated at 'Lys-5' (H3K4me0). The interaction with H3K9me3 is disrupted by the presence of H3K4me3 suggesting a readout of the combined histone H3 methylation state
The NAC domain includes a DNA binding domain and a dimerization domain
The N-terminal half of the protein contains two conserved domains I and II. Domain I includes a slightly degenerated ERF-associated amphiphilic repression (EAR) motif which seems to be involved in the activity of transcriptional repression. Domain II is required for the correct degradation of the protein through the SCF-mediated ubiquitin-proteasome pathway. Interactions between Aux/IAA proteins and auxin response factors (ARFs) occur through their C-terminal dimerization domains III and IV (By similarity)
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP9, the motif is inactive
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1A or SMC1B, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity)
The monomer structure is formed from three repeating units (RUs) that share the same structure as one another. The monomer, the active site and substrate all possess threefold rotational symmetry, to the extent that the active site possesses three potential Ser-Lys catalytic dyads. It is possible that any or all of the three active-site serines may act as nucleophile (albeit only one can do so per catalytic cycle)
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC6, forming a V-shaped heterodimer
The LIR motif is required for the interaction with ATG8 and for the association of ATG1 with autophagosomes
Contains 4 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases
The PDZ-binding motif mediates the interaction with GRIP1
The C2 domain mediates pre-localization to the membrane prior to Ca(2+) import and non-selective Ca(2+)-mediated targeting to various cellular membranes
The PH domain is not a critical determinant of the membrane localization
The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins)
The N-terminal Ras-GEF domain mediates association with F-actin
The VHS and UIM domains mediate the interaction with ubiquitinated proteins
The SH3 domain mediates the interaction with USP8
Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain
Has 2 BMC domains which can evolve independently of each other
The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way
The C-terminal region from residues 103 to 132 is important for BAK1/SERK3-binding and the host cell death suppression
The N-terminal domain is required for nuclear export of both poly(A) RNA and NAB2
The RGG domain is important for NAB2 import
Contains seven CCCH Zn fingers that bind to A-rich RNAs and fingers 5 to 7 are critical for these function (PubMed:12496292, PubMed:22560733, PubMed:28180315). Binding A(11)G RNA induces dimerization of Zn fingers 5-7 mediated by the spatial arrangement of the fingers promoting each RNA chain binding two protein chains (PubMed:28180315)
Resistance to charybdotoxin (CTX) toxin is mediated by the extracellular domain
The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition
The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain (By similarity)
The KA1 domain mediates binding to phospholipids and targeting to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (By similarity)
Contains Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, a motif known to be important for the association with nuclear receptors
Interactions between auxin response factors (ARFs) and Aux/IAA proteins occur through their C-terminal dimerization domains III and IV
The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes
The presence of a 'disulfide through disulfide knot' structurally defines those proteins as knottins
The NEAT domain binds Fe(3+) heme iron. Reduction of the high-spin Fe(3+) heme iron to high-spin Fe(2+) results in loss of the heme from the binding site of the protein due to the absence of a proximal histidine (By similarity)
The LRR (leucine-rich repeat) repeats are involved in substrate recognition with target proteins
The N-terminal region is necessary for its proteasomal degradation, transcriptional activity and interaction with EP300/P300
The SH3 domain mediates the binding to CBLB
The C-terminal domain binds 2 Fe-S clusters but is otherwise mostly in an intrinsically disordered conformation
The N-terminal domain has structural similarity with S-adenosyl-L-methionine-dependent methyltransferases, but does not bind S-adenosyl-L-methionine. It is required for correct assembly of the 2 Fe-S clusters
The truncated N-terminal protein kinase domain lacks most of its classical characteristics and in vitro, has no activity
The protein kinase domain 1 is predicted to be catalytically inactive
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with par-2/pan3
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate
The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain (Potential). The Prospero-type homeodomain is essential for repression of RORG transcriptional activator activity (PubMed:23723244)
Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity)
The Link domain interacts with various extracellular matrix components, including heparin, heparan sulfates, hyaluronan and I-alpha-I complex. It is required for binding to various chemokines
The CUB domain is necessary for calcium ion binding and transesterification reaction. It is required for binding to FN1
The N-terminal region regulates its kinase activity
The coiled-coil domain (311-350) is involved in dimerization
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). NotE as the following architecture: A1-T1-C1-A2-T2-C2. The presence of two intact modules suggests that the two modules condense L-tryptophan and L-phenylalanine together. The C-terminal condensation domain might be responsible for cyclization of the dipeptide to form the diketopiperazine structure (Probable)
The third LIM zinc-binding mediates interaction with E4F1
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent lipid-anchoring to the cell outer membrane and eventual release of the passenger domain
The translocator domain (residues 777-1084) forms a 12-stranded beta-barrel with a 10 X 12.5 Angstrom channel with its N-terminal alpha helix (residues 786-817) inside the channel. The N-terminus of the N-terminal alpha helix points to the extracellular side. The isolated beta-barrel forms a pore able to import and export antibiotics; removal of the N-terminal alpha helix enhances transport
The entire WD repeat region is required for the interaction with ORC complex components, as well as for association with chromatin and for binding to histone methylation marks
Partial trypsin digestion of this subunit (removing the first 28 residues) yields an active protein less susceptible to aggregation
The N-terminal domain (about residues 1-140) is an archaea-specific tRNA-editing domain (PubMed:15240874, PubMed:26113036) that has a highly similar structure to Dtd (D-aminoacyl-tRNA deacylase). Editing of incorrectly charged L-seryl-tRNA(Thr) by this domain is tRNA catalyzed (PubMed:26113036)
The N-terminal region is involved in phosphatidylethanolamine-binding and is required for ATG8-PE conjugation (By similarity)
The flexible region (FR) is required for ATG7-binding (By similarity)
The handle region (HR) contains the ATG8 interaction motif (AIM) and mediates binding to ATG8 (By similarity). It is crucial for the cytoplasm-to-vacuole targeting pathway (By similarity)
The 2 chromodomains are involved in the binding to the histone H3 methyllysine at position 4 (H3K4me3)
The CHD1 helical C-terminal domain (CHCT) binds DNA and nucleosomes
Adopts a GT-B fold and acts as an inverting enzyme that converts the beta-configuration in the dTDP-beta-L-rhamnose donor to the alpha configuration in the N-linked (Rha) arginine product
These WW domains interact with Arg/Gly-rich-flanked Pro-rich domains found in several WW domain-binding proteins (WBPs). The N-terminal WW domain has the greater ligand-binding ability (By similarity)
Possesses two phosphotransferase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for domain 1
The protein kinase 1 domain is also called the pseudokinase domain and has a regulatory role through the transactivation of other JAK kinases associated with signaling receptors
The protein kinase 2 domain is the catalytically active domain
The SH3 domain mediates localization to the clathrin-coated pits and vesicles
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (By similarity)
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (By similarity)
Forms a helix-turn-helix motif with helix 1 (residues 38-56) nearly parallel to helix 2 (residues 61-82); helix 1 contacts both Rpo5 and Rpo1N. The C-terminal region (residues 81-104) is required for DNA-binding
The doublecortin is involved in the binding to microtubules; however, it is not sufficient by itself and requires the partial p25alpha domain
The partial p25 alpha domain binds to microtubules
The PPIase activity resides only in the second parvulin domain. The N-terminal region and the C-terminal tail are necessary and sufficient for the chaperone activity of SurA. The PPIase activity is dispensable for SurA to function as a chaperone. The N-terminal region and the C-terminal tail are also required for porin recognition
It contains a N-terminal DNA binding region and a C-terminal metal binding region
The IQ domain mediates interaction with calmodulin when cellular Ca(2+) levels are low
The ESA1-RPD3 motif is common to ESA1 and RPD3 and is required for ESA1 histone acetyl-transferase (HAT) activity and RPD3 histone deacetylase (HDAC) activity
Intramolecular interactions between N- and C-terminal domains may be important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain, that is released upon cleavage by CASP3 or granzyme B (GZMB)
In PaxB the peptidase C39 domain, the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain, which is unstructured in its native, soluble form, and which forms a parallel in-register beta-sheet in its amyloid form
The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (NSD3, JMJD6, CHD4, GLTSCR1 and ATAD5)
The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex. It is also required for maintenance of higher-order chromatin structure
The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-434, respectively (PubMed:19828451). The exact combination of modified histone tails required to recruit BRD4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3. A number of specific inhibitors bind competitively to acetyl-lysine-binding residues Asn-140 and Asn-434, promoting removal from acetylated histones. Many of these inhibitors are benzodiazepine derivatives
Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs. One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (By similarity). Binds calmodulin in a calcium-dependent way (By similarity)
The clip domain consists of 35-55 residues which are 'knitted' together usually by 3 conserved disulfide bonds forming a clip-like compact structure
The UIM-like region mediates binding to host ubiquitin
The activation most likely occurs via a reversible conformational rearrangement of the enzyme, leading to a catalytically competent form (PubMed:32142609). Both the P- and D-loop form part of the binding interface (PubMed:22888002)
The C-terminus contains a calmodulin-binding domain, which binds calmodulin in a calcium-dependent fashion
The mature protein rapidly forms a predominantly amyloid fibril beta-sheet structure at pH 3.0 and 4.2, with less beta-sheet and more random coil at pH 10 (Probable) (PubMed:28925983). Reduced and non-reduced peptide have the same secondary structures at all pH tested, suggesting the disulfide bond is not required for fibril formation (PubMed:28925983)
The BH3 motif is required for the induction of cell death
The OPR/PB1 domain mediates the association with NCF4/p40-PHOX
The N-terminus (1-54) is necessary and sufficient for targeting to the intermembrane space by an import pathway that is distinct from the general import pathway utilized by stromal preproteins
The non-canonical ER retention motif mediates retention of the protein in the endoplasmic reticulum
KEN box sequence located in the C-terminal region is required for its mitotic degradation by the APC/C-FZR1 ubiquitin ligase and interaction capability with FZR1
The PTS EIIB type-2 domain is phosphorylated by phospho-EIIA on a cysteinyl residue. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the PTS EIIC type-2 domain
The EIIC type-2 domain forms the PTS system translocation channel and contains the specific substrate-binding site
Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Only motif 1 is essential for the association with nuclear receptors
The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself. The WXXF motif 1, which is preceded by an acidic residue and has a glycine in second position mediates specific interaction with AP-1. The WXXF motif 2, which is followed by the C-terminal carboxyl group negative charge, allows specific interaction with AP-2
The PPxY motif mediates interaction with NEDD4
The N-terminal zinc finger binds to poly(A) RNA
The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for pan2
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the pan2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of pan2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs
The region required for head formation is located in the propeptide, which itself interferes with proteolytic processing of the precursor. The mature region has the same activity as that of BMP3
The C-terminus (346-534) is specific for the interaction with PETH/FNR
The central region (247-346) is sufficient for binding to the Tic complex
The N-terminus has a dehydrogenase activity in vitro
The SH3-binding domain is buried in the tertiary structure, and it therefore unclear whether it directly mediates protein-binding
Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains. The first ABC transporter nucleotide-binding domain has no ATPase activity by itself
The C-terminal domain is necessary for protein interactions
The PIP-box mediates the interaction with PCNA
The U-box N-terminal domain (UND) is not required for in vitro ubiquitination activity
The presence of 'disulfide through disulfide knots' structurally defines this protein as a knottin. This toxin contains 2 'disulfide through disulfide knots'
This protein is considered an atypical serine/threonine kinase, because it lacks the conventional structural elements necessary for the substrate recognition as well as a lysine residue that in all other serine/threonine kinases participates in the catalytic event (By similarity). BUD32 has protein kinase activity in vitro, but in the context of the EKC/KEOPS complex, the catalytic subunit KAE1 switches the activity of BUD32 from kinase into ATPase (By similarity)
Consists of three main regions, an N-terminal coiled-coil domain that may assist in substrate recognition, an interdomain involved in PAN hexamerization, and a C-terminal ATPase domain of the AAA type
Contains three distinct domains: an adenylation (A) domain that activates the substrate amino acid which is subsequently covalently linked as a thioester (aminoacyl-S-PCP) to the 4'-phosphopantetheine prosthetic group of the second domain, the peptidyl carrier protein (PCP) domain, as well as a reductase (R) domain of the short-chain dehydrogenase/reductase (SDR) type
The protein kinase-like region mediates the threonine-protein kinase activity
The DWD boxes are required for interaction with DDB1
The chromo domain with a restricted pocket directly recognizes monomethylated substrates
The N-terminal region mediates dimerization and homooligomerization. Both the helicase ATP-binding domain and the helicase C-terminal domain form intramolecular interactions with the HRDC domain in a ATP-dependent manner. The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding
The N-terminal may interact with various proteins as a chaperone to assist in the folding and insertion of proteins into the outer membrane. The C-terminal region may serve as the link between BamA, BamC and BamE
The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins
The protein is largely disordered, with the exception of the zinc finger domain
The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases
The PDZ domain mediates interaction with PALS1
The HXHXDH motif is essential for the endoribonuclease activity of the CPSF complex
The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD/ASC-binding
The FISNA domain is a critical mediator of NLRP3 conformational during NLRP3 activation (PubMed:34524838, PubMed:36442502). It becomes ordered in its key regions during activation to stabilize the active NACHT conformation and mediate most interactions in the NLRP3 disk (PubMed:36442502)
The LRR domain mediates the interaction with IRF4 and PML
The KFERQ-like motifs mediate binding to HSPA8/HSC70 following NLRP3 paylmitoylation by ZDHHC12
The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins
Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position
Contains a central domain containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif (By similarity). The SH2-binding sites putatively bind CRKL SH2 domains (By similarity). The HLH motif confers specific interaction with the HLH protein ID2 (By similarity). It is absolutely required for the induction of pseudohyphal growth in yeast and mediates homodimerization and heterodimerization with BCAR1/p130cas (By similarity)
The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of eif3d into the full eukaryotic translation initiation factor 3 (eIF-3) complex
The Cx9C/Cx10C motifs are involved in the recognition by the mitochondrial MIA40-ERV1 disulfide relay system and the subsequent transfer of disulfide bonds by dithiol/disulfide exchange reactions to the newly imported protein
Contains a slightly degenerated ERF-associated amphiphilic repression (EAR) motif, which may be involved in the activity of transcriptional repression
The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3
The Asp-Asp-Xaa-Xaa-Xaa-Glu (DDXXXE) motif is important for the catalytic activity, presumably through binding to Mg(2+)
The SR/KY and BELL domains are responsive for the interaction between the TALE/BELL proteins and the TALE/KNOX proteins
The PPIase activity is mainly due to the first PPIase FKBP-type domain (1-138 AA)
The C-terminal region (AA 375-458) is required to prevent tubulin polymerization
The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400
The TPR repeats mediate mitochondrial localization
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3
BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity
The BH3 motif is required for XIAP-mediated ubiquitination and subsequent induction of apoptosis
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1
Contains four of the five characteristic MBL-fold metal-binding motifs, with two waters completing metal coordination
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis
Consists of two domains; the N-terminal catalytic domain (in this organism this is shorter than usual) and the editing domain; the C-terminal C-Ala domain found in most orthologs is missing. The editing domain removes incorrectly charged amino acids (By similarity)
RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer
Both the N-terminal core domain and the C-terminal headpiece domain are sufficient for binding to F-actin and necessary for actin bundling activity
The BEN domain mediates DNA-binding
The C-terminus (388-501) is important for catalytic activity or for enzyme stability. The N-terminus (1-89) appears to be dispensable for enzymatic activity
The dileucine internalization motif is required for lysosomal localization
Binds UBE2I/UBC9 and two SUMO2 molecules via its N-terminus. The most N-terminal region interacts with the SUMO2 chain that is covalently bound to the UBE2I/UBC9 active site, while the second region interacts with another SUMO2 that is non-covalently associated with the same UBE2I/UBC9 chain
The PB1 domain mediates interaction with SQSTM1
It contains an N-terminal DNA-binding domain and a metal-binding domain
The stem domain mediates specific interaction with beta-linked N-acetylglucosamine moieties of O-glycosylated proteins. It also interacts with its product, N-acetyl-beta-D-glucosaminyl-(1->2)-O-alpha-D-mannosylprotein
The PIP-box mediates the interaction with PCNA, while the UBZ4-type zinc finger mediates binding to 'Lys-48'- and 'Lys-63'-linked polyubiquitin
The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding
GRAM domain binds phosphatidylserine in the PM and mediates protein recruitment to endoplasmic reticulum-plasma membrane contact sites (EPCS) in response to excess cholesterol in the PM
VASt (VAD1 Analog of StAR-related lipid transfer) domain, also known as ASTER (Greek for star) domain is a sterol-binding domain
Both the JmjC domain and the JmjN domain are required for enzymatic activity. However ARID and PHD-type 1 domain are not required for activity per se but contributed to recognition of the H3(1-21)K4me2 substrate peptide
The 2 first PHD-type zinc finger domains are required for transcription repression activity
The DH domain mediates interaction with RHO1
The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage
The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex
The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response
The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1
The amino-acid kinase (AAK) domain mediates binding of L-arginine
The N-terminus strongly influences thyroid hormone-binding properties
N-terminus mediates homodimerization
The EIIA domain is phosphorylated by phospho-HPr on a histidyl residue. Then, it transfers the phosphoryl group to the EIIB domain
The EF-hand domain 1 cannot bind calcium due to the presence of a Lys instead of an Asp at position 429 and a Gln instead of a Glu at position 436 preventing calcium binding. The EF-hand domains 3 probably binds calcium constitutively when calcium levels are low, while the EF-hand domain 2 binds calcium following an increase in calcium levels
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive. The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains
The PH and FYVE domains may be important for TNF-induced localization to the endoplasmic reticulum and for enhanced cellular sensitivity to TNF-induced apoptosis (PubMed:18288467). The FYVE domain is important for binding to the endosomal membrane
The adenylyl-sulfate kinase (APS kinase) is non-functional. It is involved in allosteric regulation by PAPS. PAPS binding induces a large rotational rearrangement of domains lowering the substrate affinity of the enzyme
The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide
The HIT domain is required for enzymatic activity
The C2H2-type zinc finger mediates DNA-binding
Contains an alpha-helical N-terminal domain (FinO-like) and a beta-sheet C-terminal domain (Hfq-like), connected by an unstructured linker. The FinO-like domain serves as a high-affinity RNA-binding domain, whereas the Hfq-like domain is largely responsible for RNA strand exchange and duplexing
The N-terminal beta-like import receptor binding (BIB) domain mediates interaction with IPO5, IPO7, KPNB1 and TNPO1
The GxGxxG motif is important for the function, possibly through binding with ATP
The GRAM domain is required for cell membrane localization
The C-terminus domain (aa 502-617) mediates interaction with MTMR9
The Tudor domain is sufficient for binding to the N-terminus (1-14) of both unmethylated piwi or piwi symmetrically dimethylated at 'Arg-10' (PubMed:29531043). However, it may not be sufficient for binding to symmetrically dimethylated AGO3, instead this interaction may require a larger region of the C-terminus which includes the Tudor domain (257-576) (PubMed:21447556, PubMed:29531043)
The fido domain mediates the adenylyltransferase activity
The U-box domain is required for the ubiquitin protein ligase activity
Regions C1 and C2 can either interact with nucleotide-free CDC42, or interact together
The cysteine framework is VIII (C-C-C-C-C-C-C-C-C-C)
Has a modular structure: a carbohydrate-binding module (CBM) at the N-terminus, a linker rich in threonines, and a C-terminal exocellobiohydrolase catalytic module. The genes for catalytic modules and CBMs seem to have evolved separately and have been linked by gene fusion
The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids
A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter
The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis (By similarity)
The BIR repeat is necessary and sufficient for LAMTOR5 binding
The twin Cx2C motifs are involved in the recognition by the mitochondrial MIA40-ERV1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space
The tail may be important in modulation of channel activity and/or targeting of the channel to specific subcellular compartments
The DWD box is required for interaction with DDB1A
The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue
The cysteine framework is III (CC-C-C-CC). Classified in the M-2 branch, since 2 residues stand between the fourth and the fifth cysteine residues
The CUE domain mediates interaction with PGR and ESR1
The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity (Probable). The TIR domain alone is active and produces cADPR (residues 134-267) (PubMed:36048923)
The KBM 2 (Ku-binding motif 2) and XLM (XLF-like motif) mediate cooperative interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites
The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage
Calcium may be bound by the cadherin-like repeats
The region C, also named Pat-C, is required for RNA-binding and mediates the binding with the Lsm-containing SMN-Sm protein complex and the decapping machinery. It folds into an alpha-alpha superhelix, exposing conserved and basic residues on one side of the domain
BUB1 N-terminal domain directs kinetochore localization and binding to BUB3
The PH domain mediates interaction with lipid membranes that contain phosphatidylinositol-4,5-bisphosphate, but does not bind membranes that lack phosphatidylinositol-4,5-bisphosphate
Consists of a central region with similarity to the repeat domains of ACVS and GRC2, flanked by two repeat domains, each of which contains 5 direct repeats
Consists of an N-terminal non-heme diiron domain and a C-terminal flavodoxin-like domain
RRM domain 2 has moderate RNA-binding affinity. RRM domains 3 and 4 may facilitate RNA looping when binding to two appropriately separated binding sites within the same target pre-mRNA
The RRM domain is necessary for mRNA stability and mRNA translation regulation
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM)
The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities
The catalytic domain is responsible for mediating its self-association
The extracellular loops are most variable in sequence, and in some bacteria confer sensitivity to phage and/or colicins
The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif, APIM), mediates the colocalization of ALKBH2 with PCNA at the replication foci, coordinating the repair of alkylated DNA damage with DNA replication
The C-terminal RING-type zinc finger domain is sufficient for interaction with IRF2
The Ig-like C2-type 1 domain mediates homodimerization and interaction with JAML
The PDZ-binding motif mediates interaction with MPDZ and MAGI1
The T-Box domain binds to double-stranded DNA
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Leu (NPA)
The HCF repeat is a highly specific proteolytic cleavage signal
The kelch repeats fold into a 6-bladed kelch beta-propeller called the beta-propeller domain which mediates interaction with HCFC1R1
Glu-129 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-203 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group
The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins
Has 16 transmembrane helices and a cytoplasmic domain that contains the active site. Pyrophosphate binding is thought to trigger a conformation change that allows Na(+) release. Has at least two binding sites for Na(+) (PubMed:22837527)
The jas domain (202-227) is necessary and sufficient for interaction with COI1 and is required for TIFY 10A/JAI1 instability in response to jasmonate (PubMed:17675405, PubMed:18547396). The jas domain (202-227) is required for interaction with Pseudomonas syringae HopZ1a (By similarity)
Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors
Calcium-binding is structural and does not influence the alkaline phosphatase activity. At very high concentrations, calcium can however substitute for zinc at zinc-binding sites, leading to strongly reduced enzyme activity
The extracellular coiled coil domain forms an extended 170 A long semi-flexible rod-like structure important for virion retention at the cell surface and prevention of virus spreading
Despite a weak sequence similarity, retains most of the structural features of the ancestral archaeal Top6B subunit (AC O05207), including the transducer domain that interacts with the SPO11 subunit and the ATP-binding fold, also named GHKL fold
Isoform 2 contains a C-terminal PDZ-binding motif mediating the interaction with GOPC
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes. A lower affinity toward calcium can be anticipated for PLD alpha due to the absence of two potential calcium ligands
The periplasmic domain is elongated (up to 160 Angstroms long) and forms contacts to the N-terminal POTRA domains of TamA
The N-terminus is necessary for DNA-binding. The C-terminus is necessary for transcriptional activation
The cytoplasmic C-terminal region mediates interaction with STIM1, while the N-terminal lumenal region mediates regulation of SOCE activity
The PDZ domain 6 mediates interaction with the C-terminus of TJP3 and is crucial for localization to the tight junctions. The PDZ domain 8 interacts with CLDN1 but is not required for proper localization (By similarity). The PDZ domain 2 of isoform 3 mediates interactions with KCNJ10, KCNJ15, GRIN2B and NLGN2. The PDZ domain 3 of isoform 3 mediates interactions with KCNJ15, GRIN2A, GRIN2B, GRIN2C, GRIN2D and NRXN2. The PDZ domain 4 of isoform 3 mediates interaction with ASIC3
The N-terminus is important for protein stability
The C-terminus is dispensable for the formation of membrane tubules
The cysteine framework is C-C-C
Binds calcium via the C2 domains. The calcium-bound C2 domains mediate interactions with phospholipid bilayers (By similarity)
The jas domain (185-210) is required for interaction with COI1
The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2
The helical domain (68-188) is required for self-activation
Contains 3 SPKK motifs which may interact with the minor groove of A/T-rich DNA sites. Phosphorylation of this motif may regulate DNA binding. This motif is reiterated in both termini of histone H1 and in the C-terminus of plant H2A, but its presence in the N-terminus seems to be unique to sea urchin histones H2B
The TDP domain (123-605) is sufficient to confer the full phosphodiesterase activity
PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices
WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain
The number of the intragenic tandem repeats varies between different S.cerevisiae strains
Two globular domains, G1 and G2, comprise the N-terminus of the proteoglycan, while another globular region, G3, makes up the C-terminus. G1 contains Link domains and thus consists of three disulfide-bonded loop structures designated as the A, B, B' motifs. G2 is similar to G1. The keratan sulfate (KS) and the chondroitin sulfate (CS) attachment domains lie between G2 and G3
The C-terminal di-lysine-like motif may confer endoplasmic reticulum localization
The HxxHH motif is essential for ELOp function in vivo and 3-keto acyl-CoA synthase activity in vitro
The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis
Binds DNA via the 2 GATA-type zinc fingers. Each zinc finger may bind either adjacent sites in a palindromic motif, or a different DNA molecule allowing looping and long-range gene regulation
The YxKxHxxxRP motif is critical for DNA-binding and function
Consists of two distinct domains, a catalytic core and a N-terminal extension that is presumably involved in tRNA binding
The RAP domain seems to regulate mitochondrial mRNA levels
The AP2/ERF domain binds specifically to the 5'-GCCGCC-3' motif. The affinity of this binding is higher if the seventh amino-acid of this domain is basic (By similarity)
Comprises six structurally related gelsolin-like (G1-G6) domains, that, in a calcium-free environment, are packed together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur. Binding calcium may release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently. G1 and G4 bind two Ca(2+) in a type I and in a type II manner. G2, G3, G5 and G6 bind only one Ca(2+) in a type II manner. Type I Ca(2+) binding sites are shared between actin and gelsolin-like repeats G1 and G4. Type I binding governs the strength of interactions between gelsolin and actin by direct participation at the binding interface. Ca(2+) binding to G2 and G6 disrupts the interactions between G2 and G6, releases the C-terminal tail, and induces large interdomain rearrangements that result in the exposure of the F-actin-binding site on G2 and contributes to the activation of gelsolin. Binding to phosphoinositides may inhibit the severing and capping properties of gelsolin
The largest part of the sequence forms an elongated and flexible stalk structure that is connected to a C-terminal globular domain with a histone-type fold
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity
The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp
Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro) (By similarity). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro) (By similarity). The bZIP domain is able to form homomeric oligomers via formation of interchain disulfide bonds under non-reducing conditions (in vitro) (By similarity). Under reducing conditions, the disulfide-bonded homomeric species dissociates into monomers (in vitro) (By similarity)
Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself
The cysteine framework is XX (C-CC-C-CC-C-C-C-C)
The CH (calponin-homology)-like region shows high similarity to a CH (calponin-homology) domain and mediated binding to the globular domain of tubulin
Interaction with BRCA2 occurs through a hydrophobic pocket at the crossover between WD repeats 4 and 5
The coiled coil domain mediates self-association
The chromatin-association motif (ChAM) mediates association with chromatin, probably through nucleosome core particles, independently from binding to D loop, ssDNA or dsDNA structures
The M4 transmembrane segment mediates tetramerization and is required for cell surface expression
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). In microsporidia, the second signature motif differs slightly and is Asn-Pro-Gly (NPG)
The F-box domain contains an unusual insert of 18 residues (131-148)
Forms a U-shaped beta-half-barrel with a small hydrophobic cavity able to hold a triacylated lipid or triacylglyceride
The protein is composed of a N-terminal kinesin-motor domain involved in the chromosome movements, a long coil-coiled region involved in the homodimerization and an inhibitory C-tail involved in autoinhibition of the N-terminal catalytic part
Binds EIF4A1 via both MI domains
C-terminal extension may function as a nuclear localization signal (NLS)
The SH3 domains mediate binding to a proline-rich motif in RIMS1, RIMS2, CACNA1D and CACNA1B
The RCK N-terminal domain binds NAD and possibly other effectors. This is expected to cause a conformation change that regulates potassium transport (By similarity)
The EPN motif is essential for recognition of the peptidoglycan carbohydrate backbone and for efficient bacterial killing with Glu-114 playing a key role in peptidoglycan binding and bactericidal activity
The cysteine framework is XXIII (C-C-C-CC-C)
The FFAT motif is required for interaction with MOSPD2
The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex
Repression domain 1 (RD1) is involved in transcriptional repression
The SH3 domain mediates interaction with NOXO1 and NCF1 and has autoregulatory function
The TPR repeats mediate interaction with RAC1
Strong binding to neuropilin is mediated by the carboxy third of the protein
The DIX domain promotes homooligomerization
The DEP domain mediates interaction with the cell membrane
Despite low primary sequence conservation between eukaryotic catalytic subunits and bacterial and archaeal single subunit OSTs (ssOST), structural comparison revealed several common motifs at spatially equivalent positions, like the DXD motif 1 on the external loop 1 and the DXD motif 2 on the external loop 2 involved in binding of the metal ion cofactor and the carboxamide group of the acceptor asparagine, the conserved Glu residue of the TIXE/SVSE motif on the external loop 5 involved in catalysis, as well as the WWDYG and the DK/MI motifs in the globular domain that define the binding pocket for the +2 Ser/Thr of the acceptor sequon. In bacterial ssOSTs, an Arg residue was found to interact with a negatively charged side chain at the -2 position of the sequon. This Arg is conserved in bacterial enzymes and correlates with an extended sequon requirement (Asp-X-Asn-X-Ser/Thr) for bacterial N-glycosylation
The DH domain is involved in interaction with CCPG1
Is a fusion protein with two major domains exhibiting structural features of an E1 and E2 protein, and a short sequence stretch of E1 localized at the N-terminus, which is connected by a linker region to the rest of the protein
The N-terminal part (18-235) contains the information required for insertion into the coat
The TBM domain mediates interaction with TERF1
The N-terminus forms a highly conserved seven-bladed beta propeller decorated with long loops and mediates anchorage to the Nup107-160 subcomplex of the nuclear pore, synergistically with the central alpha domain. The disordered C-terminus is responsible for the interactions with chromatin (By similarity)
An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization
The jas domain (153-177) is required for interaction with COI1
In the N-terminal, the PTS system fructose-specific possesses a duplicated EIIB domain (EIIB' domain) which lacks the active site and functions to facilitate phosphoryl transfer between the EIIA domain of diphosphoryl transfer protein (DTP) and the EIIB domain. Construction of a protein lacking the EIIB' domain shows that it is functional for fructose transport in vivo as well as fructose phosphorylation in vitro. The presence of the EIIB' domain, however, is required for normal high affinity recognition of DTP by the PTS system fructose-specific as well as for normal rates of phosphoryl transfer between the EIIA and EIIB domains of DTP and PTS system fructose-specific, respectively
The L/FRRG motif is required for recruitment to PtdIns3P
The N-terminal half of the protein contains two conserved domains I and II. Domain I includes a slightly degenerated ERF-associated amphiphilic repression (EAR) motif which seems to be involved in the activity of transcriptional repression. Domain II is required for the correct degradation of the protein through the SCF-mediated ubiquitin-proteasome pathway. Interactions between Aux/IAA proteins and auxin response factors (ARFs) occur through their C-terminal dimerization domains III and IV
Glu-127 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-209 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils
Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2)
The LIR motifs (LC3-interacting region) 3 and 5 are required for its interaction with MAP1LC3B and for its autophagy-mediated degradation
The DNA-binding JBP1 domain (DB-JBP1) is necessary and sufficient for binding to J-DNA
Alanine-zipper domain is involved in homo- or hetero-dimerization via electrostatic interaction
Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids (By similarity)
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3)
The PPxY motif 1 mediates interaction with NEDD4 (PubMed:11042109). The PPxY motif 2 is required for the coactivation function (By similarity)
The C-terminal region is required for localization to paternal organelles
Has 3 domains, the N-terminal alpha-helical domain, an extended flexible linker and the C-terminal beta-sheet domain. The N-terminal alpha-helical domain stabilizes RbcL dimers and RbcL dimer-dimer interactions, facilitating RbcL(8) formation. The C-terminal beta-sheet domain probably dimerizes Raf1 (PubMed:26237510). The 2 C-terminal beta-sheet domains are swapped and pack against each other to form the dimer interface (By similarity)
The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase
The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes
The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids. The pore-forming region H5 is enclosed by the transmembrane segments S5 and S6 in the Shaker-type (1P/6TM) and contains the GYGD signature motif which seems to be involved in potassium selectivity
Consists of two structural and functional domains: an N-terminal DNA-binding domain, approximately the first 60 residues, and a larger C-terminal domain, approximately 280 residues, which imparts the function of corepressor binding and oligomerization
The RING-CH-type zinc finger domain is required for E3 ligase activity
The RBD-FIP domain mediates the interaction with Rab11 (rab11a or rab11b)
The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation
The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates
The N-terminus is sufficient for interaction with microtubules, although high affinity binding to microtubules also requires an intact C-terminal domain and ATP, which promotes oligomerization
The FAR1 domain is involved in direct DNA binding, the SWIM-type zinc finger is essential for transcriptional activation activity and both the MULE and SWIM domains are essential for dimerization
The DIX domain mediates homooligomerization
The SAM domain mediates the association with the 3'-UTR of specific mRNAs
The N-terminal methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase (D/C) domain carries both the methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities
The larger C-terminal formyltetrahydrofolate synthetase domain carries a third formyltetrahydrofolate synthetase activity
This protein has four functional calcium-binding sites; potential sites II and VI have lost affinity for calcium
The twin Cx2C motifs are involved in the recognition by the mitochondrial mia40-erv1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space
The C-terminal transmembrane domain is required for the targeting of the protein to damaged organelles
Both the BIR and NACHT domains are essential for effective inhibition of pro-CASP9 cleavage. BIR3 domain binds to procaspase-9 and the NACHT domain interacts with the NACHT domain of APAF1 forming a bridge between pro-CASP9 and APAF1
In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (By similarity). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (By similarity)
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines
The N-terminal domain interacts with glycerophospholipids and phospholipids
The G5 motif of the IRG-type G domain is missing because the IRGM protein is truncated in anthropoids
The EF-hand 2 domain within the regulatory N-terminal domain binds one calcium in the mitochondrial intermembrane space. Calcium triggers the binding of the regulatory N-terminal domain to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain. In the absence of calcium, the linker loop domain may close the vestibule and prevent substrates from entering the carrier domain
The atg8-interaction motif (AIM) is required for the association with atg8
The FFAT motif (AIM) is required for the association with the vesicle-associated membrane protein-associated proteins (VAPs) scs2 and scs22
CAHS proteins contain 2 repeats of 19-mer peptides designated as CAHS-motifs that comprise each two octapeptides connected by a tripeptide (By similarity)
The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal
The BIR2 domain is required for caspase-inhibition
The C-terminal region containing the RING finger domain is required for the initial degradation step, and the final digestion of cleavage fragments
The testis-specific N-terminal extension mediates tight association with the cytoskeletal fibrous sheath of the spermatozoa flagellum, possibly via interchain disulfide-bonding of Cys-33 with sheath components
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Gly (NPA)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase. OtaB has the following architecture: A-T-C-A
Composed of a long central coiled coil domain. The N-terminal and C-terminal regions interact with DNA
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic calcium. In the presence of phosphoinositides, regulates phospholipase A2 and lysophospholipase activities in a calcium-independent way
The N-terminal region contains a canonical wHTH DNA-binding domain. It is linked via a 21 residue-long linker to the C-terminal domain, which binds the effector molecule
The 2 Tudor domains recognize and bind methylated histones. Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails (By similarity)
Contains ten tandem EGF-like repeats strikingly similar to those found in the cysteine rich 'stalk-like' structure of integrin beta-subunits
The center of the protein encodes 8.6 repetitions of a Glu-rich sequence
Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity
The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). AMT10 is composed of only one module and misses a condensation (C) domain (Probable)
A patch of hydrophobic and neutral of amino acids (residues 89-94) forms a ring around the central pore of the pentamer, which interacts with the A2 helix of the SubA subunit; some mutations in this patch prevent SubAB5 complex formation but still allow some targeting to the host endoplasmic reticulum lumen (PubMed:23921389). One residue in this patch, Thr-92, is the only residue that contacts SubA from all 5 of the SubB subunits (PubMed:23921389)
In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern
The C1q domain mediates calcium-binding
The RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding
The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104
The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif locates to a long loop in the arm domain called the bowtie tail. Integrin-binding stabilizes an alternative conformation of the bowtie tail. Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the signal recognition particle (SRP) complex subunit SRP54 (By similarity). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (By similarity). GTPase induced rearrangement of SR drives SRP-mediated cotranslational protein translocation into the ER (By similarity)
The JmjC domain mediates the demethylation activity
The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate
Contains an ATP-binding N-terminal domain and a NrtA-like C-terminal domain, which are connected by a segment containing an abundance of glutamine, alanine and positively charged amino acids. The N-terminal domain is required for activity and the C-terminal domain is involved in regulation of the activity
The BH4 motif is required for anti-apoptotic activity. The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death
The cytoplasmic C-terminal domain is necessary for targeting the non-ubiquitinated form of this protein to the cell surface
Comprises of two domains. The C-terminal domain contains the binding site for glutamine and catalyzes the hydrolysis of this substrate to glutamate and ammonia. The N-terminal domain is anticipated to bind ATP and hydrogenobyrinate and catalyzes the ultimate synthesis of the diamide product. The ammonia produced via the glutaminase domain is probably translocated to the adjacent domain via a molecular tunnel, where it reacts with an activated intermediate
Contains a carbamoyl phosphate domain (CPD) and a second substrate domain (SSD), which are linked by two helices
The cysteine framework is I (CC-C-C). Alpha4/5 pattern
The DPH-type metal-binding (MB) domain can bind either zinc or iron ions
Usually mRNA binding pumilio repeats come in 8 copies. In the 8-fold symmetry of the NPC the 8 repeats may be provided by eight copies of NUP133
Glu-206 is essential for cation selectivity and may function as the charge sensor for cationic substrates
The tandem Agenet-like domains preferentially recognize trimethylated histone peptides
Disordered region at the C-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that stores mRNAs
The AP2 domain contains a non-canonical linker peptide between the second and third sheets
The N-terminal domain carries structural determinants essential for agonist and antagonist binding. The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. The cytoplasmic loop is an important determinant of channel inactivation kinetics
The TIR does not cause cell death, but can suppress RPS4 TIR domain-induced cell death (PubMed:24744375). The TIR domain is involved in homo- and heterodimerization, but other domains also contribute to the interaction (PubMed:24744375)
SURP motif 2 mediates direct binding to SF3A3
Contains two homologous but distinct carbohydrate-binding domains
The transmembrane domains are believed to be involved in pore formation in target cells
The Gly-rich region is probably involved in calcium binding, which is required for target cell-binding and cytolytic activity
The C-terminal domain contains an export signal that is recognized by the ABC transporter complex LktBD
The Ig-like V-type domain mediates the interaction with MHCII
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity)
2 residues (Tyr-94 and Arg-97) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for deacylation activity, but dispensable for deacetylation activity
The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1. Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface (By similarity)
The N-terminus binds InsP6 with low affinity
The C-terminus binds InsP6 with high affinity
The tetrameric structure and the presence of a connecting tunnel suggest that the activated lactim moves from the CapA active site to the CapB active site without release to solvent
The SSD (sterol-sensing) domain is necessary for the increase in cellular cholesterol uptake (PubMed:19179482)
Alternative splicing exons contribute to the specialized contractile activities of different muscle types. Exon 3 encodes the hydrophobic pocket adjacent to the ATP-binding site, exon 9 is adjacent to the actin-binding domain, exon 11 is involved in actin-binding, exon 15 in the S2 hinge and exons 18 and 19 the non-coiled tail region
The JmjC domain is required for enzymatic activity
The extracellular domain is required for the regulation of IFNG and IL22 production, but is dispensable for late T-cell polarization
The C-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions
The DD1 domain (also called RepD1 domain) mediates the corepressor function and is essential in the triggering of apoptosis
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, a motif known to be important for the association with nuclear receptors. Such motif, which is required for an efficient association with nuclear receptors, is however not essential
Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, which is essential for the association with nuclear receptors
The N-terminus interacts with KaiC, while the C-terminal histidine kinase domain autophosphorylates and is probably responsible for self-oligomerization. The N-terminal domain stimulates the C-terminus to autophosphorylate
In classical PTS systems, the PTS EIIC type-2 domain forms the translocation channel and contains the specific substrate-binding site. UlaA does not exhibit the topological features of any recognized enzyme IIC
The N-terminal 40 amino acids are necessary and sufficient for vacuolar and endosomal targeting
Adopts the six-bladed beta-propeller fold and contains six binding sites per monomer, each located between two adjacent blades (By similarity). The six binding sites that are non-equivalent, and owing to minor differences in amino-acid composition they exhibit a marked difference in specific ligand recognition (By similarity)
The N-terminus forms a highly conserved seven-bladed beta propeller decorated with long loops and mediates anchorage to the Nup107-160 subcomplex of the nuclear pore, synergistically with the central alpha domain. The disordered C-terminus is responsible for the interactions with chromatin (PubMed:23499022)
Composed of an N-terminal domain that binds STXBP1, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane
Has the CSalpha/beta fold, which comprises one or two short alpha helices connected to anti-parallel beta-sheets stabilized by three or four disulfide bonds
The RK-rich region determines the subcellular location and is required for cAMP responsiveness
The basic domain functions as a nuclear localization signal
The basic leucine-zipper domain is sufficient for association with the NF-Y trimer and binding to ERSE
Dimerizes through its coiled-coil domain
The PIF1 N-terminal (PINT) domain enhances the interaction with ssDNA through intrinsic binding activity, it also harbors DNA strand-annealing activity
The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound
The PHD fingers mediate the transcription repression in heterochromatin
The SAY domain is essential for fly viability and transcription activation
The F-box domain mediates interaction with components of SCF (SKP1-CUL1-F-box protein) complexes, while WD repeats mediate interaction with components of DCX (DDB1-CUL4-X-box) complexes
The D-box (destruction box) mediate the interaction with APC proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway
The N-terminal domain is an intra-molecular chaperone that prevents premature oligomerization of the residues on the coiled-coil region that are involved in interactions with the needle and/or itself. The residues in the C-terminal domain probably form oligomeric structures at the tip of the needle that are responsible for the regulation of secretion of other effectors (By similarity)
The winged-helix-like (wH-like) C-terminal extension is necessary and sufficient for interaction with CdvA
The C2H2-type zinc fingers mediate binding to the telomeric double-stranded 5'-TTAGGG-3' repeats (PubMed:28082411). The last C2H2-type zinc finger is required for telomeric-binding (PubMed:28500257)
The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity
The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type alpha/alpha. The C-terminal, non-coiled coil regions mediate heterodimerization type alpha/beta and interaction with PTPRD, PTPRF and PTPRS
Ubiquitin-binding motif (UBAN) is essential for its inhibitory function, subcellular localization and interaction with TBK1
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins
The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix
The ancillary domains, including the TSRs domain, are required for specific extracellular localization and for its versicanase and aggrecanase activities
The GON domain mediates protease-independent function in ER to Golgi transport
The PDZ domain-binding motif is involved in the interaction with PATJ, CASK, APBA1, DLG1 and DLG4
An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface
Binds protein substrate via an exposed loop in the N-terminus
Dimerizes via the C-terminus; dimerization is required for tetramer formation. Binds protein substrate via an exposed loop in the N-terminus
The C-terminal intracellular domain is subject to extensive post-translational modifications and binding partner interactions which regulate transporter activity, scaffolding functions, downstream events and localization
The protein contains a globular N-terminal tetramerization domain, a long stalk formed by the coiled coil region and a C-terminal olfactomedin-like domain. Interactions between dimers are mediated by the coiled coil region. The dimers interact mostly via the N-terminal tetramerization domain, giving rise to a V-shaped overall architecture of the tetramer
The leucine zipper region is essential for homo- or heterodimerization and high-affinity DNA binding. DNA binding is mediated by the basic region
The 2 HXXHC motifs are conserved in ustYa family proteins and might form active sites (By similarity). Within cctO however, the second His from the 2 motifs is not conserved (Probable)
The C-terminal DAD domain may participate in intramolecular interactions with the N-terminus
The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity)
The C-terminal transmembrane domain (TMD) is necessary and sufficient for membrane targeting
Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that capture N-terminally myristoylated target peptides. Phe residues within the hydrophobic beta sandwich are required for myristate binding (By similarity)
The transmembranous domains are involved in regulation of enzyme activity
Both bilin lyase domains bind with the bilin tetrapyrrole chromophore precursor. The domain 1 shows red, far-red light photoreversibility. The domain 2 is photochemically inactive
The N-terminal region is compact and probably functions to regulate the ATPase activity and the oligomerization. The C-terminal region contains the ATPase activity and the oligomerization domain
The helicase ATP-binding domain is implicated in early steps of nonsense-mediated decay (NMD)
Contains a predicted C4 metal binding domain at the N-terminus, which could be a zinc finger DNA binding domain
The helical domain (69-189) is required for self-activation
Pi-AnmTX Ugr 9a-1, AnmTX Ugr 9a-2 and AnmTX Ugr 9a-3 have a structural fold called the boundless beta-hairpin since its beta-hairpin is not stabilized by disulfide bonds
The CLIP domain consists of 37-55 residues which are 'knitted' together usually by 3 conserved disulfide bonds forming a clip-like compact structure
The KRAB domain mediates interaction with TRIM28
The hydrophobic-rich region (HR-A/B) corresponds to the oligomerization domain. AHA motifs are transcriptional activator elements
The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription activation
Glycine-rich region (GRR) is a critical element in the generation of p50 (Nuclear factor NF-kappa-B p50 subunit) by acting as a proteasomal 'stop signal', which leads to limited proteasomal degradation of the C-terminus, while generating p50
The cysteine framework is III (CC-C-C-CC). Classified in the M-5 branch, since 5 residues stand between the fourth and the fifth cysteine residues
The BTB domain is not required for activation of transcription or self-association
The substrate-binding apical domain region is sufficient for centrosomal association
Contains 3 inactive NDK domains that each lack the active His residue, suggesting that they have no NDP kinase activity
The transmembrane domain is a dimerization domain
The DVD domain (residues 311-334) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation (By similarity)
The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates
Iron is coordinated by two histidines and one chloride ligand, in contrast to the two-histidine/one carboxylate facial triad of other mononuclear non-haem iron enzymes. The remaining iron coordination sites are occupied by the 2-oxoglutarate and a water molecule
The PIR1/2/3 repeat is required for the covalent linkage to the cell wall
The C-terminal SM 1 domain is both necessary for the binding to the Sm-binding site of U7 snRNA and U7 snRNP assembly (PubMed:12975319). The N-terminal domain is essential for histone pre-mRNA cleavage (PubMed:12975319). Amino acids 63-82 are sufficient to interact with ZNF473 (PubMed:12975319)
The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11 homodimer (By similarity)
Alternative DNA-binding strategy due to lack of a leucine zipper dimerization segment: DNA binding domain binds to its cognate half-site, an N-terminal arm recognizes adjacent 5' AT-rich sequences in the minor groove and the intervening residues stabilize interactions of these two subdomains with DNA
Has 2 Rossmann-like domains, called R-fold-1 and R-fold-2. R-fold-1 is interrupted by an extended beta-sheet domain that loops out of the structure and is required for recognizing both PsrP substrate and coactivator GtfB. UDP and N-acetyl-D-glucosamine bind between the Rossmann-like folds
The proline-rich domain (PRD) contains repeated PPP motifs. A single PPP motif is necessary and sufficient to mediate interaction with the COPII coat subunits SEC23A and SEC23B
Although 2 transmembrane domains are predicted, it only contains one transmembrane domain. The other predicted transmembrane region is probably a hairpin-type region embedded into the membrane, which does not cross the membrane. It is unclear which of the 2 predicted transmembrane regions is the transmembrane or the hairpin-type region
The PWWP domain harbors the heparin-binding sites and is responsible for DNA-binding, while the C-terminal region is essentially unstructured
The N-terminal region does not contain a typical signal sequence but is required for secretion (PubMed:21087088). It also determines exosomal location (By similarity)
The N-terminal destruction box 2 (D-box 2) is required for APC/C ubiquitination and proteasomal degradation
The FZ domain is involved in binding with Wnt ligands
SipB membrane integration requires both hydrophobic domains and the helical C-terminal region
In Rv1747 the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. The two FHA domains are required for phosphorylation by PknF
The ADD domain predominantly interacts with histone H3 trimethylated at 'Lys-10'(H3K9me3) (and to a lesser extent H3 mono- or dimethylated at 'Lys-10') and simultanously to histone H3 unmethylated at 'Lys-5' (H3K4me0). The interaction with H3K9me3 is disrupted by the presence of H3K4me3 suggesting a readout of the combined histone H3 methylation state (By similarity)
The PX domain binds phosphatidylinositol 3-phosphate which is necessary for peripheral membrane localization
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. PUM1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine
The membrane-extrinsic domain forms parallel contacts with at least one other TatB protein
13 hexapeptides with consensus sequence were found at the carboxy end between AA 177 and 267 in a proline-rich domain
The N-terminal DNA-binding region is structurally similar to winged helix domains
Glycine-rich repeats mediate the association with the actin cytoskeleton
The cysteine framework is C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C
The C-terminus (843-1307) is sufficient for the deamination
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of atg9-containing vesicles, thereby enabling growth into autophagosomes
The C-terminal region plays a crucial role in controlling the activity of RDH16 and its required for endoplasmic reticulum (ER) retention
The central dimerization domain of the first subunit forms a two-helix antiparallel coiled coil with the dimerization domain of the second subunit
The Loki loop (specific to some members) becomes ordered on binding to rabbit actin
The C-terminal active site loop is required for the recognition and recruitment of substrates and release of hydrolyzed products
The cysteine framework is XXII (C-C-C-C-C-C-C-C)
The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain
The antibiotic resistance domain (ARD) is packed between the 23S rRNA and the acceptor arm of the P-site tRNA and inserts into the peptidyltransferase center (PTC). The C-terminal extension (CTE) contacts the small ribosomal subunit, positioned in the Shine-Dalgarno-anti-Shine-Dalgarno cavity
The C-terminal domain (249-459) is able to bind to and to accelerate the GTPase activity of GPA1
The N-terminal domain is sufficient to interact with bmp4
Composed of two structurally equivalent A and B domains that adopt a dual specificity protein phosphatase (DSP) fold
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Val (NPA)
Only the first and third SH3 domains seem to be involved in RASA1-binding; the second SH3 domain and the SH2 domains do not seem to be involved
The CW-type zinc finger domain is not required for nuclear localization
The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity
Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region
The fork-head DNA-binding domain is essential for its dimerization and interaction with NFATC2
The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell membrane (By similarity)
The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway (By similarity)
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1
The L27 domain 1 functions in targeting to the tight junctions by binding to and stabilizing PATJ
The PDZ domain binds to the C-terminus of SC6A1
The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity (By similarity)
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited
Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway
The N-terminal TOPLESS domain (TPD) (1-209) binds directly to a 12-amino acid LxLxL EAR motif peptide
The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components (By similarity)
The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM10B from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane
The fibronectin type-III domain mediates interaction with COPS5 and RYBP
The N-terminal region is composed of two iterations of forkhead-associated (FHA) domain-like structures, which could interact with other proteins in the Esx secretion system
A conserved histidine residue in the third TMD (His-191) may play an essential role in the pH sensitivity of SLCO4A1/OATP4A1-mediated substrate transport
The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination
The PAS domain may participate in sensing the overall energy level of the cell and communicate this information to the phosphatase domain
The CXXC zinc finger mediates binding to CpG-DNA
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (414-444) inactivates kinase activity under calcium-free conditions
The PTS EIIB type-3 domain is phosphorylated by phospho-EIIA on a cysteinyl residue. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the PTS EIIC type-3 domain
The SCAN domain enables PEG3 homo- or heterodimerization to control gene expression in a combinatorial fashion
The central ion permeation pathway is formed by the first transmembrane domain from each of the five subunits. Mg(2+) binding strengthens interactions between subunits and leads to the formation of a symmetrical homopentamer surrounding a closed ion permeation pathway (PubMed:23091000, PubMed:16902408, PubMed:16598263, PubMed:16857941, PubMed:23112165, PubMed:23425532, PubMed:26871634). Co(2+) binding also induces a conformation change (PubMed:21454699). Low Mg(2+) concentrations trigger both a conformation change within each subunit and a loosening of the interactions between subunits. This results in an open ion conduction pathway. In addition, this results in a less symmetrical shape of the whole complex (PubMed:23112165, PubMed:26871634)
The C-terminal third of the heavy chains forms the hub of the triskelion. This region contains the trimerization domain and the light-chain binding domain involved in the assembly of the clathrin lattice
The N-terminal seven-bladed beta-propeller is formed by WD40-like repeats, and projects inward from the polyhedral outer clathrin coat. It constitutes a major protein-protein interaction node (By similarity)
The C2H2-type zinc-finger is responsible for substrate specificity
Subfamily III proteins have a conserved RTxK motif about 40-50 residues from the C-terminus; the threonine may be replaced by serine or cysteine
The N-terminal proline-rich disordered region contributes to the interaction with PFN2
The Gly-rich repeats may be important in the extracellular secretion of this metalloprotease
2 residues (Tyr-64 and Arg-67) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The N-terminal domain contains the ATP/Pi binding site, the central domain the pyrophosphate/phosphate carrier histidine, and the C-terminal domain the pyruvate binding site
the class II DTC active site contains a DXDD motif from which the middle Asp acts as the catalytic acid in this protonation-initiated cyclization reaction, while the class I DTS active site contains a DDXXD motif that binds divalent magnesium cofactors required for the catalyzed allylic diphosphate ester ionization-initiated reaction, with the first Asp playing a particularly key role
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the active site of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity)
The Gly-rich region is probably involved in binding calcium, which is required for target cell-binding or cytolytic activity
The three transmembrane domains are believed to be involved in pore formation by the cytotoxin
The transition from the outward-facing to the inward-facing conformation is realized through the asymmetric motion of individual subunits of the transporter (PubMed:19254551). Nucleotide binding is coupled to a conformational shift at the periplasmic gate. This shift is akin to unlocking a swinging door: allowing just enough space for molybdate to slip into the cell. The lower cytoplasmic gate, identified as gate I, remains open throughout the MolBC-A mechanism, and cytoplasmic gate II closes in the presence of nucleotide (PubMed:23709218)
The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region
The GGQ domain interactS with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis
The RGG-box domain is methylated
The UBA domain specifically recognizes and binds 'Lys-6'-linked polyubiquitin chains
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (By similarity). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (By similarity)
The 2 N-terminal RRMs and a part of the linker region (between RRM2 and RRM3) are necessary for binding to EDEN of mos mRNA
The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization
The Kelch repeats mediate interaction with NFE2L2/NRF2, BPTF and PGAM5
KEAP1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins
The PID domain (phosphotyrosine interaction domain) of isoform a and isoform c is capable of binding residues 212-224 of pkc-3
The polyhistidine repeats act as targeting signals to nuclear speckles
The different N-terminus extensions of isoform 1 and isoform 2 determine their respective subcellular localization and differentiel effect on myoblast fusion and accumulation of muscle-specific proteins. The different N-terminus extensions of isoform 1 and isoform 2 are not essential for their catalytic activity
Contains 2 FAD binding domains and a single NADPH binding domain
A labile and variable specificity module composed of 3 loops determines the selectivity of scorpion Nav alpha-toxins. In this toxin, the specificity module consists of: an N-terminal loop following beta-1 and up to the first cysteine residue (residues 27-31), the tip of the beta-2-beta-3 hairpin (58-62), and a C-terminal region (75-83)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
LC3-interaction region (LIR) is required for interaction with MAP1LC3B/LC3-II and for Parkin-mediated mitophagy
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with pan3
The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway
The PDZ domain 1 binds NG2. The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT and the C-terminal PDZ-binding motif of HTR2C. The PDZ domain 13 binds CXADR (By similarity). The PDZ domain 2 binds CAMK2A and CAMK2B. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds SYNGAP1
Contains a large catalytic C-terminal domain that binds S-adenosyl-L-methionine and a smaller N-terminal domain that may play a role in tRNA recognition. Domains are connected by a linker region
The CUE domain specifically binds RPS20/uS10 ubiquitinated via 'Lys-63'-linked ubiquitin chains by ZNF598
The N-terminal region is required for constitutive signal transduction
The CBS domain of IMPDH is a negative trans-regulator of adenylate nucleotide synthesis, and this role is independent of the catalytic function of IMPDH in the de novo GMP biosynthesis. Deletion of the CBS domain derepresses the synthesis of AMP from IMP
The DAZ domain is essential for the translation activation activity
The START domain recognizes ceramides and diacylglycerol lipids, interacts with membranes, and mediates the intermembrane transfer of ceramides and diacylglycerol lipids
The PH domain targets the Golgi apparatus
The FFAT motif is required for interaction with VAPA, VAPB and MOSPD2
the C-terminus is required for calcium responsiveness but not for transactivation activity
The N-terminus is absolutely necessary for transactivation activity
Contains a death domain involved in the binding of the corresponding domain within Fas receptor
The interaction between the FAS and FADD death domains is crucial for the formation of the death-inducing signaling complex (DISC)
The main chain amide nitrogen atoms of the second glycine and its adjacent residue in the HGGXW motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage
The WWE domain mediates non-covalent PAR-binding
The MAHS motif is conserved in tardigrade MAHS proteins and forms a predicted amphipathic helix (PubMed:25675104)
Only the PABPC1-interacting motif-1 (PAM1) interferes with the binding of PABPC1 to poly(A) RNA and translation initiation
The ubiquitin-like region mediates interaction with PRKN
The proline-rich region is important for protein-protein interactions
Contains two alpha-helical subdomains, with the 8-oxoguanine binding site located in a cleft at their interface. Contains a helix-hairpin-helix (HhH) structural motif and a Gly/Pro-rich sequence followed by a conserved Asp (HhH-GPD motif)
The LIM domains exert a negative regulatory function and disruption of the LIM domains produces an activated form. In addition, two activation domains and a negative regulatory domain exist C-terminally to the homeobox
The C-terminal PABC domain is involved in the interaction with UPA1 and UPA2
The t-SNARE coiled-coil homology domain is necessary and sufficient for interaction with STX1A
Contains 4 domains, connected by flexible linkers. In the active conformation, the domains are in an extended conformation, each making extensive interactions with the RNA polymerase catalytic core (PubMed:18940669)
In the autoinhibited state, sigma-70 factor domain-1 packs closely together with sigma-70 factor domains-2 and -4, contrary to the extended conformation that is seen when the protein is part of the RNA polymerase holoenzyme
Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin (By similarity)
In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster
One bromodomain is sufficient for a partial interaction with histone H4 acetylated at 'Lys-13'
The DEMETER domain, which is present in proteins of the subfamily, is related to the J-domain, but lacks some important conserved residues
The pentapeptide insert motif is required for the stabilization of the apo-enzyme in an active closed conformation, independently of Mg(2+) binding. The motif is also required for homodimerization. This motif is only present in Apicomplexa and plant enolases
The DKSLVK motif binds to the lysine-binding Kringle domains of plasminogen from various mammalian species. This motif is present only in enolases of plant and several microbial pathogens including Plasmodium species
The RING-type zinc finger is required for E3 ligase activity
The dimerization domain is located in the N-terminus
Binds synaptic Ca(2+) with its cytoplasmic domain
The mature protein is largely unstructured in the absence of a cognate ligand, but contrary to the human protein, it does not easily form fibrillar aggregates
Cells lacking the TE domain are unable to produce methymycin, neomethymycin, narbomycin and pikromycin
The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding
Residues 389-698 form a 5-bladed beta-propeller domain which closes one end of the shell; the other end of the shell is closed by the RHS repeat-associated core domain in YenC2
The C-terminus is responsible for sequestering G-actin. The N-terminus is required for the PIP2 modulation of cap function
In the homohexamer the 2 domains (called CI and CII) self-associate to each form a 'donut' layer; the compactness and local conformation of the domains varies over the cell cycle and impacts function. CII has the autokinase and autophosphatase activities, both CI and CII have (weak) ATPase activity; CI has the clock pacemaker role
The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes
Coiled-Coils at the N-terminal half are essential for interaction with VPS30 and VPS34 and autophagy
The tetratricopep-repeat (TPR) motifs may function as protein interaction domains
The KEN box is required for the association with the APC/C complex
The C-box is required for the association with the APC/C complex
The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one HSPA5/BiP molecule as a typical substrate of an adjacent HSPA5/BiP molecule. HSPA5/BiP oligomerization inactivates participating HSPA5/BiP protomers. HSPA5/BiP oligomers probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers
Contains three complete but non-identical creatine kinase segments flanked by unique regions
The PTS EIIA type-2 domain may serve a regulatory function, through its phosphorylation activity
HTH myb-type domain confers double-stranded telomeric DNA-binding while the H15 domain is involved in non-specific DNA-protein interaction and multimerization
Specifically targeted by its C-terminus to nucleosomes in euchromatin
The MIDAS-like motif in the VWFA domain binds divalent metal cations
The SET domain is degenerated, suggesting that it has lost methyltransferase activity
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner (By similarity)
The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors (PubMed:31439799, PubMed:34074792, PubMed:36040869). CAPRIN1 molecules in the condensed phase are neutral (PubMed:36040869). mRNA-binding promotes phase separation (PubMed:31439799). Moderate concentrations of ATP enhance phase separation by reducing the electrostatic potential of CAPRIN1, thereby promoting intermolecular interactions (PubMed:34074792, PubMed:36040869). In contrast, high concentrations of ATP invert the electrostatic potential of CAPRIN1, so that CAPRIN1 molecules become negatively charged, lead to inhibition of phase separation (PubMed:36040869)
FHA domains are phosphothreonine recognition modules, FHA 1 strongly selects for Asp at position +3 relative to phosphothreonine, whereas FHA 2 selects for Ile in this position
Residues 1-150 are involved in AKAP9-binding
Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor
N-terminal part, called Am-Nogo-B(1-200), is the functional domain for RTN4B-mediated signaling in endothelial and vascular smooth muscle cells
Forms a well-packed pentamer with an overall cylindrical shape. The inner core of the pentamer is formed with the second transmembrane region and the second coiled-coil region: while the transmembrane regions pack into a five-helix bundle having a largely polar pore across the membrane, the coiled-coil outside the membrane forms a pentamer with a hydrophobic core. The inner core is wrapped by the first transmembrane region through contacts between the first and the second transmembrane regions. The second transmembrane is followed by the inner juxtamembrane region (IJMH) that orients at a wide angle relative to the second transmembrane. The two core domains are held together on the periphery by the outer juxtamembrane helix (OJMH)
The critical DXXE motif connecting the transmembrane regions forms a pentameric barrel that constitutes the mouth of the pore. Inside the barrel, two acidic residues are in position to form two carboxylate rings. In absence of SMDT1/EMRE regulator, the calcium ions cannot exit the channel, suggesting that SMDT1/EMRE-binding induces conformational rearrangements to allow calcium to exit
The N-terminal MCU domain is required for efficient Ca(2+) uptake and for interaction with MCUR1. It is not required for targeting to the mitochondria, oligomerization, interaction with MICU1 and MICU2, or assembly of the uniplex complex
Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction (By similarity)
The C-terminus orients towards the microtubules and the N-terminus orients towards the membrane in a 9-fold symmetric manner
The C-terminal PEST domain is a region rich in proline, glutamic acid, serine and threonine residues that is required for the light-dependent regulation of development and secondary metabolism (By similarity)
The RNA recognition motif (RRM) is involved in the interaction with mago. The RNA-binding activity of such domains is therefore uncertain
Both the N-terminus (61-94) and the C-terminus (99-129) of the mature peptide form alpha-helices which probably disrupt target cell membranes. The linker region (95-98) probably derives from a processing quadruplet motif (PQM), found in propeptides of many zodatoxins, hinting at a fusion of two originally separate membrane-active peptides
Consists mainly of membrane-spanning sided beta-sheets
The C-terminal domain is essential for the formation of the trimer and the high thermostability of the entire protein. The C-terminal 11 residues are important for GalN-1-P AcTase activity, but they have an inhibitory effect on the GlcN-1-P AcTase activity
The ITAM domains mediate interaction with SHB
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. FG repeat types and their physico-chemical environment change across the NPC from the nucleoplasmic to the cytoplasmic side: GLFG repeats are especially abundant in NUPs in the central region (lacking a charged environment but are enriched in Ser, Thr, Gln, and Asn)
Is structurally homologous to beta-defensins
The FYVE-type zinc finger mediates binding to phosphatidylinositol 3-phosphate and recruitment to the midbody during cytokinesis
The SAM domain is required to retain SMSR in the endoplasmic reticulum
The N-terminal domain may be involved in Cu(2+) acquisition from potential degradation products of proteins in the lysosome
The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved. Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity. In addition, the conserved Cys-352 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination
The arm domain is inserted in the first ABC transporter domain. Probably contacts ribosomal protein L1
The P-site tRNA interaction motif (PtIM domain) probably interacts with the P-site tRNA(fMet) as well as the 23S rRNA
The repeated domains of the protein form a beta-pleated sheet configuration
The RRM domains can bind to both DNA and RNA
In the N-terminal, the PTS system fructose-specific possesses a duplicated EIIB domain (EIIB' domain) which lacks the active site and functions to facilitate phosphoryl transfer between the EIIA domain of diphosphoryl transfer protein (DTP) and the EIIB domain. The presence of the EIIB' domain is required for normal high affinity recognition of DTP by the PTS system fructose-specific as well as for normal rates of phosphoryl transfer between the EIIA and EIIB domains of DTP and PTS system fructose-specific, respectively
The PHD-type zinc finger mediates the binding to H3K4me3
The third RNA recognition motif, called PUMP domain, is atypical and may rather mediate homodimerization and/or protein-protein interactions
A conserved histidine residue in the third TMD (His-107) may play an essential role in the pH sensitivity of SLCO1A4/OATP1A4-mediated substrate transport
Composed of two catalytically active A modules and four R modules. The N-terminal A domain introduces a mixture of MG-blocks and G-blocks, whereas the C-terminal A domain only generates MG-blocks
The tetratricopeptide repeat (TPR) domain, forming a carboxylate clamp (CC), mediates interaction with the highly conserved 'EEVD' motif at the C-terminal ends of HSP90 and HSP70
The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation
Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity
The C-terminal acid phosphatase-like domain binds PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity
Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions (By similarity)
Isoform B: The intracellular domain is required for glial engulfment activity. Isoform A: The intracellular domain contains an 11-residue insertion compared to isoform B and is incapable of promoting glial engulfment
The cysteine rich N-terminal region is required for activity
The CBM20 domain is involved in binding to starch
Corresponds to the N-terminal section
The cytosolic N-terminus contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which are essential for the association with INPP5D/SHIP-1 and INPPL1/SHIP-2 phosphatases and functional inhibition
The architecture of swnK is the following one: adenylation (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain, and thioester reductase (TE) domains. The presence and positions in swnK of the 2 reductase domains, ketoeductase and thioester reductase, suggests that the intermediate released from this enzyme has a hydroxyl group
Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CS-alpha/beta). Since the toxin contains only 2 disulfide bonds, it is called 2ds-CSalpha/beta
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). NotE has the following architecture: A1-T1-C1-A2-T2-C2. The presence of two intact modules suggests that the two modules condense L-tryptophan and L-phenylalanine together. The C-terminal condensation domain might be responsible for cyclization of the dipeptide to form the diketopiperazine structure (Probable)
Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains, a number of features are positioned to inhibit the kinase activity: (1) an atypical AAAS motif in an alanine-rich (A-rich) loop that replaces the canonical glycine-rich (G-rich) nucleotide-binding loop and limits ATP binding by establishing an unusual selectivity for ADP and (2) an N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket. Nucleotide-binding opens the substrate binding pocket and flips the active site from inside the hydrophobic core into a catalytically competent, solvent-exposed posture
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3
Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane
The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (By similarity)
The KH domain and the Qua2 region are involved in RNA binding
Possesses two phosphotransferase domains. The second one contains the catalytic domain, while the presence of a pseudokinase domain is required for suppression of basal activity of JAK3
The KIS (K-channel inactivation suppressor) domain is required for converting A-type Kv4 current to a slowly inactivating delayed rectifier potassium current
The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity
The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP
The RESP18 homology domain is sufficient for targeting proICA512 to secretory granules
A 90 degree bend between Pumilio repeats 3 and 4 gives rise to a L-shaped protein
The N-terminal region is necessary for its transcriptional activity
The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation (By similarity)
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain
The N-terminus may interact with a transcriptional coactivator
The C-terminus may interact with HDAC-dependent and HDAC-independent corepressors
The first protein part may form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane
The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type beta/beta. The C-terminal, non-coiled coil regions mediate heterodimerization type beta/alpha (By similarity)
Transmembrane regions consist mainly of membrane-spanning sided beta-sheets, which are not predicted by sequence analysis tools
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-99 and Arg-102) that bind to malonylated and succinylated substrates and define the specificity
Contains a short sequence motif (Phe-Xaa-Xaa-Phe-Tyr) that can bind to AR and may modulate AR activity
The C-terminal tail is required for its GEF activity
The PIP-box (PCNA interacting peptide) motif mediates the interaction with PCNA and localization to replication foci
The transmembrane region is required for the regulation of WalK activity
Upon calcium binding, the EF-hand-containing regulatory N-terminal domain binds to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain. In the absence of calcium, the linker loop domain may close the vestibule, which may prevent substrates from entering the carrier domain
The first PTPase domain interacts with SKAP1
The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure
Domains VI and IV are globular
The guanine nucleotide exchange activity is autoinhibited by the PH domain
The regulatory N-terminal domain/NTD formed of two pairs of fused calcium-binding EF-hands, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity
The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity
Linker region/H9 could directly block the transport of substrates across the transporter
The glycogen-binding domain may target AMPK to glycogen so that other factors like glycogen-bound debranching enzyme or protein phosphatases can directly affect AMPK activity
The RRM domain is necessary for mRNA stability and mRNA translation regulation (PubMed:24356969, PubMed:29358667)
Only 3 of the 4 C2H2-type zinc-fingers are required for DNA-binding. Based on its marked lack of evolutionary conservation, the fourth zinc-finger is unlikely to be required
Contains three distinct domains: an adenylation (A) domain that activates the substrate amino acid which is subsequently covalently linked as a thioester (aminoacyl-S-PCP) to the 4'-phosphopantetheine prosthetic group of the second domain, the peptidyl carrier protein (PCP) domain, as well as a reductase (R) domain of the ferredoxin-NADP reductase (FNR) type
The C-terminal part (residues 105 to 155) is required for the binding to RABA GTPasesproteins, causes redirection of the truncated effector to the cytoplasm, and leads tio the loss of the ability to inhibit the host secretory pathway
2 residues (Tyr-65 and Arg-68) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
HMG box 2 mediates pro-inflammatory cytokine-stimulating activity and binding to TLR4. However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance
The acidic C-terminal domain forms a flexible structure which can reversibly interact intramolecularily with the HMG boxes and modulate binding to DNA and other proteins
The C-terminal nitrobindin region coordinates a heme and bears the isomerase activity. The N-terminal zinc finger domain likely binds DNA and may be involved in transcriptional regulation
The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site
The GoLoco domains mediate interaction with G(i/o) alpha (By similarity). The GoLoco domains are essential for the GDI activity toward G(i/o) alpha
The first 10 amino acids are essential for nuclear localization
The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient
The PDZ 1 domain participates in the interaction with the PID domain of NUMB, and participates in the isoform-specific ubiquitination of NUMB. The PDZ 2 domain of isoform 2 participates in the interaction with IGSF5/JAM4, other isoforms containing this domain may also interact with IGSF5/JAM4
The ripply homology domain is required for transcriptional repression
The WRPW motif is required for binding to TLE/GROUCHO proteins
The chromo domain specifically binds to dimethylated H3 'Lys-9' while the chromo shadow domain is required for dimerization
The twin Cx2C motifs are involved in the recognition by the mitochondrial CHCHD4/MIA40-GFER/ERV1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space
The tripeptides QCP and QSP mediate post-transcriptional down-regulation of SLC5A1 at the trans-Golgi network. They inhibit a monosaccharide-dependent exocytotic pathway of SLC5A1
Has 3 domains, the N-terminal alpha-helical domain, an extended flexible linker and the C-terminal beta-sheet domain. The N-terminal alpha-helical domain stabilizes RbcL dimers and RbcL dimer-dimer interactions, facilitating RbcL(8) formation (PubMed:26237510). The C-terminal beta-sheet domain probably dimerizes Raf1 (Probable). The 2 C-terminal beta-sheet domains are swapped and pack against each other to form the dimer interface (By similarity)
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a acyl carrier protein (ACP) domain, a methyltransferase domain (CMeT) and a reductive NADPH-binding domain that is required for NADPH-dependent product release (PubMed:16000748, PubMed:28238725). The CMet adds methyl groups as check-point tags, which are recognized by KS, such that a lack of methylation causes release of immature products at the triketide stage (PubMed:28238725)
The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments
The C-terminal tubulin-binding domain mediates direct binding to microtubules, independently of dynein-dynactin complex, and induces their bundling and stabilization (PubMed:11956313). The 4.1-binding domain is necessary for its cortical stability and spindle orientation (PubMed:24109598)
The C-terminus acts as a transcriptional activation domain
Domains SOFL-A and SOFL-B are required for function in cytokinin-mediated development
Contains a beta-barrel that binds various ligands in its interior
The N-terminal cytoplasmic domain is likely to have a high level of intrinsic disorder
The C2 domains are not involved in calcium-dependent phospholipid binding
The C-terminal vacuolar sorting signal (VSS) (194-212) is required for vacuolar localization
Contains a N-terminal extension that is required for interaction with the BCAP31 complex
The central core of the structure is composed of a partial TIM-barrel fold deviating from the canonical TIM-barrel topology
Some of the CCHC FOG-type zinc fingers probably directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is probably essential for the interaction with GATA-type zinc fingers (By similarity)
A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity
Contains FG repeats and 4 N-P-F repeats
The EIIC type-3 domain forms the PTS system translocation channel and contains the specific substrate-binding site
The coiled coil domain is required for the interaction with LAP4
The C-terminal WXXL motif is crucial for ATG8-binding and Cvt pathway
Loop-1 binds to loop-7, enabling interaction with COPII-coated vesicles. When levels of cholesterol in the endoplasmic reticulum increase, Loop-1 binds to cholesterol instead, thereby disrupting direct binding between the two loops and preventing the SCAP-SREBP complex from exiting the endoplasmic reticulum
Cholesterol bound to SSD domain of SCAP or oxysterol bound to INSIG (INSIG1 or INSIG2) leads to masking of an ER export signal (also named MELADL motif) on SCAP possibly by moving the signal further away from the ER membrane
The first transmembrane helix plays a critical role for the insertion orientation in the endoplasmic reticulum membrane
The GAF domain is sufficient to mediate heteromerization
The Bromo domain recognizes and binds acetylated histones (PubMed:22464331). Also recognizes and binds histones that are butyrylated (PubMed:26365797)
The NtA domain, absent in TM-agrin, is required for binding laminin and connecting to basal lamina
Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan/DAG1 binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding (By similarity)
The pleckstrin homology domain (3-110) binds to phosphatidylinositol-4-phosphate (PtdIns(4)P)
Contains an N-terminal transmembrane domain, followed by a charged domain, an unstructured P/Q domain rich in proline and glutamine, and a C-terminal FtsZ-binding domain
The RK-rich region determines the subcellular location
Binds three actin monomers via the three C-terminal RPEL repeats
There is an asymmetry between active sites in the dimer, with dihydroorotate bound to the active site of subunit A and N-carbamoyl-L-aspartate bound to the active site of subunit B
The proline-knot motif may be involved in the targeting to oil bodies
The T-Box domain binds to double-stranded DNA (PubMed:26926761)
The region between residues 360 and 702 is essential for function and is required for self-association and for binding to spindle pole bodies
The region between residues 751 and 974 is an auto-inhibitory domain which inhibits MEN signaling
Rel similarity domain (RSD) or Rel homology domain (RHD) allows DNA-binding and cooperative interactions with AP-1 factors
The SMD-tail motif is highly conserved and may be responsible for structural stabilization
The lumenal and transmembrane domains are necessary for mono-ADP-ribosylation and Sec body formation
The NAC domain includes a DNA-binding domain and a dimerization domain, and confers the specificity of the transactivated target genes
The LisH domain is required for the activation of histone gene transcription
The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity
The C-terminal region mediates transcriptional repression
The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination
The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity. The coiled coil domain is important for higher order multimerization by promoting the initial dimerization
The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs (By similarity)
The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization
The KaiA C-terminal domain mediates interaction with KaiC, homodimerization, and is responsible for the clock oscillation function
The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination
Contains a small N-terminal 3-helix bundle domain and a large C-terminal TPR domain, connected by a linker region
The GoLoco domains are essential for the GDI activity toward G(i/o) alpha. The GoLoco domains mediate interaction with G(i/o) alpha (By similarity)
The first cytoplasmic domain binds ATP and nucleic acids such as RNA and DNA in vitro
The P.falciparum Export Element (PEXEL) motif, also known as the vacuolar transport signal (VTS), is a pentameric sequence (RxLxE/Q/D) required for the translocation of proteins across the parasitophorous vacuole membrane (Probable). In the endoplasmic reticulum, the motif is cleaved after the leucine residue and the N-terminus is N-acetylated (By similarity)
The PAS 1 domain is essential for dimerization and also required for AHR:ARNT heterodimerization
The DNA polymerase activity domain resides in the N-terminal half of the protein, while the C-terminus is necessary for complexing subunits B and C
The NAB domain, also called NAB (NET actin-binding) domain, is sufficient for F-actin binding
Consists of a ring of transmembrane domains, which shield a highly conserved extracellular structural funnel extending into the middle of the lipid bilayer. The conserved catalytic His residue is located at the bottom of this funnel and is connected to the intracellular DltC through a narrow tunnel
The mature peptide may form alpha-helices which disrupt target cell membranes
One side of the hexamer is concave and lined by hydrophobic residues, the other side has a slightly protruding, 6-stranded beta-barrel
The N-terminal domain (1-160) is sufficient to pilot the oligomerization process and to bind specifically single-stranded DNA, but is not functional in vivo
The KEN box is required for its ubiquitination and degradation
2 residues (Tyr-58 and Arg-61) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The C-terminal AMOP domain plays an important role in the anti-angiogenic function of ISM1
The leucine-zipper domain is required for coactivation activity. When this domain is deleted, the protein is able to stimulate transcription from a number of gene promoters (By similarity)
The H8 helix is predicted to insert into membranes and form pores by assembling into tetramers. The helix is contained within a helical bundle domain that undergoes significant conformational changes during pore formation to allow exposure of the H8 transmembrane helix and transition of the toxin from a soluble monomer to a transmembrane tetramer
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
It contains an N-terminal DNA binding region and a C-terminal metal binding region
The N-terminal domain contains a nuclear export signal. The C-terminal domain may interact with cargo proteins
Cys-418 near TM10 is a major determinant of nucleobase transport activity
Has 3 domains, the N-terminal alpha-helical domain, an extended flexible linker and the C-terminal beta-sheet domain. The N-terminal alpha-helical domain stabilizes RbcL dimers and RbcL dimer-dimer interactions, facilitating RbcL(8) formation. The C-terminal beta-sheet domain probably dimerizes Raf1 (By similarity). The 2 C-terminal beta-sheet domains are swapped and pack against each other to form the dimer interface (By similarity)
The PHD-type zinc-finger domain is required for negative regulation of autophagy
Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID) (By similarity)
The coiled-coil domains in isoform d are important for linker cell death
The HMG box DNA-binding domain mediates DNA-binding. It has both affinity and specificity for DNA damaged globally with cisplatin
The zinc-finger domain is required for terminal uridylyltransferase activity (PubMed:28589955). Together with the RRM domain, binds the 5'-area of U6 snRNA (PubMed:28589955)
The RRM domain is required for terminal uridylyltransferase activity (PubMed:28589955). Together with the zinc-finger domain, binds the 5'-area of U6 snRNA (PubMed:28589955)
The proline-rich region is dispensable for terminal uridylyltransferase activity
Plasticins have huge conformational plasticity. They can display random coil, alpha-helical, beta-sheet or beta-harpin structures
The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for GAP activity
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs
The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for PAN2
The Ig-like C2-type domain is required for the attraction of the muscle arm extensions
The RING-type zinc finger is required for the ubiquitination of target proteins
The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling
The 8-Cys3 region in the third TB domain mediates the interchain disulfide bond interaction with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1
Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region
The central ion permeation pathway is formed by the first transmembrane domain from each of the five subunits. Mg(2+) binding strengthens interactions between subunits and leads to the formation of a symmetrical homopentamer surrounding a closed ion permeation pathway. Low Mg(2+) concentrations trigger both a conformation change within each subunit and a loosening of the interactions between subunits. This results in an open ion conduction pathway. In addition, this results in a less symmetrical shape of the whole complex
The conserved DDXXD motifs as well as the NSE/DTE motif are important for the catalytic activity, presumably through binding to Mg(2+)
The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA (By similarity)
Reactive bond 1 is specific for reaction with chymotrypsin-like protease such as cathepsin G, chymotrypsin, chymase or granzyme H, while reactive bond 2 is specific for reaction with elastase-like protease such as neutrophil elastase, proteinase-3, pancreatic elastase or PSA
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity)
The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface (PubMed:21397187). PUM1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine (PubMed:21572425, PubMed:18328718, PubMed:21653694)
The transmembrane region is required for mitochondrial localization
The C-terminal domain (residues 55-85) is sufficient to interact with and neutralize VapC4; exchanging the N-terminus (residues 1-54) with VapB5 allows neutralization, while exchanging the C-terminal domain (residues 55-85) does not. Many single residue mutations in the C-terminal domain construct but not in full-length protein prevent toxin neutralization, they are not all annotated here
The switch 1 and switch 2 motifs undergo large conformational changes during GTP/GDP cycle and play important roles in the interaction with downstream effectors
The GRIP domain may serve as a Golgi targeting domain through its interaction with the ARL1 Golgi protein
Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling
The N-terminal half of the protein mediates interaction with RAB11A and functions as guanine nucleotide exchange factor. Four long alpha-helices (interrupted by a central kink) assemble into coiled coils, giving rise to a 'V' shape
The second C2 domain mediates interaction with SV2A and probably with STN2
The LC3 interacting region (LIR) motif mediates interaction with GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C
The first coiled coil domain is essential for oligomerization
The N-terminal domain (1-65) is a functional tRNA-binding domain and is involved in the interaction with DARS, but has a repulsive role in the binding to EEF1A1. A central domain (208-259) is involved in homodimerization. The C-terminal domain (452-597) is not required for interaction with AIMP2 (By similarity)
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9B-containing vesicles, thereby enabling growth into autophagosomes
The tyrosine-based sorting signal motif, also named YXX-psi motif, promotes interaction with the AP-4 complex
The F-BAR domain binds the phospholipid membrane with its concave surface. The end-to-end polymerization of dimers of these domains provides a curved surface that fits best membranes with around 600 A diameter, and may drive tubulation (By similarity)
GRAM domain is required for specific location to endoplasmic reticulum-plasma membrane contact sites (EPCS). Mediates interaction to phosphatidylinositol lipids and binding to plasma membrane
The cysteine framework is C-CC-CC-C
Modular protein that is responsible for the completion of one condensation-processing cycle. The beta-ketoacyl synthase region is responsible for the actual condensation reaction while the acyl/malonyl transferase region is responsible for incorporating carboxylic acids units onto an acyl carrier protein (ACP) domain (By similarity)
The homeobox domain is required for binding to 5'-TTAGGG-3' repeats in telomeres, and for telomere localization
Contains an asymmetric binuclear metal center in the transmembrane domain: one metal-binding site, M1, binds zinc, cadmium, and iron, while the other, M2, binds iron only and with higher affinity than M1. Zinc is transported from M1, while iron is transported from M2. Iron transport from M2 does not inhibit the zinc transport activity but slightly stimulates it
The BAR and PX domains are required for recruitment to the phagosome
The SH3 domain is involved in phagosome maturation
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable MCD1 protein, forming a ring structure (By similarity)
Has three domains each corresponding to an enzymatic activity, namely in N- to C-terminal order: ligase, kinase and cyclic phosphodiesterase (CPDase)
The BH4 motif seems to be involved in the anti-apoptotic function
The BH1 and BH2 motifs form a hydrophobic groove which acts as a docking site for the BH3 domain of some pro-apoptotic proteins. The C-terminal residues of BCL2L2 fold into the BH3-binding cleft and modulate pro-survival activity by regulating ligand access. When BH3 domain-containing proteins bind, they displace the C-terminus, allowing its insertion into the membrane and neutralizing the pro-survival activity of BCL2L2
The FERM domain mediates the interaction with phosphatidylinositol 4,5-bisphosphate
The C-terminal coiled-coil domain mediates trimerization of CNGA subunits
The Antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter
The homeodomain, which contains the nuclear localization signal, not only mediates DNA-binding, but also acts as a protein-protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y)
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 136 and 169
The first transmembrane domain may act as a type I signal anchor. The PAL motif is required for normal active site conformation
The C-terminal domain mediates interaction with MTMR2
ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18
Both, HMG box 1 and HMG box 2, show antimicrobial activity
The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites
The XLM (XLF-like motif) mediates interaction with DNA damage response proteins TRIM28/KAP1, ATM and members of the MRN complex (MRE11, NBN and RAD50)
Consists of two structural domains that are related to each other
The oligomerization domain is distantly related to APS kinases, but it is not functional and does not bind APS. It is required for oligomerization of the enzyme, although the oligomerization state has no effect on the catalytic activity of the enzyme
Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12
The ATG16L1-binding motif mediates interaction with ATG16L1
Channel opening is brought about by a conformation change that involves buckling of the second transmembrane helix and affects the position and orientation of the fourth transmembrane helix
The DDB-box is specifically required for ddb1-binding
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. The number as well as the specific sequence of the repeats determine the specificity for target mRNAs (By similarity)
The N-terminal transcriptional activation region is sufficient to induce transcriptional activity
The POU-specific domain and POU homeodomain regions are necessary for DNA-binding activity and transcriptional repression
The polyhistidine motif acts as a targeting signal to nuclear speckles
The C-terminal domain is required for high-affinity binding to chromatin
The MREC motif mediates interaction with TTC5/STRAP and may be critical for tubulin autoregulation
The coiled coil domain mediates homotrimerization
The RRM and the CTD domain are both required for proper RNA-binding activity
The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity)
ERBB receptor binding is elicited entirely by the EGF-like domain
The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core
The SAM domain is essential for RNA-binding
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS13 has the following architecture: A-T-C-A-T-C
The leucine-zipper domain and the CCHC NOA-type zinc-fingers constitute the UBAN region and are essential for polyubiquitin binding and for the activation of IRF3
The RWD domain is required for the sumoylation enhancement activity
The C-terminal domain (CTD) forms a V-shaped, dimeric metallo-chaperone-like fold and binds 1 metal cation (probably Fe in vivo, structure determined with Zn(2+)) per subunit (PubMed:29243866). The CTD is probably responsible for hetero- and homodimerization (Probable)
Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain. The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA
Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain (By similarity)
Contains a version of the YrdC-like domain which probably has a different function than that of some proteins where it has been implicated in RNA binding
Contains a unique C-terminal domain with an O-carbamoyltransferase motif
The FM region is required for binding smad2/smad4 complexes. FM2 is more effective than FM1 and only interacts with phosphorylated smad2 that is in an activated smad complex
The N-terminal region is dispensable for binding and stabilizing SseB, but is essential for export of SseB to the surface of the bacterium
The DFXDF motifs mediate the interaction with gamma-appendage subunits AP1G1 and AP1G2
The sialic acid-binding domain is essential for efficient PRRSV virus attachment and internalization to alveolar macrophages
Both the C-terminal LCP and LytR_C regions are essential for function. The N-terminal region is not strictly required
The cysteine framework is XXIX (CCC-C-CC-C-C)
The protein kinase domain may be catalytically impaired due to the lack of the conserved Asp active site at position 500, which is replaced by a His residue
The N-terminal domain binds telomeric DNA and is required for the silencing of telomers and var genes
The C-terminal domain binds ATP and is required for the binding to DNA replication origin sites
Leucine heptad repeats are essential for the binding to telomeric DNA
The HTH La-type RNA-binding and RRM domains cooperatively bind to TER RNA UUU-3'OH sequence after it is transcribed by Polymerase III (PubMed:22705372). UUU-3'OH-binding by the HTH La-type RNA-binding and RRM domains positions the xRRM domain to bind to the adjacent proximal stem-loop IV and central dinucleotide GA bulge (PubMed:22705372)
Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have different affinities for nuclear receptors. The C-terminal LTKTNPILYYMLQK motif is required for ligand-dependent interaction with RAAR and RXRB homodimers and heterodimers, for the corepressor activity, and for the formation of an HDAC3 complex with RARA/RXRB (By similarity). Contains at least four autonomous repression domains (RD1-4). RD1 functions via a histone deacetylase (HDAC)-independent mechanism, whereas RD2, RD3 and RD4 can function by HDAC-dependent or independent mechanisms, depending on cell type. RD2 is dependent on CTBP binding
The KRAB domain is necessary for its repressive activity
The last 4 C-terminal residues binds to the first 2 PDZ domains of DLG4
The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure (By similarity)
The uncleaved pseudo signal peptide prevents receptor's oligomerization and coupling to G(i) subunits. It is also responsible for the rather low receptor localization at the plasma membrane (By similarity)
Both nuclear localization signals 1 and 2 act as a monopartite signal which binds to the high affinity site on importin-alpha
Both the spacer region (also known as the recognition (R) domain) and C-terminal domain are required for stable binding to the DNA repair bubble. However, both domains are dispensable for incision of DNA bubble structures
Both nuclear localization signals 1 and 2 act as a monopartite signal which binds to the high affinity site on KPNA2/importin-alpha
Contains 6 SPKK motifs which may interact with the minor groove of A/T-rich DNA sites. Phosphorylation of this motif may regulate DNA binding. This motif is reiterated in both termini of histone H1 and in the C-terminus of plant H2A, but its presence in the N-terminus seems to be unique to sea urchin histones H2B
Heparin-binding motifs (HBMs) are characterized by an XBBXBX or XBBBXXBX sequence, where X is any neutral amino acid and B is a positively charged basic amino acid, and are defined as the consensus sequence necessary for protein-heparin interactions. The HBM motif is involved in spore adherence to host cells
The tyrosine-based internalization signal may be involved in trafficking at the TGN
The coiled-coil region probably mediates targeting to the Golgi, oligomerization and interaction with RHOQ. May also mediates association to membranes and interactions with GOLGA3 and STX6 (By similarity)
The PDZ domain mediates interaction with ADRB1 (By similarity). Mediates also interactions with FZD5, FZD8, ASIC3, GRID2, CFTR, CLCN3
Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs (By similarity)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (348-378) inactivates kinase activity under calcium-free conditions
The proline-knob motif may be involved in the targeting to oil bodies
The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to PYGL
The first RNA recognition motif binds more strongly to RNA compared to the second one
The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome
The coiled-coil domain is necessary and sufficient for recruitment to the divisome. The LytM domain is required for proper septal peptidoglycan splitting
The Asp/Ser-rich domain functions as a stalk to allow the ligand binding domain to be displayed in a functional form on the cell surface
The C-terminal region is required for dimerization
The N-terminal part (11-82) is essential for DNA binding, an internal domain (136-316) is important for homodimerization and for interaction with LHY and the C-terminal part (317-608) is necessary for interaction with CKB3
The desert hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain
The nucleotide-binding domain consists of a twisted six-stranded antiparallel beta-sheet flanked by two pairs of alpha-helices, forming an hydrophobic pocket that interacts with the adenine ring of ATP. The ATP binding site comprises residues located in alpha-1 and alpha-2 helices and beta-2 and beta-3 strands, which are involved in van der Waal's interactions, and Glu-1073 which forms an hydrogen bond with the adenine ring
The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion via the cysteine residues within the CXXC motif. The transfer of Cu(+) ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu(+)-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu(+) ion
Contains three di-leucine motifs in the C-terminus which are required for recycling from the plasma membrane to the TGN. The di-leucine 1479-Leu-Leu-1480 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1459-Leu-Leu-1460 motif is a sorting signal for retrograde trafficking to TGN via early endosomes
The transmembrane domain is not required for cleavage, but it is required for dimer formation
The calcium-binding activity is thought to be localized in the cytoplasmic tail of the protein
Contains one leucine-zipper motif and one pair of conservatively spaced Cys (Cys pair) involved in forming heterodimers
The N-terminus forms a two-stranded coiled coil
The CAAX motif is a signal for the geranylgeranylation of FBXL2 and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex
The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins
Composed of 3 domains: the N-terminal domain has structural similarity to S-adenosylmethionine decarboxylase, the central domain is made up of four beta strands and the C-terminal domain is similar in structure to spermidine synthase. The N- and C-terminal domains are both required for activity
Has two major domains which are separated by two small subdomains, that are themselves joined by a flexible hinge. The N-terminal catalytic domain forms an (alpha/beta)8 TIM barrel and binds substrate (3-methyl-2-oxobutanoate) and Zn(2+). Subdomains I and II (separated by a flexible linker) make a three-helix bundle that packs against the C-terminal domain. The C-terminal regulatory domain includes two variable number tandem repeats (VNTR) in this strain. The regulatory domain binds L-Leu (the pathway end product) in the dimer interface. The individual domains of the monomers swap between monomers (PubMed:15159544). The C-terminus (residues 426-644) is required for condensation of the 2 substrates (PubMed:22352945)
The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates
The N-terminal exonuclease domain and the exonuclease C-terminal domain form a central positively charged groove which binds the DNA
DRBM domains cooperate for the binding to nucleic acid but not for unwinding helicase activity. The helicase-associated domain-2 (HA2) region is essential for the duplex RNA unwinding helicase activity. The minimal transactivation region (MTAD) mediates interaction with the RNA polymerase II holoenzyme and stimulates transcriptional activation in a CREB-dependent manner. The oligonucleotide- or oligosaccharide-binding (OB-fold) and the repeated arginine and glycine-glycine (RGG) regions are dispensable for both RNA-binding and unwinding helicase activities. The RGG region contains both nuclear localization signal (NLS) and nuclear export signal (NES) and is necessary and sufficient for nucleocytoplasmic shuttling in a RNA-independent manner
Composed of three structural domains; a small globular N-terminal, a central alpha-helical coiled coil and a large globular C-terminal which is responsible for the motor activity (it hydrolyzes ATP and binds microtubules)
Ig-like 1 domain is indispensable for synaptogenic activity whereas Ig-like 2 domain is secondarily responsible for the activity
N-terminal RS domain has a very strong bias in favor of D over S
The glycosyltransferase domain is the Afp18 protein domain mediating toxicity
The BC-box, which mediates binding to the elongin BC complex
The TEK-boxes are required for 'Lys-11'-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue (By similarity)
Two activation domains, AD1 and AD2, C-terminal of (and distinct from) the forkhead domains are necessary for transcriptional activation
The PH domain is responsive of the binding to phosphoinositol (PubMed:19473324). The BAR domain is required and sufficient for homodimerization (PubMed:15743878)
There are two distinct domains in this protein; the catalytic N-terminal, and the C-terminal which is involved in substrate specificity
Contains an N-terminal Cup-like domain and a C-terminal peptidase domain, separated by a flexible linker. Structural modeling identifies 2 potential metal-binding sites in the Cup-like domain, with site I binding Cu(2+) and site II favoring Fe(3+). The peptidase domain may also contain an iron-binding site
Contains nine structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a left-handed superhelical assembly with a solenoid structure that wraps itself around DNA (By similarity)
The GRAM and PH domains are required for the localization of ATG26 to the preautophagosomal structure (PAS) and are involved in autophagy (By similarity)
A large substrate binding region with partially overlapping binding domains for structurally different substrates is formed by several transmembrane helix domains (TMH) including TMH 2, 4, 10 and 11, and it is alternatingly exposed to the extracellular or intracellular side during substrate transport
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity
The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to the SUN proteins
Both N- and C-terminal domains are required for transcriptional activation
The WW domains mediate interaction with PPxY motif-containing proteins (By similarity). The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2 (By similarity)
The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization
The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency
The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction
In the zymogen form, the uncleaved propeptide blocks access to the active site
The DFDF domain is unstructured by itself. It assumes a helical fold upon interaction with other proteins (By similarity)
The DEN-box is not essential for the meiotic function
The NAB domain is capable to bind actin filaments
A tripeptide motif (FEE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
The BIR domains mediate nuclear localization
The CARD domain is necessary to stabilize the protein and inhibit the activation of E3 ubiquitin-protein ligase activity of BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin donor binding and activation
The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity
The coiled-coil domain and the B30.2 domain are both necessary for interaction with HN and PAX6. They are also involved in MED15-binding
The B30.2 domain may be involved cellular protein quality control by promoting the degradation of insoluble ubiquitinated proteins
The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components
The kinase domain is required for its function
The proline-rich attachment domain (PRAD) binds the AChE catalytic subunits
The RING finger is required for ubiquitin ligase activity
The MH1 domain is required for DNA binding
The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import
The N-terminal domain interacts with the C-terminal domain of LAYN. An interdomain interaction between its N-terminal and C-terminal domains inhibits its ability to bind LAYN. In the presence of acidic phospholipids, the interdomain interaction is inhibited and this enhances binding to LAYN (By similarity)
The N-terminal region that precedes the OTU domain mediates interaction with cellular membranes
RAP domain is required for FASTKD3 function in mRNA stability and translation
The HTH La-type RNA-binding and RRM domains are required for its function in negatively regulating organ and cell size
The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch
The extracellular domain contributes to synaptic contact formation
Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel
The N-terminal disordered prodomain is required to prevent self-activation
The Tri-arginine exosite is required to recruit substrates for hydrolysis
Undergoes helix-strand structural transitions upon substrate-binding: the 130's region interconverts between an inactive helical state and the canonically active strand state. Other caspases rest constitutively in the strand conformation before and after substrate-binding
The C2 domains have an essential, but non-catalytic function. They may facilitate interactions with other proteins and are required for lipid transport function
Contains a secondary binding site for benzoate in addition to a primary effector binding site that can accommodate either cis,cis-muconate or benzoate. The existence of this secondary binding site may explain the synergistic effects of cis,cis-muconate and benzoate
The B box-type and RING-type zinc fingers although degenerate play a central role in function of the protein
A nonterminal hydrophilic domain (59-100) is essential for targeting to the chloroplast. The C-terminal part (101-329) is necessary and sufficient to select for the import site
The RING-type zinc finger domain is essential for ubiquitin ligase activity
The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family
The IGFBP N-terminal domain mediates interaction with TSC2 substrate
IncA proteins share the same general organization: a short N-terminal domain, a large bilobed hydrophobic domain, and a C-terminal cytoplasmic domain
The C-terminal region is necessary for localization to P granules
PAPA box (proline-alanine repeats) may target the kinase to a specific subcellular location by facilitating interaction with intracellular proteins such as actin or actin-like proteins
The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain
The UBA domain interacts with poly-ubiquitinated proteins
Consists of an N-terminal helix that anchors PpiD in the inner membrane, followed by three domains that face the periplasm. The first or the third domain are probably chaperone domains. The second domain is a parvulin-like domain, which is devoid of catalytic activity. It shows a parvulin fold and resembles most closely the inactive first parvulin domain of SurA, which is part of the chaperone unit of this protein and presumably involved in substrate recognition
The 244-aa domain between residues 633 and 876 is the primary occludin (OCLN)-binding site and is required for stable association with the tight junction (By similarity)
The C-terminal region (residues 1151-1372) is an actin-binding region (ABR) that interacts directly with F-actin and plays an important role in the localization of Tjp1 at junctions (PubMed:27802160). The ABR is also required for the localization to puncta at the free edge of cells before initiation of cell-cell contact (By similarity). The ABR is also necessary for Tjp1 recruitment to podosomes (By similarity)
The second PDZ domain (PDZ2) mediates homodimerization and heterodimerization with Tjp2 and Tjp3 (By similarity). PDZ2 domain also mediates interaction with Gja12 (By similarity)
The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including three histidine boxes and an N-terminal cytochrome b5 domain containing the heme-binding motif
The L-X-X-L-L repeats are both required for binding and phosphatidic acid-mediated activation of the nuclear receptor NR5A1
The PPPY motif interacts with the WW domain 1 of BAG3
The C-terminal part after residue 140 is mostly disordered
This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity
Shows a remarkable charge distribution with the N-terminus being highly negatively charged, and the cytoplasmic C-terminus positively charged
Cluster B is an all-cysteinyl-liganded 4Fe-4S cluster; cluster C is a mixed Ni-Fe-S cluster which is the active site of CO oxidation. Cluster D is also an all-cysteinyl-liganded 4Fe-4S cluster that bridges the two subunits of the CODH dimer. Contains two additional 4Fe-4S clusters, dubbed E and F, that probably transport electrons from ferredoxin to the B cluster
The KRAB domain functions to reinforce the nuclear localization of isoform 1 in addition to its transcription repression activity
The FHA domain binds threonine-phosphorylated peptides from XRCC1/4, and is responsible for the recruitment of PNKP to the sites of DNA repair. The affinity is ten times greater if peptides are also phosphorylated on the serine preceeding the phosphothreonine
The CRC domain mediates DNA-binding. It contains two CXC subdomains (joined by a flexible linker) which are both required for efficient association with target DNA. Each CXC subdomain coordinates three Zn(2+) ions
Shows an alpha-helical coiled coil structure (30 repeating heptads)
The VWFA-like region is similar to the VWFA domain. Its presence reveals similarities between the structure of the 19S proteasome and the BRCA1-A complexes
The peptidase S74 domain, also named Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecular Chaperone Domain (ICD), has protease activity and mediates autocatalytic processing of the protein to generate the Myelin regulatory factor, N-terminal active transcription factor and the Myelin regulatory factor, C-terminal components
The Olfactomedin-like domain is required for the synapse-promoting function and the interaction with FLRT3. The Olfactomedin-like and the SUEL-type lectin domains are required for the interaction with TENM1
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils. Four skip residues (Skip1: Thr-1188, Skip2: Glu-1385, Skip3: Glu-1582 and Skip4: Gly-1807) introduce discontinuities in the coiled-coil heptad repeats. The first three skip residues are structurally comparable and induce a unique local relaxation of the coiled-coil superhelical pitch and the fourth skip residue lies within a highly flexible molecular hinge that is necessary for myosin incorporation in the bare zone of sarcomeres
ITIM (immunoreceptor tyrosine-based inhibitor motif) motif is a cytoplasmic motif present in 2 copies in the intracellular part of LAIR1. When phosphorylated, ITIM motif can bind the SH2 domain of several SH2-containing phosphatases, leading to down-regulation of cell activation
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans
The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain
This inhibitor contains two inhibitory domains
Formed by 2 beta-barrels, each is capped on both ends by short alpha-helices
This enzyme shows a novel protein fold completely different from the 'isoprenoid synthase fold' that is thought to be a common structure for the enzymes relating to isoprenoid biosynthesis
The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 55 is replaced by a Glu residue (By similarity)
The GXXXG motif may mediate oligomerization. The C-terminus is necessary for its localization at ER-plasma membrane (ER-PM) junctions as well as for the store-dependent rearrangement of ER-PM junctions
The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate transcription by recruiting TBP and associated factors at the promoters of target genes
The C2H2-type zinc fingers determine the hotspot localization through its binding to specific DNA sequences. Variations in their sequence affect affinity towards DNA-binding motif
Has a particular type of basic domain which includes a helix-interrupting proline
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins
The antiaggregation activity of isoform B resides in the serine-rich region and the C-terminus
The SRCR domains mediate binding to bacteria
The 3 tudor-like domains (also named Spin/Ssty repeats) specifically recognize and bind methylated histones. H3K4me3 and H3R8me2a are recognized by tudor-like domains 2 and 1, respectively
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which is usually essential for the association with nuclear receptors
Consists of 16-stranded beta-barrel sheets, with large surface-exposed loops, that form a transmembrane pore at the center of each barrel. The pore is partially ocluded by a peptide loop that folds into the pore lumen
The CKK domain binds microtubules and specifically recognizes the minus-end of microtubules
The MBD (microtubule-binding domain) region can recognize some features of the microtubule lattice, which might contribute to the specific decoration of growing microtubule minus-ends by CAMSAP2
The GOLD domain is required for proper p24 heterooligomeric complex formation and efficient transport of GPI-anchored proteins
The lumenal domain mediates localization to the plasma membrane by partially overriding the ER retention by the cytoplasmic domain
The conserved cystein-rich region (CRR) localized between the zinc fingers is also involved in DNA-binding and transcription repressor activity (By similarity)
The Plus3 domain mediates single-stranded DNA-binding
The LIR motif (LC3-interacting region) is required for the interaction with ATG8 family proteins MAP1LC3A, MAP1LC3B, MAP1LC3C and GABARAPL1 (PubMed:28287329). Required for proteolytic activation and delipidation of ATG8 proteins (PubMed:29458288, PubMed:28287329)
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain (PubMed:3841189). The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required (PubMed:25847991)
The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding
Arg-727 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The N-terminal part is required for homodimerization and acts as a regulatory domain
The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation
This protein has 8 EF-hand domains, 6 of which may be functional calcium-binding sites
The GRAM and PH domains are infection-related pexophagy (PubMed:19363139)
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with cut14, forming a V-shaped heterodimer
In LktB the peptidase C39 domain, the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex
The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC5, forming a V-shaped heterodimer
The C2 1 domain associates with lipid membranes in a calcium-dependent manner
The zinc-finger domains are required for binding to dsRNA, and also for nuclear localization
The cytoplasmic N-terminus mediates N-type inactivation
The C-terminal cytoplasmic tail contributes to the regulation of channel inactivation and to the interaction with HAX1 and the Arp2/3 complex
The leucine-rich repeats and the NTF2-domain are essential for the export of mRNA from the nucleus
The NTF2 domain heterodimerizes with MTR2. The formation of this heterodimer is essential for mRNA export and binds to all of the nucleoporin-FG-repeats
The RNA-binding domain is conserved in most NXF proteins but may be absent in yeasts
A histidine-rich region at the N-terminus is proposed to play a role in nickel binding, both in solution and in chelated form
The translocation domain (TD) is necessary and sufficient to mediate translocation into the host cells
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities
The last 8 amino acids of the C-terminal tail are important for a proper localization as well as for the in vivo enzymatic activity
The last loop motif confers selectivity toward behenoyl-CoA (docosanoyl-CoA; C22:0-CoA) and lignoceroyl-CoA (tetracosanoyl-CoA; C24:0-CoA) as acyl donors
The ankyrin repeats and the SH3 domain are required for specific interactions with TP53
Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase
The KVKF motif mediates interaction with PPP1CB
Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1, these repeats are required for localization to chromatin which flanks sites of DNA damage marked by 'Ser-139' phosphorylation of H2AX
The PH domain binds anionic phospholipids and helps recruiting ADRBK1 from the cytoplasm to plasma membrane close to activated receptors. It mediates binding to G protein beta and gamma subunits, competing with G-alpha subunits and other G-betagamma effectors
The coiled-coil domain is necessary for interaction with TRIM21 and for TRIM21-mediated ubiquitination of NMI
The NID domains are necessary for the interaction with IFI35. The NID domain 1 is necessary and IRF7
The DKSLVK motif binds to the lysine-binding Kringle domains of plasminogen from various mammalian species (PubMed:21949403). This motif is present only in enolases of plant and several microbial pathogens including Plasmodium species (PubMed:21949403)
The periplasmic domain is involved in C4-dicarboxylate binding and sensing. The structural disorder in the cytoplasmic PAS domain has an important role in signal transduction to the kinase domain and may be the decisive structural feature that characterizes the activated kinase
The N-terminal 39 residues are essential for activity
Has 2 lobes, each of which has an 8-strand beta barrel flanked on their N-terminus by a 4-strand handle domain
Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins
The N-terminal TOM1-binding domain (residues 1-53) is a disordered domain that partially folds when bound to the GAT domain of TOM1
The PWI domain binds nucleic acids with significant help from its N-terminal flanking basic region. It has an equal preference for binding to single- or double-stranded species, and it contributes to RBM25 role in modulation of alternative splicing
The two PARP-type zinc-fingers (also named Zn1 and Zn2) specifically recognize DNA strand breaks: PARP-type zinc-finger 1 binds PARP-type zinc-finger 2 from a separate PARP1 molecule to form a dimeric module that specifically recognizes DNA strand breaks
The PADR1-type (also named Zn3) zinc-finger mediates an interdomain contact and is required for the ability of PARP1 to regulate chromatin structure
The BRCT domain is able to bind intact DNA without activating the poly-ADP-ribosyltransferase activity (PubMed:34919819). The BRCT domain mediates DNA intrastrand transfer (named 'monkey-bar mechanism') that allows rapid movements of PARP1 through the nucleus (PubMed:34919819)
The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in PARP1 that signal the recognition of a DNA break to the catalytic domain of PARP1, promoting HPF1 recruitment and subsequent activation of PARP1, licensing serine ADP-ribosylation of target proteins
The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal (PubMed:26626479, PubMed:26626480). Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition (PubMed:26626479, PubMed:26626480)
The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site
The PHD-type zinc finger forms an aromatic cage around H3K4me3
A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer
Contains two cysteine rich domains (CRD), referred to as the N- and C-terminal CRD's, n-CRD (Cys-254 and Cys-261) and c-CRD (Cys-446, Cys-468 and Cys-477), respectively. A nuclear export signal is embedded in the c-CRD, with which the nuclear export protein CRM1/exportin 1 interacts only in the absence of disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or between the c-CRD and the n-CRD
There are at least 4 possible nuclear localization signals, both N- and C-terminal regions contribute to nuclear localization
Both the DNA unwinding and positive supercoiling activities require the cooperation of both domains. The cooperative action between the helicase-like and the topoisomerase domains is specific. The helicase-like domain probably does not directly unwind DNA but acts more likely by driving ATP-dependent conformational changes within the whole enzyme, functioning more like a protein motor. The 'latch' region of the N-terminal domain plays a regulatory role in the enzyme, repressing topoisomerase activity in the absence of ATP and therefore preventing the enzyme from acting as an ATP-independent relaxing enzyme; it also helps to coordinate nucleotide hydrolysis by the ATPase domain with the supercoiling activity of the topoisomerase domain
Has an asymmetric bilobed structure, with a recognition (REC) lobe and nuclease (NUC) lobe; the sgRNA:target DNA is bound between the 2 lobes. The REC lobe (residues 1-312) is formed by the WED, ZF and REC domains, while the NUC lobe (residues 321-529) is formed by the RuvC and TNB domains. Has a split RuvC-like domain with the nuclease active sites
Interacts with the snRNP via the Nop domain
The coiled coil domain is formed by two non-contiguous helices
The kinase domain (PI3K/PI4K) is intrinsically active but has a highly restricted catalytic center
The FAT domain forms three discontinuous subdomains of alpha-helical TPR repeats plus a single subdomain of HEAT repeats. The four domains pack sequentially to form a C-shaped a-solenoid that clamps onto the kinase domain (By similarity)
The first two EGF domains mediate the interaction with DAF. A third tandemly arranged EGF domain is necessary for the structural integrity of the binding region
Binding to chondroitin sulfate is mediated by the fourth EGF domain
The protein 4.1-binding domain (654-685) is required for binding to EPB41L2 and channel activation
The calmodulin- and inositol 1,4,5-trisphosphate receptor-binding (CIRB) domain (695-724) is sufficient for the interaction with SESTD1
The spectrin-binding domain (730-758) is required for binding to SPTAN1 and SPTBN5
The C2H2-type zinc finger 5 is required for nuclear localization
The calpain catalytic domain is essential for in vivo function to promote female sexual development
The C2 domain associated with the domain III is primarily responsible for calcium binding
The VASt domains bind sterols
The Asp-Asp-Xaa-Xaa-Asp (DDXXD) motif is important for the catalytic activity, presumably through binding to Mg(2+)
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface (By similarity). The head region (residues 27-137) forms at the top of a long trimeric stalk. The head itself is almost exclusively coiled-coil that can be divided in two fragments (residues 34-48 and 85-137, respectively) separated by an insertion (residues 49-84) that forms 3 wing-like structures per trimer that pack against the N-terminus. Only residues 27-137 and 199-210 gave a defined structure (PubMed:25404323)
The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. It is essential for the translation repression activity of the protein
The N-terminal region contains FAD-dependent dehydrogenase activity and the C-terminal region contains DNA-binding activity
The HIN-200 domain 1 mediates non-specific double-stranded DNA (dsDNA)-binding via electrostatic interactions: it recognizes both strands of DNA (PubMed:23567559, PubMed:24419611). The HIN-200 domain 2 mediates homotetramerization and interaction with AIM2 (PubMed:23850291)
The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms)
The protein kinase domain plays an important role in its localization in the cell membrane
Has 3 domains; the N-terminal domain has 4 short repeats, the central region has 6 longer repeats (Probable). The C-terminal domain has 2 repeats and a highly conserved C-terminal peptide. The C-repeats serve as the encapsulation signal for the alpha-carboxysome, and are able to target foreign proteins to this organelle (By similarity)
Displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9 (By similarity)
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity)
The SH2 domain mediates interaction with SHB
The PDZ-binding motif mediates interaction with PDZ domain-containing proteins like SNTG1 and SNX27
The BH1 and BH2 motifs form a hydrophobic groove which acts as a docking site for the BH3 domain of some pro-apoptotic proteins. The C-terminal residues of BCL2L2 fold into the BH3-binding cleft and modulate pro-survival activity by regulating ligand access. When BH3 domain-containing proteins bind, they displace the C-terminus, allowing its insertion into the membrane and neutralizing the pro-survival activity of BCL2L2 (By similarity)
The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria
The N-terminal contains a GTPase-activating protein (GAP) domain (PubMed:10593930, PubMed:15252013). The ADP-ribosyltransferase domain is located within the C-terminus region (PubMed:15252013)
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases leading to down-regulation of cell activation
The Phe/Asp-rich domain at the C-terminus is necessary for its incorporation into the CSN complex
Contains a N-terminal dileucine motif (DE)XXXL(LI) important for endosomal/lysosomal and mitochondrial subcellular localization
The SPX domain has very high affinity for inositol polyphosphates. SPX domains may integrate inositol pyrophosphates (PP-InsP)-dependent signaling to adapt cytosolic phosphate concentrations to different metabolic situations
The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1
The RAMA domain recognizes and binds N(6)-methyladenosine methylation on DNA (m6A)
The Ras-GEF domain and the N-terminal Ras-GEF domain form a Ras-binding site and mediate Ras activation
The IQ domain mediates the calcium-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity
The DH (DBL-homology) domain mediates interaction with RASGRF1 and EPB49 and is required for RAC1 activation
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif is involved in PTPN11 binding
A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure (By similarity)
The second albumin domain forms a deep binding pocket that contains palmitoleic acid (in vitro). Palmitoleic acid is most likely not the physiological ligand. Instead, this pocket may accomodate the covalently bound lipid moiety of Wnt family members
The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function. MCT1 N-terminal region is required to enhance translation possibly through interaction with other proteins
EF-hand domain is involved in the detection of calcium concentration
The J domain stimulates the ATPase activity of HSPA5/BiP, while the divergent targeting domain is required for efficient substrate recognition by HSPA5/BiP. The divergent targeting domain specifically recognizes and binds to aggregation-prone sequences
The C-terminal region containing the DEP domain is required for membrane accumulation and phosphorylation. Wnt signaling and axis induction requires the DIX domain. The C-terminus contributes to the localization at the cilia base
The mitochondrial targeting sequence (MTS) is weak and only mediates import of a small fraction of YRDC in mitochondria
The PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). Does not bind phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (By similarity)
The C-terminal Cdc25-homology/Ras-GEF domain adopts a closed conformation rendering it incapable of carrying out canonical exchange factor function, this closed conformation is required for interaction with BCAR1
The FYVE-type zinc finger domain is required for localization and may confer affinity for cellular compartments enriched in phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate phospholipids
Contains a central domain containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif (PubMed:10502414). The SH2-binding sites putatively bind CRKL SH2 domains (PubMed:9020138). The HLH motif confers specific interaction with the HLH protein ID2 (PubMed:10502414). It is absolutely required for the induction of pseudohyphal growth in yeast and mediates homodimerization and heterodimerization with BCAR1/p130cas (PubMed:8668148, PubMed:10502414)
Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein (By similarity)
The longin domain regulates palmitoylation and membrane targeting
The WD repeat domain mediates binding to U1 snRNA and to U4 snRNA (PubMed:19377484, PubMed:19750007, PubMed:27834343, PubMed:27881600, PubMed:27881601). The WD repeat domain also mediates binding to the 7-methylguanosine cap that is found both on mRNA and snRNA molecules (PubMed:19750007, PubMed:27834343, PubMed:27881600, PubMed:27881601, Ref.27). The regions that bind snRNA molecules and the isolated 7-methylguanosine cap overlap at least partially (PubMed:27834343, PubMed:27881600, PubMed:27881601). Besides, the WD repeat domain mediates interaction with the 60S large ribosomal subunit (PubMed:27507887)
The cytoplasmic domain binds synaptic Ca(2+)
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex. The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer (By similarity). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (By similarity)
The proline-rich domain (PRD) contains repeated PPP motifs. A single PPP motif is necessary and sufficient to mediate interaction with the COPII coat subunits SEC23A and SEC23B (PubMed:21525241, PubMed:27551091). The coiled coil domains mediate interaction with MIA3 (PubMed:21525241). The first coiled coil domain mediates interaction with PREB (PubMed:25202031)
Contains 5 N-terminal periplasmic polypeptide transport-associated (POTRA) domains which interact with other subunits of the complex, may recruit substrates from the periplasm into the outer membrane and also act as a chaperone (PubMed:17702946, PubMed:18430136, PubMed:19081063, PubMed:21795783, PubMed:14559180). The C-terminal region forms a discontinuous 16-stranded beta-barrel transmembrane region. The central pore is ellipsoid, and probably closed by extracellular loop 6, perhaps with the aid of other loops (PubMed:24914988, PubMed:24619089)
The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins (By similarity). Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is sufficient for interaction with TSPAN15 (PubMed:26668317)
The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme
The individual domains assume different positions in the enzyme, allowing the holoenzyme to regulate the methylase, endonuclease and translocation states. Deletion of the linkers between the domains prevents movelemt and thus restriction activity
Alteration of functional properties of alpha subunit is mediated through N-terminal domain of beta subunit
The [NKR]KIAxRE motif seems to be a cyclin-binding region
The CHD1 helical C-terminal domain (CHCT) may bind DNA and nucleosomes
Kringle domains mediate interaction with CSPG4
A 7-bladed beta-propeller torus, about 54 by 55 Angstroms, with a depth of about 25 Angstroms and a central pore
The ketoreductase domain catalyzes five beta-ketoreduction steps involving substrates ranging in size from diketide to hexaketide and possesses a previously unrecognized ability to reduce the beta-ketoacyl intermediates with different stereochemical outcomes based on substrate chain length (PubMed:22406519)
The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1
The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP
The N-terminal domain interacts with RNAP and the C-terminal domain binds either to Rho or to RpsJ (NusE). These domains are separated by a flexible linker
The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity
The LXXLL motif is a coregulator signature that is essential for transcriptional corepression
Third 'degenerate' zinc-finger domain essential for function
The GATA-type zinc fingers mediate interaction with LMCD1
The glycine-rich domain, which contains a number of RGG motifs, is necessary to regulate nucleocytoplasmic localization
The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]
Extended rod-like protein with coiled-coil domains
The CBM6 domain binds the non-reducing ends of beta-glucan; this domain may therefore target the enzyme to polysaccharide termini in damaged regions of the plant cell wall susceptible to catalytic attack
The CBM56 domain modulates binding affinity for beta-glucan and aids binding to insoluble beta-glucan
The PDZ-binding motif (also named EWV motif) is required for interaction with PDZ domains of APBA3 and recycling through the trans-Golgi network
The ASD2 domain mediates the interaction with Rok and is required for apical constriction induction
The PBZ-type zinc finger (also named CYR) mediates non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and is required for its function in antephase checkpoint
The FHA domain plays a key role in the anti-proliferative properties of the protein and is involved in initiating a cell cycle arrest at G2/M
Arg-175 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity)
The tandem repeat domain, also called neck domain, mediates oligomerization
Composed of a globular head, an elongated tail (coiled-coil) and a highly acidic C-terminal domain
The NAC domain includes a DNA-binding domain and a dimerization domain
Residues 17-29 of LL-37 represent the active core of the antimicrobial peptide (PubMed:32753597). Forms ribbon-like fibrils and exhibits antibacterial activity against Gram-positive M.luteus (MIC=53 uM) (PubMed:32753597). Also exhibits antibacterial activity against Gram-negative E.coli and P.fluorescens (By similarity)
Has 2 endonuclease domains. The discontinuous RuvC-like domain cleaves the target DNA noncomplementary to crRNA while the HNH nuclease domain cleaves the target DNA complementary to crRNA
Residues 2-27 within the N-terminal intrinsically disordered regions (IDR) constitute the binding module for DHR2 which is required to coordinate the UBP10-DHR2 interaction (PubMed:26149687)
Residues 109-145 within the N-terminal intrinsically disordered regions (IDR) constitute the binding module for SIR4 which required to coordinate the UBP10-SIR4 interaction, but also to direct UBP10's functional role in telomere chromatin silencing (PubMed:26149687)
Residues 167-208 within the N-terminal intrinsically disordered regions (IDR) constitute the binding module for UTP22 which is required to coordinate the UBP10-UTP22 interaction (PubMed:26149687)
The coiled coil domains interact with the SB domain of TSG101
The PTAP motifs mediate the binding to UEV domains
The LRR domain is necessary and sufficient for localization to bacterial targets
The RING domain is required for ubiquitination
N-terminus enhances protein stability and hexamer formation, which is important for DNA binding, and is required for DNA helicase activity and, ultimately, for mtDNA replisome processivity
Contains a bacterial GIY-YIG-like domain
The DELLA motif is required for its GA-induced degradation
The bHLH domain is essential for its repressor activity towards the CLOCK-BMAL1 heterodimer
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (328-358) inactivates kinase activity under calcium-free conditions (By similarity)
Each NEAT domain binds hemin, whereas only NEAT1 and NEAT3 bind hemoglobin
C-terminus is a mobile self-inhibitory loop which interferes directly with active site
The N-terminal WD40 domain is necessary for the interaction with NOD2 and down-regulation of NOD2 function
The GLEBS region mediates interaction with bub3
Mainly composed of disordered low-complexity regions outside of the C2H2-type zinc fingers. Coacervation depends on hydrophobic and aromatic Phe and Tyr in the disordered low-complexity region, that may promote coacervation by forming intermolecular hydrophobic interactions
The microtubule-binding region is required for efficient loading of bub3 onto kinetochores and proper mitosis
Contains two C-X9-C motifs that are predicted to form a helix-coil-helix structure, permitting the formation of intramolecular disulfide bonds
Tyrosine-protein phosphatase 1 domain has enzymatic activity which is required for the negative regulation of egl-15 (PubMed:9585503). Tyrosine-protein phosphatase 1 domain is required for correct PVD dendrite formation (PubMed:26968353). The second tyrosine-protein phosphatase domain has no phosphatase activity and appears to be dispensable for clr-1 function (PubMed:9585503). Isoform c lacks both tyrosine-protein phosphatase domains and is likely to have no catalytic activity (PubMed:9585503)
The extracellular domain is required for the formation of synapses between the AVA interneurons and the PHB sensory neurons
The FXDXF motif mediates interaction the AP-2 complex
The clathrin box motif mediates interaction with clathrin
The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity and for nuclear localization and aggregation
Has a two-domain beta-structure, folded into four very similar Greek key motifs. The N-terminal domain (NPS) binds 2 calcium ions
The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor
The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner (By similarity)
The KxHxx motif mediates association with the coatomer complex
Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4
The N-terminal part of the protein controls substrate specificity
The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP)
The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization
The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P) (By similarity)
The transmembrane domain is composed of seven transmembrane helices; most of these are not strictly perpendicular to the plane of the membrane, but are tilted and/or kinked. Agonist binding promotes a conformation change in the extracellular loops that leads to an inward movement of the transmembrane helices. Antagonists can bind to an overlapping site, but block the inward movement of the transmembrane helices (By similarity)
The C-terminal region is necessary for the kinase activation in response to hyperosmotic stress
Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium. The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for translocation to the cell membrane in response to increased cytosolic calcium levels (By similarity)
The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior (By similarity)
The DEP domain mediates the interaction with KLHL22
The protein kinase domain mediates binding to phosphatidylinositol
The second SH3 domain mediates binding to a proline-rich motif in RIMS1 and RIMS2
The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 complex but not the individual proteins (By similarity). Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is sufficient for interaction with TSPAN15 (By similarity)
The RRM domain is necessary for RNA-binding, but not for splice site selection, indicating that its splicing activity does not require direct binding to RNA
The Olfactomedin-like domain is required for the synapse-promoting function and the interaction with FLRT3. The Olfactomedin-like and the SUEL-type lectin domains are required for the interaction with TENM1 (By similarity)
Binding of c-di-GMP appears to trigger the active Clp conformation into an open form or inactive state, hence abolishing its DNA-binding ability
The OapA domain binds peptidoglycan
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Unlike other voltage-gated ion channels it lacks the pore domain
The C-terminal coiled coil region mediates homodimerization and cooperative channel gating. It is essential for normal subcellular localization
The N-terminal RRM domains are responsible for recognizing the G-tract of BCL-X RNA
The helical domain (514-664) is required for self-activation
The D-box 1 (destruction box 1) mediates the interaction with APC2, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway
The N-terminal unstructured half of Pup provides a signal required to initiate unfolding and degradation by the proteasome but is not needed for pupylation, while the C-terminal helical half of Pup interacts with Mpa to target proteins to the proteasome
The ENTH domain coordinates with the clathrin-binding C-terminal domain to allow a dynamic interaction of epsin with coated pits
The WD repeats are grouped into two tandem seven-bladed beta-propeller regions
The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation
A short peptide sequence (termed the Stachel sequence) in the C-terminal part of the extra-cellular domain (ECD) functions as a tethered agonist. Upon structural changes within the ECD, e.g. due to extracellular ligand binding or mechanical movements, this intramolecular agonist is exposed to the 7TM domain, triggering G-protein activation
Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant
The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding
Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently
The FYVE-type zinc finger mediates binding to phosphatidylinositol-3-phosphate (PtdIns(3)P)
The MIM1-B motif mediates interaction with VPS4A
The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain
The WW domains mediate interaction with PPxY motif-containing proteins
The first C2 domain/C2A does not mediate Ca(2+)-dependent phospholipid binding
The second C2 domain/C2B is responsible for SYNCRIP and inositol 1,3,4,5-tetrakisphosphate (IP4)-binding
The thioredoxin domain lacks the 2 redox-active cysteines, suggesting that it lacks thioredoxin activity
The cytoplasmic region is essential for the fusiogenic function
The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo (By similarity)
The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain (By similarity). This autoinhibition is released upon competitive binding of an activated GTPase (By similarity). The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity)
The TPR repeats mediate interaction with proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type)
The WxxxF/Y motifs mediate interaction with pex14, promoting association with the pex13-pex14 docking complex
The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are required for pex5 retrotranslocation and recycling. AH2 mediates interaction with lumenal side of the pex2-pex10-pex12 ligase complex, while AH1 is required for extraction from peroxisomal membrane by the pex1-pex6 AAA ATPase complex
The JmjC domain and the C6-type zinc-finger are required for the demethylation activity
The mature protein is largely unstructured in the absence of a cognate ligand
The WD repeats are required for non-canonical autophagy but not for canonical autophagy
The N-terminal region interacts with DNA and CarS, and the C-terminal region is involved in oligomerization and binding of cobalamin
The 2 HXXHC motifs are conserved in ustYa family proteins and might form active sites
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. Upon phosphorylation of ITIM motif KLRG1 associates with the two phosphatases, PTPN11 and INPP5D
The N-terminal region (NTR) recognizes and binds poly-ADP-ribose chains produced by PARP1, leading to its recruitment to DNA damage sites
The N-terminal disordered region does not act as a key DNA-binding domain (PubMed:26704974). The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage (PubMed:26704974)
The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation (PubMed:30321391, PubMed:32939087, PubMed:33141820). The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins (PubMed:32939087)
The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal (PubMed:34108479). Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition (PubMed:34108479)
Consists of three domains. The N-terminal dimerization domain has the same fold as the IIA domain of the mannose transporter of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS). The middle domain is similar to HPr and the C-terminus is similar to the N-terminal domain of enzyme I (EI) of the PTS. The IIA domain of DhaM (via phospho-His-9), instead of ATP, is the phosphoryl donor to dihydroxyacetone (Dha). The phosphoryl flow likely involves HPr ('His-15') -> DhaM (His-430 -> His-169 -> His-9) -> DhaL-ADP -> Dha. The HPr-like domain of DhaM cannot efficiently substitute for the general carrier protein HPr
Contains an N-terminal region that probably interacts with RNA polymerase and a C-terminal region composed of 3 RNA binding domains, S1, KH 1 and KH 2
The C-terminus (residues 119-133) targets the protein to the encapsulin nanocompartment
The NEAT 1 domain binds with higher affinity than the NEAT 2 domain haptoglobin-hemoglobin complexes, haptoglobin and hemoglobin
Cell binding activity is dependent on the N-terminal segment whereas the C-terminal domain tethers the protein to the cell membrane
Composed of an N- and a C-terminal domain. The N-terminal domain carries the tetrahydrofolate (THF)-binding site and the C-terminal domain is presumably involved in positioning the Met-tRNA substrate for the formylation reaction
The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself (By similarity)
The Proline-rich domain is required for phospholipid scramblase activity
The EF-hand and C2 domains are essential for triggering Ca(2+) oscillating activity and the regulation of PLCZ1 enzyme activity
The X-Y linker region between PI-PLC X-box and Y-box domains may be a target for proteolysis and may play an important regulatory role during fertilization
The DH (DBL-homology) domain mediates interaction with RASGRF2
The F5/8 type C 2 domain mediates high-affinity binding to phosphatidylserine-containing membranes
The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity
Contains a novel ssDNA-binding fold, which is structurally and topologically distinct from the OB-fold universally found in standard SSB proteins. The disordered C-terminus of DdrB may mediate interactions with other proteins important for DNA damage recovery (By similarity)
The RWDBD (RWD-binding domain) region mediates binding to RWD domain-containing proteins, such as EIF2AK4/GCN2, IMPACT and RNF14
The long N-terminal helix forms part of the 'assembly lobe' of the SAGA deubiquitination module
The C-terminal SGF11-type zinc-finger domain together with the C-terminal catalytic domain of UBP8 forms the 'catalytic lobe' of the SAGA deubiquitination module
The PDZ domain 1 binds NG2. The PDZ domain 2 mainly binds CAMK2A and CAMK2B. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds CXADR and SYNGAP1 (By similarity). The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 10 binds the C-terminal PDZ-binding motif of HTR2C
The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex
The OSR domain is sufficient to promote organ growth
Binds 3 calcium via EF-hand domains. The cryptic EF-hand 1 does not bind calcium
The C-terminal is cytoplasmic and is important for interaction with ZO-1. Necessary for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction (By similarity)
The coiled coil region is indispensible for localization to the midbody during cytokinesis
The phorbol-ester/DAG-type zinc finger domain mediates interaction with membranes enriched in phosphatidylinositol 3,4,5-trisphosphate and is required during mitotic cytokinesis for normal attachment of the midbody to the cell membrane
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (323-353) inactivates kinase activity under calcium-free conditions (By similarity)
The protein kinase domain contains a 228 residue insertion between the ATP binding site and the active site
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable
The nuclear localization signals mediate the localization to the nucleus
The D box motifs (amino acid sequence RxxL) are involved in substrate binding, and may be ubiquitinated
The N-terminal domain (1-52) is not required for import, membrane integration or activity
The C-terminal leucine-rich repeat (LRR) region is required for responses to smooth LPS
The 377 first amino acids might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane (By similarity). Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P) (By similarity)
The L/FRRG motif is essential for the cytoplasm to vacuole transport (Cvt) pathway, for the recruitment of ATG8 and ATG16 to the PAS in nutrient-rich medium, and for its recruitment to and dissociation from the PAS under starvation conditions (By similarity)
The head-like domain S1 exhibits a much faster ATP-induced detachment from actin, and ADP affinity is more than 3-fold weaker than other myosins
An ammonia tunnel 40 Angstroms long allows transfer of ammonia from the glutaminase active site, where it is produced, to the synthetase active site, where it is used for the ATP-dependent formation of NAD(+)
The cytochrome b5 heme-binding domain acts as the direct electron donor to the active site of the desaturase, and does not require an external cytochrome
The cytoplasmic domain has Ser/Thr kinase activity (PubMed:12406230). The C-terminal extracellular domain containing the PASTA repeats binds peptidoglycan
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (By similarity). AQP3 has NPC/NSA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (By similarity)
The Pru (pleckstrin-like receptor for ubiquitin) domain mediates interactions with PSMD1 and ubiquitin. Preferential binding to the proximal subunit of 'Lys-48'-linked diubiquitin allows UCHL5 access to the distal subunit
Is organized into three distinct structural domains with interconnecting topological connectivities. The two NIF3 domains at the N- and C-terminus of the protein have the same overall fold as canonical NIF3-like proteins. The middle region of the polypeptide (residues 126-236) bulges out between the two NIF3 domains and is structured as a classical PII-like fold. The two entries to the central hollow space are capped by the two PII-like domain trimers. The trimeric PII domain may play a ligand induced signaling role and probably regulates the function of the NIF3-like domains
The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2)
The first ATP-binding region binds ATP with low affinity whereas the second ATP-binding region binds ATP with high affinity (PubMed:12006565). ATP hydrolysis mediated by the second ATP binding region releases RLP24 from pre-60S ribosomal particles whereas the ATP hydrolysis mediated by the first ATP binding region is subsequently required for RLP24 dissociation from AFG2, probably by disassembling AFG2 into monomers (PubMed:23185031, PubMed:24371142)
The regulatory N-terminal domain/NTD formed of two pairs of fused calcium-binding EF-hands, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity (PubMed:24332718)
The N-terminal pseudoreceiver domain (PsR, approximately equal to KaiA N-terminal) binds oxidized quinones (By similarity). The KaiA C-terminal domain mediates interaction with KaiC, homodimerization, and is responsible for the clock oscillation function (By similarity)
The F-BAR domain binds the phospholipid membrane with its concave surface. The end-to-end polymerization of dimers of these domains provides a curved surface that fits best membranes with around 600 A diameter, and may drive tubulation
Has protease activity which is probably neurotoxic
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (HCN and HCC) (By similarity). HCN has a lectin-like fold, HCC is the main region associated with cell recognition. Probably recognizes host cells via other residues than Clostrial botulinum-type toxins, as conserved residues important for ganglioside recognition can be mutated with little effect (PubMed:31253776)
The IBR domain is required for interaction with UBCH7 and UBCH8
Binds to actin monomers via the WH2 domain
The Spir-box targets binding to intracellular membrane structures
Contains F-X-F-G repeats
The protein contains a transactivation domain (TAD) which may be required for transcriptional activation of a subset of target genes
Binds calcium via the C2 domains. The calcium-bound C2 domains mediate interactions with phospholipid bilayers
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2 (By similarity)
Binds to vesicles enriched in neutral phospholipids via its C2 domain. The interaction is favored by Mg(2+) rather than Ca(2+) (By similarity)
C-type lectin domains 3-5 mediate the interaction with phospholipase PLA2G1B
The endocytosis signal probably mediates endocytosis via clathrin-coated pits
Heparin binding seems to require the C-terminal domain of HbhA. Progressive truncations from the C-terminal end diminish the affinity for heparin
The non-repeat region (NRR, also called binding region, BR) binds to human gp-340; binding is prevented by N-acetylneuraminic acid (NeuAc)
EF-hands 1 and 4 have been shown to bind calcium. It is not known if EF-hands 2 and 3 are capable of calcium-binding. The N-terminal 22 amino acids are necessary and sufficient for vacuolar membrane targeting
The LRR domain, the Fic/Fido domain and the uridylylation activity are required for avirulence function on Col-0
The B30.2 domain mediates interaction with GYG
The coiled-coil region mediates homodimerization and heterodimerization
The cytosolic domain interacts with sigma factor SigL
The CRAL-TRIO domain is known to bind small hydrophobic molecules
Lacks the conserved DRY and BBXXB motifs. The restoration of these motifs affects its constitutive activity
The SET domain is necessary but not sufficient for histone methyltransferase activity
Contains a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2)
The L/FRRG motif is essential for the cytoplasm to vacuole transport (Cvt) pathway and for the recruitment of ATG8 and ATG16 to the PAS in nutrient-rich medium and in both its recruitment to and dissociation from the PAS under starvation conditions
The CFEM domain mediates interactions with host proteins
The C2-domain mediates homodimerization
The CS domain mediates interaction with HSP90
The presence of a 'disulfide through disulfide kOR' structurally defines this protein as a knottin
The two SH3 domains and the SH2 domain are necessary for the reinitiation of oocyte meiosis
The APO repeats may provide ligands for 4Fe-4S centers
Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor (By similarity)
The first Sushi domain (SCR1) is not necessary for function. SCR2 and SCR4 provide the proper conformation for the active site on SCR3 (By similarity)
The N-terminus is required for RNA-binding
The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain
The DBB domain is required for dimerization
The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)). Required for association with endosomes
The PTB-like F3 module within the FERM-like domain mediates cargo recognition via their NPxY sequences, while the F1 module (Ras-associating) is responsible for interaction with membrane-bound HRAS
Binds oxysterols in a pocket within their transmembrane domains and interacts with scap via transmembrane domains 3 and 4
Contains a large substrate-binding pocket that recognizes alpha-helical transmembranes, which alternately faces the endoplasmic reticulum lumen and cytosol, while remaining accessible to the lipid bilayer through a lateral opening. The translocase alternates between two conformations: inward-open (E1) and outward-open (E2) states. Undergoes a series of conformational changes with ATP-binding, phosphorylation of the Asp active site and subsequent dephosphorylation in a Post-Albers cycle (i.e., E1 -> E1-ATP -> E1P-ADP -> E1P -> E2P -> E2-Pi -> E1). A substrate transmembrane helix with a short, preferentially positively charged lumenal segment binds to the outward-open pocket and the E2P-to-E1 transition flips the transmembrane by a switch from the outward-open to inward-open conformation
The C-terminus is involved in transcriptional repression by HDAC-independent mechanisms
The homeodomain is essential for interaction with OLIG2
The CRN proteins have modular architectures that include a signal peptide, a conserved N-terminus, and highly diverse C-terminal domains. The conserved CRN N-terminus harbors a distinct LXLFLAK motif, which is followed by the conserved DWL domain. A highly conserved HVLVXXP motif marks the end of the CRN N-terminal domains and forms a junction where diverse C-terminal domains are fused
The CRIB domain mediates interaction with CDC42
The TPR repeats mediate interaction with unfolded polypeptides and the J-domain is essential to stimulate the ATPase activity of the chaperone and to increase its substrate affinity during the folding cycle
The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate
The second extracellular domain (ECD2, aa 1395-1680) undergoes conformational change in response to its specific interaction with its substrate all-trans-retinal. Nucleotide binding domain 1 (NBD1, aa 854-1375) binds preferentially and with high affinity with the 11-cis retinal
The PKS portion of TAS1 has only a ketosynthase (KS) domain and this domain is indispensable for TAS1 activity by conducting the final cyclization step for tenuazonic acid release (PubMed:26503170, PubMed:32565425). The KS domain has intrinsic tolerance for a broad range of substrates since it is able to accept also TeA analogs containing leucine (Leu), phenylalanine (Phe) and valine (Val) instead of isoleucine (Ile) (PubMed:32565425)
The methyl-CpG-binding domain (MBD) functions both in binding to methylated DNA and in protein interactions
The LysM domains are thought to be involved in peptidoglycan binding
The C-terminal SGF11-type zinc-finger domain forms part of the 'catalytic lobe' of the SAGA deubiquitination module
Contains a N-terminal polysaccharide deacetylase domain, and a C-terminal domain required for PGA N-deacetylation that may be involved in binding to unmodified poly-beta-1,6-GlcNAc and thereby assists catalysis by the deacetylase domain
Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing
Exists in a relatively unstructured form; binding to the other subunits (UreD, UreF and apourease) may induce correct protein folding. The presence of Zn2(+) or GTP does not alter the unfolded state
The N-terminal ATP-grasp domain carries the phosphoribosylamine--glycine ligase activity
The central AIRS domain carries the phosphoribosylformylglycinamidine cyclo-ligase activity
The C-terminal GART domain carries the phosphoribosylglycinamide formyltransferase activity
A PH-like domain is involved in phosphatidylinositol phosphate binding
Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix (By similarity)
The CD6 binding site is located in the N-terminal Ig-like domain
A functional Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. The essential Lys in this region is not conserved in ABCG8 (G-S-S-G-C-R-A-S) and is not required for transport activity mediated by the heterodimer with ABCG5
The first GRAM domain is required for association with the micropexophagic apparatus (PubMed:12839986)
The MBT repeats mediate binding to histones tails; however, in contrast to other MBT repeats, does not bind specific histone lysine modifications. The MBT repeats lack the conserved Asp and aromatic cage at conserved positions (By similarity)
The DSL domain is indispensable and sufficient for binding to NOTCH2
The extracellular domain is required for sensing alterations in external pH
Has protease activity (PubMed:8505288, PubMed:8175689, PubMed:8197120)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (By similarity). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (By similarity). The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (By similarity)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. Hkm11 has the following architecture: A-T-C
the 9aaTAD motif (residues 985 to 993) is a transactivation domain present in a large number of yeast and animal transcription factors
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains (By similarity)
The Asp-Asp-Xaa-Xaa-Xaa-Asp (DDXXXD) motif is important for the catalytic activity, presumably through binding to Mg(2+)
The calcium-binding sites of the 2 EF-hand domains are required for enzyme activity
The N-terminal region seems to be important for proper quaternary structure. The C-terminal region contains the substrate-binding site (By similarity)
Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure (By similarity)
The twin-arginine signal peptide of NapA is structured in its unbound form and undergoes a small but significant conformational change upon interaction with NapD
Contains a serine-rich phosphorylation region at the N-terminal and an eukaryote-only S-adenosylmethionine (SAM)-binding domain at the C-terminal. Through asymmetric homodimerization, the two regions are positioned next to each other and N-terminal phosphorylation increases sensitivity to SAM binding and inhibition
The N-terminal domain, which is intrinsically disordered, is required for stress granule localization
The N-terminal glycosyltransferase domain (GT47) does not bind UDP and is therefore unlikely to possess glycosyltransferase activity
SH2 domain mediates interaction with RUFY1
Contains several highly conserved motifs that are important for catalytic activity including the aspartate-rich 'DDxx(x)D/E' motif and the 'NDxxSxxxD/E' motif, both of which are involved in complexing metal ions to coordinate the binding of the isoprenyl diphosphate substrate in the active site
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. FG-rich region is required for emb localization to the nuclear pore complex
12 di-nuclear ferroxidase centers are located at the interfaces between subunits related by 2-fold symmetry axes
Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors
The N-terminal transactivation domain (TAD-A) binds to and is activated by Cbp/p300. The dephosphorylated form contains two unmasked nuclear localization signals (NLS), which allow translocation of the protein to the nucleus
Isoforms C have a C-terminal part with an additional transactivation domain, TAD-B, which acts as a transcriptional activator. Isoforms B have a shorter C-terminal part without complete TAD-B which acts as a transcriptional repressor
The coiled-coil domain is required for assembly into the NuA4 complex
The C-terminal part (65-85) forms an alpha-helix which probably disrupts target membranes
The homodimer has 2 functional domains, a central cleft essential for production of soluble RbcL in which the RbcL peptide binds, and a polar surface which plays a role in correct RbcL subunit arrangement
The LFa (leucine-phenylalanine-acidic) motif bind directly to VPS35 of retromer CSC; adjacent motifs can act cooperatively to bind multiple CSCs, although there is significant variability in the affinities of different motifs for retromer
The D-box (destruction box) mediates the interaction with APC/C proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway
The initiation motif is required for efficient chain initiation by the APC/C complex E2 ligase UBE2C. It determines the rate of substrate's degradation without affecting its affinity for the APC/C, a mechanism used by the APC/C to control the timing of substrate proteolysis during the cell cycle (By similarity)
The homeobox DNA-binding domain is necessary for its nuclear localization, transcriptional and erythroid differentiation activities
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 429, which is replaced by an Asn residue
RNA recognition is mediated by a convoluted intramolecular fold of the TPR repeats (TPR eddy), which scaffolds unique additional helices that form an RNA binding cleft
The 2 RNase III domains form an intramolecular dimer where the domain 1 cuts the 3'strand while the domain 2 cleaves the 5'strand of pri-miRNAs, independently of each other
The glycine-rich region is characteristic of harpins
The PHD-type zinc finger 1 most likely mediates nuclear localization
The ePHD2 domain folds as an integrated structural module comprizing the C2HC pre-PHD-type 2 zinc finger and the PHD-type 2 zinc finger. It mediates non-specific binding to dsDNA, but does not bind histones in contrast to many PHD-type zinc fingers
The nuclear localization signals mediate the localization to the nucleus and are required for CCNB1 localization to the nucleus
The D box motifs 1-4 (amino acid sequence RxxL) are involved in substrate binding, such as FZR1/CDH1, and may be ubiquitinated
The CAP-Gly domain is essential for interactions with microtubules and its binding partners and for its motion along the microtubules. Essential for its preferential binding to tyrosinated microtubules and for promoting the sustained interaction of the dynein motor with microtubules
The YXXXXLphi motifs mediate interaction with eIF4E1
The UBZ4-type zinc finger specifically binds monoubiquitinated fancd2
Has a bilobed structure, each lobe binds a single Fe(3+) ion. Does not always bind 2 Fe(3+) ions
(Microbial infection) Binds to Neisseria transferrin-binding proteins A and B via its C-terminal lobe only. The L3 helix finger of TbpA inserts into the C-terminal lobe of TF, altering its conformation and probably disturbing the coordination of iron 2. Electron microscopy suggests that in the TbpA-TbpB-TF complex, TF is captured directly above the loop domain of TbpA in a chamber of about 1000 Angstroms(3) formed by the 3 proteins, where interactions between the proteins serve to abstract iron 2 from TF (PubMed:22343719, PubMed:22327295). Binding to TbpB does not alter the conformation of the C-terminal lobe (PubMed:22343719)
The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies
The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies
The ZZ-type zinc finger mediates the interaction with RIPK1
The UFM1-interacting sequence (UIS) motif mediates interaction with both UFM1 and LC3/GABARAP proteins (GABARAP, GABARAPL1 and GABARAPL2)
The FERM domain mediates binding to rap1
The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a nudix box and low sequence similarity with nudix hydrolase domains
The RS domain confers a nuclear localization signal, and appears to facilitate the interaction with the spliceosome
Ligands are bound in a hydrophobic pocket formed by the transmembrane helices
The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies
The cleaved signal peptide may not be degraded and may function as an intracellular angiogenesis inhibitor peptide known as parstatin
The intrinsically disordered linker region is required for recognition by RECK in brain endothelial cells
The two homeobox domains are arranged in a head-to-head orientation when bound to double-stranded DNA, each domain binding to one of the two DNA strands. Together, the homeobox domains can be considered to bind DNA with the consensus sequence 5'-TAATCTAATCA-3', but due to the head-to-head orientation of the DNA-bound domains, the first homeobox domain binds to the consensus sequence 5'-TAAT-3', and the second homeobox domain binds DNA on the opposite strand, with the consensus sequence 5'-TGAT-3' (PubMed:30322619, PubMed:30540931). Both homeobox domains confer nuclear targeting (PubMed:15709750)
The C-terminal region is required for efficient activation of transcription from target promoters (PubMed:26951377, PubMed:29618456). It mediates interaction with EP300 and CREBBP (PubMed:26951377)
The N-terminal region (1-350) contains the enzymatic activity while the C-terminal region (360-460) can bind laminarin. Both regions are allergenic by themselves
Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-298) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation
The RING domain is essential for ubiquitin E3 ligase activity
Contains an N-terminal anti-parallel coiled coil formed by two BRMS1 chains; this region can form homohexamers
Ig-like V-type domain mediates trans-homophilic cell adhesion through homodimerization and this active process is regulated by tyrosine kinase, PTPN11 and PTPN6. Ig-like C2-type and/or cytoplasmic domains mediate cis-dimer/oligomer
The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs
Contains FG repeats mediating the translocation through the NPC by interacting with transport factors
The cysteine framework is C-C-C-C-C-C-CC
The cytoplasmic region is required for subcellular sorting on the cell surface
The C-type lectin domain mediates the recognition and binding of oxLDL
The enzyme has an N-terminal penicillin insensitive transglycosylase domain (formation of linear glycan strands) and a C-terminal penicillin-sensitive transpeptidase domain (cross-linking of the peptide subunits)
The acidic C-terminus is necessary and sufficient to inhibit ARP2/3 complex activity
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRP101. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER
The M domain binds the 7SL RNA and the signal sequence of presecretory proteins
Contains an N-terminal phosphoreceiver (REC) domain and a C-terminal EAL domain that possesses c-di-GMP specific phosphodiesterase activity (PubMed:19376848, PubMed:22753070). The EAL domain contains a functional active site loop (loop 6), which plays crucial roles in stabilizing the overall protein structure and participating in catalysis, and also controls c-di-GMP and Mg(2+) ion binding (PubMed:19376848). The response regulatory domain is involved in interaction with the Hpt domain of RocS1 (PubMed:15659157)
The C-terminal domain (residues 523-782) mediates pentameric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containingbinding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). Binding is mediated by either three 'prongs' (for high affinity binding involving ITSM 1) or a combination of any two also including non-phosphorylated Tyr-284 of ITSM 1. ITSM 2 needs to be phosphoryated on Tyr-334 for SH2D1A binding
Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-645 has an important role in the selective binding of succinyl-CoA over acetyl-CoA
The BTB/POZ domain seems to direct the protein to discrete regions in the nucleus
The EXKPK motif is conserved in inositol-pentakisphosphate 2-kinases of both family 1 and 2
Deletion of the TJP1/ZO1 interaction motif (ZIM) decreases but does not abolish colocalization with TJP1/ZO1
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro/Ala-Ala/Ser (NPA)
The D box motifs 1-5 (amino acid sequence RxxL) are involved in substrate binding, such as FZR1/CDH1, and may be ubiquitinated
The N-terminus contains the redox activity while the C-terminus exerts the DNA AP-endodeoxyribonuclease activity; both function are independent in their actions. An unconventional mitochondrial targeting sequence (MTS) is harbored within the C-terminus, that appears to be masked by the N-terminal sequence containing the nuclear localization signal (NLS), that probably blocks the interaction between the MTS and Tom proteins (By similarity)
The N-terminal region is required for orexin signaling
The N-terminal region is necessary for mediating chemotactic activity
Contains 4 SPKK motifs which may interact with the minor groove of A/T-rich DNA sites. Phosphorylation of this motif may regulate DNA binding. This motif is reiterated in both termini of histone H1 and in the C-terminus of plant H2A, but its presence in the N-terminus seems to be unique to sea urchin histones H2B
The recognition sequence (54-72) is required for interaction with TRIB1
The protein kinase domain is predicted to be catalytically inactive. Its extracellular domain is capable of promoting cell adhesion and migration in response to low concentrations of ephrin-B2, but its cytoplasmic domain is essential for cell repulsion and inhibition of migration induced by high concentrations of ephrin-B2 (By similarity)
Contains a 32 AA domain highly conserved between species. Deletion of this domain leads to long-period phenotype and arrhythmia (By similarity)
The effector domain mediates the interaction with RUNDC3A
The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding. The fourth and fifth Ig-like C2-type (immunoglobulin-like) domains are sufficient for homodimerization. The fifth and seventh Ig-like C2-type (immunoglobulin-like) domains are required for autophosphorylation and further activation
Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue (By similarity)
The J domain is necessary and sufficient to stimulate DnaK ATPase activity. Zinc center 1 plays an important role in the autonomous, DnaK-independent chaperone activity of DnaJ. Zinc center 2 is essential for interaction with DnaK and for DnaJ activity (By similarity)
Both the N-terminus and ANK repeats 1 to 10 are necessary for interaction with filamins
The UIM domain is required for monoubiquitination
The GW domains are responsible for directing the proteins to the septal region
The SGF29 tudor-like domain mediates binding to methylated 'Lys-4' of histone H3 (H3K4me)
The TPR repeats bind to and activate EIF2AK1/HRI
The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity)
The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity)
The C1q domain is essential for the function in Wnt signaling
Each rhs appears to consist of a highly conserved 141 kDa amino fragment followed by a highly divergent C-terminus
Contains three distinct domains: an adenylation (A) domain that activates the substrate amino acid which is subsequently covalently linked as a thioester (aminoacyl-S-PCP) to the 4'-phosphopantetheine prosthetic group of the second domain, the peptidyl carrier protein (PCP) domain, as well as a thioester reductase (TR) release domain
The protein contains 2 transactivation domains (TAD). Each of these domains may be required for transcriptional activation of a subset of target genes
Has 2 zinc-ribbon domains (ZR-N and ZR-C); functionally important residues Lys-76, Lys-77 and Lys-78 are probably located at the tip of a domain that extends from ZR-C into the RNAP active site. The nature of these residues determines if the protein is involved in stalled transcript cleavage and thus activation (Asp and Glu residues in TFS1) or in RNAP inhibition (Lys or Arg residues in this protein TFS4). Increasing numbers of Lys residues lead to an increased ability to inhibit transcription. ZR-N interacts with Rpo1C and Rpo2 while ZR-C binds in the NTP entry funnel to sites in Rpo1N without reaching the active site (PubMed:34535646)
The C2H2-type zinc finger 2 to 6 are necessary and sufficient for discrete Cajal bodies localization. The C2H2-type zinc finger 5 to 10 are necessary and sufficient for interaction with LSM11. The C2H2-type zinc finger 2 to 8 are necessary for interaction with the SLBP/RNA complex in the histone pre-mRNAs. The C2H2-type zinc finger 2 to 10 confer activity in histone pre-mRNA processing
The UMA domain mediates association with the ESCRT-I complex
The similarity among the IL-1 precursors suggests that the amino ends of these proteins serve some as yet undefined function
In NdvA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
The SAM domain mediates homooligomerization
The PH domain mediates association with membranes
Lacks the C2H3-type zinc-finger found in all members of this family
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The cysteine framework is C-C-CC-CC-C-C-C-C
Comprised of a NH2-terminal actin-binding domain, 24 internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. The first hinge region prevents binding to ITGA and ITGB subunits
The PX domain mediates interaction with phosphatidylinositol 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, unphosphorylated state an intramolecular interaction with the C-terminal SH3 domain precludes phospholipid binding and interaction with CYBA. Phosphorylation disrupts the autoinhibited state (By similarity)
The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively
The IN box mediates interaction with AURKB and AURKC
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric
The toxin is composed of 2 domains: a highly rigid N-terminal inhibitor cystine knot (knottin) domain and a rather flexible C-terminal linear cationic cytotoxin domain that forms amphiphilic alpha-helices
The QLQ domain and WRC domain may be involved in protein-protein interaction and DNA-binding, respectively (Probable). The C-terminal region downstream of the QLQ and WRC domains is necessary for transactivation activity (PubMed:26187814, PubMed:27250747, PubMed:27107174)
The isolated charged lumenal magnetite-interacting component (MIC, residues 298-314) binds Fe(2+) and Ni(2+); Ni(2+)-binding may not be physiological. Although it binds iron the protein fragment has no effect on magnetite crystal formation in an iron co-precipitation experiment, however mutating some of its residues decreases crystal size
The DUSP and ubiquitin-like 1 domains promote ubiquitin release and thus enhance USB4 catalytic activity. However, these domains do not bind ubiquitin
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer (By similarity). Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9-containing vesicles, thereby enabling growth into autophagosomes (By similarity)
The PPxY motifs mediate interaction with NEDD4
The SMAD interaction motif is required for interaction with SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling
The LisH domain contains a nuclear targeting signal (PubMed:18710924). The LisH domain mediates head to tail dimerization (By similarity)
The binding of ZFY to DNA is mediated by the interaction of the GGCC core base pairs with zinc fingers 12 and 13
The WH1 domain mediates interaction with XIRP1
The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1
This sequence defines eighteen different domains, nine triple-helical domains (COL9 to COL1) and ten non-triple-helical domains (NC10 to NC1). The numerous interruptions in the triple helix may make this molecule either elastic or flexible
The 2 SUMO-like regions, although related to ubiquitin domains lack the conserved acceptor Gly residue in position 456
The C-terminal GTPase effector domain (GED) is involved in oligomerization and viral target recognition
The middle domain mediates self-assembly and oligomerization
Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity)
The N-terminus is involved in SEC8 and ARHQ binding
The C-terminus is required for translocation to the plasma membrane
The TSP type-1 repeats in the extracellular domain mediate binding to phosphatidylserine. They are also required for bacterial recognition and binding to bacterial outer membrane lipopolysaccharide
The C2H2-type zinc finger are necessary for DNA-binding (PubMed:26179882)
Isoform Short contains a Leu-Arg-Ile-Leu-Leu motif (ER binding motif)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (397-427) inactivates kinase activity under calcium-free conditions
The LIM zinc-binding 2 domain (LIM 2) interacts with TBX4
The LIM zinc-binding 3 domain (LIM 3) provides the structural basis for recognition of tyrosine-containing tight turn structures. This domain is necessary and sufficient for interaction with TBX5 (By similarity)
Anchored to cell periphery via its N-terminal PDZ domain
The cytoplasmic domain is a rigid structure with 4 domains (residues 276 to 401 form an unnamed domain) plus the 3 FtsK (ATPase) domains which are connected by short linkers. Binds EsxB via a small pocket (residues 1163-1208) in the third FtsK (ATPase) domain; the linkers between FtsK 1-2 and FtsK 2-3 bind in an analogous manner to FtsK 1 and FtsK 2. Linker 2 binding to FtsK 1 decreases its ATPase activity and probably controls it (PubMed:25865481)
Lacks the acidic domain of other UQCRH
Self-association may occur via interactions between DRBM domains as follows: DRBM 1/DRBM 1, DRBM 1/DRBM 2, DRBM 2/DRBM 2 or DRBM 3/DRBM3
The cysteine framework is I (CC-C-C). Alpha4/6 pattern
The SH3 domain is critical for binding to ABL1 and ABL2
TBP and TAFII18 bind to distinct domains of TAFII28
In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119, respectively
The enzyme consists of two functional domains, a catalytic core joined to a carbohydrate-binding domain (CBM) by a serine-, threonine-, and proline-rich, highly glycosylated linker sequence
The C-terminal region is part of a wide family of metallopeptidase effectors
Contains seven structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a superhelical structure with a solenoid shape (By similarity)
The juxtamembrane domain (288-383) is required for interactions with ROPGEFs, while the kinase domain (384-659) is required for pollen tube growth
The protein kinase domain may be catalytically impaired due to the lack of the conserved Asp active site at position 512, which is replaced by a Asn residue
The DSL domain is required for binding to the Notch receptor
The PDZ 2 domain is required for the interaction with the amino acid transporter protein aat-6
The PIP box serves as a PCNA(POL30)-recognition and -binding motif
The PH domain mediates binding to membranes
Based on x-ray crystallography data, the protein would be constituted of 4 tandem ACT domains instead of the 2 predicted from the sequence
The FYVE-type zinc finger is essential for its vesicular localization
The ZU5 domain mediates the interaction with MAGED1, which participates in the induction of apoptosis
The recognition loop recognizes a hydrophobic patch at the surface of interacting dehydrogenases and acts as a static anchor at the interface
The alpha7-alpha8 and alpha11-alpha12 loops of the catalytic domain may participate in the formation of an open substrate-binding site to provide sufficient space to bind 4-OH D-mannose derivatives
The core of the protein consists of three beta-propeller domains
The extracellular C-terminal domain controls the voltage dependence for amino acid transports activity
Rich in dileucine repeats, which have been implicated in trafficking of a variety of transmembrane proteins
The hemerythrin-like region acts as an oxygen and iron sensor by binding oxygen through a diiron metal-center. In absence of oxygen and iron, the protein is ubiquitinated and degraded (By similarity)
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. Can bind at least two ligands per molecule, however, the stoichiometry is debated
The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity (PubMed:22482711). The coiled coil domain is important for higher order multimerization by promoting the initial dimerization (By similarity)
The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs (PubMed:22482711)
The C-terminal domain contributes to sequence-specific DNA-binding
The phorbol-ester/DAG-type zinc finger mediates the binding and the functional activation by DAG
An internal targeting signal (103-117) is required for insertion into the mitochondrial inner membrane in a membrane potential-dependent manner. The C-terminal region is exposed on the outer surface of the outer membrane and is essential for protein import
The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance binding of the P-TEFb complex to the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II)
The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (PubMed:15452711). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (PubMed:16820361, PubMed:18357523, PubMed:14980206). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (PubMed:12754210). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation
The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation. It is required for interaction with KCNIP2, and probably other family members as well
Adopts the 'single disulfide-directed beta hairpin' (SDH) fold
The secondary structural features of this peptide are highly resistant to thermal denaturation (PubMed:26774129). In addition, this peptide can be truncated (90-103 DEL) without loss of ordered structure (PubMed:28437072)
N-terminal region is necessary and sufficient to enforce silencing of an artificial reporter gene
Comprises of two domains. The C-terminal domain contains the binding site for glutamine and catalyzes the hydrolysis of this substrate to glutamate and ammonia. The N-terminal domain is anticipated to bind ATP, and cobyrinate or Ni-sirohydrochlorin, and catalyzes the ultimate synthesis of the diamide product. The ammonia produced via the glutaminase domain is probably translocated to the adjacent domain via a molecular tunnel, where it reacts with an activated intermediate
Gln-181 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins (By similarity)
The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes
The AXH domain is required for interaction with CIC
Recognizes phosphatidyl serine via its immunoglobulin domain
Multiple cysteine residues are necessary for proper targeting to the plasma membrane
Organized into two domains: an N-terminal catalytic domain and a C-terminal arabinose-binding domain (ABD)
The PH domain mediates the binding to phosphoinositides
The C-terminal residues 660 to 699 are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12; and the C-terminal 17 residues are required for the ATG8 lipidation (By similarity)
The GxGxxG motif is important for the function, possibly through binding with ATP (By similarity)
The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with NHERF1 and for targeting NHERF1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation (By similarity). Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis
The A20-type zinc finger domain mediates regulation of NF-kappa-B activity
The AN1-type zinc finger domain mediates association with TRAF2
The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers
The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity (By similarity)
The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA synthesis
There are 3 carboxypeptidase-like domains (PubMed:12393882, PubMed:20386952). Only the first two domains seem to have catalytic activity (PubMed:12393882, PubMed:16556608, PubMed:20386952). However, in svr proteins there are two alternative carboxypeptidase-like 1 domains (CP-1), a catalytically inactive 1A form (in isoforms 3, 4 and 6) and an active 1B form (in isoforms 1, 5, and 7) (PubMed:12393882). All 3 carboxypeptidase-like domains (active CP-1, CP-2 and CP-3) appear to necessary for maintaining full viability (PubMed:20386952). The active CP-1 and CP-2 domains display redundant functions in terms of processing peptides involved in viability, and in behaviors like cold and ethanol sensitivity, as well as long-term memory (PubMed:20386952). However, the active CP-1 domain appears to preferentially remove C-terminal Arg residues while CP-2 preferentially removes C-terminal Lys residues (PubMed:20386952). The active CP-1 is sufficient for survival (PubMed:16556608). The CP-3 domain appears to be important for development from embryo to adult (PubMed:20386952)
The C-terminus in isoforms 4, 5 and 6 may be required for the retrograde transport of these proteins from the cell membrane to the trans-Golgi network
The second zinc finger in necessary for interaction with GFI1 and for alternative pre-mRNA splicing events
The region 162-220 is essential for the nuclear import of the protein in spite of the absence of a nuclear localization signal (NLS). This region is essential for the interaction with C1QBP, interaction which is required for the nuclear translocation. This region may be involved in the localization in nuclear dot-like structures and it also confers the ability of nucleo-cytoplasmic shuttling
Isoform 3 contains a C-terminus domain with homology to Drosophila TIM (THD domain). Isoform 3 interacts with Per1 and specifically down-regulates its expression, probably by facilitating its recruitment to the proteasome. The interaction with PER1 depends on the presence of the THD domain, but the THD domain is not directly involved in the interaction
The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity)
Glu-106 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-163 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group
The C-terminal lobe folds into an immunoglobulin-like domain and may mediate cell adhesion properties
The C-terminal domain negatively regulates kinase activity via an autoinhibitory association with the protein kinase and histidyl-tRNA synthetase-like domains in amino acid-repleted cells, that is counteracted by uncharged tRNAs in amino acid-starved cells (PubMed:7623840, PubMed:8798780, PubMed:10983975, PubMed:11250908). The C-terminal, histidyl-tRNA synthetase-like region and protein kinase domains are necessary for homodimer formation (PubMed:9566889, PubMed:10983975, PubMed:11250908). The C-terminal and protein kinase domains are necessary for ribosome association (PubMed:9566889, PubMed:10983975). The C-terminal and histidyl-tRNA synthetase-like regions are required for uncharged tRNAs binding in amino acid-starved cells (PubMed:7623840, PubMed:8798780, PubMed:9430731, PubMed:10983975)
Contains a large N-terminal NADP-binding domain associated with a modified Rossman fold, and a smaller C-terminal substrate-binding domain
Coiled-Coils at the N-terminal half are essential for autophagy
The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating
The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating. Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure
The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides. Instead, residues from the C-terminal domain (the so-called intrinsic ligand) bind in the cavity that would be expected to bind cyclic nucleotides. Interaction with the C-terminal region hinders interaction with CALM and reduces the affinity for CALM
Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain
The ARM repeats inhibit the NAD(+) hydrolase (NADase) activity by binding to NAD(+): NAD(+)-binding to ARM repeats facilitates inhibition of the TIR domain NADase through their domain interface. In contrast to classical ARM repeats, the last helix of ARM 6 does not fold back to interact with the first two helices, but instead turns towards the N-terminus of SARM1. As a result, the two following motifs ARM 7 and ARM 8 reverse their directions and lie perpendicularly. Moreover, ARM repeats interact with different domains not only within each protomer but also of the adjacent ones
The cytoplasmic RCK N-terminal domain regulates channel activity. It binds glutathione, resulting in inhibition of potassium efflux. In contrast, binding of the adducts formed between glutathione and electrophiles leads to activation of potassium efflux. Is expected to bind NADH, but X-ray crystallography shows bound AMP, and it would be difficult to accommodate NADH in this binding site (PubMed:21041667)
The C-terminus is required for CDK2-activation, but not CDK2-binding
Protein is very flexible, is probably able to bind membranes in many conformations. The N-terminus of DLP2 inserts into the assembly domain of DLP1; this is followed by a 9 residue DLP2 linker which allows DLP1 significant movement. The linker is long enough to allow the GTPase domains (dynamin-type G) of DLP1 and DLP2 to heterodimerize
The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation
The glycine-rich region (GRR) appears to be a critical element in the generation of p52
Contains a C-terminal (448-529) carbohydrate-binding domain (CBM)
Either the first or the fourth Ig-like C2-type domain is required for VLA4-dependent cell adhesion
Substrate binding induces conformational changes, NBD dimerization, and stabilizes an inward-facing closed pre-translocation state that binds ATP (PubMed:18344567, PubMed:23766512, PubMed:28869968). ATP binding fuels a relative motion of the NBD domains. The movement of the NBDs is coupled to reorientation of the chamber, which binds the lipid substrate, from cytoplasmic-facing to periplasmic-facing through large amplitude motion on either side of the transporter (PubMed:17927448, PubMed:20715055, PubMed:18024585, PubMed:28869968). ATP hydrolysis is then required to resolve the outward-facing conformation back to an inward-facing conformation (PubMed:23766512, PubMed:28869968). The ATP-dependent switch requires robust tetrahelix bundle interactions (PubMed:23306205)
Contains two substrate-binding sites that communicate with both the nucleotide-binding domain and with each other. One is a high affinity binding site for the physiological substrate, lipid A, and the other site interacts with drugs with comparable affinity
The PPxY motifs mediate interaction with WW domain-containing ubiquitin-protein ligases
The cytoplasmic domain (residues 431-481) is responsible for the endocytosis and localization of the protein to endocytic compartments
The thioredoxin domain lacks the 2 redox-active Cys. This strongly suggests that it lacks thioredoxin activity
The C-type lectin domain mediates dual recognition of both sulfated and mannosylated glycans
The N-terminal part (1-55) is necessary and sufficient for translocation from the cytosol to the membrane
The N-terminal domain has binding sites for ComK and probably for unfolded/aggregated proteins; the C-terminal domain interacts with ClpC
The target ssRNase active sites are probably within the 2 HEPN-like folds, and the 2 folds interact in vivo
Consists of two domains, with an N-terminal domain with structural homology to members of the SGNH (GDSL) hydrolase superfamily and a C-terminal carbohydrate-binding module (CBM) that may bind alginate
The C-terminal helix is essential for activity
The N-terminal region is involved in actin binding and actin nucleation activity
The LPQG and YXDD motifs are catalytically important and conserved among many retroviruses
The mating factor alpha-1 precursor is identical in S.italicus, S.uvarum and S.cerevisiae, except for the number of tandem repeat units: 5, 3 and 4 respectively
The N-terminus (minimally 1-122, fragment 1-136 does not bind any better) interacts with the shell proteins CsoS1A, CsoS1B and CsoS1C. A slightly longer fragment of the N-terminus (residues 1-136) is required for targeting to carboxysomes, and will direct foreign proteins to the carboxysome, with reduced efficiency compared to the whole protein
The PBZ-type zinc fingers (also named CYR) mediate non-covalent poly-ADP-ribose-binding. Specifically recognizes branched poly-ADP-ribose chains generated by PARP2. Poly-ADP-ribose-binding is dependent on the presence of zinc and promotes its recruitment to DNA damage sites
The FHA-like domain mediates interaction with XRCC1 and XRCC4
The NAP1L motif is required for the histone chaperone activity
The MIT domain may serve as an adapter for the ESCRT-III complex
The transmembrane domain is essential for localization to the endoplasmic reticulum
The C-terminal domain is able to act as both DNA-binding domain and a transcriptional activator. The N-terminal domain is also required for transactivation activity on some target genes acting as a discrete activation domain (PubMed:8621561, PubMed:9722627). Neurite outgrowth and expression of genes required for synapse formation are primarily dependent on the C-terminal domain, however the N-terminal domain is required for maximal induction (PubMed:8972215)
The cysteine framework is XXV (C-C-C-C-CC)
This protein has an antiparallel four-helix bundle architecture that represents a novel DNA-binding fold
The His-rich (HRR) region contains approximately 12 tandem internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR binds heparan sulfate and possesses antiangiogenic, antibacterial and antifungal properties through binding Candida cells, and preferentially lysing the ergosterol-containing liposomes at low pH. The tandem repeats also bind divalent metal ions and heme (By similarity)
The cystatin domains can also bind heparan sulfate. Binding is enhanced in the presence of zinc ions (By similarity)
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA (By similarity). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (By similarity). SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (By similarity)
The M domain binds the 7SL RNA in presence of SRP19 and binds the signal sequence of presecretory proteins
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (411-441) inactivates kinase activity under calcium-free conditions (By similarity)
The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The atypical PHD-type zinc finger also binds various phosphoinositides (By similarity)
The two chemically discrete steps of the overall reaction take place at distinct sites on the enzyme, mediated via conformational flexibility of the C-terminal 18 residues
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (CMeT) domain responsible for the incorporation of methyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The extracellular domain interacts with Wnt proteins and the intracellular C-terminus transmits the Wnt signal
Composed of 2 domains (approximately residues 1-64 and 89-136) joined by a flexible linker. The isolated N-terminus (1-64) forms a trimer, probably via coiled-coil interactions (PubMed:10844682, PubMed:11237622). The isolated N-terminus plus linker fragment (residues 1-89) forms homooligomers of increasing size with increasing protein concentration, while the isolated C-terminus fragment is a monomer (PubMed:10844682). A shorter fragment (residues 1-46) interacts with Hha (PubMed:23515315)
The leucine-rich hydrophobic amino acid N-terminal region probably helps to anchor the protein to the microsomal membrane
Contains four repeated domains, each composed of two transmembrane helices connected by a putative pore loop (p-loop). Four conserved glycine residues in the p-loops are part of a selectivity filter for K(+) ions
The RxLR-dEER motif acts to carry the protein into the host cell cytoplasm through binding to cell surface phosphatidylinositol-3-phosphate (Probable). The motif is not required for perception by defense protein Rpi-blb2 (PubMed:19794118)
The 8 residues at the C-terminus (residues 93 to 100) are required for the correct subcellular location at the cell periphery or around haustoria, the ability to enhance P.infestans growth, the association with C14 protease, and apoplastic C14 accumulation
The amino acids 78-82 in the C-terminal region of are important for binding to host calmodulin
The RIP homotypic interaction motif (RHIM) mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (415-445) inactivates kinase activity under calcium-free conditions (By similarity)
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1
Apoprotein is apparently conformationally labile and readily converts to different states, including inward-facing conformations for substrate access (PubMed:34110360). Contains a conserved cation-binding pocket, which directly connects to the sugar specificity pocket (PubMed:34341464)
The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases
The LIR motif interacts with ATG8 family proteins
The CRN proteins have modular architectures that include a signal peptide, a conserved N-terminus, and highly diverse C-terminal domains. The conserved CRN N-terminus harbors a distinct LXLFLAK motif, which is followed by the conserved DWL domain. A highly conserved HVLVXXP motif marks the end of the CRN N-terminal domains and forms a junction where diverse C-terminal domains are fused. The conserved CRN N-terminus mediates the translocation into the plant host cells
A di-leucine motif and a tyrosine-based motif are individually sufficient to induce both endocytosis and delivery to lysosomes
The C-terminal domain (817-956) is necessary and sufficient for Golgi and cytoplasm targeting
The C-terminal region containing the DEP domain is required for membrane accumulation and phosphorylation. Wnt signaling and axis induction requires the DIX domain. The C-terminus contributes to the localization at the cilia base (By similarity)
The N-terminal domain can bind calcium
Structure of this peptide is made of two-stranded beta-sheets (or DDH for disulfide-directed beta-hairpin) that is uncommon for a scorpion-venom peptide, since it does not contain the CSalpha/beta, CSalpha/alpha, or knottin motif common to other disulfide-rich scorpion toxins. This structure may be the evolutionary precursor to the knottin motif
The zinc knuckle motif binds zinc and is required for the DNA primase activity. It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites
The RPA1-binding motifs (RBM) mediate interaction with RPA1 and are essential for recruitment to chromatin. The interaction is primarily mediated by RPA1-binding motif 1, which binds to the basic cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-116 is required to stabilize the incoming nucleotide at the 3'-site
The AWS and SET domains are necessary for transcription repression
The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties
The RING finger domain and the coiled-coil region are required for the apoptosis-inducing activity
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases (By similarity)
The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins
Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that captures N-terminally myristoylated target peptides. Phe residues within the hydrophobic beta sandwich are required for myristate binding (By similarity)
The N- and C-terminal halves of the protein contain a hexokinase domain. In contrast to hexokinase-1 and -3 (HK1 and HK3, respectively), both hexokinase domains display catalytic activity. The region connecting the two hexokinase domains is required for the catalytic activity of the N-terminal hexokinase domain. The N-terminal half regulates stability of the whole enzyme
The complex formed by AMN and CUBN is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains
Oomycete Avh family proteins have a modular structure with an N-terminal signal peptide (SP), an RXLR-dEER domain and a C-terminus with a variable number of modules that consist of W, Y and L motifs after highly conserved residues. The C-ter of Avr4 contains 3 W motifs, 1 Y motif but no L motif. The RXLR-dEER motif functions as a host targeting signal (HTS). The region containing the W2 motif, in combination with either the W1 or W3 motif, triggers a necrotic response in host plants carrying the resistance gene R4
The coiled coil domain mediates homodimerization
In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (By similarity)
Region I is sufficient for binding TP53 and inhibiting its G1 arrest and apoptosis functions. It also binds TP73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2
B30.2 box contains a microtubule-binding site
Composed by a short N-terminal domain followed by the DNA binding, hinge, and ligand binding/dimerization domains
Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities
The Tudor domain recognizes and binds H3K36me3
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. BenZ as the following bimodular architecture: C1-A1-T1-C2-A2-T2-Ct
M-zodatoxin-Lt4a: Probably forms an alpha-helix which disrupts target cell membranes
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. Pum1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine
Binds calcium via its EF-hands. Calcium-binding mediates a conformational change. Can also bind magnesium
Contains 15 repeating units of approximately 147 AA harboring four disulfide bonds each. The most highly conserved region within the repeat consists of a stretch of 13 AA that contains cysteines at both ends
The doublecortin domains are involved in the colocalization with microtubules
The C-terminal peroxisomal targeting signal (PTS) is essential for the efficient targeting and import of AOX into peroxisomes via the PTS1 pathway
The JAMM motif is essential for the protease activity
The DCUN1 domain, also known as PONY domain, may mediate the interaction with cullins
Each ALS protein has a similar three-domain structure, including a N-ter domain of 433-436 amino acids that is 55-90 percent identical across the family and which mediates adherence to various materials; a central domain of variable numbers of tandemly repeated copies of a 36 amino acid motif; and a C-ter; domain that is relatively variable in length and sequence across the family
The YXXL motif mediates the interaction with MAP1 LC3 family proteins MAP1LC3A, MAP1LC3B and GABARAP
The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity
The C-terminal domain contains a V-shape binding site for sialyl Lewis X
The RING-type zinc-finger is degenerated and only coordinates one zinc ions, preventing E3 ubiquitin-protein ligase activity
The PPxY motif mediates interaction with WWOX
Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site
The N-terminal region is the non-catalytic domain; the C-terminus contains the active-site cysteine residue and the CGSGVTA motif probably responsible for substrate specificity
The nuclear export signal is required for export from the nucleus and the interactions with itself and p75NTR/NGFR
The BetaTrCP degron motif promotes binding to BTRC when phosphorylated
Has protease activity (PubMed:8243676, PubMed:8294407, PubMed:9886085)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (PubMed:19118561). In BoNT/E the domains are arranged differently than BoNT/A and BoNT/B; in BoNT/E the LC and RBD are on the same side of the TD and are in contact, whereas in BoNT/A and BoNT/B the LC is separated from the RBD by the TD (PubMed:19118561). The putative transmembrane region is closer to the receptor-binding regions in this toxin, which may explain why it acts faster than BoNT/A and BoNT/B (PubMed:19118561). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, partially protecting Zn(2+) in the active site (PubMed:19118561). The belt may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:17907800). The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (PubMed:18815274, PubMed:19650874, PubMed:19476346)
The OCIA domain is necessary and sufficient for endosomal localization
The WH2 domain is found in a number of putative actin-binding proteins
The profilin-binding motif has been implicated in the interaction with profilin and SH3 domains
The KLKR motif is essential for G-actin binding and for actin polymerization
The zinc-finger domain is important for DNA binding
The RING-type zinc finger domain interacts with BAP1
The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of ABRAXAS1, recruits BRCA1 at DNA damage sites
A tripeptide motif (ECD) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG)
A mutant in the N-terminal obg domain (Asp-92) impairs growth and ribosome association but has no effect on sporulation or the general stress regulon (GSR). Replacing the last 22 amino acids has no effect on growth or ribosome association, but eliminates sporulation and reduces the GSR, showing for the first time that growth promotion and the GSR phenotypes are separable
The N-terminus (about 270 residues) binds NAD(+) and GDP-alpha-D-mannose and is joined to C-terminal domain by an exposed linker
Requires a bound zinc ion for normal folding and solubility
Upon interaction with ABA, the 'latch' and 'gate' loops change in conformation leading to a tight dimerization and the creation a surface that enables the receptor to dock into and inhibit the PP2C active site
The ion transport-like region is related to the membrane segments of voltage-gated ion channels. Its function is unknown (By similarity)
Contains an N-terminal beta-lactamase-like domain harboring a di-iron center, and a C-terminal flavodoxin-like domain containing FMN. Two monomers assemble via a head-to-tail arrangement, such that the beta-lactamase and the flavodoxin domains face each other, thereby forming two separated and presumably independent active sites
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). NPS6 contains a degenerate A domain (dA) in the second module and has the following architecture: A-T-C-dA-T-T-C (PubMed:17056706)
The five zinc finger domains are necessary and sufficient to bind to DNA
The predominant structure is alpha-helical
Synaptogenic effects are mediated by the extracellular LRR region
The coiled-coil motif forms a homodimeric contact and facilitates RIX1 complex oligomerization
In response to a variety of growth factors, isoform p46Shc and isoform p52Shc bind to phosphorylated Trk receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif of the Trk receptors. Isoform p46Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation (By similarity)
Consists of two tandemly linked globin-like sequences which each bind a heme group and a C-terminal extension which may act as a cement between the eight subunits
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). AQP4 has NPA/NPS motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
Contains a PAM2-like motif, which seems to be involved in the binding to the PABC/CTC domain of PAB proteins
The PUL domain mediates the interaction with cdc-48.1 and/or cdc-48.2 C-terminus
The PFU domain mediates interaction with ubiquitin
The RRM domain mediates the association with collagen mRNAs stem-loops
The-C-terminal phosphate acetyltransferase domain is responsible for oligomerization, and is responsible for inhibition by acetyl-CoA and activation by glutamate, aspartate, and glucose-6-phosphate as shown by its deletion. The isolated domain does not catalyze the interconversion of acetyl-CoA and acetyl-phosphate
EF-hand 1 and EF-hand 2 domains bind Ca(2+); the binding induces a conformational change which facilitates the interaction with other proteins (PubMed:32759683, PubMed:34114596). EF-hand 3 and EF-hand 4 domains do not bind Ca(2+) (PubMed:32759683)
The C-terminus can bind to other proteins in a Ca(2+)-independent manner; the binding disrupts and/or prevents homooligomerization
Mostly intrinsically disordered, with residual structure localized to the IQ domain which mediates the interaction with calmodulin
Modular protein that contains an elongation/condensation domain, an adenylation domain which activates the serine residue into an aminoacyl-AMP ester, a peptidyl carrier protein domain which bears a phosphopantetheinyl arm to attach the activated amino acid and a thioesterase domain (Probable). The thioesterase domain is both a cyclotrimerizing lactone synthetase and an elongation catalyst for ester-bond formation between covalently tethered DHB-Ser moieties (PubMed:10375542). The carrier-thioesterase di-domain forms a compact structure with a well-defined domain interface; the two active sites are at a suitable distance for substrate transfer from the peptidyl carrier protein domain to the thioesterase domain (PubMed:18704088). Phosphopantetheinylation leads to enhanced interaction between the two domains (PubMed:22118682)
There is evidence to suggest that the N-terminal part may be sufficient for cell cycle arrest and the C-terminal may be necessary for some step in mating
Has a bilobed architecture with a recognition lobe (REC, residues 41-425) and a discontinuous nuclease lobe (NUC, residues 1-40 and 453-1053); the crRNA-target DNA lies in a channel between the 2 lobes (PubMed:26317473). The NUC lobe has 2 endonuclease domains. The discontinuous RuvC-like domain in NUC cleaves the target DNA noncomplementary to crRNA while the HNH nuclease domain cleaves the target DNA complementary to crRNA (PubMed:26317473)
The cysteine framework is III (CC-C-C-CC). Classified in the M-4 branch, since 4 residues stand between the fourth and the fifth cysteine residues
Consists of three domains A, B and C. The C-terminal C domain possesses catalytic function while the N-terminal A domain confers protein instability in response to chlorophyll b accumulation
The CR1 and CR2 motifs mediate sequence-specific DNA binding, and are important for binding to the MYOD1 enhancer
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain. DNM1 binding abolishes autoinhibition (By similarity)
The dehydratase activity is contained in the N-terminal region while the epimerase and reductase activities are in the C-terminal region
The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site
Probably exists in a closed and an opened conformation due to interaction of the C-terminal coiled-coil domain with an N-terminal region including the calponin-homology (CH) and the LIM zinc-binding domain. The conformational change is regulated by RAB13 (By similarity)
The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends
The STIM1 Orai1-activating region/CRAC-activating domain (SOAR/CAD) mediates interaction with ORAI1 to activate the channel
The FU repeat is required for activation and stabilization of beta-catenin
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes. In PLD delta, all the calcium-coordinating acidic amino acids are conserved
The C-terminal portion of EID2B is required for nuclear localization
Proteolytic cleavage leads to an important conformation change. This reduces the affinity for steroids
The FU repeats are required for activation and stabilization of beta-catenin
The N-terminal portion of EID2 is required for nuclear localization
The transmembrane domains are required and sufficient for its oligomerization
The C-terminal domain (residues 356-586) is required to alleviate the deleterious effects of UV or ciprofloxacin (CFX) treatment in a double radA-radD mutant; its effect on ionising irradiation (IR) survival in the single radD mutant were not reported (PubMed:25425430). Crystals have 4 domains; helicase ATP-binding (residues 7-185), helicase C-terminal (residues 187-365), a zinc finger domain (residues 376-425) and the C-terminal domain (429-574) (PubMed:31035307)
The helicase C-terminal domain mediates interaction with ALYREF/THOC4
The C-terminal domain (556-725) is necessary and sufficient for Golgi targeting
The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane
The S3b-S4 and S1-S2 loops of repeat IV are targeted by H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b depends on S1-S2 loops of repeat IV
The OTU domain mediates the hydrolase activity and the interaction with CDC48
The KEN and D (destructive) boxes are required for the cell cycle-controlled NINL degradation by the APC/C pathway
The UPAR/Ly6 domain is sufficient for inhibiting alpha-3:beta-4 and alpha-7-dependent nAChR currents
The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA. The interdomain linker (411-429) acts as a hinge to fix the relative orientation of the 2 RRMs. The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs. A continuous hydrophobic interface is formed between the 2 RRM
Contains an N-terminal signal reception (A) domain, followed by a hinge region (B domain), a transcription activation (C) domain and a C-terminal D domain. The A domain directly responds to external signals, the C domain contains the ATP-binding region that provides energy, and the D domain contains a helix-turn-helix DNA binding motif
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM8 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The PIP-box (PCNA interacting peptide) motif mediates both the interaction with PCNA and cleavage of the SDE2 precursor by a deubiquitinating enzyme
The SAP domain is necessary for specific binding to DNA
The propeptide displays a ubiquitin-like fold
Contains LRR and Ig-domains that can mediate low-affinity interaction with EGFR (PubMed:25765764). The LRRs and the Ig-domains are each sufficient for EGFR/ERBB1 binding. This interaction is abolished only when both the LRRs and the Ig-domains are deleted (PubMed:15282549)
The N-terminal DNA-binding domain is a ssDNA-dependent ATPase and has ATP-dependent 3'-5' helicase function. This domain interacts with RecC
The C-terminal domain has nuclease activity and interacts with RecD. It interacts with RecA, facilitating its loading onto ssDNA
One of the DRDB could be involved in RER binding
The C-terminal contains the tubulin binding domain (TBD)
The C-terminal region (aa 207-280) represents the dimerization motif
The ZP domain mediates polymerization, leading to the formation of long filaments. The core of the filament consists of interlocked ZP domains which assemble into a helical structure. Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit. The heavily glycosylated N-terminal part of the protein (containing several EGF-like domains) forms branches which protrude from the core and are involved in pathogen capture
Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein
A construct containing set1 C-terminal fragment of 692-920 is able to form H3K4me
The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (By similarity). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (By similarity)
The amphipathic helix mediates embedding into the lipid droplet phospholipid monolayer, promoting phosphatidic acid-binding, thereby facilitating triacylglycerol transfer
The CIDE-N domain is involved in homodimerization which is crucial for its function in promoting lipid exchange and transfer
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. VerP has the following architecture: A-T-C-A-T-C
The SH2 domain mediates interaction with tyrosine-phosphorylated proteins (By similarity). However, not involved in the binding to phosphorylated BCAR1 (By similarity). Required for cell cycle progression in response to INS/insulin (By similarity). Required for regulation of EGF-induced DNA synthesis (By similarity)
The Ras-GEF domain appears to adopt a closed conformation rendering it incapable of carrying out canonical exchange factor function, this closed conformation is probably required for interaction with BCAR1
The thioredoxin domain lacks the conserved redox-active Cys at position 414 which is replaced by a Ser residue, suggesting that it lacks thioredoxin activity
Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PIK3CA) results in its targeting to the plasma membrane
Proteins of this family have an N-terminal nuclease domain and a C-terminal helicase/ATPase domain. In some CRISPR/Cas systems the domains are swapped, in others they are encoded separately
The START domain recognizes ceramide and mediates the intermembrane transfer of ceramide
The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore
The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 (By similarity)
Contains a tandem atypical propeller in EMLs (TAPE) domain. The N-terminal beta-propeller is formed by canonical WD repeats; in contrast, the second beta-propeller contains one blade that is formed by discontinuous parts of the polypeptide chain
The N-terminal coiled coil is required for association with microtubules
The TIR domain is a signaling domain involved in cell death induction. It is involved in heterodimerization of RPS4B with RRS1B, but other domains also contribute to the interaction
The LIM zinc-binding domains mediate glucocorticoid receptor coactivation and interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG, TCF3, TCF7L2, SLC6A3 and SMAD3. The LIM zinc-binding 2 and LIM zinc-binding 3 domains mediate targeting to focal adhesions and actin stress fibers. The LIM zinc-binding 3 and LIM zinc-binding 4 domains mediate interaction with TRAF4 and MAPK15. The LIM zinc-binding 4 domain mediates interaction with HSPB1, homooligomerization and targeting to the nuclear matrix. The LIM zinc-binding 3 domain mediates interaction with PTPN12 (By similarity)
The LD (leucine and aspartate-rich) motif 3 mediates interaction with GIT1 and functions as a nuclear export signal
The BRCT 1 and 2 domains mediate the interaction with PAGR1A
The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex (PubMed:26744420). The BRCT 5 and 6 domains function as a single module and are necessary and sufficient for in vitro phospho-specific binding (substrates phosphorylated by the kinases ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) in response to gamma irradiation). In contrast, in vivo two pairs of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more efficiently
The DEP domain is involved in membrane localization independent from regulation by cAMP
The GoLoco domains mediate interaction with G(i/o) alpha. The GoLoco domains are essential for the GDI activity toward G(i/o) alpha
The N-terminal Mn(2+)-dependent polymerase/primase domain (Pol) functions as an independent domain, binds DNA, is sufficient for DNA-directed and non-DNA-directed DNA synthesis (PubMed:15778718) and interacts with Ku (PubMed:16023671)
The central 3'-phosphoesterase domain (PE) has exonuclease activity probably constituted of 3'-ribonuclease and 3'-phosphatase activity (PubMed:15499016). It does not function as an independent domain (PubMed:16023671)
The C-terminal ligase domain (Lig) binds dsDNA and functions as an independent domain (PubMed:14985346, PubMed:16023671)
Each subunit is composed of three triple-helical domains interspersed with non-collagenous domains. The globular domain at the N-terminus of type IX collagen molecules represents the NC4 domain which may participate in electrostatic interactions with polyanionic glycosaminoglycans in cartilage
Lethal factor (LF) is composed of four domains: domain I contains the first ATLF domain that binds the membrane-translocating component protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK before cleavage (PubMed:11700563). Domain IV contains the catalytic center (PubMed:11700563)
The N-terminal region appears to be involved in lipid binding
Forms a U-shaped beta-half-barrel with a large hydrophobic cavity (2835 Angstroms(3)) which is large enough to hold a single phthiocerol dimycocerosate (PDIM) molecule
The KRAB domain and the zinc finger domain are both necessary for the regulation of NR3C1/GR transcriptional activity
Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates
A tripeptide motif (VGE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
The cysteine-rich domain encodes putative cell-fusion peptides, which could be involved in sperm-egg fusion
The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor
The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium (By similarity)
The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel
The C-terminal cytosolic region confers the pH-dependence
The RxLR-dEER motif acts to carry the protein into the host cell cytoplasm through binding to cell surface phosphatidylinositol-3-phosphate (PIP). However ATR1 does not bind to PIPs, even though it harbors the RxLR-dEER motif at the N-terminus, suggesting that the RxLR-dEER motif is insufficient for PIP binding
The tandem repeated WY domains are involved in the recognition of the RPP1 defense proteins of the different Arabidopsis thaliana ecotypes
The N-terminal AAA+ ATPase domain and the C-terminal winged-helix (WH) domain are both required for stimulation of MCM activity
The LIM domain specifically interacts with the POU1F1/Pit-1 POU domain and is required for synergistic interactions with POU1F1, but not for basal transcriptional activation events
The structure consists of 2 domains of very similar conformation, suggesting a common evolutionary origin. However, the sequences of the 2 domains are very different
The PHD-type zinc fingers mediate the binding to acetylated histones
The protein kinase domain may be catalytically impaired due to the lack of the conserved Asp active site at position 466, which is replaced by a His residue
The juxtamembrane domain (274-319) is necessary for a relatively uniform plasma membrane localization. The C-terminal domain (614-647) is required for the induction of pollen tube depolarization. Both domains are required for the interaction of PRK2 with ROPGEF12
The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function. MCT1 N-terminal region is required to enhance translation possibly through interaction with other proteins (By similarity)
The Flo11 domain contains aromatic residues that form two hydrophobic bands on the surface of the protein that confer homophilic binding (PubMed:32286952). The hydrophobic bands are lined by stretches of acidic residues that may sensitise the protein to environmental pH (By similarity)
The cysteine framework is III (CC-C-C-CC). Classified in the M-3 branch, since 3 residues stand between the fourth and the fifth cysteine residues. This peptide has a cysteine scaffold similar to the M superfamily of conotoxins, but it displays a disulfide pattern previously unknown in native cone snail peptides
The RNA binding domains RRM2 and RRM3 are required for NAM8 meiotic function (PubMed:21788335, PubMed:21208980). Within the U1 snRNP complex, the RRM2 domain of NAM8 is positioned to bind to the intronic region immediately down-stream of nucleotide +13 (PubMed:31485080)
The B-box zinc finger is responsible for inhibition of SPI1-mediated transcriptional activation
The PH domain is responsible for the interaction with the 3-phosphoinositides. The activation loop within the kinase domain is the target of phosphorylation. The PIF-binding region on the kinase domain of PDK2 acts as a docking site, enabling it to interact with and enhance the phosphorylation of substrates containing the PIF motif (By similarity)
The PIF-pocket is a small lobe in the catalytic domain required by the enzyme for the binding to the hydrophobic motif of its substrates. It is an allosteric regulatory site that can accommodate small compounds acting as allosteric inhibitors
Contains 27 repeats of a CXXC motif
The BC2 (basic cluster 2) motif is necessary and sufficient for the nuclear localization and contains the catalytic active site. The localization in the nucleus is however not required for the enzyme activity (By similarity)
The Smr domain has nicking endonuclease activity, but no significant double strand cleavage or exonuclease activity
The Asp-Asp-Xaa-Xaa-Asp (DDXXD) and Asn-Xaa-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Glu (NSE) motifs are important for the catalytic activity, presumably through binding to Mg(2+)
The DXDD and DEXXE motifs are important for the catalytic activity
Binds three calcium ions (via EF-hands 2, 3 and 4) when calcium levels are high. Binds Mg(2+) when calcium levels are low
The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif
The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides (By similarity)
The C-terminus is essential for the interaction with the srp68/7SL RNA complex
Binds cholesterol in a hydrophobic pocket; there are no hydrogen bonds between the sterol and the protein
The UIM repeat increases the specificity and efficiency of the enzyme toward 'Lys-63'-linked polyubiquitin
Specificity is not given by the S1' ubiquitin-binding site within the OTU domain (composed of the Cys-, His- and Variable-loops)
The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3) (By similarity)
The FISNA domain is a critical mediator of NLRP3 conformational during NLRP3 activation. It becomes ordered in its key regions during activation to stabilize the active NACHT conformation and mediate most interactions in the NLRP3 disk
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (337-367) inactivates kinase activity under calcium-free conditions
The C-terminal tail (residues 301-325) is not required for the kinase activity and for translocation into human cells
The NID domains are necessary for the interaction with IFI35 (PubMed:26342464). The NID domain 1 is necessary and IRF7 (By similarity)
The GoLoco 1 and/or GoLoco 3 domains exhibit GDI activity towards GDP-bound G(i) alpha protein, but not the GoLoco 2 domain
2 residues (Tyr-53 and Arg-56) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The amino acid residues contacting the FNR target site on the DNA (5'-TTGATNNNNATCAA-3') are located in the putative DNA-recognition helix (alphaF), which contains the FNR motif (EXXSR). Three surface-exposed loops forming activating region 1 (AR1) in the downstream subunit of the dimer contact the C-terminal domain of the alpha subunit (alphaCTD) of RNA polymerase for activation of class I promoters (the 161-121 loop is the major AR1 activating determinant). At class II promoters, the AR1 of the upstream subunit contacts alphaCTD, promoting open complex formation; activating region 3 (AR3) of the downstream subunit contacts region 4 of the sigma70 subunit of RNA polymerase, to effect direct activation. At promoters repressed by FNR, tandem FNR dimers might interact with each other at AR1 to restrict access to a promoter or jam the promoter by their dual interaction with RNA polymerase alphaCTD
The CMP/dCMP deaminase domain 1 confers deoxycytidine deaminase activity, whereas the CMP/dCMP deaminase domain 2 mediates RNA-dependent oligomerization and virion incorporation
Loop L3 (residues 116-133) extends along the inner side of the beta barrel wall and may constrict the pore mid-length
The alpha-helical N-terminus (residues 1-72) mediates interaction with AIMP1 and thereby contributes to the assembly of the multisynthetase complex
A central region that included the first H15 (linker histone H1/H5 globular) domain binds at the entry/exit site of the nucleosomal DNA
The C-terminal region is necessary for nucleus and cytoplasmic localization. The N-terminal region is necessary for nucleus and nuclear bodies localization. Regions containing Arg-Gly-Gly repeats (RGG/RXR-box) may be preferentially methylated by PRMT1
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). The provided sequence of ACTTS1 contains only 1 condensation (C) domain (Probable)
The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphocholine
The SMP-LBD domain is a lipid transport module, which binds glycerolipids with a preference for phosphatidylinositol (PI)
The FZ domain is involved in binding to Wnt ligands egl-20, cwn-1 and mom-2 (PubMed:15371357, PubMed:17942487). The domain is required for the final positioning of migrating ALM, CAN, BDU and HSN neurons, and maybe QR neuroblast descendants during development and for neurite pruning of AIM neurons (PubMed:14651925, PubMed:19561603). Required for the establishment of ALM polarity (PubMed:25917219)
The domain is required to establish correct polarity in ALM neurons (PubMed:25917219). May play a role in QR neuroblast descendant migration (PubMed:25373777). The kinase domain is dispensable for ALM, CAN, BDU and HSN neuron migration, V cell asymmetric division, acr-16 localization, for the positioning of the nerve ring and probably for the negative regulation of neurite pruning of AIM neurons (PubMed:14651925, PubMed:15944127, PubMed:19855022, PubMed:19561603)
The cytoplasmic domain is required for the negative regulation of neurite pruning of AIM neurons
Contains an ordered core and an extensive dynamic surface formed by two regions, dynamic loop1 and dynamic loop2. The core is stabilized by a disulfide and ressembles the cystatin family
The PDZ domain 2 mainly binds CAMK2A and CAMK2B. The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 10 binds the C-terminal PDZ-binding motif of HTR2C. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds SYNGAP1 (By similarity). The PDZ domain 1 binds NG2. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT. The PDZ domain 13 binds CXADR
Contains a unique short C-terminal alpha-helix compared to the known structures of the structurally similar homotetrameric L-ribulose 3-epimerases and D-allulose 3-epimerases (PubMed:33838083). The length of the C-terminal alpha-helix was thought to be involved in tetramerization and increasing stability, however, the addition of residues to MetLRE at the C terminus does not lead to tetramer formation (PubMed:33838083)
The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK2 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them (By similarity)
Contains long series of C-terminal alanine-rich repeats that serve to maintain the protein in the cytoplasm
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-98 and Arg-101) that bind to malonylated and succinylated substrates and define the specificity
The RVVP region and palmitoylation sites are required for compartmentalization inside cilium to prevent distal cilium and nuclear targeting
The PPC (Plant PI4K Charged) region is involved in membrane targeting and phospholipid binding
The transmembrane domains are required for its ability to shape the endoplasmic reticulum membrane into tubules
Probably a beta-barrel protein
Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate
Autoinhibited by its C-terminal basic region
The chromo domain recognizes and binds histone H3K9me3, histone H3K27me2 and histone H3K27me3
The acetyl-CoA-binding domain mediates crotonyl-coA hydratase activity (PubMed:28803779). The acetyl-CoA-binding domain is required for recruitment to sites of DNA double strand breaks and for binding to poly (ADP ribose) moieties (PubMed:29177481)
The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. At least 2 of the odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue
The SCP domain is necessary and sufficient for lipid export and sterol-binding
The PXY motifs are required for binding WW domains. PXY1 is required to promote transactivation of beta-globin and for hyperacetylation of histone H3, but not for binding to the HS2 promoter site
The N-terminal helical domain blocks the interaction with the potential target PSII subunit chlorophyll protein 47 (CP47)
The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature (By similarity)
Binds to membranes enriched in PtdIns3,4P2 via the C-terminal PH domain
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (327-357) inactivates kinase activity under calcium-free conditions (By similarity)
The LIR motif (LC3-interacting region) is required for the interaction with ATG8 family proteins MAP1LC3A, MAP1LC3B, MAP1LC3C and GABARAPL1. Required for proteolytic activation and delipidation of ATG8 proteins
Contains a guanine-nucleotide-specific nucleotide-binding site (about residues 1-276) that shows slow GTP hydrolysis (PubMed:12446835, PubMed:23104801). When a non-hydrolyzable GTP analog binds to the trimeric N-terminal domain, it induces a structural shift which opens a pore (PubMed:19629046)
The N-terminal domain (about residues 1-143) is an archaea-specific tRNA-editing domain (PubMed:16902403) that has a highly similar structure to Dtd (D-aminoacyl-tRNA deacylase); the domain binds L-serine and L-cysteine and most D-amino acids but not L-threonine (PubMed:15908961, PubMed:16902403). Editing of incorrectly charged L-seryl-tRNA(Thr) by this domain is tRNA catalyzed (PubMed:16902403, PubMed:21098258, PubMed:26113036)
Atypical domain architecture: contains 2 receiver domains
The ubiquitin-like domains are essential for its antiviral activity
Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site
The N-terminal region associates with membranes, the coiled-coil region binds to microtubules and the WH2 domains promotes actin nucleation
The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3). The tudor-like regions simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first tudor-like subdomain and unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains. The linker region plays a role in the formation of a histone H3-binding hole between the reader modules formed by the tudor-like regions and the PHD-type zinc finger by making extended contacts with the tandem tudor-like regions (By similarity)
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA). It contains a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. 2 specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other 3 bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand. The YDG domain also recognizes and binds 5-hydroxymethylcytosine (5hmC) (By similarity)
The light chain is composed of three structural domains: a large globular N-terminal domain which may be involved in binding to kinesin heavy chains, a central alpha-helical coiled-coil domain that mediates the light chain dimerization; and a small globular C-terminal which may play a role in regulating mechanochemical activity or attachment of kinesin to membrane-bound organelles
The C-terminal di-lysine motif may confer endoplasmic reticulum localization
The WQQ domain consists of a repetition of W-x(2)-Q-x(4)-Q-x(2) motifs
The unliganded VWA domain has an inactive 'locked' conformation whereby the scissile Arg-259|Lys-260 bond is protected from proteolytic activation
The C-terminal transmembrane domain is indispensable for the localization to the ER
HKT transporters are proposed to contain 4 pore-forming regions enclosed by transmembrane segments with each containing a potassium channel-like selectivity filter motif
The CARD domain may be involved in the regulation of caspase activity in the context of programmed cell death
The ricin B-type lectin domain binds glycan structures
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-119 is required to stabilize the incoming nucleotide at the 3'-site
The TIR domain alone is active and produces cADPR
Recognizes stalled ribosomes via two separate and partially redundant sensor domains: the C-terminal domain (CTD) that binds the 18S ribosomal RNA (18S rRNA) and the sensing domain (S)
The ankyrin repeats, mainly ANK 2, ANK 3 and ANK 4, mediate interaction with a wide array of PxLPxI/L motif-containing proteins including HDAC4 and LRP2. The PxLPxI/L motif of interactors can contain a Ser or a Thr residue in position 2, which phosphorylation prevents the interaction with ANKRA2
The cysteine framework is XXVIII (C-C-C-CC-C-C-C-C-C)
Each of the immunoglobulin-binding region repeats can bind the Fc region of an immunoglobulin
Contains at least one active inhibitory domain for trypsin (domain 6)
The macro domain mediates non-covalent poly(ADP-ribose)-binding and recruitment to DNA damage sites. Mediates auto-inhibition of ATPase activity by interacting with the N-terminal ATPase module, encompassing the helicase ATP-binding domain and helicase C-terminal domain. Binding to poly-ADP-ribosylated histones upon DNA damage releases the auto-inhibition by the macro domain and trigger ATPase activity. Does not bind monomeric ADP-ribose and mono-ADP-ribose fails to release the auto-inhibition of the ATPase module by the macro domain
Domain B contains 41 X 9 AA tandem repeats. Domains C1 and C2 may be involved in membrane binding
Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity (By similarity)
The KEN and D (destructive) boxes are required for the cell cycle-controlled ALK1 degradation by the anaphase promoting complex (APC) pathway
The protein kinase domain is predicted to be catalytically inactive. However, weak kinase activity was experimentally demonstrated
Possesses two phosphotransferase domains. The second one probably contains the catalytic domain (By similarity), while the presence of slight differences suggest a different role for domain 1
The ankyrin-repeat region is necessary for ATP-dependent protein disaggregase activity. It plays an important role in stabilizing the substrate-bound homododecamer by mediating contacts between the two homohexamers
An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes
The SH3 domain is required and sufficient for the interaction with UVRAG
The C-terminal region is probably involved in protein stability
The NEAT 1 domain binds with higher affinity than the NEAT 2 domain haptoglobin-hemoglobin complexes, haptoglobin and hemoglobin (By similarity). More than one IsdH NEAT 1 domain interacts with a single hemoglobin
Mainly composed of Cys-rich (CR), Gly-rich (GR) and Ser-rich (SR) repeats
The GPS domain is necessary, but not sufficient for receptor cleavage, which require the entire extracellular stalk
An N-terminally truncated L27 domain is predicted in isoform 2 at positions 1 through 27
The olfactomedin-like domain mediates NFASC/neurofascin and NRCAM binding
The N-terminus is involved in the initial binding to heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (PubMed:27560376). The N-terminus masks the TSP type-1 (TSR) domain which maintains the sporozoites in a migratory state, enabling them to complete their journey to the salivary gland in the mosquito vector and then to the host liver. The unmasking of the TSP type-1 (TSR) domain when the sporozoite interacts with the host hepatocyte also protects sporozoites from host antibodies (By similarity)
The N-terminal and the C-terminal domains contain respectively the lysine ketoglutarate reductase and saccharopine dehydrogenase activity
The SAP domain is necessary for specific binding to nuclear scaffold/matrix attachment region (S/MAR) elements in DNA. The RNA-binding RGG-box region is necessary for its association with inactive X chromosome (Xi) regions and to chromatin-associated RNAs (caRNAs). Both the DNA-binding domain SAP and the RNA-binding RGG-box region are necessary for the localization of Xist RNA on the Xi. The ATPase and RNA-binding RGG-box regions are necessary for oligomerization
The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments
The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2
The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA
The 2 circularly premutated PDZ domains act to negatively regulate protease action on intact RseA
Has a disordered N-terminal domain of about 225 residues that functions as a cargo-loading domain (tested with GFP) and a conserved C-terminal cysteine desulfurase domain. The first 100 residues also function as a cargo-loading domain but not as well as the first 225 residues
Has three domains with a flexible linker between the domains II and III, and assumes an 'L' shape. Domain III has weak interactions with the adjacent subunit (PubMed:8832889, PubMed:9628481, PubMed:9493263, PubMed:10890893). In complex with Holliday junction (HJ) DNA, an approximately square planar DNA molecule is bound to the tetramer's concave face, with the DNA accessible to solution on one side. Domain III moves 4-5 Angstroms toward the protein-DNA interface upon DNA binding (PubMed:9628481, PubMed:10890893). The isolated N-terminus (domains I and II) forms tetramers and binds HJ DNA but does not bind RuvB (PubMed:9493263, PubMed:10772859). Alterations of bulky residues on the surface of domain III prevent binding to RuvB (PubMed:9493263). Domains I and II crystallize with the same tetrameric structure and are dominant negative to wild-type in vivo. In intact protein, domain III is quite flexible in solution. Isolated domain III inhibits the ATPase activity of RuvB (PubMed:10772859). The acidic pin (Glu-55 and Asp-56) seems to push the DNA backbone away from the HJ/RuvA complex center. It prevents binding to non-HJ dsDNA and constrains the rate of branch migration (PubMed:10890893, PubMed:11080172)
Subfamily II proteins have an EGMGR motif about 50 residues from the C-terminus (By similarity). This motif lies near the metal-binding residues in the putative substrate-binding cleft 2 (By similarity). Subfamily II proteins occur only in eukaryotes, in two forms: as a stand-alone unit in plants, and as a C-terminal domain of pantothenate kinases in plants, animals, and chytrid fungi (By similarity)
The tight homopentamer forms a pore with an opening of about 3.5 Angstroms in diameter which is positively charged (PubMed:18292340). A short loop (residues 30-33) protrudes above the center of the concave face to different degrees (Probable)
Some isoforms lack the first Ig-like domain which may confer homophilic adhesion activity. However, they can bind and activate FGFR1 (By similarity)
The N-terminal DMA/Gly-rich region (also called GAR domain) is rich in Gly and Arg and functions in nucleolar targeting
Transmembrane regions are predicted by sequence analysis tools, but these regions probably constitute hydrophobic domains associated to phospholipids
The proline-knot motif (120-129) may be involved in targeting to lipid bodies
The C-terminal domain (829-953) is involved in cold sensitivity
The RRM domains are required for mRNA stabilization
The N-terminus is necessary and sufficient for nuclear envelope targeting
The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel. The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits. The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells. The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons
Folds into two domains, a large PLP-binding domain (residues 63-276) and a small C-terminal domain
The C2H2-type zinc fingers are involved in discrete Cajal bodies localization, interaction with LSM11 and the SLBP/RNA complex and histone pre-mRNA processing
The C-terminal region containing both MHD domains and the third C2 domain is required for synaptic vesicle priming activity
The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity
The N-terminal 35 amino acids, including the potential transmembrane alpha-helix, function as a non-cleaved mitochondrial targeting sequence that targets the protein to the cytosolic side of the outer mitochondrial membrane
The N-terminal domain contains LysM domains that are thought to be involved in peptidoglycan binding, while the C-terminal domain is endowed with the catalytic activity
Contains two target DNA recognition domains (TDR), each specifying recognition of one of the two defined components of the target sequence (Probable). The TDRs show high structural similarity and each forms a globular structure. The two TDRs are separated by 2 long, conserved antiparallel helices that form a coiled coil structure. These conserved regions may act as a molecular ruler for the separation between the two recognized DNA sequences (PubMed:15728358)
Heparin binding seems to require the C-terminal domain of HbhA. Progressive truncations from the C-terminal end diminish the affinity for heparin (By similarity)
The ShKT domain associates with, and blocks several potassium channels in the nanomolar to low micromolar range. The relative affinity is Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4
The C-terminal part of the protein in required for plasmodesma localization
Isoform 1 N-terminus domain is necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation. Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively
The DNA-binding domain is intrinsically unstructured
The coiled coil mediates dimerization
Sushi 1-3 domain represents the minimal unit capable of cofactor activity. The property to discriminate self surfaces from non-self surfaces depends on the C-terminal region made of Sushis 19-20
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (309-339) inactivates kinase activity under calcium-free conditions (By similarity)
The PH 1 domain and amino acids 621-782 (a region called TSS; otherwise known as CC-Ex) are necessary for membrane localization. The PH 1 and TSS domains are necessary for Rac1 activity. The PH 2 domain is engaged in the enhancement of the catalytic activity of the adjacent DH domain. The PH 1, TSS and DH domains are necessary to induce neurite-like structure (By similarity)
Contains an N-terminal cytidylyltransferase (CyTase) domain and a C-terminal phosphoenolpyruvate phosphomutase domain
The MSP domain is required for binding to the FFAT motif of target proteins
The chromo domain mediates interaction with methylated 'Lys-9' of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3)
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space (By similarity). Then, trimerization and insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface (PubMed:22155776). Trimerizes to make a lollipop-shaped form which consists of three domains: a C-terminal membrane-anchor domain, an extended coiled-coil stalk domain which binds IgG Fc, and an N-terminal head domain (By similarity)
The ubiquitin-like domain mediates interaction with ATXN3
The ubiquitin-like (UBL) and the UBA (ubiquitin-associated) domains interact intramolecularly in a highly dynamic manner, as each UBA domain competes for an overlapping UBL domain surface. Binding of ubiquitin or proteasome subunit PSMD4 disrupt the UBL-UBA domain interactions and drive RAD23A in to an open conformation
The N-terminal hydrolase domain has an NADP-independent formyltetrahydrofolate hydrolase activity, releasing formate and tetrahydrofolate
The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity. It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2
The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2. The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2
Binds its carbohydrate substrate close to the active site, but also via regions close to the N-terminus; this may result in increased affinity and therefore increased catalytic efficiency
The C-terminal PDZ-binding motif may mediate interaction with the PDZ domains of DSH (Dishevelled) family proteins
The proline-rich region localized between residues 270 and 307 is important for the binding to RAF1 and activation of MAP2K1/MEK1
Has an N-terminal region with 8 leucine-rich repeats (LRR) and has 3 GW repeats in the C-terminus (Probable). Residues 241-319 form an Ig-like region, followed by a 72 residue-long flexible B repeat region (PubMed:12411480) (Probable). The GW repeats mediate non-covalent binding of the protein to lipoteichoic acid (LTA) on the bacterial membrane (PubMed:10594817). The GW domain mediates binding to host complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) and to heparin; heparin binding dissociates InlB from the bacterial surface (PubMed:12411480). The LRR domain forms a curved tube, the N-terminus of which has a cap that binds 2 Ca(2+) ions (PubMed:10635330, PubMed:15020228). The LRR domain alone (31-241) binds mammalian MET and stimulates its Tyr-phosphorylation; the LRR plus Ig-like region (31-321) are required for receptor dimerization, and the GW domains, especially GW2 and GW3, potentiate MET activation (PubMed:11081636, PubMed:15049825)
Upon tRNA-binding, the alphaC region transforms into a helix, which together with the alpha6 helix secures both ends of the tRNA variable loop. The N-terminal disordered region is part of the catalytic pocket and essential for methyltransferase activity: upon S-adenosyl-L-methionine- and tRNA-binding, the N-terminal disordered region becomes ordered, sandwiched between the bound cofactor and the tRNA, and the WDR4 C-terminus attaches to the METTL1 N-terminus to stabilize the bound tRNA together. Together with WDR4, which also binds tRNAs, tRNAs undergo bending to facilitate G46 flipping into the catalytic pocket to be modified
Has the structural arrangement of two alpha-helices stabilized by disulfide bonds (CSalpha/alpha 2(S-S))
The C-terminal domain binds 1 Fe-S cluster but is otherwise mostly in an intrinsically disordered conformation
In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (PubMed:12893818)
The L/FRRG motif is required for recruitment to phosphatidylinositols including phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)
Contains 3 N-terminal periplasmic polypeptide transport-associated (POTRA) domains which may serve as a binding site for the preprotein in the chloroplast intermembrane space, and provide a chaperone-like activity to prevent misfolding or aggregation in the intermembrane space (Probable). Transmembrane regions consist mainly of membrane-spanning sided beta-sheets, which are not predicted by sequence analysis tools (Probable)
The third CXXC-type zinc finger mediates binding to DNA containing unmethylated CpG dinucleotides
The transcriptional repression domain (TRD) is involved in transcription repression and in protein interactions
The RAP domain is essential for RNA-binding
The jas domain (204-229) is required for interaction with COI1 and Pseudomonas syringae HopZ1a
The coiled coil domain mediates interaction with MTMR9
Contains two subdomains, SD1 and SD2. SD1 is composed of an antiparallel beta-sheet covered by an alpha-helix and displays a ferredoxin-like fold. SD2 displays a new protein fold made of loops connected by four disulfide bridges
The RanBP2-type zinc fingers, also called NZFs, mediate the interaction with ubiquitin and determine linkage specificity. RanBP2-type zinc fingers 1 and 2 (also named NZF1 and NZF2) specifically recognize and bind 'Lys-29'- and 'Lys-33'-linked ubiquitin. RanBP2-type zinc finger 3 (also named NZF3) binds 'Lys-33'-linked ubiquitin and shows weak binding to 'Lys-6'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin chains but it does not interact with 'Lys-29'-linked chains
The OTU domain mediates the deubiquitinating activity
The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts with ubiquitin hydrophobic patch and contributes to linkage specificity
The association domain (AD) is necessary for self-association
The acidic domain may be involved in the interaction with histones
The BAR domain is necessary and sufficient for mediating homotypic and heterotypic interactions; associates with cytoplasmic membrane structures; mediates interaction with TBC1D1 and ADIPOR1 (PubMed:24879834, PubMed:19661063). The PH and PID domains mediate phosphoinositide binding. The PID domain mediates phosphatidylserine binding and allows localization to cytosolic membrane structures and nucleus. The PH domain allows localization to the plasma membrane, cytosolic vesicles and distinct nuclear and perinuclear structures and is sufficient for RUVBL2 interaction (By similarity)
A C-terminal domain (252-356) is required for dimerization
The C-terminal acidic tail is required for nuclear localization and is involved in the binding to SCF E3 ligase complexes, and more specifically with the CUL1 subunit
The C-terminal domain (CTD) is probably responsible for hetero- and homodimerization and binds 1 Fe cation per subunit (Probable). The CTD assumes a V-shaped, dimeric metallo-chaperone-like fold (By similarity)
The elastin-binding domain is located between residues 13-33 at the surface-exposed N-terminus, whereas the C-terminus, containing the LysM peptidoglycan-binding domain, is not exposed on the surface of intact cells and presumably remains buried within the peptidoglycan. The presence of the TNSHQD sequence, corresponding to residues 18-23, is essential for EbpS activity but not sufficient, additional flanking amino acids in the amino- or carboxy-terminal are required for elastin recognition (By similarity)
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 137 and 161
The TIR domain catalyzes the NAD(+) cleavage (NADase) activity (PubMed:31439793). In contrast to classical TIR-NB-LRR receptor-like proteins, only contains a TIR domain (Probable)
The N-terminal extension forms a projection that reaches into the active site of cognate toxin Tre1-Sp where it occludes the active site
Requires the intact death domain to associate with TNFRSF1A/TNFR1
The C-terminal part (143-188) is required for insertion in the mitochondrial inner membrane
The N-terminal domain has an alkylhydroperoxide reductase activity
The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling
The nucleotide binding domain binds ATP with low affinity
The Ig-like V-type 1/D1 domain contains three complementarity determining region-like loops CDR1-3, which mediate interaction with IgA and IgM
The PX domain is essential for its localization to the early endosomes
The first protein kinase domain appears to be a pseudokinase domain as it does not contain the classical characteristics, such as the ATP-binding motif, ATP-binding site and active site
Contains 1 DXTW motif
The LRR domain forms a horseshoe-shaped structure that interacts tightly with target RNases via a large protein interaction surface on its interior side
Contains seven structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a superhelical structure with a solenoid shape
The RRM domain is essential for the recognition of specific adenine bases in the poly(A) tail, but not sufficient for poly(A) binding
The ricin B-type lectin domain directs the glycopeptide specificity. It is required in the glycopeptide specificity of enzyme activity but not for activity with naked peptide substrates, suggesting that it triggers the catalytic domain to act on GalNAc-glycopeptide substrates (By similarity)
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of a N-terminal amphipathic helix (AH) in the membrane (By similarity)
Repeat 2 contains the catalytic domain
His-123 is a strong candicate for an active site that hydrogen bonds to a water molecule which in turn hydrogen bonds to the C-3' amino group. However, it is not conserved in related S.venezuelae DesVI methyltransferase and its mutagenesis does not completely abolish catalytic activity (PubMed:21142177)
The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore (By similarity). The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex (By similarity)
The ITAM domain displays no close similarity to any existing ITAMs, except for four conserved positions. The phosphorylated ITAM domain binds ZAP70 and SYK
(Microbial infection) FG repeats mediates interaction with HIV-1 capsid protein p24 (CA)
The C-terminus (residues 312-335) targets the protein to the encapsulin nanocompartment
Consists of a small non-helical N-terminal domain and a rod domain with a 29 residue repeat pattern based on four heptads followed by a skip residue. This alpha-helical protein is characterized by the ability to form a special segmented coiled coil and to assemble into striated fibers of 2 nm protofilaments (By similarity)
The FERM domain mediates interaction with JAKMIP1
Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activities while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation
The PARP-type zinc finger is required for DNA ligase activity
The SH3 domain interacts with FYB1
The RING-type zinc finger domain is essential for its E3 ubiquitin-protein ligase activity, ability to positively regulate the NF-kappa-B signaling pathway and its antiviral activity
Contains nine structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a left-handed superhelical assembly with a solenoid structure that wraps itself around DNA
The molybdenum cofactor biosynthesis protein-like region may not be functional
Contains G-L-F-G repeats. The FG repeat domains have a direct role in the transport (By similarity)
Contains an N-terminal rubredoxin domain, a central kinase domain and a C-terminal TPR domain
The cytoplasmic domain is required for SH3GL2- and SNX9-binding
Disintegrin domain binds to integrin alphaV-beta3
The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4
The DH domain and the PH domain are both required to mediate interaction with EPHA4
The N-terminal domain binds cAMP and is responsible for homodimerization, while the C-terminal domain binds DNA when cAMP is bound
The nuclear localization signal (NLS) is required for localization to the host nucleus and RNA silencing suppression activity
The single WY domain is required for binding to host PINP1 and subsequent RNA-silencing suppression activity, pathogenicity and perturbation of plant development
The middle domain of ADA2b is sufficient for interaction with the HAT catalytic domain of GCN5
The N-terminal domain is an archaea-specific tRNA-editing domain that hydrolyzes incorrectly charged L-seryl-tRNA(Thr). Catalysis of tRNA editing is performed by the charged tRNA itself
Each HMA domain can bind a copper ion, they are tightly packed and closely interact with each other. Wild-type ATP7B can usually be loaded with an average 5.5 copper atoms per molecule
Contains an N-terminal conserved nucleotide-binding domain and a C-terminal domain bound with a [4Fe-4S] cluster. The C-terminal domain forms a stable loop region and interacts with the N-terminal domain
The ART domain is toxic when expressed as a protein fragment
Almost exclusively composed of repeats of the decapeptides APPPAWTAWK and ATPKPWTAWK
Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) regions. These regions lack the critical Cys residues required for ubiquitination but retain the ability to bind ubiquitin
Contains a large substrate-binding pocket that recognizes alpha-helical transmembranes, which alternately faces the endoplasmic reticulum lumen and cytosol, while remaining accessible to the lipid bilayer through a lateral opening (PubMed:32973005). The translocase alternates between two conformations: inward-open (E1) and outward-open (E2) states (PubMed:32973005). Undergoes a series of conformational changes with ATP-binding, phosphorylation of the Asp active site and subsequent dephosphorylation in a Post-Albers cycle (i.e., E1 -> E1-ATP -> E1P-ADP -> E1P -> E2P -> E2-Pi -> E1) (PubMed:32973005). A substrate transmembrane helix with a short, preferentially positively charged lumenal segment binds to the outward-open pocket and the E2P-to-E1 transition flips the transmembrane by a switch from the outward-open to inward-open conformation (PubMed:32973005)
C2 domains are necessary for calcium-dependent cell membrane association. C2 domains are necessary for neuronal progenitor cell differentiation in a calcium-independent manner
The two fingers are functionally distinct and cooperate to achieve specific, stable DNA binding. The first finger is necessary only for full specificity and stability of binding, whereas the second one is required for binding (By similarity)
The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of psm1, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable rad21 protein, forming a ring structure (By similarity)
The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3
The C-terminal part after residue 140 is mostly unstructured
Composed of 4 domains; in the N-terminus the PAS2-GAF-PHY domains form the photosensor while the C-terminal PAS9 domain is the output module. Long linker helices serve as connectors within the GAF-PHY and PHY-PAS9 domain pairs, forming a helical spine where the dimer interface is assembled. Thus both the photosensor and PAS9 domains are required for dimerization. Within the PHY domain is the mobile tongue domain (residues 452-480) that probably serves as a gatekeeper to the chromophore-binding pocket, in the Pr form it is a beta-sheet, in a R.palustris Pfr crystal it is an alpha helix (AC B3Q7C0). In the dark (Pfr) state the protein is compact and protease resistant, far-red light treated protein (Pr) is quickly degraded to its domains, with important cuts occurring in the hinge region (just before the PAS9 output domain at about residue 512) and in the tongue domain (about residue 469)
The acidic domains are probably involved in the interaction with histones
In CydD the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
The jas domain (120-144) is required for interaction with COI1
The region involved in interaction with ZAP70 is a non-canonical immunoreceptor tyrosine-based activation motif (ITAM)
The central ion permeation pathway is formed by the first transmembrane domain from each of the five subunits. Mg(2+) binding strengthens interactions between subunits and leads to the formation of a symmetrical homopentamer surrounding a closed ion permeation pathway (PubMed:23091000). Low cytoplasmic Mg(2+) concentrations trigger both a conformation change within each subunit and a loosening of the interactions between subunits. This results in an open ion conduction pathway. In addition, this results in a less symmetrical shape of the whole complex (PubMed:26051127)
Composed of three domains: a modulating N-terminal domain (AF1 domain), a DNA-binding domain and a C-terminal ligand-binding domain (AF2 domain)
LIM zinc-binding domain 1 is required for self-association. LIM zinc-binding domain 1 and LIM zinc-binding domain 2 both are required for optimal actin-bundling activity. LIM zinc-binding domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates binding to SPTB
The DOCKER domain mediates GEF activity
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium. The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (By similarity)
The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (By similarity)
A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-150
Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif known to be essential for phosphatidate phosphatase activity
Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, a motif known to be a transcriptional binding motif
The KEN box is required for the association with the APC/C-Cdh1 complex
Has two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1
The PH domain strongly binds to phosphoinositides and is required for targeting the protein to the membrane
The FFAT (two phenylalanines in an acidic tract) motif is required for interaction with SCS2 and proper localization of the protein
The OSBP-related domain (ORD) mediates binding of sterols and phospholipids. It displays an incomplete beta-barrel containing a central hydrophobic tunnel that can accommodate a single lipid molecule with a flexible lid covering the tunnel entrance. The ORD can bind two membranes simultaneously. It has at least two membrane-binding surfaces; one near the mouth of the lipid-binding pocket and a distal site that can bind a second membrane. These structural features correlate with the phosphatidylinositol 4-phosphate (PI(4)P)-coupled lipid transport optimized in closely apposed membranes, such as organelle contact sites. The lipid transfer cycle starts from the association of the LTP with a donor membrane, which accompanies conformational changes that uncover the ligand-binding pocket. The tunnel opening is generally mediated by displacement of the lid covering the binding pocket allowing uptake or release of a lipid molecule. The LTPs extract the lipid from the membrane by providing a hydrophobic environment as well as specific interaction. Dissociation from the donor membrane shifts the conformation to a closed form. Then, the LTPs loaded with a cargo lipid diffuse through the aqueous phase. Lid opening may be induced by the interaction of a hydrophobic side of the lid with the target membranes
The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity (PubMed:22219199). The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3 (PubMed:21625540). The J domain is required to reduce PRKN cytoplasmic aggregation (PubMed:20889486)
The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome (PubMed:15936278). The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation (PubMed:21625540). The UIM domains are not required to reduce PRKN cytoplasmic aggregation (PubMed:20889486)
The pre-SET, SET and post-SET domains are all required for methyltransferase activity. The 347-amino-acid insertion in the SET domain has no effect on the catalytic activity
Isoform 2 lacks all domains required for histone methyltransferase activity
The SUEL-type lectin domain, the transmembrane domain and the C-terminal region are required for the guidance of the muscle arm extensions to the midline neurons
Contains 2 Inka boxes (also named iBox or inca box). The Inka boxes bind and inhibit PAK4 by binding a substrate-like manner
The regulatory domain shows changes in the ESRP sequence, which is involved in the allosteric binding of phenylalanine. These changes suggest the desensitization of the enzyme to inhibition by phenylalanine and would permit the overproduction of phenylalanine
Contains 2 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The first one is essential for the association with ESR1 and ESR2
The ANK repeats bind H3K9me1 and H3K9me2
The SET domain mediates interaction with WIZ
The J-like region, although related to the J domain does not have co-chaperone activity
The domain III mediates oligomerization
Deletion of the C-terminal 34 residues abolishes ATR1 activity, while deletion of the C-terminal 23 residues have a minor effect
The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues (PubMed:31292544). This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons (PubMed:31292544)
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is required for the activation of substrate transport
All seven C2 domains associate with lipid membranes in a calcium-dependent manner. Domains C2 1 and 3 have the highest affinity for calcium, the C2 domain 1 seems to be largely unstructured in the absence of bound ligands (By similarity)
The N-terminal and the C-terminal halves of the protein can associate with each other, thereby hindering interactions with other proteins
The fourth EF-hand domain has been proven to bind calcium
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residue at position 81
All cysteine residues are arranged in C-X-C groups. These are thought to be the metal-binding sites in other metallothioneins
The BC-box, which mediates binding to the elongin BC complex, has the consensus sequence [APST]-L-x(3)-C-x(3)-[AILV]
The C-terminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface
Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain
The C-terminal domain regulates the auto-processing and controls the juxtacrine signaling
Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin
The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1
The PDZ-binding motif mediates interactions with NHERF1 and SCL4A7
The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (By similarity). The N-terminal palmitoylated peptide is cleaved at the Heparan sulfate-binding Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (By similarity)
The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation (By similarity)
The heptad repeat (HR) motif is sufficient for interaction with kinesin heavy (KHL) chains and ODF1. The TPR region is involved in mitochondrial binding
The Asp-Asp-Xaa-Xaa-Xaa-Glu (DDXXXE) and Asn-Xaa-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Glu (NSE) motifs are important for the catalytic activity, presumably through binding to Mg(2+)
The C-terminus is required for mitochondrial or peroxisomal localization, while the N-terminus is necessary for mitochondrial or peroxisomal fission, localization and regulation of the interaction with DNM1L
The destruction boxes (D-box) may act as recognition signals for degradation via the ubiquitin-proteasome pathway
A minimal inhibitory domain prevents pancreatic beta cell apoptosis in vitro, and prevents activation of c-jun by MAPK8, MAPK9 and MAPK10
The cytoplasmic domain plays an important role in regulation of cell-matrix adhesion and cell motility
The BRCT domain is able to bind intact DNA without activating the poly-ADP-ribosyltransferase activity. The BRCT domain mediates DNA intrastrand transfer (named 'monkey-bar mechanism') that allows rapid movements of PARP1 through the nucleus
The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; 2 acyl-carrier protein (ACP) domains that serve as the tether of the growing and completed polyketide via its phosphopantetheinyl arm; and a C-terminal thioesterase (TE) domain that facilitates the release of the final product from the enzyme
The WxxxF/Y motifs mediate interaction with PEX14, promoting association with the PEX13-PEX14 docking complex
The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains
The dimerization region encompasses helices both from the N- and C-terminal of the protein kinase domain
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 or REC8 protein, forming a ring structure (By similarity)
The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2
The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol (By similarity). It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (By similarity)
Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains can simultaneously bind to both TENT5C and CEP192
The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity
The N-terminal domain is sufficient to interact with BMP4
The coiled coil is formed by helices from two subunits in the MSL1 homodimer
Contains an N-terminal DNA binding domain (DBD) and a C-terminal regulatory domain (RD)
Both the RRM domain and the arginine, glycine (RGG) rich domain are necessary for binding to the TXN 3'-untranslated region. Both the RRM domain and the arginine, glycine (RGG) rich domain (RGG repeats) are necessary for optimal recruitment into SGs upon cellular stress. The C-terminal domain containing RGG repeats is necessary for translational repression (By similarity)
The LysM domains bind chitin and potentially related carbohydrates, and might be involved in damping host defense
The N-terminal region is an inactive protease, the C-terminal region may have transporter activity which could activate the MamE protease
The type I copper site in NIR plays a crucial role for electron transfer from pseudoazurin to the type II copper site of NIR, which comprises the catalytic center of NIR for the reduction of nitrite
The F-BAR domain mediates oligomerization, binds membranes, and constrains plasma membrane protrusions
Contains a C-terminal (456-532) carbohydrate-binding domain (CBM)
The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of ABRAXAS1, recruits BRCA1 at DNA damage sites (By similarity)
The GTD-binding domain is sufficient for myosin binding
The C-terminal domain (CTD) is probably responsible for hetero- and homodimerization; it assumes a V-shaped, dimeric metallo-chaperone-like fold that can open and close. Val-260 forms the hinge between the dimers. Binds up to 3 divalent metal cations (probably iron in vivo); upon binding there is a conformational shift to a tighter dimer (PubMed:24658343, PubMed:30811856) (Probable). If the CTD cannot fold correctly the function of the whole protein is decreased, suggesting the CTD confers functionality on the transmembrane domain (TMD), perhaps activated by ligand binding to the CTD (Probable)
Most plant PPOX proteins have both a pyridoxamine 5'-phosphate oxidase domain and an extra YjeF N-terminal domain
the PDZ-binding motif mediates interaction with PDZ domain-containing proteins MAGI1, MAGI2, DLG2, DLG3 and DLG4 and is required for is required for synaptic localization in photoreceptors
The cysteine framework is I (CC-C-C). Alpha9/4 pattern
Contains 3 EAR motifs associated with active repression of several target genes (PubMed:24336200, PubMed:24336215). The D1 domain (195-440) is essential for the strigolactone-dependent D53-D14 interaction (PubMed:24336215)
The N-terminal domain (1-290) does not play any direct role in catalysis and is not required for product binding
In an autoinhibited form the C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. An ADP-mediated interaction between the NBD and the WHD also contributes to the autoinhibition (PubMed:23765277)
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 73 and 106
The LRR 5 repeat can inhibit BMP2-induced cytodifferentiation and may be involved in the interaction with BMP2 (By similarity). The repeats LRR 10, LRR 11 and LRR 12 are involved in binding type I collagen. The poly-Asp region is involved in binding calcium
Adopts a simplified PTP fold, which combines features of the conventional PTPs and dual-specificity phosphatases (PubMed:16271885). In the presence of OMTS inhibitor, the enzyme undergoes a large conformational change, allowing the inhibitor to bind deep in the active-site pocket (PubMed:17437721)
The N-terminal region does not contain a typical signal sequence but is required for secretion (By similarity). It also determines exosomal location (By similarity)
The C-terminal DC effector region contains a helix-hairpin-helix (HhH) DNA-binding domain involved in the binding to heat shock elements (HSEs), which are conserved in the promoter regions of HSP genes at promoters of targeted heat shock protein coding genes
The PLAT domain can bind calcium ions; this promotes association with membranes
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. BenY as the following monomodular architecture: A-T-C
The TID (telomerase inhibiting domain) domain is sufficient to bind TERT and inhibits its activity
The conserved DxD and QxxRW domains are necessary for the full function
The PH domain mediated binding to phospholipids with phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate (By similarity)
The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions. The second domain also recognizes and binds histones that are butyrylated and crotonylated
The RxLR-dEER motif is required for the delivery of the effector to the host cell cytoplasm but does not bind phosphatidylinositol monophosphates (PubMed:17914356, PubMed:22977236). The motif is cleaved after the RxLR sequence (PubMed:28522546). The RxLR motif (residues 44 to 47) plays a crucial role in the intracellular processing before secretion (PubMed:28522546). The Glu-rich part localized just after the cleavage site (residues 48 to 59) is required for homodimerization (PubMed:28522546)
The conserved, positively charged effector domain (residues 77 to 147), rather than the RxLR-dEER motif, is required for binding to phosphatidylinositol monophosphates (PIPs). PIP binding is necessary for accumulation of CMPG1 and Avr3a in host plants
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA
Possesses 2 methionine sulfoxide reductase domains (A/MsrA and B/MsrB) and 1 N-terminal thioredoxin domain. The domain B exhibits a thioredoxin dependent methionine sulfoxide reductase activity; the Cys-495 is probably involved in the reduction of MetSO and in formation of the sulfenic acid derivative. The regeneration of Cys-495 is probably done via formation of a disulfide bond with Cys-440 followed by its reduction by thioredoxin
The PH domain is essential for regulated exocytosis and binds phospholipids
The ATP-binding domain is structurally related to aminoglycoside phosphotransferase family
The transmembrane domain is composed of seven transmembrane helices; most of these are not strictly perpendicular to the plane of the membrane, but are tilted and/or kinked. Agonist binding promotes a conformation change in the extracellular loops that leads to an inward movement of the transmembrane helices. Antagonists such as AZD1283 can bind to an overlapping site, but block the inward movement of the transmembrane helices (PubMed:24670650, PubMed:24784220)
The N-terminal and the C-terminal half of the protein have a very similar 3D-structure, suggesting they arose from duplication (PubMed:30280012). Requires a bound zinc ion for normal folding and solubility (PubMed:30260988)
Isoform 2 subcellular localization at the cell membrane and resistance to proteasomal degradation is mediated by the sequences within the first 120 amino acids
Only isoform a (Tra-1L), is thought to bind DNA. Zinc fingers 3, 4 and 5 are the most important for DNA binding; removal of finger 5 almost abolishes DNA binding and prevents the selection of binding sites
The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the mre11 homodimer (By similarity)
The C-terminus contains a R-domain composed of 2 autoinhibitory regions (863-885 and 904-919)
The BAH domain mediates binding to dimethylated histone H4 'Lys-20' (H4K20me2), which is enriched at replication origins
Contains an N-terminal receiver domain, a central output domain, which hydrolyzes ATP, interacts with RNA polymerase and is required for phosphorylation-dependent oligomerization, and a C-terminal domain, which is involved in DNA binding, dimerization and phosphorylation-independent oligomerization
The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain
The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding. Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated
The C-terminal part of Nlrp1a oligomerizes to form the core of the Nlrp1a inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments. The UPA region reduces the threshold needed for filament formation and signaling
The 6 Cys residues of the EGF-like domain are arranged in a disulfide pattern different from the one found in the canonical EGFs. The function of this domain is unclear. It may be a binding site for other proteins or the docking site for a putative alliinase receptor
The acidic C-terminal domain mediates interaction with histone H3/H4 complexes
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (By similarity). AQP1 has NPN/NSA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (By similarity)
The leucine-zipper domain is involved in the interaction with LRPICD
Displays a mini-granulin fold, a structure composed of two short, stacked beta-hairpins connected by two parallel disulfide bonds. This newly described fold is derived from the same cysteine connectivity as knottins (ICK fold). The name 'mini-granulin fold' comes from the structural homology with the N-terminal region of the human granulin
The cysteine framework is XXVII (C-C-C-CC-C-C)
The KH domains mediates poly(C) binding
The C-terminal short (CTS) helix is essential for catalytic activity (By similarity). It may be accommodated as a transmembrane helix in the thinned membrane environment of the complex, similarly to the signal peptide in the complex substrates (By similarity)
The 35 nM long coiled-coil domain mediates homodimerization while the globular N-terminus links the dimers at an angle of 40 degrees to form the inner ring
The S0 segment is essential for the modulation by the accessory beta subunits
The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+) (By similarity)
The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation (By similarity)
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensor regions required for activation of the channel
The subunit can be divided into two domains: an N-terminal four-helical bundle (residues 2 to 74) involved in interactions with subunits Nqo1 and Nqo3, and a thioredoxin-like C-terminal domain (residues 75 to 180) that coordinates the binuclear cluster N1a
The ShKT and Thr-rich domains are required for body morphogenesis
The C-terminus of the protein contains 3 potential CHEK1-binding motifs (CKB motifs). Potential phosphorylation sites within CKB motif 1 and CKB motif 2 are required for interaction with CHEK1 (By similarity)
The acidic patch region is required for normal DNA replication. Interacts with the N-terminal segments and inhibits binding to DNA and PCNA. Mediates the interaction with the kinase CDC7 as well as some replisome factors and DNA polymerases
The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and phosphorylated HERC2 (By similarity). This domain is also required for proper recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent (By similarity)
In the CSD domain, Trp-63 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring
Is composed of a ring composed by 9 residues, a 5 residue-loop (SVSGQ) and a C-terminal tail (PubMed:26534965). The peptide is threaded when the C-terminal tail is inserted throught the isopeptide-bonded ring. The loop region serves as a recognition element for the isopeptidase AtxE2 (Probable)
The BURP domain located at the C-terminus has not been identified in non-plant proteins
The DPH-type metal-binding (MB) domain can also bind zinc. However, iron is the physiological binding partner as zinc binding impairs the protein electron donor function
The CKS-17 immunosuppressive domain is present in many retroviral envelope proteins. As a synthetic peptide, it inhibits immune function in vitro and in vivo (By similarity)
The LRRCT domain mediates homodimerization and LRRNT mediates trimerization of the dimers
The KRAB domain is required for transcriptional repression
Residues 7-17 are sufficient for TtrD recognition
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (408-438) inactivates kinase activity under calcium-free conditions (By similarity)
The WRKY domain (213-266) is required to bind DNA
The C-terminal region (267-348) is required for the repressing activity on gibberellic acid (GA)-induced promoters
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases (By similarity)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (Probable). AneB has a monomodular A-T-C architecture (Probable)
The cysteine framework is I (CC-C-C). Alpha4/3 pattern
The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase, glycogen synthase and phosphorylase kinase
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes. A lower affinity toward calcium can be anticipated for PLD alpha C2 due to the absence of two potential calcium ligands
The N-terminus contains the redox activity while the C-terminus exerts the DNA AP-endodeoxyribonuclease activity; both function are independent in their actions. An unconventional mitochondrial targeting sequence (MTS) is harbored within the C-terminus, that appears to be masked by the N-terminal sequence containing the nuclear localization signal (NLS), that probably blocks the interaction between the MTS and Tom proteins
The PPIase activity resides only in the second parvulin domain. The N-terminal region and the C-terminal tail are necessary and sufficient for the chaperone activity of SurA. The PPIase activity is dispensable for SurA to function as a chaperone. The N-terminal region and the C-terminal tail are also required for porin recognition (By similarity)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Tim13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
There are two conserved domains in the globular part of the catalytic subunit: the N-terminal domain (domain A) contains the conserved DXD motif and is possibly involved in catalysis and substrate binding. The C-terminal domain (domain B) contains the QXXRW motif and is present only in processive glycosyl transferases. It could be involved in the processivity function of the enzyme, possibly required for holding the growing glycan chain in the active site
The C-terminus is necessary for mitochondrial or peroxisomal targeting, while the N-terminus is necessary for mitochondrial or peroxisomal fission
The c-terminal part (253-337) is necessary and sufficient for the interaction with BRI1
The first four residues of target peptides with a free N-terminal Pro (a Pro/N-degron) are bound inside a deep and narrow beta-barrel structure
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 98 and 125
Each subunit has 12 transmembrane (TM) domains, arranged with an internal layer (TM1, TM3, TM6, TM8 and TM10) surrounded by the outer layer (TM2, TM4, TM5, TM7, TM9, TM11 and TM12). TM1 and TM6 are interrupted by short, non-helical, Gly-containing loops in the middle of their transmembrane spans. Homodimerization is mediated by TM3, TM10, TM11 and TM12. Each subunit has a central cavity which binds substrates (PubMed:19478139). Upon Arg-binding the N-terminus of TM6 and Trp-202 move to prevent Arg from return to the periplasm (PubMed:20090677)
The N-terminal zinc-finger domain but not the C-terminal one is required for rpa12 function
The pseudo DED region (pDED) mediates the interaction with HIP1
The cytoplasmic tail appears to be dispensable for TLR7-mediated signaling
The C-terminal region contains clusters of proline regularly alternating with a hydroxyamino acid. This domain might act as a spacer to elevate sites active in cell contact into the extracellular space
Is composed of three domains: an N-terminal TIM barrel (residues 1-368) which binds FMN, the 4Fe-4S cluster, and the substrate; a flavodoxin-like fold (residues 369-467 and 626-671) which binds FAD; and an NADP(H)-binding domain (residues 468-625)
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and disassembling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis (By similarity)
Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain. Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein
Exploits its two major loops and engages more positions in its interaction with V2R. The pharmacophore defined by numerous amino acids positioned in loop 1 (9 to 18) and loop 2 (34, 39 and 44) may be at the origin of the absolute selectivity of this protein for V2R
The Ig-like C2-type 1 domain may mediate homodimerization
The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes 'Lys-63'-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin (By similarity)
The OTU domain mediates the deubiquitinase activity
The presence of 'disulfide through disulfide knots' structurally defines this protein as a knottin. This toxin contains 2 'disulfide through disulfide knots' (By similarity)
Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein (PubMed:18356159)
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. This toxin contains 2 'disulfide through disulfide knots' that are separated by a short linker
The WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex
The F-box domain mediates interaction with SKP1
Isoforms A, C, D and E contain an additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties
Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions. Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively). The bromo domains also recognize and bind a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac)
Binds FRP via the C-terminal domain (residues 170-317) (PubMed:23716688). Upon RCP generation the carotenoid translocates 12 Angstroms into the N-terminal domain, altering its binding and photochemical properties (PubMed:26113721)
A 7-bladed beta-propeller torus, about 55 by 55 Angstroms, with a depth of about 25 Angstroms and a central pore
The ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
The C2 domains have an essential, but non-catalytic function. They may facilitate interaction with PstB2 and are required for lipid transport function
Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors (PubMed:14570920)
The three transmembrane domains are involved in pore formation by the cytotoxin
The C-terminal region is important in conferring inhibition
Contains FG repeats
The RanBP2-type zinc fingers mediate binding to RNA
The C-terminal WxxxxxRY motif is frequently found in terpene synthases and is important to guide product formation
The cysteine framework of the terepressin is C-C
Contains a C-terminal cysteine rich domain (c-CRD), but lacks the N-terminal CRD (n-CRD) found in its paralog YAP1. It probably also contains embedded in the c-CRD a nuclear export signal, with which the nuclear export protein CRM1/exportin 1 may interact in the absence of inter- or intramolecular disulfide bonds (or otherwise oxidized/modified cysteines) within the c-CRD
The DOCKER domain may mediate some GEF activity
Modular protein that contains a condensation/cyclization domain involved in the cyclization of the cysteine, an adenylation domain which activates the cysteine residue into an aminoacyl-AMP ester, a peptidyl carrier protein (PCP2) domain which bears a phosphopantetheinyl arm to attach the activated cysteine and a thioesterase domain (TE) that may release the newly synthesized peptide from the enzyme
The loss of the C-terminal domain partially abolishes the inhibitory function, but can be partially compensated by higher level of protein expression
The internal MTS-like signal (iMTS-L) mediates targeting to mitochondria thermogenic fat cells
Can mediate both protein-protein and protein-RNA interactions via the NTF2 domain and RNA-binding domain RRM; protein-protein and protein-RNA interactions are essential for undergoing liquid-liquid phase separation (LLPS)
The acidic disordered region acts as a negative regulator of phase separation
The NTF2 domain mediates interaction with CAPRIN1 and USP10 regulators, thereby regulating assembly of stress granules
The core of the protein consists of three WD40 beta-propeller domains
The N-terminal region (residues 1-69) is required for activity, unlike the B.subtilis ortholog where their removal increases c-di-AMP production
The J domain mediates interaction with HSPA8
Binding to misfolded proteins is mediated by a hydrophobic patch forming a large groove within the first two TPR repeats
The N-terminal BTB domain mediates protein oligomerization. The C-terminal glutamine-rich region is required for transcriptional activation activity
The phospho-regulated basic and hydrophobic (PRBH) motif is necessary and sufficient for interaction with phospholipids permitting cortical localization (PubMed:26481050). Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane (PubMed:26481050)
The DELLA motif is required for its GA-induced degradation but not for the interaction with GID2
Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic interaction with CDH23
Structurally similar to the bacterial FadR protein (fatty acid metabolism regulator protein)
Associates with PDIA3 through the tip of the extended arm formed by the P-domain
The PHD-type zinc finger mediates binding to H3K4me3
The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases
The C-terminal domain mediates homodimerization (By similarity). By mediating SBF2/MTMR13 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By similarity)
The GRAM domain mediates binding to phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3,4,5-trisphosphate
The PH domain binds preferentially phosphatidylinositol 3,4,5-trisphosphate (By similarity). Appears to be dispensable for localization to membranes (By similarity)
Contains an acidic N-terminal A domain, a central N domain and a C-terminal GTPase G domain that can bind and hydrolyze GTP. Contains at least two lipid-binding sites. The first site contains the first 14 amino acids (helix 1) and the second binding site is an amphipathic alpha-helix located at the interface between the A- and the N-domain (helix 2)
The pre-methyltransferase (preMT) region is responsible for mitochondrial localization
The motif interacting with ubiquitin (MIU) and ZUFSP ubiquitin-binding domain (zUBD, also called ZUFSP helical arm ZHA) are responsible for binding the distal (outgoing) ubiquitin units S1 and S2 respectively
C2H2-type zinc finger 4 is a ubiquitin-binding zinc finger (UBZ) and required for polyubiquitin binding, possibly binding the proximal ubiqutin, and for catalytic activity. C2H2-type zinc fingers 1-3 are required for localization to sites of DNA damage
The autoinhibitory region (AIR) inhibits the activity of the kinase domain
At its N-terminus, contains L-isoaspartate and S-adenosylmethionine (AdoMet) binding motifs. Also contains an extended SOCS box motif, where the Cul-box is separated from the BC-box by ~90 residues, within its C-terminus
CARD is critical for both extrinsic and intrinsic apoptotic pathways (PubMed:15383280). CARD domain mediates a protective effect against myocardial ischemia/reperfusion, oxidative stress and TNF-induced necrosis (By similarity). The C-terminal domain (amino acids 99 to 221) is involved in calcium binding and plays a protective role in calcium-mediated cell death (By similarity)
The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating (PubMed:23975098). Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure
The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides (PubMed:19671703). Instead, residues from the C-terminal domain (the so-called intrinsic ligand) bind in the cavity that would be expected to bind cyclic nucleotides. Interaction with the C-terminal region hinders interaction with CALM and reduces the affinity for CALM
Binds RNA through its KH domains
The LysM domain is not required for resuscitation activity in vitro; in its absence the protein is active in the fM range
Each subunit comprises two distinct structural domains: the catalytic domain (residues 1-150 and 288-340/345) and the nucleotide-binding domain (residues 151-287)
The fourth coiled coil region is involved in Golgi targeting and in the interaction with DCTN2
The PQA region (for proline, glutamine and alanine-rich) helps stabilize SOX9 and facilitates transactivation. It lacks intrinsic transactivation capability
The transmembrane plays critical roles in migration to the chloroplasts and/or subsequent insertion into the membrane
The Ig-like V-type domain 1 mediates interaction with CXADR (By similarity). The Ig-like V-type domain 2 may also play a role in the interaction (PubMed:15800062)
The C-ter region (residues 578-626) is not directly involved in DNA unwinding activity but functions by tethering cyt-19 to structured RNAs, so that it can efficiently disrupt exposed, non-native structural elements, allowing them to refold
The mature protein has 2 regions in the N-terminus capable of forming amyloid rods of slightly differing conformation; intact protein makes longer fibrils. Amyloid formation depends on polar residues between amino acids 45 and 70
Consists of three sections from the N- to the C-terminus: FAD-binding domain, capping domain and helical domain. The FAD-binding domain and the capping domain slightly overlap and form a channel that may transport the substrate
Subfamily II proteins have an EGMGR motif about 50 residues from the C-terminus (Probable). This motif lies near the metal-binding residues in the putative substrate-binding cleft 2 (Probable). Subfamily II proteins occur only in eukaryotes, in two forms: as a stand-alone unit in plants, and as a C-terminal domain of pantothenate kinases in plants, animals, and chytrid fungi (Probable)
Contains one Leu-Xaa-Xaa-Leu-Leu (LxxLL) motif that is essential for the association with nuclear receptors
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containingbinding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3)
In contrast to classical PTS systems, the fructose-like PTS has no requirement for HPr and Enzyme I; PtsA combines a IIA domain with an Enzyme I and a HPr domains
Has 3 domains, the N-terminal alpha-helical domain, an extended flexible linker and the C-terminal beta-sheet domain. The 2 C-terminal beta-sheet domains are swapped and pack against each other to form the dimer interface
The C-terminal extension has little effect on the function of API
The RUN domain and the FYVE-type zinc finger are essential for its function in the positive regulation of macroautophagy
Has 4 domains; N-terminal, PAZ, Mid and PIWI. The N-terminal and PAZ domain are joined by linker 1, the PAZ and Mid domain are joined by linker 2. The domains assemble in 2 lobes; the PAZ lobe consists of the N-terminal, L1, PAZ and L2 domains, while the PIWI lobe has the Mid and PIWI domains. The PIWI box is exposed on the surface of the protein. The PIWI domain assumes an RNase H fold and has the catalytic residues (PubMed:16061186, PubMed:17027504, PubMed:17130125). The N-terminal and PAZ domains are relatively mobile and move further apart when in complex with RNA (PubMed:17027504, PubMed:17130125)
The loss of the C-terminal domain partially abolishes the inhibitory function
The Sumo interaction motif mediates Sumo binding, and is required both for sumoylation and binding to sumoylated targets
Contains two helicase domains. The N-terminal helicase domain has catalytic activity by itself, contrary to C-terminal helicase domain that may have a regulatory role and enhance the activity of the first helicase domain
The N-terminal region functions as an arginine-rich RNA-binding motif (ARM)
The fibrinogen C-terminal domain mediates calcium-dependent binding to carbohydrates and tethering to the cell surface in monocytes and granulocytes. The domain undergoes a conformational switch at pH under 6.2, and looses its carbohydrate-binding ability
Activates the Arp2/3 complex and binds actin through the C-terminal VCA (verprolin homology/cofilin homology/acidic) domain consisting of a WH2 domain followed by an Arp2/3-binding acidic motif (A), separated by a conserved linker region (C). Binds BRK1 through the N-terminal Scar homology domain (SHD)
The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA. It is necessary and sufficient to mediate the localization into centromeres
Both the JmjC domain and the JmjN domain are required for enzymatic activity (By similarity). However ARID and PHD-type 1 domain are not required for activity per se but contributed to recognition of the H3(1-21)K4me2 substrate peptide (By similarity)
The D-box motifs play a key role in RNF157 stabilization (PubMed:28655764)
The function of the Tudor-knot domain, also named chromodomain-like, is uncertain (PubMed:22247551, PubMed:29408527). One study suggests that it mediates binding to lysine-methylated histone tails, with strongest affinity for H4K20me3 and H3K36me3 (PubMed:22247551). However, another study failed to find any interaction between this domain and histone H4K20me3 peptide (PubMed:29408527)
The peroxisomal targeting signal allows recruitment to the peroxisomal membrane by pex19
There are 3 rolling circle replication (RCR) motifs. RCR-2 may be involved in metal coordination. RCR-3 is required for phosphodiester bond cleavage for initiation of RCR
Contains an N-terminal nucleotide-binding domain and a C-terminal substrate-binding alpha/beta domain
The C-terminal SPRY domain is required for the transcriptional suppressor activity, probably by mediating correct nuclear localization. Residues 491-494 are essential for nuclear localization and nuclear bodies formation
The RING domain is essential for antiviral activity and for TRIM22 nuclear bodies (NB) formation but is not necessary for nuclear localization
Regions 91-102 and 109-130 are immunodominant T-cell epitopes. Mutations in the C-terminus (135-145) reduce allergenic activity but do not change the ability to stimulate allergen-specific T-cells
Contains a tandem repeat of a PAM2-like motif, which seems to be involved in the binding to the PABC/CTC domain of PAB proteins
The presence of two CXXXC motifs with connectivity I-IV, II-III structurally identifies this peptide as an alpha-hairpinin
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (Probable)
The 55 kDa regulatory domain is involved in regulating binding of SPTB/spectrin (beta chain) and SLC4A1/erythrocyte membrane protein band 3
The ANK repeat region forms a spiral around a large central cavity and is involved in binding of ion transporters. Adopts a T-shaped arrangement, in the ankyrin-1 complex, in which ANK 1-5 repeats are orthogonal to ANK 6-24 repeats, with the peptide binding groove of ANK 1-5 repeats oriented toward the membrane (PubMed:35835865). The rearrangement of the ANK 1-5 repeats orients the canonical protein binding groove to directly face the membrane, to interact the membrane-embedded targets RHCE and AQP1 (PubMed:35835865)
The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin's function other than binding to spectrin (By similarity)
The bHLH domain mediates transcriptional repression by inhibiting TCF3 transcriptional activity through heterodimerization
The UBA-like domain has no influence on ubiquitin hydrolysis
Specificity is given by the S1' ubiquitin-binding site within the OTU domain composed of the Cys-, His- and Variable-loops
The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response
Contains at least 2 actin-binding sites per coiled-coil dimer
The SET domain specifically recognizes and binds actin, suggesting that it does not accommodate substrates diverging from actin
The WRPW motif is required for binding to tle/groucho proteins
The MBD (methyl-CpG-binding) domain, also named TAM domain, specifically recognizes and binds a conserved stem-loop structure the association within pRNA
The legume-lectin like region mediates RGD motif recognition
The N-terminal DNA-binding helix-turn-helix (HTH) domain and the C-terminal membrane-binding amphipathic helix (AH) are both required for the function in chromosome segregation and for its proper subcellular location
The D-box (destruction box) mediate the interaction with APC proteins, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway
The PEST region is essential for the interaction with ITPR1, and, when phosphorylated, is also the RRM1-binding region. The PDZ-binding region is required for maximal interaction with ITPR1 and is also responsible for the IP3-insensitive interaction with ITPR1 (By similarity)
The coiled-coil is necessary for the cytoplasmic localization
The RING-type zinc finger is necessary for ubiquitination and for the IRF3-driven interferon beta promoter activity. Interacts with SKP2 and CUL1 in a RING finger-independent manner. The RING-type zinc finger is necessary for ubiquitination of NMI
The B30.2/SPRY domain is necessary for the cytoplasmic localization, the interaction with IRF3 and for the IRF3-driven interferon beta promoter activity. The B30.2/SPRY domain is necessary for the interaction with NMI
C-terminal helices from the four subunits associate to form atypical coiled coil structure; this region is probably involved in binding the inositol polyphosphates that are required for optimal channel activity (in vitro)
The ANK repeat domain consists of a convex stem structure formed by five ANK repeats and 11 additional ANK repeats that form a crescent-shaped structure that surrounds the protein core
The PUA and the SUI1 domains may be involved in RNA binding
The first protein kinase domain is predicted to be catalytically inactive
The C-terminal region is required for APC inhibition
The N-terminal non zinc-finger region mediates the repressor activity
The C-terminus of LRR N-terminal cap (LRRNT) and LRR 1 are essential for the inhibition of the Wnt signaling pathway
The protein kinase domain may be catalytically impaired due to the lack of the conserved Asp active site at position 485, which is replaced by a His residue
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and LC3A/B/C
The N-terminal regioninterferes with the interaction between AKT1 and the C-terminal regionof PKN2
The apoptotic C-terminal cleavage product inhibits EGF-induced kinase activity of AKT1 phosphorylation at 'Thr-308' and 'Ser-473' sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ phosphorylations
The two PARP-type zinc-fingers (also named Zn1 and Zn2) specifically recognize DNA strand breaks: PARP-type zinc-finger 1 binds PARP-type zinc-finger 2 from a separate parp1 molecule to form a dimeric module that specifically recognizes DNA strand breaks
The PADR1-type (also named Zn3) zinc-finger mediates an interdomain contact and is required for the ability of parp1 to regulate chromatin structure
The BRCT domain is able to bind intact DNA without activating the poly-ADP-ribosyltransferase activity. The BRCT domain mediates DNA intrastrand transfer (named 'monkey-bar mechanism') that allows rapid movements of parp1 through the nucleus
The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in parp1 that signal the recognition of a DNA break to the catalytic domain of parp1
Contains a N-terminal ordered domain (NOD) (1-117), central internal disordered domain (IDD) (118-349) and a C-terminal domain (CTD) (350-608) with an atypical Tudor domain containing probably two large unstructured loops
Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which may be required for an association with nuclear receptors
Contains an N-terminal Nudix hydrolase domain, followed by a linker region and a C-terminal histidine phosphatase domain. The C-terminal domain is necessary for efficient catalysis by the Nudix hydrolase domain
Essentially composed of an array of serine- and threonine-rich tandem repeats which is highly polymorphic, the variable number of tandem repeats (VNTR) region
A conserved histidine residue in the third TMD (His-115) may play an essential role in the pH sensitivity of SLCO1B3/OATP1B3-mediated substrate transport
The VOZ region includes a DNA-binding domain and a dimerization domain. Contains an atypical zinc-finger followed by a basic region structurally related to the NAC domain
The PH domain does not bind phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate. This lack of binding activity is due to Leu-591, compared to Arg found in other family members (By similarity)
The RanBP2-type zinc fingers, also called NZFs, mediate the interaction with ubiquitin and determine linkage specificity (PubMed:25752577). RanBP2-type zinc fingers 1 and 2 (also named NZF1 and NZF2) specifically recognize and bind 'Lys-29'- and 'Lys-33'-linked ubiquitin (PubMed:25752573, PubMed:25752577). RanBP2-type zinc finger 3 (also named NZF3) binds 'Lys-33'-linked ubiquitin and shows weak binding to 'Lys-6'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin chains but it does not interact with 'Lys-29'-linked chains (PubMed:25752573)
The UBZ4-type zinc finger specifically binds monoubiquitinated FANCD2
The KEN box and D-box are required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination
The PxP motifs mediate interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA)
The TQT motifs mediate interaction with the dynein light chain proteins DYNLL1 and DYNLL2, tethering AMBRA1 to the cytoskeleton in absence of autophagy
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP and MAP1LC3B
The elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]
The KASH domain is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains
The PB1 domain mediate mutually exclusive interactions with SQSTM1 and PARD6B
The MBT repeats mediate binding to histones tails; however, in contrast to other MBT repeats, does not bind specific histone lysine modifications. The MBT repeats lack the conserved Asp and aromatic cage at conserved positions (PubMed:23592795)
The mature protein has 4 domains; a metalloprotease domain (S1, approximately residues 111-786), S2 (877-882, equivalent to PKD), and 2 collagen-binding domains (CBD) S3a (997-1003) and S3b (1008-1118) (PubMed:9922257, PubMed:11121400). The S1 domain has collagen hydrolytic activity (PubMed:11121400, PubMed:18937627). The metalloprotease S1 domain is composed of 3 subdomains which together resemble a saddle; an activator domain (residues 119-388), the catalytic peptidase subdomain (398-670) and a helper subdomain (679-790) joined by a Gly-rich hinge (387-397) (PubMed:21947205, PubMed:23703618). The S2 domain (799-880, PKD) is flexible within a larger structure (S1 plus S2, residues 119-880) (PubMed:21947205, PubMed:21871007). Binding to Ca(2+) renders the midsection of S2 more flexible; Ca(2+) binding confers thermostability (PubMed:25760606). S3a and S3b each have collagen-binding activity; collagen is bound more efficiently when both S3a and S3b are present (PubMed:11121400). CBD S3a plus S3b binds to many types of collagen in vitro and in vivo (PubMed:11913772). The structure of CBD S3b becomes more compact and thermostable when it is bound to Ca(2+) and its N-terminal linker (approximately residues 1008-1020) changes from an extended alpha-helix to a beta-sheet anchored to the rest of the CBD (PubMed:12682007, PubMed:23144249). S3b may act as a Ca(2+)-activated molecular switch to trigger domain reorientation (PubMed:12682007). Isolated CBD S3b binds unidirectionally to the C-terminus of the collagen triple helix via a surface cleft (PubMed:19208618, PubMed:23144249). The S3b domain binds preferentially to undertwisted segions of collagen (PubMed:22898990)
The protein has two highly different native conformations, an inactive open conformation that cannot bind CDC20 and that predominates in cytosolic monomers, and an active closed conformation. The protein in the closed conformation preferentially dimerizes with another molecule in the open conformation, but can also form a dimer with a molecule in the closed conformation. Formation of a heterotetrameric core complex containing two molecules of MAD1L1 and of MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation and the conversion of the open to the closed form, and thereby promotes interaction with CDC20
The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub
The fourth SRCR domain plays an important role in optimizing the catalytic activity of the lysyl-oxidase like (LOX) catalytic domain
FsqF lacks the condensation domain that is essential for canonical peptide bond formation, and bioinformatic analysis of the vicinity of fsqF did not reveal any genes that could code for a second NRPS or free-standing condensation domain
The C-terminal sequences affect heptamer stability and proteasome affinity
The N-terminal proline-rich region interacts with the SH3 domain of PLCG1
The SH2 domain is important for restoration of BCR-induced calcium response and JNK2 activation in BLNK-deficient DT40 cells expressing LAT
The bHLH, as well as cooperation between the central Orange domain and the C-terminal WRPW motif, is required for transcriptional repressor activity
The protein kinase domain is catalytically inactive but contains an unusual pseudoactive site with an interaction between Lys-230 and Gln-356 residues (By similarity). Upon phosphorylation by RIPK3, undergoes an active conformation (By similarity)
The coiled coil region 2 is responsible for homotrimerization
The ATG16L1-binding motif mediates interaction with ATG16L1 and promotes autophagy
Contains an N-terminal domain with structural similarity to ARM repeat regions; this domain functions as scaffold for protein-protein interactions, but is not required for RNA binding or for ATP-dependent RNA helicase activity
The GTPase domain modulates a rate-limiting step in mitochondrial membrane fission
The conserved lumenal (CL) domain (84-162) is present only in some FtsH homologs from organisms performing oxygenic photosynthesis
The isolated adhesin domains have hemolytic activity (in vitro)
The leucine-zipper domain 1 is essential for its localization in the caveolae
Comprised of 3 domains; an N-terminal DNA-binding domain, a centrally located transcriptional activation domain and a C-terminal domain involved in transcriptional repression
The N-terminal domain binds zinc and is important for activity (PubMed:31863583)
KRAB domain 1, but not KRAB domain 2, is required for transcriptional repression. Both contribute to interaction with TRIM28. Differences in repressive activity between KRAB domain 1 and 2 are likely due to amino acid differences at multiple residues
The disordered region, when incubated at high concentration, is able to polymerize into labile, amyloid-like fibers and form cross-beta polymerization structures, probably driving the formation of hydrogels. In contrast to irreversible, pathogenic amyloids, the fibers polymerized from LC regions disassemble upon dilution. A number of evidence suggests that formation of cross-beta structures by LC regions mediate the formation of RNA granules, liquid-like droplets, and hydrogels
Contains a C-terminal catalytic domain, and an N-terminal region which modulates catalytic activity. Domains are connected by a linker of approximately 25 amino acids (PubMed:33187094). The structural disorder in the region homologous to the pentapeptide-binding site in E.coli may be related to the failure to bind pentapeptides (PubMed:33187094)
the N-terminal domain (1-84) is required for cadmium resistance
CARD is critical for both extrinsic and intrinsic apoptotic pathways (By similarity). CARD domain mediates a protective effect against myocardial ischemia/reperfusion, oxidative stress and TNF-induced necrosis (PubMed:15004034). The C-terminal domain (amino acids 99 to 208) is involved in calcium binding and plays a protective role in calcium-mediated cell death (PubMed:15509781)
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP hydrolysis
The coiled coil domain mediates the interaction with the N-terminal t-SNARE domain of SNAP25
The IQ motif, which is involved in calmodulin binding, overlaps with the binding domain for nuclear receptors and transcription factors. Its phosphorylation probably allows a switch between the two activities of the protein (By similarity)
The TPR repeat domain mediates recognition of protein substrates
EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity
The RRM domain mediates interaction with EIF3J
The RanBP2-type zinc fingers mediate the specific interaction with 'Lys-63'-linked ubiquitin
The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment
Contains an N-terminal RNP-like domain, a C-terminal element with a KOW sequence motif and a species-specific immunoglobulin-like fold
The PWWP domain is a H3 reader and strongly binds DNA
In the dehydrogenase domain, the conserved NAD(P)H-binding sites and sequence similarity to plant dehydrogenases suggest that this protein may have oxidoreductase activity. However, since the active site is not conserved, the dehydrogenase domain seems to serve as a catalytically inert oligomerization module
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tin-13/tim-13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The C-terminus (targeting peptide) is probably responsible for targeting to the encapsulin nanocompartment; it is separated from the rest of the protein by a flexible 37-residue linker
The architecture of swnK is the following one: adenylation (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain, and thioester reductase (TE) domains (PubMed:28381497). The presence and positions in swnK of the 2 reductase domains, ketoeductase and thioester reductase, suggests that the intermediate released from this enzyme has a hydroxyl group (PubMed:28381497)
Segments of the N- and C-terminal domains (residues 24-41 and 508-525, respectively) are predicted to be amphipathic helices and are essential for endoplasmic reticulum and lipid dropplet association (PubMed:25093817)
The cytoplasmic region is involved in protein stability
2 residues (Tyr-67 and Arg-70) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The PTS EIIA type-1 domain may serve a regulatory function, through its phosphorylation activity
The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate
The alpha 1 and alpha 2 helices (residues 58-108) are required for the localization the plasma membrane
The periplasmic portion confers toxicity; dimerization is not required for toxicity
Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity
WG/GW repeats are involved in AGO4 binding
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of timm10b from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane
The NHL repeats form six-bladed beta-propeller that mediate the interaction with the pumilio repeats of pum, and are essential for translational effector function
The Asp-Xaa-Asp-Asp (DXDD) and Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motifs are important for the catalytic activities, presumably through binding to Mg(2+)
N-terminal WD region interacts with TIP and C-terminal region mediates lysosomal localization (Probable). The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46
The N-terminal CBM15 domain binds xylan, including decorated xylans and xylooligosaccharides, but the physiological role of this domain is unclear. It may act as a product capture system: large xylooligosaccharides generated by Xyn10C would bind to CBM15 and this would restrict the diffusion of these polymers into the environment and therefore increase the selective utilization of these molecules by C.japonicus. Xylanase activity resides in the C-terminal domain
The N-terminus (11-116) contains a fully active minimal DNA-binding domain
The N-terminal part contains the methyltransferase and kinase domains that are essential for chain termination and polymer export. The C-terminal region is required for targeting both WbdD and WbdA to the inner membrane
The UBP-type zinc finger has lost its ability to bind ubiquitin and usp13 is not activated by unanchored ubiquitin
The UBA domains mediate binding to ubiquitin
Has 4 domains; the Pyr domain which binds the pyrimidine moiety of the thiamine pyrophosphate cofactor, the FAD-binding domain, the PP-binding domain which binds the pyrophosphate portion of thiamine pyrophosphate and the C-terminal membrane binding region, which includes the in vitro-derived alpha-peptide (residues 550-572). The C-terminus is held closely against the rest of the protein and covers the active site; during activation it detaches from the rest of the protein and folds into an amphipathic helix upon membrane binding. Comparison of full-length and proteolyzed structures shows activation is a result of conformational changes that expose the active site
The cytoplasmic domain is required for correct mitotic spindle orientation and internalization of sdn-1
the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors
The LIR motif is required for the interaction with ATG8 and for the association of ATG1 with autophagosomes (By similarity)
The C-terminal region of ATG1 responsible for ATG13-binding comprises six alpha-helices which fold into two antiparallel three-helix bundles resembling each other (PubMed:24793651)
The putative Groucho interaction domain between the N-terminal CTNNB1 binding domain and the HMG-box is necessary for repression of the transactivation mediated by TCF7L1 and CTNNB1
The DAD domain regulates activation via an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity)
The regulatory domain (RS) also called auto-inhibitory domain (AID) inhibits kinase activity of the protein kinase domain (KD) (By similarity)
The ubiquitin-associated domain (UBA) localized within the AID dampens kinase activation, probably by restraining alpha-gamma associations (By similarity)
The C-terminal domain (159-213) is required for the ability to respond to pH and calcium variations
The N-terminus region encompasses a short hydrophobic sequence bound to the sarcoplasmic reticulum membrane, whereas the C-terminus catalytic domain faces the myoplasm
The second C2 domain/C2B domain binds phospholipids regardless of whether calcium is present
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA (PubMed:28319136), and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. Also mediates interaction with the RNA polymerase subunits RpoB and RpoC (By similarity)
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA (PubMed:28319136). The domain also mediates interaction with the RNA polymerase subunit RpoA (By similarity)
The Tudor-like region mediates binding to histone H4 dimethylated at 'Lys-20' (H4K20me2) (PubMed:17190600). Interaction with NUDT16L1/TIRR masks the Tudor-like domain and prevents recruitment to chromatin (PubMed:28241136)
The UDR (ubiquitin-dependent recruitment) motif specifically recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15ub) (PubMed:23760478, PubMed:24703952). Phosphorylation of the UDR blocks interaction with H2AK15ub (PubMed:24703952)
The C-terminal WRPW motif is a transcriptional repression motif which is necessary for interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins
The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity
The N-terminal domain comprising the first 217 amino acid residues is mostly unstructured
The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2
The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis
The 2 cysteine and histidine-rich (CHORD) domains bind each 2 zinc ions, and the plant-specific 20 amino acid cysteine and histidine-containing motif (CCCH motif), located between the two CHORDs, binds 1 zinc ion
The BAR domain is necessary and sufficient for mediating homotypic and heterotypic interactions; associates with cytoplasmic membrane structures; mediates interaction with TBC1D1 and ADIPOR1 (PubMed:18034774) (By similarity). The PH and PID domains mediate phosphoinositide binding (PubMed:18034774). The PID domain mediates phosphatidylserine binding and allows localization to cytosolic membrane structures and nucleus (PubMed:18034774). The PH domain allows localization to the plasma membrane, cytosolic vesicles and distinct nuclear and perinuclear structures and is sufficient for RUVBL2 interaction (PubMed:18034774, PubMed:19433865)
The MYO6-binding domain is required for autophagy-mediated degradation of infecting bacteria such as Salmonella typhimurium, but not for bacteria targeting to autophagosomes
The LGALS8-binding domain is essential for the recruitment to cytosol-exposed infecting bacteria
The CLIR (LC3C-interacting region) motif is required for interaction with MAP1LC3C, but dispensable for CALCOCO2-mediated autophagosome maturation
The LIR-like motif is required for interaction with MAP1LC3A, MAP1LC3B and GABARAPL2, as well as for CALCOCO2-mediated autophagosome maturation
Histone binding is mediated by the concave surface of the LRR region
The EGFR-binding region prevents binding of a cyclin-like activator to the EGFR kinase domain, and thereby keeps EGFR in an inactive conformation. Also maintains EGFR in an inactive conformation by preventing formation of an asymmetric homodimer (By similarity)
Each monomer is composed of a small N-terminal alpha-helical domain and two larger core domains that have nearly identical tertiary structures and are related by approximate two-fold symmetry, but lack homology
Contains two adenine nucleotides bound at the active site. One ATP molecule is involved in catalysis, the second adenine nucleotide functions as a selective anchor for the C- and N-terminus of the Lys substrate and is responsible for protein stability
The fibrinogen-like domain (FBG) contains calcium-binding sites that may be involved in carbohydrate binding
Each ALS protein has a similar three-domain structure, including a N-ter domain of 433-436 amino acids that is 55-90 percent identical across the family and which mediates adherence to various materials; a central domain of variable numbers of tandemly repeated copies of a 36 amino acid motif; and a C-ter domain that is relatively variable in length and sequence across the family
The C-terminal (1107-1447) part mediates the histone acetyltransferase (HAT) activity
Contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (CMeT) domain responsible for the incorporation of methyl groups; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The F-box domain (1-55) is required for activity of the protein and for the interaction with SKP1A/ASK1
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a acyl carrier protein (ACP) domain, a methyltransferase domain and a reductive NADPH-binding domain that is required for NADPH-dependent product release (PubMed:25015739)
The calcium-binding site is structurally similar to that of EF-hand proteins, but is in two parts, with the last calcium ligand provided by Glu-228
The N-terminal domain mediates intranuclear attachment to the nuclear pore complex. The C-terminal domain mediates its nuclear import (By similarity)
The homeobox domain is required for the induction of distal tip cell fate
The MRH (mannose 6-phosphate receptor homology) domain is required for the ERAD-L activity
The N-terminal domain contains the alpha-glucan binding site, the central domain the pyrophosphate/phosphate carrier histidine, and the C-terminal domain the ATP binding site
Composed of an N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule) and a central to C-terminal alpha-helical coiled coil domain that mediates the heavy chain dimerization
The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are probably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (By similarity)
The PH domain binds phosphoinositides
May be secreted as a 4 coiled-coil complex with EsxB (PubMed:16048998)
The N-terminal half of the protein contains the conserved domain II which is required for the correct degradation of the protein through the SCF-mediated ubiquitin-proteasome pathway. Interactions between Aux/IAA proteins and auxin response factors (ARFs) occur through their C-terminal dimerization domains III and IV
The B/A element (residues 122-124) is present in cca2 but not cca1 and is thought to position tRNA-NCC for terminal A addition
The absence of a C-terminal alpha-helix in cca2 as compared to cca1 might allow for binding of the tRNA-NCC substrate, or prevents binding of the tRNA-N or tRNA-NC substrates
The ERhxxExxxhh motif (residues 234-244) has been suggested to serve to distinguish between A-adding and CC-adding proteins as A-adding enzymes have a small amino acid in the first position while CC-adding enzymes have an E in the first position
Consists of nine domains. Domain 1 contains two EF-hand calcium-binding domains. Domains 2-4, 6, and 8 are almost entirely alpha-helical, configured as a series of peptide repeats of varying regularity, and are thought to form a single-stranded alpha-helical rod stabilized by ionic interactions. Domain 6 is the most regular and may bind KIF directly by ionic interactions. Domains 5 and 7 are less well organized and may induce folds in the molecule. Domain 9 contains the C-terminus, conserved among different species
The ANK repeat region forms a spiral around a large central cavity and is involved in binding of ion transporters. Adopts a T-shaped arrangement, in the ankyrin-1 complex, in which ANK 1-5 repeats are orthogonal to ANK 6-24 repeats, with the peptide binding groove of ANK 1-5 repeats oriented toward the membrane. The rearrangement of the ANK 1-5 repeats orients the canonical protein binding groove to directly face the membrane, to interact the membrane-embedded targets RHCE and AQP1
The molecule consist primarily of eight antiparallel beta-pleated strands, which enclose a hydrophobic pocket, and an alpha-helix
The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are required for PEX5 retrotranslocation and recycling. AH2 mediates interaction with lumenal side of the PEX2-PEX10-PEX12 ligase complex, while AH1 is required for extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex
The ligand binding pocket consists mainly of extracellular loops ECL2 and ECL3, as well as transmembrane regions TM6 and TM7
The RGD RLK-binding motif is required for binding to host legume-type lectin receptor kinases and disruption of the attachments between the host plasma membrane and cell wall
The conserved W motif is found in already well characterized effectors and is essential for triggering RGA2/Rpi-blb1-mediated cell death
The highly acidic C-terminal region may bind cations such as calcium
Binds three calcium ions (via EF-hands 2, 3 and 4) when calcium levels are high (PubMed:17997965). Binds Mg(2+) when calcium levels are low
The C-terminal 22 AA is required and sufficient for localization to telomeres at the nuclear envelope
The DACHbox-N domain forms a structure containing a DNA binding motif similar to that of the forkhead/winged helix domain
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP4, the motif is inactive
The N-terminal PBS-linker domain (residues 19-157 in this experiment) interacts with the C-phycocyanin beta subunit (cpcB)
The N-terminal domain alone (residues 1-287) is sufficient to bind both tetrahydrofolate and dihydropteroate with the same affinity as the intact enzyme, but is not able to bind ATP and has no enzymatic activity
The C2 domain does not bind calcium ions, and does not bind phosphoinositides
The PAS (PER-ARNT-SIM) domains are required for the binding of FMN chromophores
Contains one SPKK motif which may interact with the minor groove of A/T-rich DNA sites. Phosphorylation of this motif may regulate DNA binding. This motif is reiterated in both termini of histone H1 and in the N-terminus of sea urchin histones H2B, but its presence in the C-terminus seems to be unique to plant H2A
The mature peptide (62-81) probably forms alpha-helices which disrupt target cell membranes
The F-box is necessary for the interaction with SKP1
The repetitive domain may provide a calcite binding matrix
Has an N-terminal beta-trefoil domain and a C-terminal pore-forming domain. The trefoil domain has barrel and cap subdomains; the cap has 3 carbohydrate-binding modules while the barrel is involved in host cell receptor binding. At neutral pH the carbohydrate-binding modules are accessible on the toxin surface but the barrel subdomain is not (PubMed:27680699). The crystal is very stable at neutral pH, upon ingestion by larvae the crystals dissolve in the alkaline midgut. As the pH rises the 2 subunits compact, while deprotonation at up to 4 sites (including the N- and C-termini) increases the accessibility of the propeptides and moves subdomains. The combined pH-induced changes are thought to expose the previously hidden receptor-binding motif and lead to crystal dissolution (Probable)
2 residues (Tyr-57 and Arg-60) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The cysteine framework is I (CC-C-C). Alpha2/8 pattern
The chymotrypsin fold (25-276 and 574-722) is the catalytic domain and the alpha-helical domain (277-573) is the regulatory domain necessary for exopeptidase activity
TPR repeats 1-7 mediate homodimerization while TPR repeats 8 and 10-13 bind to hcn1, burying its N-terminal acetyl-methionine
The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2
The nucleolar localization signal (residues 29 to 38) is required for host nucleolar accumulation but not for the nuclear localization, nor for the augmented plant susceptibility to pathogens
Has 3 domains; the N-terminal domain has 4 short repeats and binds RuBisCO. The central region has 6 longer repeats. The C-terminal domain has 2 repeats and a highly conserved C-terminal peptide. The C-repeats serve as the encapsulation signal for the alpha-carboxysome, and are able to target foreign proteins to this organelle
Contains an outward-open, amphipathic cavity. Contains only two acidic residues along the transport path, Asp-46 and Glu-135, which can undergo cycles of protonation and deprotonation. Asp-46 and Glu-135 have an essential role, coupling proton translocation and substrate recognition (PubMed:20877283). Sugar binding probably induces a conformational change in which the outward-facing cavity closes, thereby bringing Trp-38 and Trp-278 into close proximity around the bound sugar to form an occluded intermediate (PubMed:22930818)
The SH2 domain mediates interaction with tyrosine-phosphorylated proteins (PubMed:10896938, PubMed:22801373). However, not involved in the binding to phosphorylated BCAR1 (PubMed:10896938). Required for cell cycle progression in response to INS/insulin (By similarity). Required for regulation of EGF-induced DNA synthesis (By similarity)
The N-terminal catalytic domain contributes to tetramerization and the C-terminal domain provides additional dimerization. Both domains are required for full catalytic activity. The C-terminal domain may play a role in stabilizing the active conformation
The orange domain and the basic helix-loop-helix motif mediate repression of specific transcriptional activators, such as basic helix-loop-helix protein dimers
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho, a transcriptional corepressor recruited to specific target DNA by Hairy-related proteins
The coiled-coil domain mediates oligomerization
Adopts a GT-A fold and acts as an inverting enzyme that converts the alpha-configuration in the UDP-N-acetyl-alpha-D-glucosamine donor to the beta configuration in the N-linked (GlcNAc) arginine product
The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding. The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides
Each monomer has two 4-stranded beta sheets and the shape of a prolate ellipsoid. Antiparallel beta-sheet interactions link monomers into dimers. A short loop from each monomer forms the main dimer-dimer interaction. These two pairs of loops separate the opposed, convex beta-sheets of the dimers to form an internal channel
Adopts the three-dimensional structure 'proline-hinged asymmetric beta-hairpin-like' (PHAB) fold
The prepropeptide contains 10 domains separated by dibasic cleavage sites: a signal peptide, three cysteine-containing propeptide domains (CysPro), three cysteine-free propeptide domains (LinearPro) and three Kappa-actitoxin-Ate1a (PHAB) domains. The sequence 'CysPro-LinearPro-PHAB' is repeated three times
The SH3 domain mediates binding to HIV-1 Nef
The N-terminal zinc-finger domains are required for the appropriate production of 28S rRNA and the formation of pre-60S particles
The stress-sensor region regulates proteolysis and activation
The third KH domain (KH3) recognizes specifically 5'-YCAY-3'
The SH3 domain mediates interaction with NOS3, DNM2 and WASL
The F-BAR domain is necessary for membrane targeting
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Leu residues, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins
The PDZ-binding motif interacts with PDZ-domain of scaffolding protein DLG4
The GRID (GABA(A)R-interacting domain) is critical for its subcellular localization and interaction with GABA(A)R
Homodimerization involved an interaction between amino and carboxy termini involving LXXLL motifs and steroid binding domain (AF-2 motif). Heterodimerizes with NR5A1 and NROB2 through its N-terminal LXXLL motifs (By similarity)
Displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9
The RAP domain is essential to regulate MT-ND3 mRNA levels
The acetyltransferase domain is necessary for activation of both class I and class II transcription
The GTP-binding motif doesn't confer GTPase activity but promotes nuclear localization
The central alpha-helical coiled-coil IF rod domain mediates elementary homodimerization
The entire WD repeat region is required for the interaction with ORC, CDT1 and GMNN, as well as for association with chromatin and for binding to histone H3 and H4 trimethylation marks H3K9me3 and H4K20me3
Ubiquitin ligase activity is mediated by two distinct domains, PHD-type zinc fingers 2 and 3. The use of these distinct domains may allow ubiquitination of different targets by each domain. The HECT domain is catalytically inactive and does not contribute to this activity
Region 2 (296-437) and region 5 (645-966) are involved in the acquisition of C4-specific properties. Region 5 (645-966) is involved in L-malate tolerance
The alpha-K amphipathic helix mediates targeting to the phagosome membrane via binding to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3)
The N-terminal sensor region consists of closely linked GAF and PAS domains (PubMed:22115998). Binds c-di-GMP via the GAF domain (PubMed:33772870). Copper and NO are detected through a dicysteine motif in the GAF domain (PubMed:34003742)
The tyrosine-based internalization signal is proposed to function at the level of clathrin-mediated endocytosis and recycling
The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane
The WXG motif and the C-terminal tail are crucial for secretion
Consists of an N-terminal domain, followed by a linker domain, and a C-terminal domain, which forms the translocation motor involved in chromosome segregation. The C-terminal domain can be further subdivided into alpha, beta and gamma subdomains. Specific interactions between the gamma subdomain and specific SpoIIIE recognition sequences (SRS) regulate the compartment-specific activation of a mother-cell SpoIIIE complex. Interactions with nonpermissive SRS in the forespore lead to inactivation of the complex
The bifunctional copalyl diphosphate synthase is composed of an N-terminal type II terpene cyclase (TC) catalytic domain and a C-terminal prenyltransferase (PT) catalytic domain which are separated by a linker region
The conserved DXDD and DDXXD motifs are important for the catalytic activity, presumably through binding to Mg(2+)
The transmembrane domain is essential for membrane insertion, phospholipid scramblase activity and proper calcium-binding
The activation loop within the kinase domain is the target of phosphorylation
The NID domain 1 is involved in the negative regulation of p65/RELA transcription and the negative regulation of NF-kappa-B pathway activation
Contains two cysteine rich domains (CRD), referred to as the N- and C-terminal CRD's, n-CRD (Cys-259, Cys-278, Cys-285 and Cys-290) and c-CRD (Cys-501, Cys-523 and Cys-532), respectively. Cys-259 and Cys-290 are not conserved in orthologs in other yeast species. A nuclear export signal is embedded in the c-CRD, with which the nuclear export protein crm1/exportin 1 interacts only in the absence of disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or between the c-CRD and the n-CRD
The six transmembrane regions are tightly packed within each subunit without undergoing domain swapping. Transmembranes TM1-TM3 are positioned on the inner circle of the channel tetramer and participate in inter-subunit interactions that are central to the assembly of the ion conduction pore. The RxxxFSD motif within transmembrane TM1 coordinates a network of specific inter- and intra-subunit interactions with other conserved residues on TM2 and TM3 and plays a key role in the tetrameric assembly of the channel. Transmembrane TM4-TM6 are positioned on the periphery of the channel and do not contribute to contacts with neighboring subunits. Transmembranes TM1 and TM2 are linked by an extended strand-like tail and two short helices (H1 and H2) which protrude outwards from the main body of the transmembrane domain and enclose the external open entrance of the ion conduction pore in the channel tetramer. Transmembrane TM1 forms the pore-lining inner helix at the center of the channel, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three hydrophobic residues on the C-terminal half of the TM1 helix form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Ile-16 is probably responsible for channel selectivity
Binds DNA via its N-terminal domain and the inducer molecule via the C-terminal domain
Both MBD and PWWP domains are necessary for chromocentric localization
The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (PubMed:11007484). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (PubMed:9635436)
The interaction with MYO5B is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades
The PH domain most probably contributes to the phosphoinositide-dependent regulation of ADP ribosylation factors
The LIR motif (LC3-interacting region) is required for the interaction with ATG8 family proteins. Required for proteolytic activation and delipidation of ATG8 proteins
Both the catalytic N-terminal domain and the extensional C-terminal domain play key roles in tRNA binding and methylation
The IMD domain forms a coiled coil. The isolated domain can induce actin bundling and filopodia formation. In the absence of G-proteins intramolecular interaction between the IMD and the SH3 domain gives rise to an auto-inhibited state of the protein. Interaction of the IMD with RAC1 or CDC42 leads to activation (By similarity)
The SH3 domain interacts with ATN1, ADGRB1, WASF1, WASF2, SHANK1, DIAPH1 and ENAH
The TIR domain mediates NAD(+) hydrolase (NADase) activity. The N-terminal region is required for localization to the host cell membrane
The Rab-GAP TBC domain is essential for phosphoinositide binding
The EF-hands may also bind magnesium ions in the presence of high Mg(2+) levels and low Ca(2+) levels
The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization
The PH domain binds to phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) resulting in its targeting to the plasma membrane
Contains two SDR domains
The second EGF domain mediates the interaction with the putative ligand
The EGFR-binding region prevents binding of a cyclin-like activator to the EGFR kinase domain, and thereby keeps EGFR in an inactive conformation. Also maintains EGFR in an inactive conformation by preventing formation of an asymmetric homodimer
The SAM domain is essential for function
Contains 1 atypical KH domain
The VASt domain bind sterols
The N-terminal extension helix acts as an autoinhibitory domain, preventing ATP hydrolysis, unless the N-terminus of the protein is displaced by RNA binding, allowing cleft closure to bring key side chains into position for catalysis
The Ripply homology domain and the WRPW motif are both necessary for its transcriptional corepressor activity on the transcription activator tbx1
The B30.2/SPRY domain is required for the negative regulation of cell proliferation
The FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC
The jacalin-type lectin domain has strong affinity for high-mannose glycans with terminal non-reducing ends of Man(alpha-1,2)Man or Man(alpha-1,3)Man
Has 2 Rossmann-like domains, called R-fold-1 and R-fold-2. R-fold-1 is interrupted by an extended beta-sheet domain that loops out of the structure. UDP and N-acetyl-D-glucosamine bind between the Rossman-like folds, which move closer together upon binding
When the BTB domain is lacking, AHR signaling induction promoted by IVNS1ABP is massively increased; Thus, the BTB domain inhibits AHR signaling induced by IVNS1ABP
The BAR domain mediates dimerization and interaction with membranes enriched in phosphatidylinositides
In contrast to other proteins of the family, the C-terminus is shorter and lacks the leucine-zipper
The CUE domain binds ubiquitin, which may facilitate intramolecular monoubiquitination
The PDZ-binding motif is involved in the interactions with PARD6A and PALS1
Contains a C-terminal ANTAR domain, which is a RNA binding domain
The two SXIP sequence motifs are important for targeting to the growing microtubule plus ends
Two TOG regions display structural characteristics similar to HEAT repeat domains and mediate interaction with microtubules
The N-terminal domain (1-374) is sufficient for the exchange factor activity
The N-terminal region and DSL domain may be involved in interacting with Notch receptors
The 3D structure excludes the ability of the enzyme to bind homoserine and acetyl-CoA, indicating that it cannot function as a homoserine acetyltransferase
The RRM domains mediate interaction with U snRNPs
The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs
The entire ARM repeats region mediates binding to CDH1/E-cadherin. The N-terminus and first three ARM repeats are sufficient for binding to DSG1. The N-terminus and first ARM repeat are sufficient for association with CTNNA1. DSC1 association requires both ends of the ARM repeat region (By similarity)
The C-terminal segment can alternate between an ordered and disordered state (PubMed:22976985). Ordering of the C-terminal helix shields a large positively charged patch on the protein surface, potentially used for interaction with other cellular components (PubMed:22976985)
Homophilic adhesion is primarily mediated by the interaction of the second Ig-like domains
Kinase-interacting sequence (KIS) is specific for the alpha catalytic subunit interaction and Association with SNF1 Complex (ASC) is specific for the gamma non-catalytic regulatory subunit interaction
Binds cholesterol in a cavity lined by the transmembrane spans
TSP type-1 domain 0 binds to TSP type-1 domain 4, and TSP type-1 domain 1 binds to TSP type-1 domain 6 (By similarity). These interactions mediate multimerization (By similarity)
Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import (By similarity)
Three regions of the protein are predicted to form a coiled-coil. It may adopt a rod-shaped rather than a globular configuration
Contains an N-terminal ATP-grasp domain, a specialized central substrate-binding domain for L-glutamine and a C-terminal phospho-histidine domain
The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2 (By similarity)
The transmembrane domains are indispensable for pollen tube guidance
The TPR repeats are required for proper localization into the axoneme and proper function in flagella beating and motility
The surface residues of the concave side of the superhelical ARM repeat region contribute to, but are not essential for NLS binding
The C2 domain 1 binds phospholipids in a calcium-independent manner and is not necessary for calcium-mediated translocation and association to the plasma membrane. The C2 domain 2 binds phospholipids in a calcium-dependent manner and is necessary for calcium-mediated translocation and association to the plasma membrane. The linker region contributes to the calcium-dependent translocation and association to the plasma membrane. The VWFA domain is necessary for association with intracellular clathrin-coated vesicles in a calcium-dependent manner
The DFDF domain is unstructured by itself. It assumes a helical fold upon interaction with DDX6 (By similarity)
The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion
Contains an N-terminal catalytic domain and two C-terminal tandem repeat sequences that play an important role in peptidoglycan binding
The 2 PHD-type zinc fingers are required for transcriptional activity
Consists of 2 domains; the N-terminus (residues 1-593) probably has the N-acyltransferase activity while the C-terminus (residues 594-874) has polyprenol monophosphomannose (PPM) synthase activity. The whole protein has higher PPM synthase than the second domain alone when expressed in M.smegmatis, suggesting the N-acyltransferase domain plays a stimulating role in PPM synthesis
GcoB has an unusual three-domain structure, with an N-terminal 2Fe-2S domain and a C-terminal region that consists of an FAD-binding domain followed by an NADH-binding domain
The SMB domain mediates interaction with SERPINE1/PAI1. The heparin-binding domain mediates interaction with insulin (By similarity)
The PDZ 1 domain mediates interaction with ANKS4B, USHBP1, USH1G, SLC4A7
The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity
The cytoplasmic region is required for GABA(A) receptor clustering
The extracellular region is required for the localization to synapses and for GABA(A) receptor clustering
The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage
The PXDLS motif binds to a cleft in CtBP proteins
EF-1 binds magnesium constitutively under physiological conditions, EF-3 and EF-4 bind calcium cooperatively and EF-2 binds neither calcium nor magnesium
The contact of the 5th EF-hand domain from each monomer allows the formation of the homodimer and also appears to mediate the contact between the large catalytic subunit and small regulatory subunit for the formation of the heterodimer
EF-hand domains are paired. EF-hand 1 is paired with EF-hand 2 and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand domain, left unpaired, does not bind the calcium but is responsible of the dimerization by EF-embrace. The first four EF-hand domains bind calcium, however it is not sure if the binding of EF-hand 4 to calcium is physiologically relevant
The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions
The WD repeats assemble into a seven-bladed WD propeller
The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase
The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3
The C-terminus is probably located inside the membrane
The MH2 domain mediates phosphorylation-dependent trimerization through L3 loop binding of phosphoserines in the adjacent subunit
The nonribosomal peptide synthase is composed of three domains. The adenylation (A) domain is responsible for the adenylation and activation of beta-alanine using ATP (PubMed:12900414, PubMed:25229196). The thiolation (T) or peptidyl carrier protein domain (PCP) contains the prosthetic group 4'-phosphopantetheine, which activated beta-alanyl-AMP is transferred to via thiolation (PubMed:12900414, PubMed:25229196). The condensation (C) domain both performs the selection of the amine substrate, dopamine or histamine, and the condensation of these amines with beta-alanine via an amide bond (PubMed:12900414, PubMed:25229196, PubMed:30705105)
A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion
The C-terminal histidine triad (HIT) motif and the N-terminal domain are required for the decapping activity. The N-terminus is necessary but not sufficient for binding cap structures
The proline-rich domain (PRD) contains repeated PPP motifs. A single PPP motif is necessary and sufficient to mediate interaction with the COPII coat subunits SEC23A and SEC23B (PubMed:21807889). The coiled coil domains mediate interaction with MIA3. The first coiled coil domain mediates interaction with PREB (By similarity)
The jas domain (155-182) is required for interaction with COI1
Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side
The FFAT motif is required for interaction with SCS2 and proper localization of the protein
The interaction between PNRC1 and nuclear receptors is dependent on the SH3 binding motif
In response to a variety of growth factors, isoform p47Shc and isoform p52 bind to phosphorylated receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif. Isoform p47Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation
Has an elongated cradle shape
Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure (By similarity)
Contains a tandem atypical propeller in EMLs (TAPE) domain. The N-terminal beta-propeller is formed by canonical WD repeats; in contrast, the second beta-propeller contains one blade that is formed by discontinuous parts of the polypeptide chain (By similarity)
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins (PubMed:23201271, PubMed:19617556). The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities (PubMed:23201271). This domain is also involved in CAND1-, cullins- and RBX1-binding (PubMed:25349211, PubMed:26906416)
The N-terminus adopts a forkhead-associated (FHA) like fold
BRCT domain is characteristic of proteins involved in DNA damage signaling (By similarity). It is required for localization to chromatin which flanks sites of DNA damage marked by phosphorylation of hta1 and hta2
The YEATS domain specifically recognizes and binds acylated histones, with a preference for histones that are crotonylated
The N-terminal domain of the beta subunit mediates closure of delayed rectifier potassium channels by physically obstructing the pore
The N-terminal extension of FolP is essential for the reducing activity and binds FMN
The two SXIP sequence motifs mediate interaction with MAPRE1; this is necessary for targeting to the growing microtubule plus ends
Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 887. These domains are therefore predicted to be inactive
In the homohexamer the 2 domains (called CI and CII) self-associate to each form a 'donut' layer (PubMed:35507871, PubMed:26113641). The KaiC CI domain mediates interaction with KaiB, CikA and SasA (PubMed:22512339, PubMed:24112939, PubMed:28302851). ATP hydrolysis by the CI domain causes a conformational change that allows KaiB binding (PubMed:28302851). The 2 domains communicate to control ATPase activity (PubMed:35507871)
The Fibronectin repeats 5 and 6 mediate interaction with RGM family molecules
The PTS EIIB type-1 domain is phosphorylated by phospho-EIIA-Glc (EIII-Glc) on a cysteinyl residue. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the PTS EIIC type-1 domain
The EIIC domain type-1 forms the PTS system translocation channel and contains the specific substrate-binding site
The RS domain is required for the interaction with the phosphorylated C-terminal domain of RNA polymerase II
The first L27 domain binds DLG1 and the second L27 domain probably binds LIN7
The protein kinase domain mediates the interaction with FCHSD2
The cytoplasmic N-terminus preceding the first transmembrane (residues 1-22) regulates volume-regulated anion channel (VRAC) conductance, ion permeability and inactivation gating
The PDZ domain 3 mediates interaction with ADR1B
The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to postsynaptic density
Intramolecular interactions between the N-terminal moiety and the leucine-rich repeats (LRR) may be important for autoinhibition in the absence of activating signal
The LRR repeats recognize and bind muramyl dipeptide (MDP)
The NACHT domain recognizes and binds sphingosine-1-phosphate in response to endoplasmic reticulum stress
The PUB domain mediates interaction with the PIM motifs of VCP and RNF31, with a strong preference for RNF31
The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin
The UBA domain mediates association with RBCK1/HOIL1 via interaction with its UBL domain
RING 1 and IBR zinc-fingers catalyze the first step transfer of ubiquitin from the E2 onto RING 2, to transiently form a HECT-like covalent thioester intermediate
The linear ubiquitin chain determining domain (LDD) mediates the final transfer of ubiquitin from RING 2 onto the N-terminus of a target ubiquitin
Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds. The RRN7-type zinc finger plays an essential postrecruitment role in Pol I transcription at a step preceding synthesis of the first 40 nucleotides (PubMed:21921198, PubMed:21921199)
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The zinc finger domain binds AU-rich regions in the 3'-UTR of mRNAs
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a acyl carrier protein (ACP) domain, a methyltransferase domain and a reductive NADPH-binding domain that is required for NADPH-dependent product release
Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein
The Orange domain, downstream sequence and the bHLH are required for efficient heterodimerization with hes/hairy proteins, and for transcriptional repressor activity
The C-terminal YRPW motif is not required for transcriptional repressor activity and is unable to recruit groucho
The Tudor domain specifically recognizes and binds asymmetric dimethylation of histone H3 'Arg-17' (H3R17me2a) and histones H4 'Arg-3', 2 tags for epigenetic transcriptional activation
The LIR motif interacts with ATG8 family proteins and is necessary to target the ER fragments to autophagosomes for lysosomal degradation
The reticulon homology domain provides capacity to bend the membrane and promotes ER scission (By similarity). It is required for homooligomerization (By similarity). This domain does not show relevant similarities with reticulon domains, preventing any domain predictions within the protein sequence
The EF-hand 2 domain within the regulatory N-terminal domain binds one calcium in the mitochondrial intermembrane space. Calcium triggers the binding of the regulatory N-terminal domain to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain (By similarity). In the absence of calcium, the linker loop domain may close the vestibule and prevent substrates from entering the carrier domain (By similarity)
The PX domain binds to phosphatidylinositol 3-phosphate which is necessary for peripheral membrane localization to the punctate structures
The PH domain mediates AP-3 binding
Crystal structures show a large (N-terminal) and small (C-terminal) domain; the C-terminal domain is mobile and can block access to the active site
SAHS-c1, SAHS-c2 and SAHS-c3 are 3 highly conserved regions within the SAHS protein family (By similarity)
The N- and C-terminal halves of this hexokinase contain a hexokinase domain. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule
The Kunitz domains 1 and 2 serve as protease inhibitor domains
FAD-binding region regulates cry stability, cry-tim interaction, and circadian photosensitivity
Photolyase/cryptochrome alpha/beta domain is sufficient for light detection and phototransduction
Forms a well-packed pentamer with an overall cylindrical shape. The inner core of the pentamer is formed with the second transmembrane region and the second coiled-coil region (residues 293-316): while the transmembrane regions pack into a five-helix bundle having a largely polar pore across the membrane, the coiled-coil outside the membrane forms a pentamer with a hydrophobic core, which may contribute to stabilizing the transmembrane pore structure. The transmembrane pore is wrapped by the first transmembrane region through contacts between the first and the second transmembrane regions. The second transmembrane is followed by the inner juxtamembrane region (IJMH) that orients at a wide angle relative to the second transmembrane. The two core domains are held together on the periphery by the outer juxtamembrane helix (OJMH), which contains a kink around Glu-204 and interacts with the IJMH
The critical DXXE motif connecting the transmembrane regions forms a pentameric barrel that constitutes the mouth of the pore. Inside the barrel, both acidic residues are in position to form two carboxylate rings: the Asp-240 ring is solvent exposed, and the Glu-243 ring is located deeper, guarding the entrance of the second transmembrane pore. In absence of emre-1 regulator, the calcium ions cannot exit the channel, suggesting that emre-1-binding induces conformational rearrangements to allow calcium to exit
The five C-terminal amino acid residues are inserted into the active site cleft in the closed conformation, protect the aminoacrylate intermediate and are involved in sulfur donor selectivity
The 3 cNMP binding domains are required for localization to the endoplasmic reticulum (PubMed:28887301). The cNMP binding domain 3 is involved in the binding to lipid droplets (PubMed:28887301)
The A20-type zinc finger directly binds polyubiquitin chains and associates with the 26S proteasome. The zinc-finger A20-type domain is essential for inhibition of NF-kappa-B activation
Isoforms A, C, D and E contain and additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties
The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation
Forms a U-shaped beta-half-barrel with a small hydrophobic cavity which is large enough to hold a single diacylated glycolipid molecule
The SH3 domains mediate interaction with RALGPS1 and SHB
The FF domains preferentially binds peptides with the consensus sequence [DE](2-5)-[FWY]-[DE](2-5) and mediate interaction with HTATSF1 and probably bind the phosphorylated C-terminus of the largest subunit of RNA polymerase II
The WW domains bind Pro-rich domains
The tight homopentamer forms a pore with an opening of 4-5 Angstroms in diameter which opens into a wider tunnel at the base of the truncated pyramid. The pore is positively charged
Forms a beta-barrel structure that accommodates bilirubin in its interior
The alpha-1 domain is a structural part of antigen-binding cleft
The alpha-2 domain is a structural part of antigen-binding cleft
The C-terminus (residues 163-181) targets the protein to the encapsulin nanocompartment (PubMed:24855650). Interestingly the C-terminus is localized iside the ferritin cage, in theory it does not touch the interior of the nanocompartment (PubMed:34342280)
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Cys (NPA)
The ABC transporter 2 domain is necessary and sufficient for association to the 40S ribosome subunit
Contains an N-terminal AAA+ ATPase domain and a C-terminal winged-helix (WH) domain. Domains are separated by a rigid linker
The EGF-like domains 2 and 3 and part of the acidic domain interact with the galectin-like domain of MIC1. The presence of at least one of the EGF-like domains, EGF-like domain 2 or EGF-like domain 3, is required for targeting of MIC1 and MIC4 into the microneme
The C-terminal KXD/E motif functions as a Golgi retention signal, certainly through the binding to the COP1 coatomer
The ATP-binding site is essential for assembly of pili
The 66 residues C-terminal tail is not present in other species
The SMB domain mediates interaction with SERPINE1/PAI1
The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains
The regulatory domain (RS) also called auto-inhibitory domain (AID) inhibits kinase activity of the protein kinase domain (KD) (PubMed:19474788, PubMed:20823513). The AID is sequestered by SNF4 within the AMP-activated protein kinase complex which might correspond to the activated SNF1 form (PubMed:17851534)
The ubiquitin-associated domain (UBA) localized within the AID dampens kinase activation, probably by restraining SNF1-SNF4 associations (PubMed:25869125). Moreover, the UBA domain influences life span in a FKH1- and FKH2-dependent mechanism (PubMed:25869125)
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of smc6, forming a V-shaped heterodimer
The C-terminal conserved inhibitory domain (CCID) negatively regulates the transcriptional activity of the protein
14 cysteine residues are arranged in C-X-C groups. These are thought to be the metal-binding sites in other metallothioneins
The regulatory N-terminal domain/NTD, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity
Isoform VEGF-190 contains a basic insert which acts as a cell retention signal
EF-hand 2 and EF-hand 3 domains are the low-affinity and the high-affinity calcium binding sites, respectively. EF-hand 1 and EF-hand 4 domains do not bind calcium due to substitutions that disrupt their respective Ca(2+) binding loops. The cooperative binding of calcium to the EF-hand 2 domain following EF-hand 3 domain calcium binding requires myristoylation (By similarity). Calcium binding to the 2 EF-hand domains induces exposure of the myristoyl group through a protein conformation change, this process known as the calcium-myristoyl switch facilitates binding to photoreceptor cell membranes (By similarity)
It is uncertain whether the five sets of tandem repeats at the N terminus are required, or not, for maximal enhancement of carboxylase activity
The N-ter domain (residues 1-67) homodimerizes and interacts with H3-H4 independently of acetylation while the double pleckstrin-homology (PH) domain (residues 68-301) binds the 'Lys-56'-containing region of H3
The Cys-rich C-terminus (111-145) is essential for the interaction with WAK1
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit, a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone, a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA, a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone, an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm, a methyltransferase domain and a reductive NADPH-binding domain that is required for NADPH-dependent product release
The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9A-containing vesicles, thereby enabling growth into autophagosomes
Contains an N-terminal aldehyde dehydrogenase (ALDH) domain and a C-terminal iron-dependent alcohol dehydrogenase (ADH) domain, interconnected by a short linker (PubMed:31586059, PubMed:32188856). ALDH and ADH activities are topologically separated in the compact spirosome architecture (PubMed:31586059)
In contrast to classical PTS systems, the fructose-like PTS has no requirement for HPr and Enzyme I; FryA combines a IIA domain with an Enzyme I and a HPr domains
The COP1-binding motif (355-360) is required for regulation activity (PubMed:24003916)
The C-terminus (351-372) is required for interaction with COP1 (By similarity)
The protein kinase active site is incompatible with ATP binding and is inactive (By similarity)
The MPN (JAB/Mov34) domain has structural similarity with deubiquitinating enzymes, but lacks the residues that would bind the catalytic metal ion
Contains a region with structural similarity to reverse transcripase, presenting the classical thumb, fingers and palm architecture, but lacks enzyme activity, since the essential metal-binding residues are not conserved
Contains a region with structural similarity to type-2 restriction endonucleases, but the residues that would bind catalytic metal ions in endonucleases are instead involved in hydrogen bonds that stabilize the protein structure
Contains a region with structural similarity to RNase H, but lacks RNase H activity
The N-terminal C2 domain mediates the association with lipid membranes upon calcium binding (Probable). An additional second C2 domain may stand in between the C2 domain and the PLA2c domain (Probable)
Partially oxidized VKORC1 forms a cysteine adduct with substrates, vitamin K 2,3-epoxide, inducing a closed conformation, juxtaposing all cysteines (S-S or SH) for unimpeded electron transfer. VKOR becomes fully oxidized with an open conformation that releases reaction products, vitamin K quinone, or hydroquinone. Cys-132 and Cys-135 constitute the catalytic redox-active center. Cys-43 and Cys-51 are the cysteine pair that mediates transfer of reducing equivalents during catalysis
The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interaction with proteins that mediate endocytic trafficking and autophagy
The ball and chain domain mediates the inactivation of KCNMA1. It occludes the conduction pathway of KCNMA1 channels, and comprises the pore-blocking ball domain (residues 1-17) and the chain domain (residues 20-45) linking it to the transmembrane segment. The ball domain is made up of a flexible N-terminus anchored at a well ordered loop-helix motif. The chain domain consists of a 4-turn helix with an unfolded linker at its C-terminus (By similarity)
The N-terminal part of the mature protein (59-105) probably forms an alpha-helix which acts as a membrane-active peptide. It is necessary and sufficient for the toxin's antimicrobial, insecticidal, cytolytic and cytotoxic activity
Consists mainly of an outer membrane-spanning beta-barrel formed by beta-strands both N- and C-terminus residing in the periplasm
The coiled-coil region mediates homodimerization
The Leu-lock (Leu-114) site inserts into a hydrophobic pocket in xrcc4
Zinc fingers 3, 4 and 5 are required for DNA-binding and for interaction with SPI1
The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors
The coiled coil domain may be involved in RPA2-binding
The uncleaved signal sequence interacts with HDL fluid lipids and mediates incorporation into the HDL particle
The oxygen-dependent degradation (ODD) domain is required for cytoplasmic localization in normoxia
The coiled-coil domain mediates homodimerization (PubMed:14530412). Also mediates interaction with SBF1/MTMR5 and SBF2/MTMR13 (By similarity)
The NRPS-like protein ATRR has an unusual domain arcitecture (A-T-R1-R2), with the adenylation domain A activating and thioesterifying glycine betaine which is then channeled through the phosphopantetheine arm of the T domain, the thioester reductase domain R1 reducing glycine betainoyl thioester to glycine betaine aldehyde, and the aldehyde reductase domain R2 converting glycine betaine aldehyde into choline
Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal
The N-terminal domain may form a hydrophobic cleft involved in microtubule binding and the C-terminal may be involved in the formation of mutually exclusive complexes with APC and DCTN1
Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1, these repeats are required for localization to chromatin which flanks sites of DNA damage marked by 'Ser-139' phosphorylation of H2AX (By similarity)
Has 4 domains; the relaxase domain (residues 1-330), an unknown domain (residues 330-990), the helicase domain (residues 990-1450) and the C-terminal domain (1450-1756) which is required for conjugative DNA transfer, possibly via interaction with TraM
Each of the two pore-forming region (also called P-domain or P-loop) is enclosed by two transmembrane segments (2P/4TM) and contains the GYGD signature motif which seems to be involved in potassium selectivity
The extracellular domain coupled to the a single transmembrane region are sufficient for full responsiveness to alpha-latrotoxin
The periplasmic region found in the proximity of the transmembrane appears to be critical for a stable interaction with EpsL
This protein is considered an atypical serine/threonine kinase, because it lacks the conventional structural elements necessary for the substrate recognition as well as a lysine residue that in all other serine/threonine kinases participates in the catalytic event (By similarity). Bud32 has protein kinase activity in vitro, but in the context of the KEOPS complex, the catalytic subunit Kae1 switches the activity of Bud32 from kinase into ATPase (PubMed:23945934)
Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand-binding domains triggers channel gating
Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with NHERF1 and for targeting NHERF1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation (By similarity)
The myosin motor domain binds ADP and ATP but has no intrinsic ATPase activity. Mediates ADP-dependent binding to actin (PubMed:23990465)
The hydrophobic-rich region (HR-A/B) corresponds to the oligomerization domain. AHA motif is a transcriptional activator element
The importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import confers import only, but not re-export out of the nucleus
The phospho-regulated basic and hydrophobic (PRBH) motif is sufficient and important for interaction with phospholipids permitting cortical localization (By similarity). Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane (By similarity)
The N-terminal domain mediates secretion by SPI-2 TTSS and targeting of late endocytic compartments in host cells
A short N-terminal, probably helical sequence targets this enzyme and foreign proteins (tested with GST, MBP and eGFP) to the BMC. 10 residues give poor localization while 14 is better and 18 is better yet. The cargo is only detected by Western blot in broken shells, strongly suggesting this protein is normally found inside the BMC and not on its exterior (PubMed:20308536, PubMed:22927404, PubMed:26283792). This N-terminal sequence interacts with the C-terminus of PduA, and possibly also with PduJ, to encapsulate PduP into BMCs (PubMed:22927404). PduD and PduP compete for encapsulation in BMCs (PubMed:26283792)
Has an N-terminal beta-trefoil domain and a C-terminal pore-forming domain. The trefoil domain has barrel and cap subdomains; the cap has 3 possible carbohydrate-binding modules while the barrel is involved in host cell receptor binding. At neutral pH the carbohydrate-binding modules are accessible on the toxin surface but the barrel subdomain is not (PubMed:27680699). The crystal is very stable at neutral pH, upon ingestion by larvae the crystals dissolve in the alkaline midgut. As the pH rises the 2 subunits compact, while deprotonation at up to 4 sites (including the N- and C-termini) increases the accessibility of the propeptides and moves subdomains. The combined pH-induced changes are thought to expose the previously hidden receptor-binding motif and lead to crystal dissolution (Probable)
The N-terminal region is involved in phosphatidylethanolamine-binding and is required for ATG8-PE conjugation
The flexible region (FR) is required for ATG7-binding
The handle region (HR) contains the ATG8 interaction motif (AIM) and mediates binding to ATG8. It is crucial for the cytoplasm-to-vacuole targeting pathway (By similarity)
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 612, which is replaced by an Asn residue. However, according to Ref.9, the kinase activity is conserved
Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side (By similarity)
The exosite polybasic region mediates non-specific RNA-binding, acting as a bridge for RNA-binding target proteins, such as PARP1 (PubMed:22451931, PubMed:31586028, PubMed:34156061). The exosite is also required for interaction with non-RNA-binding proteins, such as Hsp90 co-chaperone PTGES3 (PubMed:34156061)
Experimental and modeling studies suggest an alpha-helix beta-sheet beta-sheet alpha-helix structure; the protein is insoluble in all media tested. It is thought the beta-strands form the hydrophobic interior surface, while the alpha-helices form the exterior (PubMed:21542854, PubMed:28898511, PubMed:22580065) (Probable). Extensive mutagenesis shows that many mutations leading to loss of gas vesicles are probably on the exterior of the gas vesicle. Arg-15 and other nearby residues (Leu-9 to Arg-19, modeled as alpha helix 1 on the exterior) are essential for gas vesicle formation, perhaps by forming salt bridges with adjacent monomers. The beta-sheet region (residues Val-23 to Leu-31 and Glu-35 to Val-43 with a beta-turn Val-32 Gly-33 Ile-34) may line the interior forming internal contacts between monomers; the hydrophobic surface is thought to minimize water condensation. Many mutations between Leu-31 and Thr-38 result in long, cylindrical vesicles that span the whole cell; Gly-33 in the beta-turn cannot be mutated to Val. Mutations in the second amphiphilic helix (Val-48 to Thr-67, modeled on the exterior) are in general less mutagenic than those in helix 1; Tyr-54, predicted to be on the exterior of the gas vesicle, must aromatic for gas vesicles to form. A few mutations make many small gas vesicles (at Asp-5, Arg-28, Glu-57, Lys-60 and Ile-61); they may have stalled early in gas vesicle formation (PubMed:28898511)
The first domain (residues 2-265) is structurally homologous to the membrane attack complex-ferforin/cholesterol-dependent cytolysin (MACPF/CDC) pore-forming domain. It makes numerous contacts with the FAT domain and comprise essentially the core pore-forming machinery
The second domain is structurally homologous to the focal adhesion-targeting (FAT) domain (266-385). It makes numerous in cis contacts with the MACPF/CDC domain (first domain) and the thioredoxin (THX) domain (third domain) as well as extensive in trans interactions at the SNTX-alpha/beta interface
The third domain corresponds to the thioredoxin (THX) domain. It makes numerous contacts with the second domain (FAT domain). Since it lacks the canonical catalytic residues, it may only play a purely structural role
The fourth domain corresponds to the B30.2/SPRY domain. This domain would be responsible for initial interaction with the cell surface through either lipid- or protein-mediated interactions
Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin
The cohesin domains bind to the dockerin domain born by the catalytic components of the cellulosome
Two unstructured ubiquitin-binding sites (UBSs) mediate interaction with ubiquitin. UBS-I is the strong and UBS-II the weak binding site
Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane
The intermediate part (284-372) is important for enzyme stabilization
The C-terminal part (373-485) is required to determine enzyme responsiveness to a broad range of heavy metals
The kinase domain is not required for ligand binding
The homodimer can be superposed on the Cro helix-turn-helix binding domain, suggesting it probably binds DNA and can act as a transcription factor as is often the case with antitoxins in type II TA systems (Probable). The C-terminus of the antitoxin inserts into the putative NAD(+)-binding site of toxin Res, blocking access to the active site (PubMed:30315706)
The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal with critical basic and hydrophobic residues, that is necessary and sufficient for targeting the PP2A holoenzyme to the outer mitochondrial membrane (OMM) and does not affect holoenzyme formation or catalytic activity
The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that confers resistance to the unfolding step process required for import and therefore prevents PPP2R2B matrix translocation and signal sequence cleavage
The WW domains are essential for localization to nuclear speckles
The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding
The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain
The Gly-Asn rich domain is required for the cooperative interaction with RNA and for regulating the splicing activity
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). The first NPA motif is truncated since it corresponds to DPA (Probable)
The first coiled-coil region mediates most of the interaction with TEAD transcription factors
The NPTY motif mediates the interaction with clathrin (By similarity). The clathrin-binding site is essential for its association with X11-alpha, -beta, and -gamma. The sequence specific recognition extends to peptide residues that are C-terminal to the NPXY motif. This interaction appears to be independent of phosphorylation (By similarity)
The repeat region is missing in the pyrimethamine-resistant isolates BUR-98 and BUR-151
The ATG8-interaction motif (AIM) is required for the association with ATG8
The C-terminal Lys-rich domain (711-818) is dispensable for the proteolytic activity
The UBA domain mediates binding to PSEN1 and PSEN2. It also binds ubiquitin with micromolar affinity, independently of polyubiquitin linkage type. Essential for its association with microtubule-associated protein 1 light chain 3 (MAP1LC3)
The ubiquitin-like domain mediates its association with the subunits of the proteasome
Dimerization is dependent upon the central region of the protein containing the STI1 domains and is independent of its ubiquitin-like and UBA domains
Has 3 domains, the N-terminal alpha-helical domain, an extended flexible linker and the C-terminal beta-sheet domain. The 2 C-terminal beta-sheet domains are swapped and pack against each other to form the dimer interface (By similarity). The N-terminal alpha-helical domain stabilizes RbcL dimers and dimer-dimer interactions, facilitating RbcL(8) formation. It binds to the same region of RbcL as RbcS (PubMed:32636267). The C-terminal beta-sheet domain dimerizes Raf1 (Probable) (PubMed:32636267)
The UBP-type zinc finger binds 3 zinc ions that form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. It recognizes the C-terminal tail of free ubiquitin
The first serine protease domain is catalytically active, whereas the second domain lacks the essential His residue of the catalytic triad at position 387, and the third domain lacks the essential Asp residue of the catalytic triad at position 697. The second and third domains are therefore predicted to be inactive
The RRM domain is required for single stranded RNA binding
Has a tridomain structure comprised of an N-terminal metzincin protease-like domain and two tandem C-terminal carbohydrate-binding domains
The 6 Cys residues of the EGF-like domain are arranged in a disulfide pattern different from the one found in the canonical EGFs. The function of this domain is unclear. It may be a binding site for other proteins or the docking site for a putative alliinase receptor (By similarity)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; a methyltransferase (CMeT) domain responsible for methylations; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The C2 domain 1 binds phospholipids in a calcium-independent manner and is not necessary for calcium-mediated translocation and association to the plasma membrane (PubMed:9886090, PubMed:26175110). The C2 domain 2 binds phospholipids in a calcium-dependent manner and is necessary for calcium-mediated translocation and association to the plasma membrane (PubMed:9886090, PubMed:26175110). The linker region contributes to the calcium-dependent translocation and association to the plasma membrane (PubMed:21087455, PubMed:26175110). The VWFA domain is necessary for association with intracellular clathrin-coated vesicles in a calcium-dependent manner (PubMed:21087455)
Contains several lipid molecules that are bound within the central cavity of the protein
The C-terminal part associates with the ATPase head of SMC1A, while the N-terminal part binds to the ATPase head of SMC3
The myosin motor domain contains the derminants for dextral twisting
The two IQ domains are essential for activity in determining left-right asymmetry
The actin-binding domain is essential for activity in determining left-right asymmetry
Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds (CS-alpha/beta) (PubMed:23137439). The alpha-helix is amphipathic (PubMed:23137439)
The C-terminal domain may function as glutaredoxin and mediates the interaction of the enzyme with glutathione (GSH). Active in GSH-dependent reduction of hydroxyethyldisulfide, cystine, dehydroascorbate, insulin disulfides and ribonucleotide reductase (By similarity)
Sulfur-rich hordein which possesses an N-terminal half composed of proline-glutamine blocks organized in repeating units and a C-terminal half where the repeats are dispersed and less conserved
Each subunit can be divided into 4 domains that are consecutive along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH, respectively. Domain 4 forms the interface
The CUE domain (Coupling of ubiquitin conjugation to ER degradation) is monoubiquitin-binding and is required for intramolecular ubiquitination
The C-terminal domain interacts with the N-terminal domain of RDX
The N-terminal Gln-rich region is required for the formation of amyloid-like oligomers and for the stability of long-term potentiation and spatial memory
Two conserved structural elements specific among monoglycylases, IS1 and IS2, are involved in glycyl chains initiation. Two conserved structural interfaces likely constitute the binding platforms for tubulin tail and microtubule
Arg-482 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Homodimerization involved an interaction between amino and carboxy termini involving LXXLL motifs and steroid binding domain (AF-2 motif). Heterodimerizes with NR5A1 and NROB2 through its N-terminal LXXLL motifs
The di-leucine motif is required for lysosomal localization
The B chain is composed of two domains, each domain consists of 3 homologous subdomains (alpha, beta, gamma)
This keratin differs from all other IF proteins in lacking the C-terminal tail domain
The FFAT motif is required for interaction with VATA and proper localization of the protein
The PH and the Ala/Gly-rich domains control cholesterol binding without affecting 25-hydroxycholesterol binding
The second coiled-coil domain is required for interaction with the tyrosine phosphatase
Corresponds to the C-terminal section
Is a multimodular protein that comprises seven distinct domains. The catalytic glycoside hydrolase domain resides in domain 3 (residues 602-893). Possesses four potential carbohydrate-binding modules (CBMs) (By similarity)
The VHS domain binds phosphatidylinositol PtdIns(3)P and PtdIns(4)P
The GAT domain binds phosphatidylinositol PtdIns(3)P, PtdIns(4)P, PI(3,5)P2 and PtdIns(4,5)P2
The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, are known to interact with the EH domain
The DUF35 C-terminal region is not required for hydratase activity (PubMed:25203216). This region is involved in interaction with LtpA and is required for optimal LtpA aldolase activity (PubMed:29109182)
The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop
The TOS (TOR signaling) motif is essential for activation by mTORC1
Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 874
The C-terminal domain regulates nucleolar localization
The extra mass and high charge density that distinguish the neurofilament proteins from all other intermediate filament proteins are due to the tailpiece extensions. This region may form a charged scaffolding structure suitable for interaction with other neuronal components or ions
The number of the intragenic tandem repeats varies between different S.cerevisiae strains. There is a linear correlation between protein size and the extend of adhesion: the more repeats, the stronger the adhesion properties and the greater the fraction of flocculating cells (By similarity)
The N-terminal region (2-282) contains the glycosylase and lyase activities
The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template
The PTS EIIA type-4 domain may serve a regulatory function, through its phosphorylation activity
In unstressed cells, spontaneous homotrimerization is inhibited. Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation. Furthermore, intramolecular interactions between the regulatory domain and the nonadjacent transactivation domain prevents transcriptional activation, a process that is relieved upon heat shock. The regulatory domain is necessary for full repression of the transcriptional activation domain in unstressed cells through its phosphorylation on Ser-303 and Ser-307. In heat stressed cells, HSF1 homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity. The D domain is necessary for translocation to the nucleus, interaction with JNK1 and MAPK3 and efficient JNK1- and MAPK3-dependent phosphorylation. The regulatory domain confers heat shock inducibility on the transcriptional transactivation domain. The regulatory domain is necessary for transcriptional activation through its phosphorylation on Ser-230 upon heat shock. 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors
The C-terminal region is distantly related to RuvA domain 2, a DNA-binding domain
The N-terminal 26 amino acids are sufficient for its extracellular functions in the regulation of inflammation and wound healing. Acylated peptides that contain the first 26 amino acids of the mature protein can activate signaling via the formyl peptide receptors
The NPXY motif mediates the interaction with clathrin
The histidine box domains may contain the active site and/or be involved in iron binding
Contains one cupin domain that is not required for interaction with the G protein alpha subunit
The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme
Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to the myosin tail domain (PH-like) present in its tail domain (By similarity)
The disordered region interacts with HSPA1 and HSPA8
The OCIA domain is necessary and sufficient for endosomal localization (PubMed:23972987)
The PY-motifs are required for the interaction with RSP5 ubiquitin-ligase and important for resistance to o-dinitrobenzene
The PTS EIIB type-1 domain is phosphorylated by phospho-EIIA on a cysteinyl residue. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the PTS EIIC type-1 domain
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage. Finally, the mature protein remains tightly associated with the bacterium (Probable)
The C-terminal half (AA 188-389) is able to bind cyclin-B and shows a self-ubiquitination activity (mono-, poly, or multi-ubiquitination) in a HECT-like sequence dependent manner
The actin binding residues are poorly conserved between Plasmodium and other organisms. The Plasmodium-specific profilin mini-domain may have a role in binding to membrane phospholipids
Has an N-terminal cyclic nucleotide-binding domain and a C-terminal Toll/interleukin-1 receptor-like domain (TIR) that probably has the NAD(+) hydrolase activity
Arg-218 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The extreme C-terminus binds to the first 2 PDZ domains of DLG4
Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1
The SUN domain may play a role in nuclear anchoring
The C-terminal PDZ-binding motif mediates interaction with the PDZ domains of DSH (Dishevelled) family proteins
The Gln-54 residue in the globular domain forms a hydrogen bond with the main chain carbonyl of Met-52 and is spatially oriented away from the nucleosome dyad axis, leading to lower affinity towards Four-way junction DNA and reconstituted 5S mononucleosomes
The RxLR-dEER motif is required for the delivery of the effector to the host cell cytoplasm but does not bind phosphatidylinositol monophosphates
The 'lock' site stabilizes the complex made of PP2C, ABA and PYR/PYL/RCAR receptor by keeping receptor 'gate' and 'latch' loops in closed positions
Contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold (PubMed:29374258). Transmembrane domain 1 functions as a signal for Golgi targeting (PubMed:29374258)
The C3H1-type zinc finger domains are necessary for ARE-binding activity
The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated
Has 2 domains; domain A (residues 1-97 and 252-365) and domain B (residues 98-251). The active site with bound substrates is found between them. Upon substrate binding His-60 moves into the active site
Contains an extended N-terminal domain, which probably binds RNA, connected by an interdomain linker to a C-terminal catalytic domain, which adopts a typical SPOUT fold
Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1 (By similarity)
The di-leucine motif is required for basolateral targeting in polarized epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells
The DRBM 3 domain appears to be the major RNA-binding determinant (By similarity). This domain also mediates interaction with XPO5 and is required for XPO1/CRM1-independent nuclear export
The PID domain binds to predominantly non-phosphorylated NPXY internalization motifs present in members of the LDLR and APP family; it also mediates simultaneous binding to phosphatidylinositol 4,5-bisphosphate
The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of EPS15, EPS15R and ITSN1
The YEATS domain specifically recognizes and binds acylated histones (acetylated and crotonylated) (PubMed:26341557, PubMed:27089029, PubMed:30385749). Binds crotonylated lysine through a non-canonical pi-pi-pi stacking mechanism (PubMed:27089029, PubMed:30385749)
The Ring-type zinc finger domain is required for its function in down-regulation of NFKB2 proteolytic processing
The subunit can be separated roughly into four domains: an N-terminal domain (residues 7 to 72) ending with a glycine-rich loop, followed by a Rossman-fold domain (73 to 240), a ubiquitin-like domain (241 to 335) and a C-terminal four-helical bundle containing cluster N3 (336 to 438)
The C-terminus is important for mediating light-induced rhodopsin endocytosis
The RING-type zinc finger domain is essential for ubiquitin ligase activity (PubMed:10230407). It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924)
Consists of two domains: a nucleotide-binding N-terminus that hydrolyzes GTP and a C-terminus domain necessary for polymerization. The domains are bridged by a long, central helix (PubMed:20534443, PubMed:20974911, PubMed:24550513). The C-terminus is required for binding to the TubR-iteron DNA complex; its gradual deletion leads to decreasing binding to TubR-DNA (PubMed:20534443). Interactions between the C-terminus and the following monomer drive polymerization (By similarity). The C-terminus is required for filament formation (PubMed:24550513). In the absence of GTP's gamma phosphate the intersubunit interface is weakened, linking GTP hydrolysis to treadmilling (PubMed:20974911)
Consists of a small non-helical N-terminal domain and a rod domain with a 29 residue repeat pattern based on four heptads followed by a skip residue. This alpha-helical protein is characterized by the ability to form a special segmented coiled coil and to assemble into striated fibers of 2 nm protofilaments
Has 4 domains; an N-terminal arm not found in the type 1 subfamily, a discontinuous peripheral domain (P), an elongated loop (E) and the discontinuous axial domain (A)
2 residues (Tyr-92 and Arg-95) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The PEXEL motif is involved in the protein translocation through the parasitophorous vacuole membrane and into the host erythrocyte cytoplasm
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space (By similarity). Then, trimerization and insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface (PubMed:22155776). The crystallized passenger domain (residues 161-440) is an entwined, elongated trimer with a head domain, a neck and 2 extended coiled-coil regions of differing handedness separated by a saddle region. There are a number of cavities in the first (right-handed, RHcc) coiled-coil domain that may allow bending of the extended structure. Smaller cavities in the second (left-handed, LHcc) coiled-coil bind 5 Cl(-) and one water molecule. The Fc portion of IgG has been modeled to bind to the LHcc domain just under the saddle; up to 3 Fc can bind to the trimer (PubMed:21742268)
Contains a degenerated N-terminal LAGLIDADG homing endonuclease (LHE) domain, a linker region and a C-terminal helix-turn-helix (HTH) domain
Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro) (PubMed:28981703). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro) (PubMed:28981703). The bZIP domain is able to form homomeric oligomers via formation of interchain disulfide bonds under non-reducing conditions (in vitro) (PubMed:32542236). Under reducing conditions, the disulfide-bonded homomeric species dissociates into monomers (in vitro) (PubMed:32542236)
Contains a protease-associated domain (PA) of unknown function
The Mn regions are involved in microtubule-binding and stabilization at low temperature. They are required and sufficient for cilium targeting
The N-terminal region (residues 1-29) might play a role in centriole retention
Both the N-terminal docking peptide and the catalytic core domain must bind the UBA3-NAE1 complex simultaneously for optimal transfer of NEDD8
Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per monomer. NBD1 is primarily responsible for ATP hydrolysis. NBD2 is crucial for oligomerization (By similarity)
The connecting peptide (CP) domain is essential for signal transmission in response to antigenic stimulation, likely downstream from ZAP70 recruitment
Both the BTB domain and C2H2-type motifs are necessary for transcriptional repression activity. The BTB domain is also necessary for oligomerization and efficient sumoylation. The hydrophobic cluster preceding Lys-328 enhanced sumoylation efficiency (By similarity)
The UBZ-type zinc finger domain is required for targeting ZBTB1 to UV damage sites and for PCNA monoubiquitination. UBZ-type zinc finger domain mediates binding to 'Lys-63'-linked polyubiquitin chains (in vitro)
The type-1 glutamine amidotransferase domain is defective
The transcriptional activation domain 1/TA1 and the transcriptional activation domain 2/TA2 have direct transcriptional activation properties (By similarity). The 9aaTAD motif found within the transcriptional activation domain 2 is a conserved motif present in a large number of transcription factors that is required for their transcriptional transactivation activity (By similarity)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (409-439) inactivates kinase activity under calcium-free conditions (By similarity)
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-73 and Arg-76) that bind to malonylated and succinylated substrates and define the specificity
The interaction between PNRC2 and nuclear receptors is dependent on the SH3 binding motif
The TPR repeat domain is required for substrate binding and oligomerization
The N-terminus (36-79) resembles a truncated EF hand, the LRR region (80-262) has a curved form while residues 263-343 form an Ig-like region
The N0, N1, N2 and N3 domains are periplasmic, while the secretin and S domains form a channel that is partially inserted in the outer membrane. The N1, N2 and N3 domains each form a periplasmic ring. The secretin domain forms a double beta-barrel structure; the outer barrel has a diameter of about 110 Angstroms while the inner barrel forms the central gate with a small pore in the closed state
The UBZ4-type zinc finger binds ubiquitin
The regulatory loop blocks the catalytic center by bridging the methyltransferase domain and the C-terminal CCHC-type zinc finger, resulting in an autoinhibitory conformation
The C-terminal region is involved in Claisen-type cyclization of the second ring of naphthopyrone
The Glutaredoxin 2 domain is sufficient for interaction with all BOLA
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS5 has the following architecture: A-T-C-A-T-C-T
Inhibitory activity is regulated via a pH-induced conformational change of the structure. At pH above 7, Gfh1 is in an inactive flipped orientation that prevents binding to RNAP. At lower pH, Gfh1 switches to an active orientation, which enables binding to RNAP and inhibitory activity (By similarity)
Forms a U-shaped beta-half-barrel with a large hydrophobic cavity
The C-terminus of SapM is required for interaction with RAB7 and SapM-mediated autophagy block
The FF domains bind the phosphorylated C-terminus of the largest subunit of RNA polymerase II, probably mediate interaction with HTATSF1 and preferentially bind peptides with the consensus sequence [DE](2-5)-[FWY]-[DE](2-5)
The C-terminal activation region (AD) is used for downstream signaling. Seems to be essential for coactivator function with nuclear receptors and with the aryl hydrocarbon receptor (By similarity)
The N-terminal activation region (AD) is necessary and sufficient for synergistic activation of LEF1-mediated transcription by CTNNB1. Contains a EP3000 binding region which is important for synergistic cooperation (By similarity)
Recruitment by nuclear receptors is accomplished by the interaction of the coiled-coiled domain with p160 coactivators
Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit
The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4
The SH2 domain preferentially binds phosphopeptides with the consensus sequence Y-[TVI]-X-L and mediates interaction with PDGFRA, PDGFRB, FGRFR1, IL2RB, IL2RG, CD3Z and CRK/CrKII
Atypical domain architecture: contains 12 HAMP domains and two receiver domains
The pyrin domain is sufficient for suppression of NF-kappaB activity, it adopts a typical death domain fold, but in contrast to several NLRP family pyrin domains it doesn't bind homotypically to the ASC adapter, which supports the observation that NLRP4 has no effect on IL1B activation
The PX domain binds phosphatidylinositol 3-phosphate which is necessary for peripheral membrane localization of ATG20 to the perivacuolar punctate structures
The DAD domain regulates activation via by an autoinhibitory interaction with the N-terminus. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity)
The C-terminus PTS1 domain (474-476) is required for biotin biosynthesis activity and peroxisomal subcellular localization
The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments
The PFVFL motif is required for interaction with TPL
The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3)
Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines (By similarity)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. FlvI has a monomodular A-T-C architecture
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes. In PLD gamma, all the calcium-coordinating acidic amino acids are conserved
A conformation change in the N-terminal region spanning the first 42 residues plays an important role in the regulation of enzyme activity by malonyl-CoA
The periplasmic segment (residues 30-163) defines the sensory domain (PubMed:9401031). Conformational changes in the cytoplasmic HAMP domain modulate the mobility of the central alpha-helices (which bend at Ser-238 and Pro-253) that allows formation of 1 kinase-active state
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2
The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3
The two fibronectin type-III-like domains contained in the C-terminal part form together a cytokine-binding domain
The C-terminal domain mediates copper(1+) binding and is involved in the copper(1+)-dependent-ATOX1 interaction. The C-terminal domain appears to act to limit transport through the pore by regulating the rate of exit of copper ions at the intracellular side. The N-terminal domain can collect copper(2+) from copper(2+) carriers in blood. The N-terminal domain, in the trimeric arrangement, tunes its reactivity with copper, promoting copper(2+) reduction and copper(1+) stabilization. The bis-His motif directly coordinate to copper(2+)
Residues 69 to 86 are required for the interaction with host TAP1 and its re-localization into nuclear speckles
The nuclear localization signal (NLS) is required for localization into nucleus
Has an N-terminal beta-trefoil domain and a C-terminal pore-forming domain. The trefoil domain has barrel and cap subdomains; the cap has 3 carbohydrate-binding modules while the barrel is involved in host cell receptor binding. At neutral pH the carbohydrate-binding modules are accessible on the toxin surface but the barrel subdomain is not
The C-terminal region is essential for structural folding and for interaction with SpxH/YjbH (PubMed:24942655). A conformational change during oxidation of Spx to the disulfide form likely alters the structure of Spx alpha helix alpha4, which contains residues that function in transcriptional activation and Spx/RNAP-promoter interaction (PubMed:20084284)
The coiled coil domain mediates the interaction with dystrophin and utrophin
Isoform 1 and isoform 2 N-terminus domains are necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation (By similarity). Isoform 1 transmembrane signal-anchor domain is necessary for its own mRNA to be recruited to the endoplasmic reticulum (ER) which will undergo unconventional ERN1-dependent splicing in response to ER stress (PubMed:19394296, PubMed:21233347). Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively. Isoform 2 N-terminus and C-terminus regions are necessary for DNA-binding and strong transcriptional activity upon ER stress, respectively (PubMed:11779464, PubMed:8657566). Isoform 2 C-terminus region contains a nuclear exclusion signal (NES) at positions 186 through 208. Isoform 2 C-terminus region contains a degradation domain at positions 209 through 261 (PubMed:16461360)
The GRIP domain may serve as a Golgi targeting domain
The Myb domain is not required for TOUSLED binding
PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1 and EPHB2 and with the C-terminus of PPFIA1 and PPFIA4. PDZ 4 and PDZ 5 mediate interaction with the C-terminus of GRIA2 and GRIA3. PDZ 4, PDZ 5 and PDZ 6 mediate homomultimers. PDZ 7 mediates interaction with PDZ domain of GRASP1. PDZ 7 domain binds CSPG4. PDZ 6 mediates interaction with the C-terminus of liprins-alpha. PDZ 1, PDZ 2 and PDZ 3 mediate interaction with the PDZ-binding motif of FRAS1 (By similarity). PDZ 4 and PDZ 5 mediate interaction with PRLHR
The C-terminal cytoplasmic region found only in isoform L-MAG is required for normal myelination in the central nervous system (CNS), but is apparently not required for normal myelination in the peripheral nervous system (PNS)
The extracellular domain is required to protect against axon degeneration (By similarity). The first three Ig-like domains mediate interaction with RTN4R and RTN4RL2, but are not sufficient to inhibit neurite outgrowth (PubMed:19420245). The two C-terminal extracellular Ig-like C2-type domains are required for inhibition of axon longitudinal growth (PubMed:9298990, PubMed:19420245, PubMed:19367338). Besides, the two C-terminal extracellular Ig-like C2-type domains are required for protection against apoptosis after nerve injury (By similarity)
TPR repeats are required for the binding with phytochromes
The zinc-finger domain is required for terminal uridylyltransferase activity. Together with the RRM domain, binds the 5'-area of U6 snRNA
The RRM domain is required for terminal uridylyltransferase activity. Together with the zinc-finger domain, binds the 5'-area of U6 snRNA
Highly repetitive protein characterized by regions of polyalanine and glycine-rich repeating units
The PIR1/2/3 repeats are required for the covalent linkage to the cell wall (By similarity). Their number varies among different strains of S.cerevisiae
The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization (By similarity)
Contains X-F-X-F-G repeats
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8B from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The N-terminal domain is required for multimerization. The C-terminal domain is involved in DNA-binding
The N-terminus (residues 1-126) is homologous to YaiA and HPF of E.coli and can associate with ribosomes, while the C-terminus (residues 126-185) seems to be a functional paralog of E.coli RMF
The tyrosine-protein phosphatase domain is predicted to be catalytically inactive
The RING-type zinc finger domain coordinates an additional third zinc ion
The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members (By similarity)
The C-terminal region may confer species specificity; C-terminal hybrids do not all rescue deletions in S.elongatus PCC 7942 (PubMed:16227211). Has 2 forms, fold switches to a thioredoxin-like fold (KaiB(fs)) when bound to KaiC (PubMed:28302852, PubMed:26113641). The KaiB(fs) form binds faster to KaiC than wild-type, thus less fully phosphorylated KaiC forms; the KaiB(fs) form activates signaling through CikA and inhibits signaling through SasA (PubMed:26113641) (Probable). A mutant locked in the KaiB(fs) form binds the CikA PsR domain (PubMed:26113641)
The C-terminal hydrophobic region contains two helices that mediate interaction with membranes. Contrary to predictions, this region does not contain transmembrane helices
The N-terminal region mediates interaction with MARCHF6, leading to SQLE ubiquitination and proteasomal degradation when cholosterol levels are high (PubMed:24449766, PubMed:26434806, PubMed:28972164). The first part of the N-terminal region contains a hydrophobic region that inserts into the membrane; contrary to predictions, there are no transmembrane helices (PubMed:26434806). The second part contains a region that can form an amphipathic region that associates with membranes. This region is ejected from the membrane by high cholesterol levels and becomes disordered in an aqueous environment. This is critical for cholesterol-dependent proteasomal degradation. Additional parts of the N-terminal region are predicted to be disordered and contribute to flagging the protein for proteasomal degradation already under basal conditions (PubMed:28972164)
The RING-type zinc finger domain interacts with an ubiquitin-conjugating enzyme (E2) and facilitates ubiquitination
A protein-embedded tunnel connects the potassium ion in KdpA to a water molecule at the canonical cation site in the transmembrane domain of KdpB (PubMed:28636601, PubMed:30478378, PubMed:34272288). The structures suggest a translocation pathway for potassium via two inter-subunit half-channels along KdpA and KdpB, integrating KdpB directly in the transport process (PubMed:30478378). The periplasmic potassium ion probably enters the selectivity filter of KdpA, travels through the water-filled tunnel to reach KdpB, and is released to the cytoplasm by KdpB (PubMed:34272288). KdpB undergoes conformational changes, whereas KdpA, KdpC and KdpF remain static (PubMed:34272288)
Both zinc finger regions are required for the transcriptional activation of PBX1
The FHA domain plays a key role in the anti-proliferative properties of the protein and is involved in initiating a cell cycle arrest at G2/M. The FHA domain may be required to interact with phosphorylated proteins
The SAC1 domain is capable of hydrolyzing phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)
The FYVE-type zinc finger mediates interaction with PTK2/FAK1, and also interaction with PI(3)P and association with endosomes
The C-terminal region exhibits a structure similar to canonical PH domains, but lacks a positively charged interface to bind phosphatidylinositol phosphate
Has an N-terminal methyltransferase (MTase) domain linked to a C-terminal DNA-binding domain by a 10 residue linker. The MTase of one monomer recognizes, binds and modifies the target strand while C-terminal domain of the other monomer binds the non-target strand
Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity)
The segment S6 is involved in the inhibition of voltage-gated potassium channel activity by KCNE4
The H2A.Z-interacting domain (ZID) mediates a direct interaction with H2A.Z/H2AZ1
The CUE domain specifically binds RPS20/uS10 ubiquitinated by HEL2
The UIM domains bind molecules modified by monoubiquitin or ubiquitin chains and promote coupled monoubiquitination
SAM and DDHD domains together are required for phospholipid binding
The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24171105, PubMed:19464178). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (PubMed:31263273). The activating sterol is likely to be cholesterol (PubMed:31263273, PubMed:35658032). The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH (PubMed:35658032)
A short helical region is required and sufficient for Cu(2+) binding
EF-hand 1 domain binds Ca(2+) with low affinity (PubMed:32759683). EF-hand 2, EF-hand 3 and EF-hand 4 domains do not bind Ca(2+) (PubMed:32759683)
The PH domain is required for membrane targeting
The extracellular loop 3 (ECL3) is involved in binding porphyrins and transfer them to other carriers, probably albumin
The C-terminus peroxisomal targeting signal tripeptide is important for peroxisomal import. Once in the peroxisome, it is involved in intersubunit interactions
Three specific residues, Phe-177, Leu-180 and Asn-196 are conserved between non-primate mammals whereas the respective residues are serine, phenylalanine and threonine in primates. The two residues at positions 177 and 180 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil. The presence of an asparagine at position 196 is important for the maintenance of the quaternary structure resulting in stability at cold temperature and improved catalytic activity toward retinal
The DH (DBL-homology) domain mediates interaction with RASGRF1 and probably EPB49 and is required for RAC1 activation
The protein kinase domain has an atypical kinase fold which lacks the glycine-rich loop that is critical for ATP binding in canonical protein kinase domains
Lacks a typical peroxisomal sorting signal
Has a highly basic region with many copies of the sequence KKEE and KKEI/V, repeated but not at fixed intervals, which is responsible for the binding of MAP1B to microtubules
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the active site of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases
The Homeobox transactivates the Ret-1 element in the presence of CRX and NRL
The FM region is required for binding SMAD2/SMAD4 complexes. FM2 is more effective than FM1 and only interacts with phosphorylated SMAD2 that is in an activated SMAD complex (By similarity)
The N-terminus (residues 1-268) and C-terminus (271-552) form 2 separate domains; the N-terminus is globular while the C-terminus is elongated. The N-terminus binds to S.suis cells while the C-terminus binds to human HEp-2 cells. Incubation with the C-terminus stimulates ERK and p38 phosphorylation in HEp-2 cells
The PDZ domain is required for localization to apical junctions
NFRKB seems to be mostly disordered. The wing-helix like domain doesn't bind DNA
The N-terminal region consists of two globular folded domains that contain prolyl isomerase and chaperone activities
The C-terminal region binds nickel ions
The first serine protease domain is catalytically active, whereas the second domain lacks the essential His residue of the catalytic triad at position 363, and the third domain lacks the essential Asp residue of the catalytic triad at position 673. The second and third domains are therefore predicted to be inactive
Modular protein made up of an N-terminal effector binding GAF-type domain and a C-terminal wHTH DNA binding domain, separated by a helical linker
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex. The cytosolic N-terminus part of the protein destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC. The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer (By similarity). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (By similarity)
The C-terminal domain (CTD) serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing
The RING domain is essential for autoubiquitination
Disordered region at the N-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of membraneless compartments that store maternal mRNAs in oocytes
The B30.2/SPRY domain mediates the interaction with the substrate RIGI
The coiled-coil domains mediate homodimerization and the bridging of viral RNA-associated RIGI filaments
The proximal coiled coil domain mediates trimerization required for binding to nesprins. The distal coiled coil domain is proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation (PubMed:26688217). The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton (By similarity)
The SUN domain may play a role in nuclear anchoring and/or migration
IleRS has two distinct active sites: one for aminoacylation and one for editing. The misactivated valine is translocated from the active site to the editing site, which sterically excludes the correctly activated isoleucine. The single editing site contains two valyl binding pockets, one specific for each substrate (Val-AMP or Val-tRNA(Ile)) (By similarity)
The holoenzyme may undergo conformational shifts upon DNA binding: the nuclease domain of RecB may swing away from the DNA exit tunnel in RecC. When Chi DNA binds to the RecC tunnel the nuclease domain may then swing back to its original position (that seen in crystal structures), allowing it to nick the DNA 3' of the Chi site and then rotate to load RecA. At high Mg(2+) the nuclease domain may swing back more frequently, explaining differences seen in assays performed at high Mg(2+) (PubMed:25073102). As ssDNA is unwound and fed to the RecD subunit the latter transmits conformational changes through each subunit to activate the RecB nuclease (PubMed:27644322)
Contains two functional domains. The central domain is sufficient for general mitochondrial translation but not suppression of COX2 mutants. The C-terminus sequence is sufficient for dosage suppression of COX2 mutants
Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel
Displays an unusual domain structure in comparison to other known cyclotides as the cyclotide is followed by a C-terminal albumin-like region
The B-chain consists of six tandemly repeated subdomains. Only subdomains 1-alpha and 2-gamma possess a functional carbohydrate-binding site
In contrast to other members of the phospholipase D family, contains only one PLD phosphodiesterase domain, suggesting that it has a single half-catalytic and requires homodimerization to form a complete active site
C2H2-type zinc fingers 3 interacts with DNA-binding site G-clusterinc fingers. C2H2-type zinc fingers 6 and 7 interact with DNA-binding site core sequence (By similarity)
The U-box-like region is a truncated U-box domain. It is unknown whether it is functional or not
Composed of two domains, each domain consists of 3 homologous subdomains (alpha, beta, gamma)
The N-terminus has a gamma-class carbonic anhydrase-like domain (CA), while the C-terminus has 4 repeats that are similar to the small subunit of RuBisCO (rbcS), called SSUL. The SSUL are connected by flexible linkers. The N-terminal domain forms a scaffold on which CA and other carboxysomal proteins assemble, while the C-terminus binds RuBisCO
Microtubule association is inhibited by the ANK repeats and the Golgi localization region (GoLD)
The KH domain consists of approximately 70 amino acids and includes a conserved hydrophobic core, an invariant Gly-X-X-Gly motif, and an additional variable segment. The third KH domain (KH3) binds a hairpin RNA loop containing the 5'-UCAY-3' motif on targeted molecules. RNA binding by KH3 requires residues C-terminal to the KH domain
The second tetratricopeptide repeat (TPR 2) mediates the interaction with SARS-CoV accessory protein 7a
Neurogranin is intrinsically unstructured; however, upon binding with CaM, The IQ domain adopts a helical conformation
Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue (PubMed:691057)
The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors
Contains an N-terminal domain that binds arabinose and mediates dimerization, an inter-domain linker region, and a C-terminal domain that binds DNA (PubMed:9103202, PubMed:9367758, PubMed:26800223). Arabinose is bound within a beta barrel and is completely buried by the N-terminal arm of the protein (PubMed:9103202). The DNA-binding domain contains seven helices arranged in two semi-independent subdomains, each containing one helix-turn-helix DNA binding motif, joined by a 19 residue central helix (PubMed:19422057)
The N-terminal domain is required for targeting to the mitochondrion
The C-terminal region after the fibronectin type-III domain presents structural similarity to annexin domains and binds calcium ions
The ligand binding region binds directly to 5 L-amino acids
In the homohexamer the 2 domains (called CI and CII) self-associate to each form a 'donut' layer; the compactness and local conformation of the domains varies over the cell cycle and impacts function. CII has the autokinase and autophosphatase activities, both CI and CII have (weak) ATPase activity
The DAZ domain mediates the interaction with DAZAP1 and DAZAP2
The JmjC domain mediates demethylation activity and is required for satellite silencing
The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins
Folds into three structural domains: the first domain harbors all the residues involved in catalysis, the second domain is characteristic of PchP and is involved in the recognition of the choline moiety of the substrate, the third domain stabilizes the relative position of the other two (PubMed:22922065). Contains two sites for alkylammonium compounds: one catalytic site near the metal ion-phosphoester pocket and one inhibitory site (PubMed:21515416, PubMed:21660097, PubMed:22922065). Sites are adjacent and share residues (PubMed:21515416). Contains a high and a low affinity site for phosphorylcholine (PubMed:10387109, PubMed:15886911). The signal peptide is the fundamental factor responsible for decreasing the affinity of the second site, and catalytic efficiency increases notably after cleavage of the signal peptide (PubMed:17106798)
The leucine-zipper domain is not essential for apoptosis, but is required for sensitization of cells to exogenous apoptotic insults and for interaction with its partners
The SAC domain is a death-inducing domain selective for apoptosis induction in cancer cells. This domain is essential for nuclear entry, Fas activation, inhibition of NF-kappa-B activity and induction of apoptosis in cancer cells (By similarity)
The B30.2/SPRY domain-binding motif mediates recognition by proteins containing a B30.2/SPRY domain
Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion
The C2 domain 1 is not necessary for calcium-mediated translocation and association to the plasma membrane (PubMed:26175110). The C2 domain 2 is necessary for calcium-mediated translocation and association to the plasma membrane (PubMed:26175110)
The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1
This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa (By similarity)
The WPP domain is required for the nuclear envelope localization
The CCHC-type zinc finger is required to retain the protein within the nucleus and prevent its shuttle back to the cytoplasm via the CRM1 pathway
Interactions with ROPs and SEC3A require an intact C-terminal coiled-coil domain
The central DNA-binding region is composed of 16 tandem core repeats with 1 base-specifying residue (BSR residue 13, also called repeat variable diresidue, RVD, residues 12 and 13). The BSR is probably the only residue to contact DNA in a sequence-specific manner, although other repeat residues effect repeat activity and specificity
The C-terminus encodes a plant transcriptional activation domain. Replacement of the 295 last residues of AvrBs3 (AC P14727) with the same region of this protein activates transcription in transformed N.benthamiana leaves
Interaction with SMN1 requires at least one of the RGG-box regions
The proline-knot motif (117-126) may be involved in targeting to lipid bodies
Each subunit consists of two domains: an N-terminal NADH-binding domain adopting an alpha/beta structure and a C-terminal functional domain adopting an alpha-helical structure
Although both SET and pre-SET domains are present, the absence of the post-SET domain may explain the lack of methyltransferase activity. Besides, the Cys residues in the SET domain that normally bind a zinc ion are not conserved
Each quasi-RRM repeat bound poly(RG), while only the N-terminal QRRM bound poly(RC) and poly(RU). None of the repeats bound detectable amounts of poly(RA)
D-box [RxxLxx(L/I)xN] is the common motif recognized by the E3 ubiquitin ligase APC specifically acting during transition from metaphase to anaphase
The GYF domain interacts with GRB10
Comprised of a NH2-terminal actin-binding domain, 24 internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. The first hinge region prevents binding to ITGA and ITGB subunits (By similarity)
The tudor domains recognize and bind to proteins with dimethylated arginine residues
The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region
The Rieske domain induces apoptosis
Consists of two putative central coiled-coil regions flanked by putative globular regions at the N- and C-termini
The D1, D2, D3, (Q/R)XXRW motif is a critical part of the GCS active site, involved in catalysis and UDP-sugar binding
The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage. Finally, the mature protein remains tightly associated with the bacterium (Probable)
The jas domain (121-145) is required for interaction with COI1
LIM region interacts with CTNNA1. The preLIM region binds directly actin filaments
LIM-2 and LIM-3 domains mediate the interaction with the N-terminal region of AURKA. The association between LATS2 and AJUBA required the second LIM domain of AJUBA
Consists of two domains. The 20 kDa N-terminal domain repairs the Sp diastereomer of methylphosphotriesters and, in its methylated form, binds DNA in a sequence-specific manner. The 19 kDa C-terminal domain repairs the mutagenic lesions O6-methylguanine. Each domain retains its activity when separated form the other
The RS2 (Arg/Ser-rich domain 2) and RNP-CS (ribonucleoprotein consensus sequence) domains are required for both male sterility and female-specific dsx splicing but the RS1 domain is dispensable
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 18 and 71, which are replaced by Lys and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). The presence of two intact modules suggests that the two modules condense L-tryptophan and L-phenylalanine together (PubMed:24677498). The C-terminal condensation domain might be responsible for cyclization of the dipeptide to form the diketopiperazine structure (PubMed:24677498)
The didomain protein contains an adenylation domain (A domain) and a thiolation domain (T domain)
AtrA has an A-T-TE domain architecture (Probable). The adenylation (A) domain recognizes and activates the aryl acid substrates, and loads them onto the thiolation (T) domain (Probable). The thioesterase (TE) domain shares the missing condensation (C) domain function, and is responsible for condensation and final product release (Probable)
The C-terminal periplasmic region is necessary and sufficient for septal targeting. The transmembrane region contributes to localization to the cell division site. Three periplasmic subdomains are involved in the interactions with other cell division proteins. Localization and recruitment require two separate domains
Consists of a compact arrangement of structured domains linked by long, flexible linkers. The N-terminal region interacts with UvrA, the central region interacts with RNAP, and the C-terminal DNA translocase region possesses ATPase activity. Activity is regulated by a conformational switch from a dormant closed state to an active open state upon substrate binding
The mature peptide (65-92) probably forms alpha-helices which disrupt target cell membranes
Consists of two modules with a C-terminal epimerization domain. Each module incorporates one amino acid into the peptide product and can be further subdivided into domains responsible for substrate adenylation, thiolation, condensation (not for the initiation module), and epimerization (optional), and N methylation (optional)
The P-S-E-R-S-H-H-S repeats give rise to an antiparallel beta-structure
The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding and actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for self-association (By similarity)
The RING-type domain is required for ubiquitination
Consists of two distinct domains (I and II) connected by two strands that presumably function as a hinge (PubMed:8527431, PubMed:8563629). Undergoes conformational change upon substrate binding (PubMed:10537211)
The BH4 motif seems to be involved in the anti-apoptotic function. Intact BH1 and BH2 motifs are required for anti-apoptotic activity (By similarity)
The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2
The HTH domain is an independent structural unit and mediates binding to telomeric DNA
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage (Probable)
The LIM domains exert a negative regulatory function and disruption of the LIM domains produces an activated form. In addition, two activation domains and a negative regulatory domain exist C-terminally to the homeobox (By similarity)
Both extracellular leucine-rich repeats and protein kinase domains are required for flg22-binding. The LRR 9 to LRR 15 domains are involved in flg22-binding
EGF2 and EGF3 form a rigid rod via an interdomain calcium ion binding site, while the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1
The BROMO domain 2 is essential for the interaction with smo-1 and E2 enzyme ubc-9
Contains 1 EAR motif required for the interaction with TPR2
The RRM 3 domain is required for binding to poly(A) RNA, for the association with polysomes and with the EIF4F cap-binding complex and for the stimulation of translation (PubMed:20064466). The RRM 1 and RRM 2 domains may contribute to polysome association and stimulation of translation (PubMed:20064466)
Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, regions involved in trimerization do not move
The C2H2-type zinc finger 1, also named C2HR, mediates the interaction with NSD1
The PPxY motif mediates interaction with WWOX and NEDD4
The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes. It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate
The C2 domain binds phospholipid membranes in vitro in a Ca(2+)-independent manner; this binding is important for its tumor suppressor function
The N-terminal domain mediates interaction with FAB1 and VAC7 while the C-terminal domain mediates interaction with FIG4
The CoCUN region mediates binding to ubiquitin (PubMed:31319543). Does not interact with NEDD8 (PubMed:31319543)
The galectin domain is atypical and does not bind beta-galactoside sugars
The N-terminal region, which is highly basic, is required for interaction with calmodulin
The F-box domain is required for interaction with SKP1 and defense against methylmercury toxicity
Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 239, and the second one lacks the essential Glu active site residue at position 872
The jas motif (82-103) lacks the canonical degron LPIARR that strongly interacts with COI1 in the presence of JA-Ile in other TIFY/JAZ proteins. Contains 1 EAR motif required for the interaction with TPL
The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of timm9/timm10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The N-terminal part contains two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1
The C-terminal domain forms a four-stranded coiled coil
The disordered structure between residues 82 and 99 contributes to the effector function in cell death activation
The SH3-binding motif is buried in the tertiary structure, and it is therefore unclear whether it directly mediates protein-binding
The Rab-GAP TBC domain is essential for phosphatidylinositol binding
The C-terminal part (1231-1309) serves an autoinhibitory function and is dislodged upon substrate binding
The transglutaminase activity is contained within the periplasmic domain (180-544)
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro/Leu-Ala/Ser (NPA)
Possesses an unusual extended V-shaped dimeric structure with each monomer consisting of three distinct domains arranged along a curved 'spinal' alpha-helix. The N-terminal catalytic domain specifically recognizes the glutamate moiety of the substrate. The second domain is the NADPH-binding domain, and the third C-terminal domain is responsible for dimerization (By similarity)
The PDZ domain in the N-terminal part of the neuronal isoform participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes in muscles (By similarity). Mediates interaction with VAC14
Has the canonical translocation motif RxLR, but lacks the canonical EER motif, which characterizes most oomycete effectors identified so far
The leucine heptad repeat region contains five protein variants with 12 amino acid polymorphisms. Leucine heptad repeats are a feature of coiled coils where the leucines are embedded in an alpha helical region. Three of the different variants were recognized by RPP13-Nd, suggesting that alteration of the amino acid sequence in this region is tolerated
All ATR13 variants contain at least one 11-amino-acid direct repeat region. This region is involved in nucleolar localization. A single repeat unit is found in ATR13-Aswa1, ATR13-Emco5, ATR13-Goco1-A and ATR13-Goco1-B (ATR13-Hind2 has one repeat unit followed by an additional 3 amino acids), preventing nucleolar localization, whereas three units are present in ATR13-Bico1, ATR13-Waco5 and ATR13-Wela3, and four units are present in ATR13-Maks9, ATR13-Hiks1, ATR13-Cala2, ATR13-Cand5, ATR13-Hind4, ATR13-Emwa1-A, ATR13-Emwa1-B, ATR13-Emoy2, ATR13-Noks1 and ATR13-Ahnd1. In addition there are 14 polymorphic positions, resulting in a total of seven variant forms within this domain. No association between the number or sequence identity of these repeats and recognition by RPP13-Nd could be detected
The highly variable C-terminus domain and is involved in the specificity for the recognition by RPP13-Nd. Thr-119 and Arg-148 are critical for recognition by A.thaliana RPP13-Nd
Contains two binding domains, first site for small ligands and second site for ssRNA
Binding of ligands causes significant conformational changes
The B-box zinc finger and the linker region between the coiled coil and B30.2/SPRY domains contribute to higher order self-association
SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31
The KLERQ domain binds to SNAP-25 and SNAP-23
In an autoinhibited form the SH3 domain 5 may bind intramolecularly to the DH domain, thus blocking the CDC42-binding site
The disordered N-terminal region is not required for diguanylate cyclase activity
The C2 domain is a Ca(2+)-dependent membrane-targeting module
The PH domain mediates interaction with the surface membrane by binding to PIP2
Forms a stable homopentamer with a convex and concave side. A short loop (residues 60-69) protrudes above the center of the convex face to different degrees. The tight homopentamer forms a pore with an opening of about 2.9 Angstroms in diameter at its most narrow, surrounded by the amino acids Ser-Gly-Ser-Ala-Ala (one from each subunit)
The ENTH domain is required for PtdIns(3)P affinity and EPSIN2 subcellular location
The MTERF repeats form a half-donut shaped, right-handed superhelix, where the concave side displays a positively charged path for nucleic acid interaction
DRBM domains cooperate for the binding to nucleic acid but not for unwinding helicase activity. The helicase-associated domain-2 (HA2) region is essential for the duplex RNA unwinding helicase activity. The minimal transactivation region (MTAD) mediates interaction with the RNA polymerase II holoenzyme and stimulates transcriptional activation. The oligonucleotide- or oligosaccharide-binding (OB-fold) and the repeated arginine and glycine-glycine (RGG) regions are dispensable for both RNA-binding and unwinding helicase activities. The RGG region contains both nuclear localization signal (NLS) and nuclear export signal (NES) and is necessary and sufficient for nucleocytoplasmic shuttling in a RNA-independent manner
The HP1 box is both necessary and sufficient for HP1 binding
The PHD-type zinc finger enhances CEBPB transcriptional activity. The PHD-type zinc finger, the HP1 box and the bromo domain, function together to assemble the machinery required for repression of KRAB domain-containing proteins. Acts as an intramolecular SUMO E3 ligase for autosumoylation of bromodomain
The RING-finger-B Box-coiled-coil/tripartite motif (RBCC/TRIM motif) is required for interaction with the KRAB domain of KRAB-zinc finger proteins. Binds four zinc ions per molecule. The RING finger and the N-terminal of the leucine zipper alpha helical coiled-coil region of RBCC are required for oligomerization
The C-terminal di-lysine motifs may confer endoplasmic reticulum localization
Contains a beta-propeller domain involved in specific binding of phosphatidylinositol 3,5-bisphosphate
Consists of two domains: a nucleotide-binding N-terminus that hydrolyzes GTP and a C-terminus domain necessary for polymerization. The domains are bridged by a long, central helix (By similarity). Interactions between the C-terminus and the following monomer drive polymerization (By similarity)
The C-terminal extension (CTE) is used to better adjust the substrates into the active sites and mediates in vivo subcellular localization of the protein
The zinc finger domain is essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain
The 2 Tudor domains recognize and bind methylated histone H3 'Lys-4' residue (H3K4me). Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails. Trimethylated H3 'Lys-4' (H3K4me3) is bound in a cage of 3 aromatic residues, 2 of which are from the Tudor domain 2, while the binding specificity is determined by side-chain interactions involving residues from the Tudor domain 1. The Tudor domains are also able to bind trimethylated histone H3 'Lys-9' (H3K9me3), di- and trimethylated H4 'Lys-20' (H4K20me2 and H4K20me3). Has high affinity for H4K20me2, blocking recruitment of proteins such as TP53BP1
Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting
The cholesterol recognition/amino acid consensus (CRAC) region directly binds cholesterol, as well as campesterol and 27-hydroxycholesterol. Has much lower affinity for epicholesterol
The coiled-coil domain mediates homodimerization. Also mediates interaction with SBF1/MTMR5 (By similarity). By mediating MTMR2 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By similarity)
The GRAM domain mediates binding to phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP2, the motif is inactive
The STI1 2 domain (373-412) has a stimulatory effect on HSP93 ATP hydrolysis
Consists of an N-terminal THUMP domain fused to a catalytic Rossmann-fold MTase (RFM) domain
Second PDZ domain is a type I PDZ domain that tethers type I PDZ ligand inaC by interaction with its C-terminus
The C-terminal zinc finger domain functions as a transcriptional transactivator
The BTB (POZ) domain possesses repressor activity
The intracellular cytoplasmic domain forms a funnel-shaped homopentamer. 25 well-defined Cl(-) ions were observed and some of these binding sites are highly conserved within the ZntB family. The presence of the bound Cl(-) ions increases the stability of cations along the pore suggesting they could be important in enhancing cation transport
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. FG repeat types and their physico-chemical environment change across the NPC from the nucleoplasmic to the cytoplasmic side: FXFG repeats are especially abundant in NUPs on the nucleoplasmic side (in a highly charged environment and enriched in Ser and Thr)
The coiled-coil domains are involved in microtubule-binding
The beta domain is required for enhancement of transcriptional activity
The Ig-like C2-type domains 3 and 4 are required for interaction with CD81
The short cytoplasmic domain is very basic, interacts with membrane PIPs, and mediates plasma membrane localization
The ankyrin repeats and the SH3 domain are required for a specific interactions with TP53
The 2 adenine-specific methylase motifs of the protein participate in modification of the two strands; the first motif modifies the sequence 5'-GGATG-3', the second motif modifies the sequence 5'-CATCC-5'
Almost exclusively composed of repeats of a decapeptide
Calponin-like repeats 1-3 are required for actin binding and acting bundling activity
The C-terminal is cytoplasmic and is important for interaction with ZO-1. Necessary for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction. The second extracellular domain may also be implicated in the permeability barrier function of the tight junction
The N-terminal domain seems to play a role in the reaction cycle of the catalytic subunit such as ATP8A2
Has an N-terminal Jag-N domain, a linker with a phosphorylated Thr, and 2 RNA-binding domains (KH and R3H)
The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes
Binds to transcription factors via its WW domain
Amino acids 1-191 are essential to mediate susceptibility to infection with CCV (in canine/human chimeric studies)
The rim domain (28-96 and 152-211) is accessible from the external milieu and is partially embedded in the outer membrane. The stem domain (131-148) is inaccessible from the outside and embedded in the outer membrane, while loop 6 (121-127) is thought to be in the periplasm
PCI domain is required for interaction with polysomes but not the interaction with sbr
The C-terminus interferes with binding to non-phosphorylated RHO. Interaction with phosphorylated RHO triggers displacement of the C-terminus and leads to a conformation change that mediates high-affinity RHO binding
The SUN domain may play a role in nuclear anchoring and/or migration (By similarity). The SUN domain is required for interactions with WIP proteins (PubMed:22270916)
Contains an unselective bimetallic binding site, with a high-affinity site (H-site) and a low-affinity site (L-site). Metal binding to the H-site triggers the binding to the L-site. This bimetallic center may play a structural more than a catalytic role
A conformation change implying rotational movement of the cytoplasmic domains plays an important role in channel opening and closing. Release of polyamines from their binding sites on the cytoplasmic domain may block the ion permeation pathway, preventing the efflux of intracellular potassium ions
The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding
The C-terminus (residues 536-662) is dispensable for DDX3X trafficking
The A region binds phospholipids with a preference for negatively charged species
Contains at least 4 autonomous repression domains (RD1-4)
Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have different affinities for nuclear receptors
The Ligand-dependent nuclear receptor binding region is required for ligand-dependent interaction with RAAR and RXRB homo- and heterodimers, for the corepressor activity, and for the formation of an HDAC3 complex with RARA/RXRB
Binds target DNA that contains at least one unmethylated cytosine via the CXXC-type zinc-finger domain
The fourth transmembrane region (161-181), which is missing in isoform 3, isoform 5 and isoform 6, is necessary for integration into tight junctions
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (328-358) inactivates kinase activity under calcium-free conditions
N-terminal zinc-finger domains are similar to the Ikaros clan but may not have the same binding specificity. Key residues involved in binding to the consensus Ikaros target site (5'-GGGA-3'), found in the promoter regions have diverged
The N-terminal region (residues 1-7) is involved in phosphatidylethanolamine-binding and is required for ATG8-PE conjugation
The handle region (HR) contains the ATG8 interaction motif (AIM) and mediates binding to ATG8. It is crucial for the cytoplasm-to-vacuole targeting pathway
Has a conserved RxLR motif that acts to carry the protein into the host cell cytoplasm. Lacks the 'so-called' EER motif, which is found closely behind the RxLR motif in most of RxLR effector family members, but the presence of an EER motif is not always essential for the translocation of every RxLR effector into host cells, or for inducing a hypersensitive response
Contains a N-terminal domain similar to that of the N-terminal section of DKK3
The AF-1 domain mediates transcription activation. The N-terminal region (1-292) directly interacts with the C-terminal LBD (380-627): the interaction is potentiated by AF-1-mediated recruitment of NCOA2
The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain
Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL SH2 domains. The HLH motif is absolutely required for the induction of pseudohyphal growth in yeast and mediates heterodimerization with NEDD9
A serine-rich region promotes activation of the serum response element (SRE)
The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK1
Retains a single open conformational state for both the apo- and ligand-bound forms
The UBA domain specifically recognizes Lys-48-linked diubiquitin units (Ub2), which is mediated by the two binding sites within a single UBA domain
The ricin B-type lectin domain directs the glycopeptide specificity. It is required in the glycopeptide specificity of enzyme activity but not for activity with naked peptide substrates, suggesting that it triggers the catalytic domain to act on GalNAc-glycopeptide substrates
Modular protein that contains an aryl carrier protein (ArCP) domain which bears a phosphopantetheinyl arm to attach the activated salicylic acid, a condensation/cyclization domain involved in the formation of the oxazoline ring, an adenylation domain which activates the serine or threonine residue into an aminoacyl-AMP ester, and a peptidyl carrier protein (PCP) domain which bears a phosphopantetheinyl arm to attach the activated serine or threonine
A C-terminal ubiquitin-binding domain (UBD) is essential for transcription-coupled nucleotide excision repair activity, interaction with RNA polymerase II, association with chromatin after UV irradiation and for mediating the UV-induced translocation of ERRC8 to the nuclear matrix
The N-terminal domain exerts an inhibitory effect on the helicase ATP-binding domain in such a manner that its ATPase activity is restricted (PubMed:29203878). Phosphorylation at Ser-10 and Ser-158 promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (PubMed:29203878)
The MyMOMA (MYO19-specific mitochondrial outer membrane-association) region mediates association with the mitochondrion outer membrane via electrostatic interaction
The linker region, also named autoinhibitory interface, is less inhibitory on its own than that of CARD9 (PubMed:31296852). The linker region together with the inhibitory domain (ID) are required to prevent constitutive activation and maintain CARD11 in an autoinhibitory state (PubMed:31296852). Disruption of the inhibitory domain (ID) region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments (PubMed:31296852)
The CXXC zinc finger plays a role in TET1 chromatin loading and participates in binding to CpG-DNA (PubMed:29276034). However, the global chromatin binding can be mediated by the entire N-terminus and occurs even in the absence of the CXXC domain (By similarity). The zinc finger domain impedes association DNA replication sites and prevents aberrant 5mC oxidation (PubMed:36056023)
A short internal peptide (residues 452-470) has been used as a miniprotein to examine protein folding and stability
The EXS domain is essential for Pi efflux out of cells and is necessary for the endomembrane localization
The SPX domain provides a basic binding surface for inositol polyphosphate signaling molecules (PubMed:27080106)
Forms 2 domains with an elongated structure; Rpo4 packs into the hinge region between the 2 domains
The GPPX3Y motif mediates interaction with CEP55
The bromo domain is required for interaction with histone H4K16ac
The bromo domain is required for localization to DNA damage sites
The MYND-type zinc finger domain is required for localization to DNA damage sites
The PWWP domain is required for interaction with histone H3.1K36me2
The N-terminus (residues 22-369) partitions into an aqueous phase and is predicted to be periplasmic, while the C-terminus (residues 426-837) partitions into Triton X-114 and has the hallmarks of a beta-stranded protein, suggesting it is membraneous
The ZAS2 domain binds DNA as dimers, tetramers, and multiple of tetramers and readily forms highly ordered DNA-protein structures
Binds ADP-ribose via the N-terminal cytoplasmic region (PubMed:30250252). Other family members contain a C-terminal Nudix hydrolase domain that binds ADP-ribose and is important for channel gating. In zebrafish, the corresponding region is highly divergent and has only low affinity for ADP-ribose (PubMed:30467180). Still, the region is required for channel activity (PubMed:30250252)
The cytoplasmic domain appears to contain the autoantigenic epitopes
Requires the transmembrane domain (TMD), a short segment (the import sequence) in the cytoplasmic domain localizing separately from the TMD and the C-tail signal in the C-terminal domain for efficient targeting and integration into the TOM complex (By similarity). The N-terminal domain (residues 1-62) is important for binding to the unfolded mature imported proteins. Residues (49-71) of the cytoplasmic domain interacts with TOMM20 while the C-terminal segment (residues 63-82) binds presequence of preproteins
The SSD (sterol-sensing) domain is necessary for the increase in cellular cholesterol uptake
Lacks the C-terminal sugar-binding domain
The NPXY motif mediates the interaction with ldlrap1
There are three Gb3-binding sites in each subunit B monomer, allowing for a tighter binding to the target cell. Binding sites 1 and 2 have higher binding affinities than site 3
The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies
The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA (PubMed:26249698). It may also be involved in localization to stress granules (By similarity)
HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence
The TIR domain is a signaling domain involved in cell death induction
Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with zmynd11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 74-106, leaving each N-terminal inhibitory region (residues 26-52) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 26-52) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity (By similarity)
DRFs are regulated by intramolecular GBD-DAD binding where Rho-GTP activates the DRFs by disrupting the GBD-DAD interaction
The CCT domain is essential for the interaction with SPA1
The last loop motif confers selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) to behenoyl-CoA (docosanoyl-CoA; C22:0-CoA) as acyl donors
Interaction with PSEN1 causes partial unwinding of the transmembrane helix, facilitating access to the scissile peptide bond
Consists of two domains; the N-terminal catalytic domain and the editing domain; the C-terminal C-Ala domain is replaced by an unrelated sequence in this strain. The editing domain removes incorrectly charged amino acids (By similarity)
The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function
Region A confers human cells susceptibility to infection by Gibbon Ape Leukemia Virus (GaLV) and Feline leukemia virus subgroup B (FeLV-B). Substitution of Human SLC20A1 region A by region A of murine SLC20A1 prevents viral infection
Intrinsically unstructured in the absence of binding partners. Folds upon binding to DNA or RNF2 (By similarity)
The L13 loop movement regulates the transition between active and inactive conformations by repositioning Lys-402, which, in turn, mediates the rearrangement of the binuclear metal center
TSP type-1 domain 0 binds to TSP type-1 domain 4, and TSP type-1 domain 1 binds to TSP type-1 domain 6 (PubMed:15491616, PubMed:28264884, PubMed:31507604). These interactions mediate multimerization (PubMed:15491616, PubMed:28264884, PubMed:31507604)
The IQ motif, which is involved in calmodulin binding, overlaps with the binding domain for nuclear receptors and transcription factors. Its phosphorylation probably allows a switch between the two activities of the protein
The cysteine framework is C-C-CCC-C-C-C
The function of the Tudor-knot domain, also named chromodomain-like, is uncertain. One study suggests that it mediates binding to lysine-methylated histone tails, with strongest affinity for H4K20me3 and H3K36me3. However, another study failed to find any interaction between this domain and histone H4K20me3 peptide
Contains 1 OTU domain with intact active sites. No deubiquitinase activity has been detected when tested (PubMed:23827681)
The SH2 domain mediates interaction with phosphorylated CD6 (PubMed:16914752). The SH2 domain mediates interaction with SHB (PubMed:12084069)
A beta-hairpin (residues 322-332) fits into a pocket in cognate immunity protein CdiI-o11 and helps confer immunity protein specificity (PubMed:23236156, PubMed:26449640). The inner membrane translocation domain (IMTD) targets the toxin to a specific target cell inner membrane protein (YciB in this case), which delivers the toxin to the target cell cytoplasm. Exchanging this IMTD between CdiA proteins alters the inner membrane protein delivery system but not the CdiI immunity protein, strongly suggesting CdiI recognizes only the toxic domain (PubMed:26305955)
The proline-knot motif (79-88) may be involved in targeting to lipid bodies
Has a GGDEF domain (residues 175-303) preceded by a PAS-like domain (residues 74-137) which together may have ATPase activity (By similarity). This is followed by a region with a DHH (342-498) and a DHHA1 (592-645) domain which together have c-di-AMP phosphodiesterase activity (PubMed:23716572, PubMed:25965978). The PAS-like domain is important for heme b-binding (By similarity)
Interaction with Rnp4 is mediated by the N-terminus; short deletion mutants are still able to reconstitute RNase P activity
The N-terminal region contains the ATLF domain responsible for binding to the cleaved form of protective antigen (PA-63) (PubMed:11807546). The C-terminal region contains the calmodulin-dependent activation domain and the catalytic site (PubMed:11807546). This region is composed of three globular domains: CA, CB and a helical domain connected to CA by a linker (PubMed:11807546). The active site lies at the interface of CA and CB (PubMed:11807546). The metal ion is coordinated by residues from CA; calmodulin probably binds in a multistep fashion first to residues in CA and then to residues present in the linker and the helical domain (PubMed:11807546)
Proteolytic cleavage leads to an important conformation change. This reduces the affinity for steroids (By similarity)
The SBD domain (substrate-binding domain) mediates the interaction with substrate proteins. It is related to the TRAF family
The WW domain is required for the interaction with STIL and KIF20B
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. Upon phosphorylation of ITIM motif KLRG1 associates with the two phosphatases PTPN11 and INPP5D (By similarity)
Contains a small N-terminal domain involved in dimerization and a large C-terminal Bet v1-like fold catalytic domain
Contains an N-terminal domain (1-190), a central domain (206-433) and a C-terminal region (444-513) (PubMed:8449883, PubMed:8444880, PubMed:17222426). The N-terminal domain is required for transcription activation functions, dimerization and ATP-independent aromatic amino acid binding (PubMed:8449883, PubMed:8407813, PubMed:8444880, PubMed:17222426, PubMed:30680497). The central domain is involved in ATP binding and hydrolysis, and is responsible for ATP-dependent tyrosine binding and hexamerization associated with tyrosine-mediated repression functions (PubMed:8449883, PubMed:8444880, PubMed:11923293). The C-terminal region contains a classical helix-turn-helix motif responsible for binding to DNA targets known as TyrR boxes (PubMed:8449883, PubMed:10197993)
The channel pore is formed by TM3 and the loop between TM2 and TM3. After a sharp turn at Gly-113, an alpha-helix (residues 114-127) is oriented nearly parallel to the plane of the putative lipid bilayer. On the intracellular side of the channel, the permeation pathway of MscS does not connect directly to the cytoplasm but instead opens to a large chamber that is connected to the cytoplasm. This chamber resembles a molecular filter that could serve to prescreen large molecules before they are allowed passage to the transmembrane pore. The TM1 and TM2 helices appear to be likely candidates for mediating the tension and voltage sensitivities of MscS. Gating requires large rearrangements of at least the C-terminus, and is probably influenced by freely exchangeable membrane lipids that bind in grooves and pockets between the transmembrane helices and enhance the stability of the closed channel conformation. In a hypoosmotic environment the membrane is stretched, and lipids may be pulled into the lipid bilayer and away from the protein, which is predicted to destabilize the closed conformation and promote channel gating
The calcium-binding domain (165-176) of the EF-hand 4 can also interacts with a manganese ion. The N-terminal 18 amino acids are sufficient for the cell membrane targeting of a heterologous protein
The intramembrane domain also contains the signal for ER targeting
The regulatory domain (RD) contains the auto-inhibitory domain (AID) that inhibits kinase activity of the protein kinase domain (KD)
The PPI motif mediates the interaction with the ABI (abscisic acid-insensitive) phosphatases
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The C1 zinc finger does not bind diacylglycerol (DAG)
The pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins, except the presence of a non-phosphorylatable residue in place of Ser, it modulates activity by competing with substrates
Interacts with MBIP through the leucine-zipper motif
Each subunit is composed of an apical domain that binds non-folded proteins and GroES, an intermediate domain and an equatorial domain that binds ATP and is involved in inter-ring interactions (PubMed:7935790, PubMed:16288915). Forms a large central channel that appears to traverse the entire length of the cylinder with no obstruction (PubMed:7935790). The central channel of GroEL functions as two cavities, one in each ring, that are separated from each other by the crystallographically disordered 23-amino-acid C-terminal segments of the seven subunits (PubMed:9285585). The entry and exit of polypeptide seem to be restricted to the apical end of each ring (PubMed:9285585)
Modulating the volume of the GroEL central cavity affects folding speed in accordance with confinement theory. Small proteins fold more rapidly as the size of the cage is gradually reduced to a point where restriction in space slows folding dramatically. For larger proteins, either expanding or reducing cage volume decelerate folding (PubMed:16751100). A stepwise reduction in cage size results in a gradual loss of cell viability (PubMed:18418386)
The pro-region is necessary but not sufficient for wnt-inhibitory activity. The central region is required for muscle induction activity
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (370-400) inactivates kinase activity under calcium-free conditions
Contains an N-terminal domain that anchors the protein to the inner membrane, a central domain (domain II), and a C-terminal domain (domain III), which is the functional portion of the protein (PubMed:2068069). The C-terminal domain is involved in interaction with TolB and Pal, and is also involved in direct interaction with colicins and phages. It adapts its conformation upon binding to various partners (PubMed:11115123, PubMed:11994151, PubMed:15701516)
The LDLR maturation activity resides in the N- and C-terminal unstructured regions
The C-terminal C2 domain shows Ca(2+)-dependent phospholipid binding. It binds to phosphatidylserine, phosphatidylinositol and various phosphoinositides. The other C2 domains do not retain all 5 conserved Asp residues found in calcium-binding C2 domains
The N-terminal region is required for binding to phosphorylated substrates while the C-terminal region binds to the other R2TP complex components
The ligand-binding domain (LBD) forms a four-helix bundle (4HB), and both ligand binding sites of the dimer are occupied with the high-affinity ligands protocatechuate and quinate, whereas the lower-affinity ligands benzoate and salicylate are present in only one site. Ligand binding causes rigid-body scissoring movements of both monomers of the dimer
There are 3 carboxypeptidase domains. Only the first two domains have any catalytic activity. The first domain preferentially cleaves C-terminal Arg residues, whereas the second preferentially cleaves C-terminal Lys residues. The third domain binds to pre-S, hepatitis B virus large envelope protein
The RNA recognition motif domains RRM 2 and RRM 3 are necessary and sufficient for binding to uridine-rich target pre-mRNA
The RRM 1 and RRM 2 domains are required for the localization to stress granules (SGs) and for the recruitment of TIAR1 and poly(A) RNA to SGs in response to stress
The RRM2 domain and the C-terminal residues 287-340 contribute to nuclear localization
The RRM3 domain mediates nuclear export
The C-terminal glutamine-rich (Q) sequence in combination with the RRM 1 domain is required for the interaction with SNRPC/U1-C and to facilitate recruitment of spliceosomal U1 snRNP to 5' splice sites
Each monomer consists of two domains: a C-terminal catalytic domain and a putative N-terminal regulatory domain
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and 2 acyl-carrier proteins (ACPs) that serve as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
Has a putative N-terminal zinc-finger, a middle region with homology to RecA with ATPase motifs including the RadA KNRFG motif, while the C-terminus is homologous to Lon protease (By similarity). Absence of the zinc-finger domain gives a slight increase in sensitivity to gamma and UV irradiation, absence of the Lon protease domain gives slightly increased resistance to gamma and UV irradiation
Contains repeated alternating basic mature peptide and acidic propeptide domains
Both CR1 and CR2 regions are required for speckled nuclear localization
The DVD domain (residues 311-334) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation
The N-terminal part seems to be a myosin/calmodulin-binding domain, and the C-terminal a tropomyosin/actin/calmodulin-binding domain. These two domains are separated by a central helical region in the smooth-muscle form
The N-terminal part (1-87) is not required for enzymatic activity
Amino acid residues 138-160 are probably part of the polyprenyl diphosphate-binding domain
The editing domain removes incorrectly charged amino acids, i.e. Ser-tRNA(Ala) or Gly-tRNA(Ala) become uncharged tRNA(Ala) and the amino acid. It is specific for the acceptor stem of tRNA(Ala)
The C-terminal C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs. This C-Ala domain can be replaced in vitro by the corresponding domain of Aquifex aeolicus or man. Recognition of tRNA(Ala) by the 2 domains is independent, that is one enzyme recognizes the same tRNA(Ala) in 2 different manners
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containingbinding partners. Especially they mediate the with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3)
The dileucine internalization motif is critical for intracellular sequestration
The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B
The atypical Tudor domain at the C-terminus contains two large unstructured loops, and does not bind methylated residues
The SET-like region, although related with the SET domain is not detected by any prediction method
The N-terminus region is necessary for interaction with actin retrograde filament flow and accumulation in neuronal growth cones
The helix containing the catalytic Tyr-132 (residues 127-133) is highly mobile. Recognition of the 5-base sequence immediately preceding the cleavage site is mediated by base-pairing to an imperfect palindrome, by sandwiching the fifth nucleotide between Tyr-30 and Trp-107 and hydrogen bonding to His-32, and by main chain atoms of Leu-106 and Trp-107
DRBM domains cooperate for the binding to nucleic acid but not for unwinding helicase activity (PubMed:9111062, PubMed:25062910). The helicase-associated domain-2 (HA2) region is essential for the duplex RNA unwinding helicase activity (PubMed:25062910). The minimal transactivation region (MTAD) mediates interaction with the RNA polymerase II holoenzyme and stimulates transcriptional activation in a CREB-dependent manner (PubMed:11416126). The oligonucleotide- or oligosaccharide-binding (OB-fold) and the repeated arginine and glycine-glycine (RGG) regions are dispensable for both RNA-binding and unwinding helicase activities (PubMed:25062910). The RGG region contains both nuclear localization signal (NLS) and nuclear export signal (NES) and is necessary and sufficient for nucleocytoplasmic shuttling in a RNA-independent manner (PubMed:10207077, PubMed:11149922)
Each ChpT monomer is composed of an N-terminal dimerization and histidine phosphotransfer (DHp) domain and a C-terminal domain that is structurally similar to the catalytic and ATP-binding domain found in histidine kinases but that lacks regions required for ATP binding
The phospholipase A2-like domain represents the fully processed form after N- and C-termini are cleaved off. It is the secreted mature form found in biological fluids
The N-terminal tandem family 41 carbohydrate-binding modules (CBM) are involved in carbohydrate binding (PubMed:17187076, PubMed:21565699). The C-terminal glycosyl hydrolase 13 (GH13) domain is involved in catalysis (PubMed:21565699)
Inhibitory activity is regulated via a pH-induced conformational change of the structure. At pH above 7, Gfh1 is in an inactive flipped orientation that prevents binding to RNAP. At lower pH, Gfh1 switches to an active orientation, which enables binding to RNAP and inhibitory activity (Probable)
The N-terminal 12 amino acids are sufficient for cell membrane targeting
The EH domain (1-93) is critical for vesicular localization
The C-terminal UPF0157 domain is involved in the proper folding of the full length enzyme
The PHD-type zinc finger 1 mediates both nucleolar localization and interaction with UBTF
The ePHD2 domain folds as an integrated structural module comprizing the C2HC pre-PHD-type 2 zinc finger and the PHD-type 2 zinc finger. It mediates non-specific binding to dsDNA, but doesn't bind histones in contrast to many PHD-type zinc fingers
The cysteine framework is I (CC-C-C). Alpha4/8 pattern
The WW domain 4 mediates interaction with ENTREP1
The protein is evolutionarily related to retrotransposon Gag proteins: it contains large N- and C-terminal domains that form a bi-lobar architecture similar to the capsid domain of human immunodeficiency virus (HIV) gag protein (PubMed:29328916, PubMed:25864631). It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells (PubMed:29328916). Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons (PubMed:29328916)
The run of Gly-Thr is implicated in the maintenance of circadian period at different temperatures. Deletion of the repeat leads to a shortening of the courtship song cycle period, and thus could be important for determining features of species-specific mating behavior (By similarity)
Contains 7 A-type repeats and 14 B-type repeats similar to those found in maize, rice and barley dehydrin and rab proteins
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (PubMed:14700635). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:14700635). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) or reductase domain (R) that releases the newly synthesized peptide from the enzyme (PubMed:14700635). LpsB is composed of only one module which is required for the activation of D-lysergic acid activation and its incorporation in the final ergot alkaloid (PubMed:19139103)
4Fe-4S iron-sulfur-binding is required for helicase activity
DOMON domain could bind one heme b
The RING-type zinc finger mediates interaction with SUMO2 and localization to the nucleus (By similarity). Also required for the E3 ubiquitin ligase activity
The B box-type zinc finger mediates homodimerization
The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif)
The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis
The unstructured hinge region contains clathrin-binding but no autoinhibitory (DXXLL) motifs
The GAE domain binds accessory proteins regulating GGAs function
The cytoplasmic domain is involved in the binding of DAB1 and in the recruitment of JNK-interacting proteins. Isoforms, which lack part of the cytoplasmic domain, are unable to recruit members of the family of JNK interacting proteins (JIP) to the cytoplasmic tail
Has several major domains; the N-terminal cytoplasmic domain is followed by 2 transmembrane helices that anchor the protein in the membrane; the periplasmic domain between the helices interacts with MrzA. The cytoplasmic C-terminal domain has a HAMP domain joined by a flexible linker to a histidine kinase domain. The HAMP domain by itself is intrinsically disordered. The cytoplasmic dimerization domain (CDD) forms an osmosensitive core and includes the autophosphorylated histidine residue
The peptide 129-Asp--Trp-139 is responsible for the carbohydrate binding
The coiled coil regions mediate binding to kinetochores
Binds three calcium ions (via EF-hand 2, 3 and 4)
The matrix-exposed C-terminus contains a 14-3-3-like domain which is necessary and sufficient for interaction with mitochondrial ribosomes
The LID domain is a solvent-exposed domain that closes over the site of phosphoryl transfer upon ATP binding
Consists of four structural domains: the ATP binding site resides in domain I (DT1); DT3 binds the positive effector maltotriose with a low affinity, and the binding affinity is increased in the presence of DT2; the C-terminal domain DT4 contains the helix-turn-helix DNA binding motif. DT1 also contains the region that interacts with MalY (but not with MalK), and the binding site for Aes is also likely to be contained in the N-terminal portion of MalT encompassing DT1 and DT2 (PubMed:12003949). Domain DT3 may mediate oligomerization (PubMed:11709169)
Probably has 2 alpha-helices (resides 3-26 and 39-83); both helices alone target to PHB granules, although helix 2 may be the main anchor. Both helices are required for oligomerization
The N-terminal AAA+ ATPase domain and the C-terminal winged-helix (WH) domain are both required for DNA binding
The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes (By similarity)
12 dinuclear ferroxidase centers are located at the interfaces between subunits related by 2-fold symmetry axes
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-101 and Arg-104) that bind to malonylated and succinylated substrates and define the specificity
Composed of two catalytically active A modules and four R modules. The N-terminal A domain introduces a mixture of MG-blocks and G- blocks, whereas the C-terminal A domain only generates MG-blocks
The PDZ-binding motif is required for neurite outgrowth promotion and interaction with DLG1, DLG3- and DLG4
Requires the intact death domain to associate with tnfrsf1a
AFL adopts the six-bladed beta-propeller fold and contains 6 binding sites per monomer, each located between two adjacent blades (PubMed:25760594). The 6 binding sites that are non-equivalent, and owing to minor differences in amino-acid composition they exhibit a marked difference in specific ligand recognition (PubMed:24340081, PubMed:25760594)
The core amyloid fragment (CAF) represents the amyloidogenic unit of melanosomal fibrils
The highly O-glycosylated repeat (RPT) domain drives the generation of the fibrillar amyloid sheet structures within melanosomes. The O-glycosylation sites rather than its primary amino acid sequence are conserved across species
The Kringle-like domain (KLD) contains six highly conserved cysteine residues that are critical for dimer formation
The N-terminal domain likely catalyzes substrate activation by formation of an initial acyl-AMP intermediate, the central region contains the phosphopantetheine attachment site, and the C-terminal domain catalyzes the reduction by NADPH of the intermediate thioester formed from the attack of the phosphopantetheine thiol at the carbonyl carbon of acyl-AMP
The RRM domain is necessary for interaction with SMAD4. Both the RRM domain and the C-terminus are required for TGFB1/Smad-mediated transactivation activity (By similarity)
The homodimer has swapped domains; the N-terminus of one monomer interacts with the C-terminus of the other
The N-terminal region (the pseudo-receiver, PsR), does not enhance KaiC autophosphorylation. It may have an amplitude-amplifier function and may be involved in transducing input signals to the KaiABC complex. This domain is not conserved in all other species (PubMed:15007067). PsR binds oxidized but not reduced quinones (PubMed:20231482, PubMed:23020633). The flexible linker and C-terminal domain mediate the interaction with KaiC, homodimerization, and are responsible for the clock oscillation function (PubMed:15007067). The C-terminal domain also binds an oxidized quinone in a crystal (PubMed:23020633)
The C-terminus contains also a calcium binding site (residues 215-224) that might be involved in NADase activity regulation (PubMed:33712585). The calcium-binding site is not alweays present since it emerged in the order Eurotiales, which includes Aspergillus species (PubMed:33712585)
Contains an N-terminal DNA-binding domain, followed by a dimerization domain and a C-terminal domain, called the small MutS-related (Smr) domain, which is absent from MutS and contains the endonuclease activity
The N-terminal domain is an intra-molecular chaperone that prevents premature oligomerization of the residues on the coiled-coil region that are involved in interactions with the needle and/or itself. The residues in the C-terminal domain probably form oligomeric structures at the tip of the needle that are responsible for the regulation of secretion of other effectors
The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments. Interacts with UBE2I
MVP 3 mediates interaction with PTEN
MVP 4 mediates interaction with PARP4
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate (PubMed:24880344). However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs (By similarity)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (PubMed:23116177)
The AH domain mediates binding to F-actin
The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization (By similarity)
C2 domain is a calcium-binding fold, and the binding induces conformational changes, promoting the protein association with membranes. These conformational changes occure at millimolar Ca(2+) concentrations. Binds also PIP2. A lower affinity toward calcium can be anticipated for PLD alpha due to the absence of two potential calcium ligands
The LIR motif (LC3-interacting region) is required for its interaction with lgg-2
The THAP-type zinc finger mediates DNA-binding and specifically recognizes sequence elements in a bipartite manner using both the major and minor grooves of its target DNA site. Minor-groove recognition is achieved by a combination of direct base contacts and indirect sequence readout of DNA deformation through a variable, basic loop. By contrast, the adjacent major groove is sequence-specifically recognized by the central beta-sheet of the domain (PubMed:20010837)
The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation. The zinc fingers and the N-terminus are independently important for establishing the L/R axis (By similarity)
The cysteine framework is I (CC-C-C). Alpha4/2 pattern
Composed of an N-terminal domain that binds Munc18-1 and LIN-2/CASK, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane
The autoinhibitory helix linker occludes the APP binding site
The PID domain, truncated by 11 amino acids, as observed in isoform 2, but not full-length, mediates the interaction with RAB6A and RAB6B
The Ig-like V-type domain mediates interaction with JAM2
The region between Ser-201 and Leu-335 is required recruitment of SLX5 to ub-hotspots via interacion with EUC1
The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (By similarity). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits (PubMed:22056818). The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells. The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons (By similarity)
The carbohydrate-binding module-67 (CBM67) binds L-rhamnose, it does not bind L-galactose or L-fucose, demonstrating that stereochemistry of the sugar at C4 and/or C2 are important specificity determinants. Also, removal of calcium through chelation or mutation abrogates L-rhamnose binding, confirming the importance of calcium in the binding of its ligand
C-terminal half contains cytoplasmic retention domains as well as determinants involved in its stress-induced nucleolar accumulation
The N-terminal domain is required for the positive control of neuroblast asymmetric divisions
The RING-type zinc finger is involved in CANX ubiquitination and degradation, but is not required for interaction with CANX
The N-terminal domain is involved in FliG binding, the C-terminal domain is involved in FliM binding
The PilZ domain is able to bind c-di-GMP, but with a lower affinity (dissociation constant of 1.45 uM) compared to the whole protein (dissociation constant of 0.84 uM)
The bromodomain-like (BRDL) region specifically recognizes and binds acetylated histones
The YYX motif is required for the association with the proteasome
The N-terminal PX domain interacts specifically with phosphatidylinositides
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the USP domain mediates interaction with PAN3
The binding pocket contains an arc of aromatic residues that complements the natural helical structure of starch and imposes this conformation on bound maltoheptaose. Binds cyclic oligosaccharides with higher affinity than linear forms (PubMed:18611383)
The protein kinase domain mediates interaction with NGEF
Composed of only a NusG N-terminal (NGN) domain and a KOW domain, similar to bacterial NusG. The NGN domain is the effector domain of the complex that mediates the interaction with RNAP and is essential for elongation activity
The C-terminus mediates interaction with mSin3A corepressor complex
The N-terminus is involved in transcriptional repression by HDAC-independent mechanisms
The ARID domain is involved in stabilizing the mSin3A corepressor complex on DNA
The LysM domains are involved in substrate recognition and binding to cortical peptidoglycans. They are also involved in directing protein localization
The RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling (By similarity)
The TBM domain mediates interaction with TERF2
Intrinsically disordered protein that undergoes folding upon phosphorylation. Hypophosphorylated form interacts strongly with EIF4E using (1) the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and (2) the secondary EIF4E binding sites (residues 78-82). Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000
The Link domain interacts with various extracellular matrix components, including heparin, heparan sulfates, hyaluronan and I-alpha-I complex (PubMed:15917224, PubMed:15060082). It is required for binding to various chemokines (PubMed:27044744)
The CUB domain is necessary for calcium ion binding and transesterification reaction (PubMed:26468290). It is required for binding to FN1 (PubMed:18042364)
The RGG repeats are required for interaction with ddx6/Xp54 and accumulation in ribonucleoprotein complexes
The CRM-I motif (C-X-C-X3-C-X-C-X2-C-X2-H) and CRM-II motif (C-C-X3-C-X-C-X4-C-X-C-X3-C-C-X-C-C-X2-C-X-C) correspond to cystein-rich copper-binding domains
The protein is composed of 2 domains; the N-terminal domain contains the phospholipase C active site (PLC), in a cleft which is also occupied by the 3 zinc ions. The C-terminal domain is a putative phospholipid-recognition domain, which shows structural homology with phospholipid-binding C2-like domains from a range of eukaryotic proteins. The ability to bind membrane phospholipids in a Ca(2+) dependent manner and toxicity is conferred by this C-terminal domain, which also contributes to the sphingomyelinase activity
The active phytochrome binding (APB) motif (3-17) is involved in interaction with PHYB
The Gln-rich domain in the C-terminal region functions to modulate the transcriptional activity of BHLH72/PIF7
Has 16 transmembrane helices and a cytoplasmic domain that contains the active site
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (377-407) inactivates kinase activity under calcium-free conditions
The N-terminal anti-sigma domain (residues 1-85) is necessary and sufficient to bind sigma-E and inhibit its activity. The C-terminal domain (residues 86-194) is required to respond to singlet oxygen (PubMed:17803943)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tim-10/tin-10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The protein goes through several conformation states during the reaction cycle, giving rise to hysteresis. In the initial state, the ligand-free protein is in an inactive conformation (E*). Substrate binding triggers a change to the active conformation (E). UDP-xylose binding triggers the transition to a distinct, inhibited conformation. The presence of an intrinsically disordered C-terminus promotes a more dynamic protein structure and favors a conformation with high affinity for UPD-xylose
The allosteric switch region moves by about 5 Angstroms when UDP-xylose is bound, and occupies part of the UDP-glucose binding site. At the same time it promotes domain movements that disrupt the active hexameric ring structure and lead to the formation of a horseshoe-shaped, inactive hexamer
The coiled coil domain interacts directly with the BAR domain of ARHGAP17
The angiostatin binding domain (871-1005) allows the binding to angiostatin
The IQ domain mediates association with calmodulin
Contains a nuclear localization signal between amino acid positions 75 and 98. Contains a nuclear export signal between amino acid positions 228 and 272
Effector proteins that bind to TolB can both negatively (Pal) and positively (colicin E9) regulate association of the distal N-terminal TolA box with TolA by influencing the conformational equilibrium experienced by these residues
The DHOase domain is defective
The SAWADEE domain (138-244) binds to mono-, di-, or trimethylated H3K9 histone peptides, but this interaction is impaired if H3K4me2/3 methylation is present (PubMed:23637343, PubMed:23636332)
The C-terminal domain is necessary for the induction of long fine actin-containing filopodia-like structures in fibroblast and neurite-like outgrowth
The Ig-like V-type 2 domain is necessary and sufficient for interaction with integrin alpha-L/beta-2
The basic domain (B) allows nucleolar localization in the absence of GTP. The intermediate domain (I) inhibits nucleolar localization by the B domain and is required for exit from the nucleolus. Exit from the nucleolus to the nucleoplasm requires both the I and the acidic (A) domains, and may be triggered by GTP hydrolysis
The POU-specific domain mediates interaction with PKM
The N-terminal destruction box (D-box) probably acts as a recognition signal for degradation via the ubiquitin-proteasome pathway
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (391-421) inactivates kinase activity under calcium-free conditions (By similarity)
The mature protein has 4 domains; a metalloprotease domain (S1, approximately residues 41-717), S2a (718-810, equivalent to PKD 1), S2b (811-904, equivalent to PKD 2) and a collagen-binding domain (S3, 905-1021) (PubMed:9922257, PubMed:9452493). The protein has an elongated shape, which lengthens further in calcium-chelated conditions; calcium-chelation also increases its susceptibility to exogenous proteases (PubMed:23561530). The S1 domain has the collagen hydrolytic activity (PubMed:9452493, PubMed:18937627). The metalloprotease S1 domain is composed of 3 subdomains which together resemble a saddle; an activator domain (residues 41-320), the catalytic peptidase subdomain (330-601) and a helper subdomain (609-721) (PubMed:23703618). Unlike the S2 domain in ColG, upon binding to Ca(2+) the midsections of S2a and S2b remain rigid; Ca(2+) binding confers thermostability (PubMed:25760606). Ca(2+)-binding also alters the orientation of the N-terminal linker of S2b so it lies along the long axis of the domain (PubMed:25760606). S3 has collagen-binding activity (PubMed:9452493). The structure of S3 becomes more thermostable when it is bound to Ca(2+) (PubMed:23144249). Isolated CBD S3 binds unidirectionally to the C-terminus of the collagen triple helix via a surface cleft (PubMed:23144249)
The B box-type zinc finger interacts, possibly intramolecularly, with the pyrin domain; this may be an autoinhibitory mechanism released by PSTPIP1 binding
The cytosolic domain interacts with sigma factor SigK
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins. Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain (By similarity)
The RRM 3 domain is required for binding to poly(A) RNA, for the association with polysomes and with the EIF4F cap-binding complex and for the stimulation of translation (By similarity). The RRM 1 and RRM 2 domains may contribute to polysome association and stimulation of translation (By similarity)
The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner
The Bromo domains specifically recognize and bind acetylated histones
Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR1
Contains three distinct domains: an N-terminal catalytic domain that contains a binuclear Zn(2+) cluster, a central dimerization domain that ensures resistance to high concentrations of SDS and a C-terminal domain that provides a hydrophobic groove, presumably to recruit long aliphatic substrates (PubMed:16684886). Although separated by the dimerization domain in terms of sequence, the N-terminal and C-terminal domains are spatially directly adjacent (PubMed:16684886)
The phorbol-ester/DAG-type zinc finger is the principal mediator of the targeting to membranes and is required for functional activation through DAG-binding
The N-terminal inhibitory domain contains conserved sequence elements important for cytoplasmic retention (Region I) and proteolytic processing (Region II) of the protein. Region I is also required for ASI1/2/3-mediated negative regulation of transcription (By similarity)
The ASD1 domain mediates F-actin binding
For most of its length, paramyosin appears to form an alpha-helical coiled coil and shows the heptad repeat of hydrophobic amino acid residues and the 28-residue repeat of charged amino acids characteristic of myosin heavy chains. However, paramyosin differs from myosin in having non-helical extensions at both termini and an additional 'skip' residue that interrupts the 28-residue repeat. The distribution of charged residues is also different from myosin heavy chains
Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL SH2 domains
The SH3-binding sites that bind to the SRC SH3 domain are required for interaction with CRK and are implicated in promotion of serum response element (SRE) activation. The SH3 domain interacts with PTK2/FAK1
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with XCAP-E, forming a V-shaped heterodimer
The active-site cavity can accommodate both the hydrophobic substrate for the OSBS reaction and the substrates for the racemase activity. Accommodation of the components of the N-acyl linkage appears to be the reason that this enzyme is capable of a racemization reaction on these substrates, whereas the orthologous OSBS from E.coli lacks this functionality
The Pyrin domain mediates LPS recognition and homooligomerization
The coiled-coil domain (134-201) is necessary for SPA1, SPA3 or SPA4 binding. The DWD box is required for interaction with DDB1A
The QA motif is able to mediate transcriptional repression
The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity)
The histidine-rich N terminus is essential for interaction with Spx
The DAZ domains are essential and mediate the interaction with DAZAP1 and DAZAP2
Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds. The RRN7-type zinc finger plays an essential postrecruitment role in Pol I transcription at a step preceding synthesis of the first 40 nucleotides (By similarity)
The BPTI/Kunitz inhibitor domain is required for elastase inhibitory activity. BPTI/Kunitz inhibitor and WAP domains are involved in the protein antibacterial activity
The coiled-coil domain is involved in microtubule-binding
Shows a pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs
The C-terminal part is similar to retroviral Gag protein. This putative protein seems to be the result of a fusion between an Ig-like domain-containing protein and a ERV
The PH domain is essential for regulated exocytosis and binds phospholipids and plasma membrane. It however does not mediate binding to DCVs (By similarity)
The coiled coil domains mediate homooligomerization and are required for location at microtubules
The BAH domain is required for localization at H3K27me3
The C2 domain 2, but not the C2 domain 1, is necessary for calcium-mediated membrane association (PubMed:21087455, PubMed:26175110). The linker region is necessary for calcium-dependent cell membrane association (PubMed:21087455)
Globular monomeric protein mainly composed by alpha-helices sheltering internal cavities in a fold resembling the 'palm' domain found in siderophore biosynthetic enzymes
The protein is evolutionarily related to retrotransposon Gag proteins: it contains the capsid (CA)subdomain of gag
The BH3-like domain is required for association with BAX and for mediating apoptosis. The three BH domains (BH1, BH2, and BH3) of BAX are all required for mediating protein-protein interaction
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins MAP1LC3A, MAP1LC3B and MAP1LC3C
The Cys-rich domain is responsible for the localization of the protein to the plasma membrane
Has an N-terminal Jag-N domain and 2 RNA-binding domains (KH and R3H)
The linker domain is the critical region for polar localization
The C-terminal domain mediates copper(1+) binding (PubMed:26745413) and is involved in the copper(1+)-dependent-ATOX1 interaction (PubMed:26745413, PubMed:24837030). The C-terminal domain appears to act to limit transport through the pore by regulating the rate of exit of copper ions at the intracellular side (PubMed:23658018). The N-terminal domain can collect copper(2+) from copper(2+) carriers in blood (PubMed:30489586). The N-terminal domain, in the trimeric arrangement, tunes its reactivity with copper, promoting copper(2+) reduction and copper(1+) stabilization thanks to the presence of histidine (His) and methionine (Met) motifs (PubMed:32914794, Ref.24). The bis-His motif directly coordinate to copper(2+), whereas the Mets motif is involved in copper(1+) binding (Ref.24). The ligand switching between the bis-His motif and the Mets motif is regulated by pH (PubMed:35601835)
The ALG-2-binding site motif-2 (ABS-2) contains a PXPGF sequence that binds hydrophobic pocket 3 of PDCD6
The basic region and the leucine zipper structure are necessary for association with HOXD12 and PRRX1
PH and FYVE-type zinc finger domains are required for lysosomal location
The C-terminal cysteine-rich region may function as a fungal cell wall binding domain
The C-terminus of the protein cannot be tagged, suggesting it is required for function
In contrast to KCNAB1, the shorter N-terminal domain of KCNAB2 cannot mediate closure of delayed rectifier potassium channels by physically obstructing the pore
Lys-187 and Leu-195 residues are specific to human and destabilize the interactions with short DNA, shifting the specificity toward the detection of curved long DNAs (PubMed:30007416). Lys-187 and Leu-195 also restrain cGAMP production and, therefore, immune activation, allowing a more fine-tuned response to pathogens (PubMed:30007416)
The N-terminal disordered part (1-160) binds unspecifically dsDNA and expands the binding and moving range of CGAS on dsDNA (PubMed:28214358, PubMed:28363908). The disordered and positively charged residues enhance CGAS-DNA phase separation by increasing the valencies of DNA-binding (PubMed:29976794). The N-terminus is required to sense chromatin and its phosphorylation blocks its activation by chromatin DNA (PubMed:33542149). When the N-terminal part (1-160) is missing the protein bound to dsDNA homodimerizes (By similarity)
The arginine-anchor tightly binds to the canonical H2A acidic-patch residues
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2 (By similarity)
The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3 (By similarity)
The N-terminal CRISPR-associated Rossman fold (CARF) probably binds the cA6 effector. ssRNase activity resides in the C-terminal HEPN domain
The BTB domain mediates the interaction with the androgen receptor/AR and HDAC1 (PubMed:20812024, PubMed:25514493). Also mediates the interaction with SP1 (PubMed:12004059)
The N-terminal HD domain has ssDNase activity (PubMed:25773141). The C-terminal GGDEF domain has the cOA synthesis activity (By similarity)
The PHD finger domain specifically binds the N-terminal tail of histone H3 and this binding is inhibited by H3K4 di- or trimethylation (PubMed:22700931). No effect of H3K9 methylation on the binding (PubMed:22700931). The N-terminal domain (1-592) is required for interactions with IDM2 (PubMed:24920332)
A large substrate binding region with partially overlapping binding domains for structurally different substrates is formed by several transmembrane helix domains (TMH) including TMH 2, 4, 10 and 11, and it is alternatingly exposed to the extracellular or intracellular side during substrate transport (By similarity). Amino acids in TMH 1 confer major functional differences between human and mouse orthologs (PubMed:35469921)
The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus
The KH domain is required for binding to RNA
The Pro-rich domains are flanked by Arg/Gly-rich motifs which can be asymmetric dimethylated on arginine residues to give the DMA/Gly-rich regions. Selective methylation on these motifs can modulate protein-protein interactions (By similarity)
The fibronectin type-I domain mediates binding to fibrin, and the kringle domain apparently mediates fibrin-induced stimulation of activity
A shared internal Thr-Glu-Thr-Pro repeat defines a family of D.discoideum spore germination specific proteins
The domain that induces A-SMASE is probably identical to the death domain. The N-SMASE activation domain (NSD) is both necessary and sufficient for activation of N-SMASE
Both the cytoplasmic membrane-proximal region and the C-terminal region containing the death domain are involved in the interaction with TRPC4AP
Glutamate binding is mediated by the extracellular domain. In contrast, the allosteric modulator ivermectin binds between subunits at the periphery of the transmembrane domain, proximal to the extracellular side
There are three Gb3-binding sites in each subunit B monomer, allowing for a tighter binding to the target cell. Binding sites 1 and 2 have higher binding affinities than site 3 (By similarity)
The MYND-type domain is not required for oxygen-mediated hif-1 degradation or for inhibiting hif-1 transcriptional activity (PubMed:19737748). Susceptibility to S.aureus infection requires the Ser-rich region but not the MYND-type or Fe2OG dioxygenase domains (PubMed:22792069)
The 3'-5' exonuclease domain lacks the conserved Asp-Glu-Asp-Asp (DEDD) residues that coordinates divalent ions essential for exonuclease activity
The beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity
Histidine box-1 and -2 together with other histidine residues are essential for catalytic activity
Contains 2 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which are usually required for the association with nuclear receptors
Contains 44 copies of AFGP8 and two copies of AFGP7
The WW and FF domains bind to the phosphorylated carboxy-terminal domain of RPB1
The cysteine framework is C-C-C-C-C-CCC
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). AsaC contains an amino acid adenylation domain (A), a peptidyl carrier protein (PCP) domain with a phosphopantetheine prosthetic group, and a short-chain dehydrogenase/reductase terminus (R), but it does not have an identifiable condensation (C) domain required for the formation of peptide bonds during non-ribosomal peptide synthesis (PubMed:29674152)
The intracellular kinase domain and all four extracytoplasmic PASTA domains are essential for PknB function and cell survival (PubMed:24706757). The PASTA domains interact with peptidoglycans and are required for PknB localization (PubMed:21829358)
The cleavage site containing the double Phe-Phe motif acts as negative regulator of shedding by BACE2
The SH3 domain interacts with FYB1 and PTK2B
The transmembrane plays critical roles in migration to the peroxisome and/or subsequent insertion into the membrane
The ankyrin repeats (ANK) mediate interactions with hexoses-containing lipids present in organellar membranes (e.g. chloroplast), such as monogalactosyldiacylglycerol (MGDG) and phosphatidylglycerol (PG)
The ThrRS, GTPase, SpoT (TGS) domain is not necessary for GTP binding nor for the GTPase activity. It appears to play a regulatory role favoring GTP hydrolysis mediated by DFRP1/ZC3H15
The twin Cx9C motifs are involved in the recognition by the mitochondrial MIA40-ERV1 disulfide relay system and the subsequent transfer of disulfide bonds by dithiol/disulfide exchange reactions to the newly imported protein
Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-298) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation (By similarity)
The acidic tract A2 mediates histone binding
The GILK motif mediates interaction with PPP1CB
The J domain co-chaperone activity is required for chloroplast photorelocation movement
Contains an N-terminal domain that binds non-specifically to RNA and a C-terminal domain that binds specifically and tightly to hairpin 92 of 23S rRNA. Undergoes a conformation change in the helicase core upon binding of RNA and ATP
The KEN box motif is required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination
The two IQ domains are probably not interacting with calcium/calmodulin
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Here, the second motif is Asn-Pro-Val (NPV)
Contains large globular domains required for ATP hydrolysis at each terminus and a third globular domain forming a flexible hinge near the middle of the molecule. These domains are separated by coiled-coil structures
Ig-like C2-type domains 7 to 9 are sufficient for interaction with NTN1 and commissural axon outgrowth. The transmembrane domain is necessary for interaction with DCC
The olfactomedin-like domain is involved in the interaction with cadherin
The DVD domain (residues 377-400) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation
The D domain (residues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates
Contains an N-terminal PPIase domain and an IF (Insert in the Flap) domain. The IF domain, formed by an insert in the flap loop, is required for the chaperone-like activity but not for the PPIase activity
Contains an N-terminal 4Fe-4S dicluster domain and a C-terminal pyridine nucleotide-disulfide oxidoreductase domain
Adopts an inhibitor cystine knot (ICK) fold. Has 4 disulfide bonds (ICK+1)
The four-helical bundle region mediates binding to phospholipids, such as phosphatidylserine and phosphatidic acid (PubMed:27023605). This promotes localization to the inner face of the cell membrane close to small GTPases (PubMed:27023605)
The IQ motif is involved in calmodulin binding
Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CSalpha/beta). Since the toxin contains only 2 disulfide bonds, it is called 2ds-CSalpha/beta
The PIR1/2/3 repeats are required for covalent linkage to the cell wall (By similarity). Their number varies among different strains of S.cerevisiae
The N-terminal domain is involved in RNA and SUMO homeostasis while the C-terminal part is required for nuclear pore association
The coiled-coil region mediates interaction with EPC1 and CHD4. The B box and coiled-coil domains mediate interaction with PML. The B box and the distal coiled-coil domains mediate homomultimerisation. The B30.2 domain mediates interaction with EIF3S6
Ubiquitin-binding motif (UBAN), also called UBD, is essential for subcellular localization to recycling endosomes and for proper trafficking of transferrin to the juxtanuclear region. It is involved in interaction with ubiquitinated TFRC
Residues 239-252 form a flexible loop which appears to affect the polymerase fidelity
The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin
A hairpin loop (about residues 4-24) tethers the protein in the inner membrane. The isolated PHB domain (also called SPFH) oligomerizes, but does not bind lipids (PubMed:25635948). The C-terminal 24 residues are not required for correct localization, but the last 300 residues are required (PubMed:22753055). The C-terminus determines the oligomerization state of the protein; there are few large foci for FloT. Swapping with the C-terminus of FloA leads to many smaller foci (PubMed:25909364)
The C-terminal region contains a right-handed beta-helix (RHbetaH) fold, which is common among proteins that bind and cleave long-chain linear polysaccharides
The ZP domain mediates dimerization
The N-terminal OR region is composed of two intertwined domains (OR1 and OR2) with a common, novel fold. Each contains 12 beta-strands that form a parallel beta-helix-like structure, plus a single alpha-helix. The OR1 region mediates interaction with GDF2
Contains a region with structural similarity to type-2 restriction endonucleases, but the residues that would bind catalytic metal ions in endonucleases are instead involved in hydrogen bonds that stabilize a highly conserved loop
The FHA domain is required for the proper localization at the SPB
The Delta-Serrate-Lag2 (DSL) domain is required for binding to the Notch receptor
The RING-type zinc finger domain is required but not sufficient for ubiquitin ligase activity. It mediates the interaction with the RING finger of COP1
Consists of three domains: two complementary catalytic domains and one substrate-binding module
Ubiquitin ligase activity is mediated by two distinct domains, PHD-type zinc fingers 2 and 3. The use of these distinct domains may allow ubiquitination of different targets by each domain. The HECT domain is catalytically inactive and does not contribute to this activity (By similarity)
The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity (PubMed:11524436). It mediates both barbed-end actin capping and actin bundling activities (PubMed:20532239). The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (PubMed:20532239)
The SH3 domain mediates interaction with SHB
Isoform 7 has an L27 domain close to N-terminus
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils (PubMed:26150528, PubMed:26573747). Four skip residues (Skip1: Thr-1188, Skip2: Glu-1385, Skip3: Glu-1582 and Skip4: Gly-1807) introduce discontinuities in the coiled-coil heptad repeats. The first three skip residues are structurally comparable and induce a unique local relaxation of the coiled-coil superhelical pitch and the fourth skip residue lies within a highly flexible molecular hinge that is necessary for myosin incorporation in the bare zone of sarcomeres (PubMed:26150528)
The alpha-1 domain is a structural part of the peptide-binding cleft (PubMed:25808313). Residues 101-107 determine Bw4/Bw6 motifs, which serologically distinguish HLA-B alleles. Each HLA-B allele posseses either the Bw4 or Bw6 motif. Only HLA-B alleles bearing the Bw4 epitope are recognized by NK cell inhibitory receptor KIR3DL1 (PubMed:25480565, PubMed:22020283)
The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:25808313). Mediates the interaction with TAP1-TAP2 complex (By similarity)
The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor
Forms a U-shaped beta-half-barrel with a small hydrophobic cavity (1500 Angstroms (3)) which holds a triacylated PIM in 1 crystal structure; the 3 acyl chains are within the cavity while the sugar moieties bind to the protein surface (PubMed:20694006). In the structure bound to triacylglycerides (TAG) 2 of the 3 acyl chains are buried in the cavity, the third is solvent exposed (PubMed:26751071). A flexible lid region may move to accommodate different TAG molecules (PubMed:26751071). Fragments of the mature protein (residues 81-100, 141-160 and 218-236) prevent uptake of M.tuberculosis by a human macrophage-like cell line; lesser effects are seen on bacterial uptake by a human lung epithelial cell line (PubMed:25041568)
The PDZ domain-binding motif is involved in the interaction with MPDZ
The Asn-Pro-Ala (NPA) motifs may contribute to the formation of two hemipores that could generate a narrow channel
The FYVE domain mediates phosphatidylinositol 3-phosphate binding and is necessary and sufficient for targeting to endosome and vacuole membranes
The tandem GAF domains bind cGMP, and regulate enzyme activity. The binding of cGMP stimulates enzyme activity
The tandem repeats might be heavily glycosylated to produce a rigid elongated structure that holds the adhesive N-terminal domain at the cell surface
DXXLL motif is required for a proper endocytosis and retrograde transport to the trans-Golgi network, as well as for regulation of lysosomal degradation
The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP
The C-terminal is cytoplasmic and is important for interaction with ZO-1. Sufficient for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction (By similarity)
The beta-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the alpha-1 domain of HLA-DRA. Forms hydrogen bonds with the peptide main chain via conserved amino acid in most HLA-DRB molecules. The polymorphic residues accomodate the side chains of the peptide conferring peptide specificity to distinct HLA-DRB3 alleles (PubMed:17583734, PubMed:18697946). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of TCR (By similarity)
The beta-2 Ig-like domain mediates the interaction with CD4 coreceptor
The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import
An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface (By similarity). Essential for synaptic vesicle endocytosis (PubMed:21029864). Plays a role in unc-57 localization to synaptic vesicles (PubMed:21029864). Dimerization and membrane-bending activity are required neither for binding to synaptic vesicles nor for unbinding following synaptic vesicle exocytosis (PubMed:21029864)
The SH3 domain is required for unc-26/synaptojanin localization to synapses but is dispensable for endocytosis and unc-57 targeting to synaptic vesicles
Contains a DNA-binding region joined by a short variable segment to a region similar to E.coli korA and trbA
The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type alpha/alpha. The C-terminal, non-coiled coil regions mediate heterodimerization type alpha/beta and interaction with PTPRD, PTPRF and PTPRS (By similarity)
The WHEP-TRS domains are involved in RNA binding
The UIM repeats 3 and 4 are required for binding to ubiquitinated EGFR and 'Lys-63'-linked ubiquitin
The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity (PubMed:10585460, PubMed:7822273, PubMed:17302434). It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2 (Probable)
The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2 (PubMed:17884809). The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2 (PubMed:10585460, PubMed:7822273, PubMed:17884809, PubMed:17302434)
The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or FCGR2A (By similarity). It also mediates the interaction with p130Cas/BCAR1 (By similarity)
Oomycete Avh family proteins have a modular structure with an N-terminal signal peptide (SP), an RXLR-dEER domain and a C-terminus with a variable number of modules that consist of W, Y and L motifs after highly conserved residues (PubMed:19694952). The C-ter of Avr4 contains 3 W motifs, 1 Y motif but no L motif. The RXLR-dEER motif functions as a host targeting signal (HTS) (PubMed:18842095). The region containing the W2 motif, in combination with either the W1 or W3 motif, triggers a necrotic response in potato plants carrying the resistance gene R4
The PDZ-binding motif is required for neurite outgrowth promotion. This motif is also involved in DLG1-, DLG3- and DLG4-binding (By similarity)
C-type lectin domains 3 to 8 are not required for calcium-dependent binding of mannose, fucose and N-acetylglucosamine. C-type lectin domain 2 is responsible for sugar-binding in a calcium-dependent manner (By similarity)
Fibronectin type-II domain mediates collagen-binding
Ricin B-type lectin domain contacts with the second C-type lectin domain
The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains (By similarity)
The dimethylated RG motifs (RG[X0-4]RG[X0-4]RG) motif mediates interaction with TDRD6 and is required for Balbiani body formation
The START domain mediates lipid-transfer between membranes. It contains a hydrophobic cavity able to accommodate one lipid molecule, thereby serving as a 'hydrophobic bridge' across the aqueous gap between donor and acceptor organelle membranes
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol
The first transmembrane domain is not required for stability, membrane association, interaction with LCB2, or enzymatic activity. The second and third transmembrane domains are required for stability and interaction with LCB2
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane
Interaction with corepressors through the BTB domain is needed to facilitate the rapid proliferation and survival of GC B-cells but is not involved in the T(FH) formation and BCL6-mediated suppression of T(H)2 and T(H)17 differentiation required for GC formation
Interacts with RALA through the TIG domain
The CCHC-type zinc finger probably plays a role in the ability of SLU7 to bypass the requirement for PRP18
The acidic domain carries the potential to activate transcription
Contains an N-terminal DNA-binding domain and a C-terminal ligand binding pocket
The extracellular cysteine-rich region is necessary for association with collagen, dimer formation and optimal dipeptidyl peptidase activity
The DCB (dimerization and cyclophiln-binding) and HUS (homology upstream of Sec7) domains are necessary for dimerization. The DCB domain is proposed to support constitutive homodimerization; the HUS domain interacts with the DCB domain which may occur intramolecular or intermolecular
The ulvan-binding domain binds strongly to ulvan, it does not bind other polymers like alginate, heparin, dextran sulfate or iota carrageenan. Presumably it serves to anchor the enzyme at the substrate, thus improving catalysis. Notably, the catalytic domain alone is more active than the full-length enzyme with the binding domain attached. Possibly, the ulvan-binding domain helps the enzyme to act on ulvan in its insoluble form embedded in the algal cell wall
Has a helicase-type domain in its N-terminus and an endonuclease-type domain in its C-terminus
The cytoplasmic domain is able to inactivate SigW and the extracellular and transmembrane domains are crucial for sensing and transducing the signal that triggers SigW activation (PubMed:15130127). The N-terminus binds the zinc ion and is followed by a long helix (about residues 40-80) that fits into a hydrophobic surface groove on SigW, probably blocking its ability to interact with the -10 and -35 promoter elements (PubMed:28319136)
Can be divided into a N-terminal domain with significant homology to S100-like calcium-binding proteins, a central domain containing a series of short tandem repeats, and two flanking segments with low homology to the consensus sequences of the central repeats
The HMA-like (RATX1) domain is responsible for the specific recognition of AVR effectors
No conformational changes occur upon c-di-AMP binding
The C-terminal region (CTD) is necessary and sufficient for secretion by the T9SS. The CTD may be cleaved during secretion
The C-terminal fragment, containing the TAP domain (also called UBA-like domain) and part of the NTF2-like domain, named the NPC-binding domain, mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF1 to the nuclear rim
The YTH domain mediates RNA-binding. It recognizes and binds N6-methyladenosine (m6A)-containing RNAs
The cysteine framework of the conopressin is C-C
The first 132 residues are not conserved outside of Helicobacter. Important for protein stability; a depletion mutant expressing this truncated protein accumulates more ureI mRNA than a depletion mutant able to express low levels of wild-type protein. The trunated protein still stimulates ATPase activity of RNA helicase RhpA
The CRIB domain is required for the association with CDC42
Metalloprotease with an atypical HExxxH zinc-binding motif instead of HExxH, which interrupts the active site-containing helix without affecting the integrity of the catalytic site arrangement
The N-terminal disordered region enhances its anchoring on microtubules, while dampening processivity on the polymerized substrate
The fifth BAG domain is responsible for the interaction with HSP70 nucleotide-binding domain
The Lon N-terminal domains are crucial for the overall structure of the protein, maintaining it in a conformation allowing its proper functioning
The AP-domain (ATP-binding and proteolytic domains) has a closed-ring conformation in the presence of AMP-PNP and its N-terminal entry gate appears closed. Upon ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens
The proteolytic site is connected to the ATP binding site through the GG loop (Gly-893 and Gly-894) and the loop containing Trp-770. Binding of a protein substrate such as beta-casein appears to trigger movement of both these loops as part of the conformational changes which lead to enhanced ATPase and peptidase activities
The ANK repeats recognize and bind RELA subunit of NF-kappa-B, when RELA is monomethylated at 'Lys-310' (By similarity). They also specifically recognize and bind H3K9me1 and H3K9me2
The MADS-box domain is essential for the function but dispensable for nuclear localization
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit srp101. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER
The CBM6 domain lost its carbohydrate binding capacity
The MFD (multi-functional domain) domain is involved in transcription transactivation, nuclear body targeting and dimerization. Inhibits dendritic growth in cultured neurons
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residue at position 79
The CXXC motif was initially thought to constitute the active site of a potential protein disulfide isomerase activity. However, such motif is not essential, suggesting that it has no disulfide isomerase activity. Its precise role remains unclear
The fourth transmembrane region (161-181) is necessary for integration into tight junctions
The N-terminal domain (1-76) is sufficient, but not required, to target DMI1 to the nucleus
The leucine-zipper is involved in homodimerization
The inhibitory region sequesters the protein in the nucleus
The positive regulatory region is essential and contains an amphipathic helix with hydrophobic and positive charged faces involved in the localization of the protein to the membranes through its binding to phospholipids
The region downstream of Arf-GAP domain is essential to GAP activity in vivo. This region may be required for its targeting to Golgi membranes (By similarity)
A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites
The extracellular WIF domain is responsible for Wnt binding
The transmembrane regions are not required for calpain activity but may play regulatory roles
The Rab-GAP TBC domain possesses GTPase activator activity
RRM 1 and RRM 2 bind cooperatively to AU-rich sequences in target mRNAs. RRM 3 binds to poly-A mRNA sequences (By similarity)
The PH domain specifically binds phosphatidylserine, which is enriched in recycling endosome membranes, it doesn't recognize PIPs
The C-terminal region is required for secretion by the ESX-1 system
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of MAVS recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines (PubMed:25636800)
Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with RIGI and IFIH1/MDA5
The transmembrane domain and residues 300-444 are essential for its interaction with DHX58/LGP2
The glycosyl hydrolase-1 3/region III carries the phlorizin hydrolase/glycosylceramidase activities (By similarity). The initial assignment of the activities to different regions was revised by the authors using alternative approaches (PubMed:1388157, PubMed:9762914)
The glycosyl hydrolase-1 4/region IV carries the lactase activity (By similarity). The initial assignment of the activities to different regions was revised by the authors using alternative approaches (PubMed:1388157, PubMed:9762914)
The pyrin and ATP-binding domains are required to elicit cytokine release following bacterial infection
The NACHT domain is required for inhibition of CASP1 autoprocessing
Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per monomer. NBD1 is primarily responsible for ATP hydrolysis. NBD2 is crucial for oligomerization
Composed of an N-terminal domain, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane
The cysteine framework is XXVI (C-C-C-C-CC-CC)
Extended rod-like protein with long coiled-coil domains
The nuclear localization signal (cNLS) mediates interaction with importin-alpha, recruiting importin-alpha to the Golgi membrane and liberating TPX2
The C2 domains have an essential, but non-catalytic function (Probable) (PubMed:24366873). Both C2-1 and C2-2 facilitate interaction with PstB2/PDR17 and are required for lipid transport function (PubMed:24366873)
Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Only motif 1 is essential for the association with nuclear receptors, while adjacent Ser-884 displays selectivity for nuclear receptors
The N-terminal domain (residues 1-62) is important for binding to the unfolded mature imported proteins. Residues (49-71) of the cytoplasmic domain interacts with TOMM20 while the C-terminal segment (residues 63-82) binds presequence of preproteins. Requires the transmembrane domain (TMD), a short segment (the import sequence) in the cytoplasmic domain localizing separately from the TMD and the C-tail signal in the C-terminal domain for efficient targeting and integration into the TOM complex (By similarity)
Has 2 BMC domains, is thought to trimerize giving a hexamer that may interact with CcmK proteins in the carboxysome shell
The activation loop within the kinase domain is the target of phosphorylation (By similarity). The PAS (PER-ARNT-SIM) domains are required for the binding of FMN chromophores
The zinc-finger domain mediates direct interaction with DNA and phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate). In vitro oxydation causes reversible disulfide bond formation between Cys residues in the zinc-finger domain and reversible loss of zinc ion binding
The bromo domain and the PHD-type zinc finger recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac). These 2 domains play a central role in the recruitment of chromatin silencing proteins such as DNMT1, DNMT3B and HDAC1
The MBD (methyl-CpG-binding) domain, also named TAM domain, specifically recognizes and binds a conserved stem-loop structure the association within pRNA. Binding to pRNA induces a conformational change of BAZ2A/TIP5 and is essential for targeting the NoRC complex to the nucleolus
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). InpB has the following architecture: T0-C-A-T-C-A-T (PubMed:18804170)
There are 3 carboxypeptidase-like domains. Only the first two domains seem to have kept a catalytic activity
The extracellular leucine-rich repeats are required for the specificity of the elicitor protein recognition
The LITAF domain is stabilized by a bound zinc ion (PubMed:27927196, PubMed:27582497). The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes (PubMed:23166352, PubMed:27927196, PubMed:27582497). It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate (PubMed:27927196)
The BIR and RING-type domains are dispensable for anti-apoptotic function
The positively charged inner surface of the NAC-A/B domain is crucial for NACA localization in the nucleus and DNA-binding. This region is blocked from binding nucleic acids in the heterodimeric complex by a helix region in the beta-subunit, it also displays much higher affinity for RNA than DNA
Each subunit has 12 transmembrane (TM) helices; TM1 and TM6 are interrupted by short non-helical Gly-rich loops in the middle of their transmembrane spans. Each subunit has a central cavity which binds substrate
The cytoplasmic domain 3 and the C-terminus tail domain contain the lysosomal sorting signals and are necessary and sufficient for intracellular retention and delivery to lysosomal and melanosomal, respectively in melanocytic and non-melanocytic cells
The RCC1 repeat region mediates interactions with RPGRIP1
The C-terminal domain (residues 55-86) does not neutralize non-cognate antitoxin VapC4; exchanging the N-terminus (residues 1-54) with VapB4 however allows neutralization of VapC4, while exchanging the C-terminal domain (residues 55-86) does not
The MFD (multi-functional domain) domain is involved in transcription transactivation, nuclear body targeting and dimerization
The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding. F5/8 domains mediate the recognition and binding to R/KXXR/K CendR motifs
RGD motif 2 (but not RGD motif 1) is involved in integrin ITGAV:ITGB3 binding
Intrinsically disordered protein with multiple low-complexity regions that confer binding to multiple RNA translation, deadenylation and decapping factors
The YXXXXLphi motif mediates interaction with eIF4E (EIF4E and EIF4E2)
The ion transport-like region is related to the membrane segments of voltage-gated ion channels. Its function is unknown
The PDZ domain mediates the interaction with PALS1
Has a penicillin-insensitive transglycosylase/glycosyltransferase (GT) N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits). Transmembrane signal-anchor is required for the synthesis of longer, 20-30 disaccharide units containing, glycan chains
Lacks a cytoplasmic PDZ-binding domain, which has been implicated in function of related Lrfn proteins
The N-terminal cytosolic domain interacts with sigma-E. After degradation by RseP binds to SspB, targeting RseA for degradation by the ClpX-ClpP protease (By similarity)
The C-terminal periplasmic domain interacts with RseB and is also the target for DegS
The N-terminal sensor (heme-containing) domain is covalently linked to the C-terminal, DNA-binding response domain
The N-terminal domain (1-77) is essential for regulation by S-adenosyl-L-methionine and AMP, but not for dimerization
The KASH domain, which contains a transmembrane domain, mediates nuclear envelope targeting
The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of EIF3D into the full eukaryotic translation initiation factor 3 (eIF-3) complex
Contains an N-terminal DNA-binding domain, followed by a dimerization domain and a C-terminal domain, called the small MutS-related (Smr) domain, which is absent from MutS and contains the endonuclease activity. The Smr domain can also bind DNA
Consists of two distinct domains; a N-terminal heme-containing oxygen-binding domain and a C-terminal reductase domain with binding sites for FAD and NAD(P)H
The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and 2 acyl-carrier protein (ACP) domains that serve as the tethers of the growing and completed polyketide via their phosphopantetheinyl arm
Only zinc fingers 2 and 3 contact DNA. Zinc finger 1 interacts with zinc finger 2
Interacting regions A, B and C form intramolecular interactions in the full-length translation product at acidic ambient pH, keeping the protein in a 'closed' conformation preventing proteolytic cleavage by the processing protease
The cytoplasmic N-terminal domain interacts with actin, while the lumenal C-terminal domain contributes to the activity of xyloglucan galactosyltransferase
Comprises two structural domains, the molybdenum cofactor/Moco sulfurase C-terminal (MOSC) domain and the MOSC N-terminal region, forming a cleft that accommodates Moco. The MOSC domain, which contains a large seven-stranded mostly antiparallel beta-barrel, engages multiple interactions with Moco both pterin ring and phosphate group, allowing for a tight coordination of Moco within the core of the enzyme
Solid state NMR studies suggest the protein has an alpha-helix beta-strand beta-strand alpha-helix structure. The beta-strands are thought to make an extended cross-beta structure which forms the hydrophobic core of the GV
The integrin I-domain (insert) is a VWFA domain (PubMed:2537322). Integrins with I-domains do not undergo protease cleavage. The I-domain is necessary and sufficient for interaction with ICAM1 and F11R (PubMed:15528364)
The thioredoxin-like regions Trxb 1 and 2 lack a redox-active CXXC motif
Thioredoxin domains 3 and 4 are the primary reductase domains
The PAM2 motif, and therefore interaction with pAbp, is essential for binding to the 5' cap of pre-mRNAs
The jas domain (335-359) is required for interaction with COI1
The C-helix is required for assembling the Ca(2+)-free homohexamer (PubMed:24514027). It also plays a key role in mitochondrial calcium uptake, probably by mediating interaction with MICU2 (PubMed:24503055, PubMed:24514027)
The EF-hand domains have high affinity for calcium and act as sensors of calcium levels (PubMed:23101630, PubMed:24560927)
Composed of only a NusG N-terminal (NGN) domain and a KOW domain, similar to bacterial NusG. The NGN domain is the effector domain of the complex that mediates the interaction with RNAP. The NGN domain closes the RNAP active center cleft to lock nucleic acids and render the elongation complex stable and processive. The KOW domain may interact with RNA and/or other factors
The RING-type zinc finger domain mediates polyubiquitination of the interacting protein
The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2) (By similarity)
The CKK domain binds microtubules. Might be required for microtubule stabilization (PubMed:27661253)
The Calponin-homology (CH) domain might negatively regulate the CKK domain
The coiled-coil domain contributes to microtubule binding and might negatively regulate the CKK domain
AtrA has a A-T-TE domain architecture (Probable). The adenylation (A) domain recognizes and activates the aryl acid substrates, and loads them onto the thiolation (T) domain (Probable). The thioesterase (TE) domain shares the missing condensation (C) domain function, and is responsible for condensation and final product release (Probable)
Contains a N-terminus DWNN domain, a zinc-finger domain and a C4C4 zinc-binding RING finger domain (PubMed:22130672). The ring finger may indeed be a U-box domain (PubMed:22130672)
The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes
The GoLoco domain is necessary for GDP-dissociation inhibitor (GDI) activity, translocation out of the nucleus and interaction with G(i) alpha subunits GNAI1, GNAI2 and GNAI3
The RBD domains are necessary for localization to the nucleus and centrosomes
The MTBD (microtubule binding domain) region mediates binding to microtubules and tubulin
Composed of 3 homologous Luciferase domains: each of the individual domains are most active at pH 6.3, and there is very little activity at pH 8.0
The N-terminal 45 amino acids are necessary and sufficient for secretion and translocation into host cells. This N-terminal region binds the SpaK/InvB chaperone. Contains a C-terminal HECT-like domain
The lumenal magnetite interacting component (MIC, residues 36-56) binds magnetite in vitro when fused C-terminally to maltose-binding protein (PubMed:26970040). Isolated MIC binds poorly to Fe(2+), Fe(3+), or Ni(2+), but improves quality of iron particles during iron co-precipitation experiments (PubMed:30405554). The lumenal loop (MIC) probably has to form a helix to interact with magnetite (PubMed:29372895)
The N-terminal region contains repression functions that are divided into three independent repression domains (RD1, RD2 and RD3). The C-terminal region contains the nuclear receptor-interacting domains that are divided in two separate interaction domains (ID1 and ID2)
The two interaction domains (ID) contain a conserved sequence referred to as the CORNR box. This motif is required and sufficient to permit binding to unligated TR and RARS. Sequences flanking the CORNR box determine nuclear hormone receptor specificity
The C-terminal region (631-636) is indispenasble for homodimerization
The N-terminal extracellular domain is required for high efficient zinc transport
The two metal binding sites M1 and M2 that are halfway through the membrane form a binuclear metal center. M1 is essential to Zn(2+) transport, while the other, M2 appears to have an auxiliary role presumably by acting as an additional transport site that can modulate the properties of the primary transport site (PubMed:28875161, PubMed:31914589). The binuclear metal center plays a key role in Zn(2+) sensing (PubMed:32348750)
The SH3 domain mediates interaction with CLNK (By similarity). The SH3 domain also mediates interaction with RALGPS1 (PubMed:10747847)
Head-neck domain associates with cytoplasmic (transvacuolar) F-actin in areas coinciding with the tracks of fast organelles
The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK3 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. The POLO box domains mediates localization to the centrosome (By similarity)
The NHL domain, containing the 6 NHL repeats, is necessary and sufficient to target RNA but not to repress mRNA. The minimal region needed to execute repression consists of the coiled coil domain and the Filamin repeat. The RING-type domain is dispensable for mRNA repression
The N-terminal region contains a fused PE/PPE homology domain. The C-terminal region is disordered
The N-terminal domain contains the ATP/Pi active site, the central domain the pyrophosphate/phosphate carrier histidine, and the C-terminal domain the pyruvate active site
The N-terminal region (1-41) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet
The catalytic activity is found in the N-terminal region formed by subdomains I and II. The peptide that connects subdomains II and III is also essential for activity. The C-terminal domain may be important for the recognition and/or interaction with long polyP chains
Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine
The SGF29 C-terminal (also named tudor-like) domain mediates binding to methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3)
Glu-498, located within the entrance channel of the trinuclear center, plays a key role in the protonation events that occur at the trinuclear center and in its stabilization, controlling therefore the binding of dioxygen and its further reduction (PubMed:20822511, PubMed:20200715). Asp-116, situated in the exit channel of the trinuclear center, and its hydrogen bond connectivity are highly relevant for the overall reactivity of the laccase but do not appear to play a critical structural role (PubMed:22481612)
The zinc-finger is responsible for substrate specificity
Contacts FliW via its C-terminus (residues 49-58)
The helical domain (70-190) is required for self-activation
Tudor domain specifically binds peptides with symmetrically dimethylated arginines (sDMA) and may facilitate protein-protein interactions
Consists mostly of well conserved tandem repeats
The coiled-Coil domain is essential for autophagy (PubMed:28067330)
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperones AHA1, CDC37, CNS1, CPR6, CPR7, HCH1, SBA1, SSE1 and STI1. CNS1, CPR6, CPR7 and STI1
The helix-loop-helix (HLH) region is essential for immunity function of Immunity protein HalI and interaction with Halocin-C8
Contains 2 fused PPK2 domains. The N-terminal domain seems to be catalytically inactive and might be responsible for the protein dimerization
Arg-403 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The MATH domain mediates interaction with protein-ubiquitin ligase substrates
Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities (By similarity)
The N-terminus is involved in the initial binding to heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity). The N-terminus masks the TSP type-1 (TSR) domain which maintains the sporozoites in a migratory state, enabling them to complete their journey to the salivary gland in the mosquito vector and then to the host liver. The unmasking the TSP type-1 (TSR) domain when the sporozoite interacts with the host hepatocyte also protects sporozoites from host antibodies (By similarity)
TSP type-1 (TSR) domain is required for sporozoite development and invasion. CSP has two conformational states, an adhesive conformation in which the TSP type-1 (TSR) domain is exposed and a nonadhesive conformation in which the TSR is masked by the N-terminus. TSR-exposed conformation occurs during sporozoite development in the oocyst in the mosquito vector and during host hepatocyte invasion. TSR-masked conformation occurs during sporozoite migration through the hemolymph to salivary glands in the mosquito vector and in the host dermis
The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (PubMed:20547484)
The LIM domain 3 is critical for focal adhesion targeting and the suppression of paxillin (PXN) tyrosine phosphorylation. The LIM domain 3 alone or both LIM domains 3 and 4 can mediate interaction with AR
The PID domain mediates interaction with the NPXY internalization motif of LDLR
The C-terminal region binds cholesterol, 25-hydroxysterol and acidic phospholipids and is required for localization to microtubules
The PH domain selectively interacts with phosphatidylinositol-4-phosphate
Full-length S1 protein and the C-terminal domain (residues 285-479) bind tmRNA, the interaction is not disrupted by POA. Unlike M.tuberculosis (strain H37Rv) the S1 motif 4 does not bind POA, which may explain why M.smegmatis is resistant to the antibiotic PZA, the precursor to POA
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 107 and 131
SH3-1 and SH3-4 bind to ARHGAP31 (By similarity). SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin
The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression
The ZP domain mediates polymerization, leading to the formation of long filaments (PubMed:12021773, PubMed:26673890). The core of the filament consists of interlocked ZP domains which assemble into a helical structure. Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit. The heavily glycosylated N-terminal part of the protein (containing several EGF-like domains) forms branches which protrude from the core and are be involved in pathogen capture (By similarity)
The N-terminal coiled-coil domain mediates homodimerization
Two basolateral sorting signals (BSS) in its C-terminal cytoplasmic tail are required to direct SLC16A3 to the basolateral membrane
The IQ domains provide the interaction surface for the myosin light chain MLC1
The calponin homology (CH) domain binds to actin filaments
The LXXLL motif is a transcriptional coregulator signature
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-44 in the first module and Ile-271 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity
The PDZ domain binds to the last three or four amino acids of DGKZ. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity)
The cytoplasmic C-terminal domain contains an Arg-Val motif, which is involved in the anterograde ER-to-Golgi transport of the protein
The PX domain mediates specific binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3))
The N-terminus is necessary for DNA-binding. The C-terminus is necessary for transcriptional activation (By similarity)
The cryptic mitochondrial transit peptide is revealed after cleavage by caspase upon oxidative stress and cell death (PubMed:22441018). It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria (PubMed:22441018)
Contains 4 domains, connected by flexible linkers. In the active conformation, the domains are in an extended conformation, each making extensive interactions with the RNA polymerase catalytic core (By similarity)
The WH2-domain binds actin monomer and mediates actin bundle assembly
The RING-type zinc finger domain (1-158) is involved in the increase of catalase activity and zinc ion binding is required for this increase
The interaction with CAT2 is through the C-terminal TPR-containing domain (159-405)
The AxLyCxL motif is required for myoblast fusion
The GAAKAK motif at position 73-78 is required for host plasma membrane localization
The LIM zinc-binding domains mediate interaction with LPAR2 and with S.typhimurium protein sseI
The PI3K/PI4K domain is required for the recruitment of HAT complexes, and the MYC-dependent transactivation. Although it is strongly related to the PI3/PI4-kinase family, it lacks the typical motifs that constitute the catalytic site of PI3/PI4-kinase proteins, and lacks such activity (By similarity)
The last 4 C-terminal residues bind to the first 2 PDZ domains of DLG4
The mature protein is largely unstructured in the absence of a cognate ligand, and has a strong tendency to form fibrillar aggregates. Homodimerization may be the first step of amyloid formation
The di-lysine motif (KxKxx) acts as an endoplasmic reticulum retrieval signal
Consists of two domains: an N-terminal lipid X binding domain (LXD) attached by a flexible linker to a C-terminal catalytic domain (ICD). Binding of UDP-2,3-diacylglucosamine by LpxI induces a conformational switch that brings the catalytic domain close to the lipid-binding domain for specific recognition of the substrate and catalysis
DMA domain interacts with ubiquitin
The CARD domain is involved in ced-4 binding
Is composed of two distinct domains: an N-terminal DNA binding domain that adopts the winged HTH fold (residues 2-72) and a C-terminal dimerization domain (residues 79-153) that consists of four alpha helices organized in a four-helix bundle
The coiled coil domains differentially mediate trimerization required for binding to nesprins and are proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation (By similarity). The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton
The mitochondrial intermembrane region is required for generation but not stabilization of the TIM23 complex
The FCP1 homology domain does not contain the canonical D-x-D-x-[TV] active site, suggesting that it probably does not display phosphatase activity
The short coiled coil domain is proposed to be not involved in load-bearing and force transmission from the cytoskeleton but in mere nucleus anchorage instead
The BTB domain is important for homodimerization and for its function in negative regulation of class switch recombination
The linker region, also named autoinhibitory interface, is less inhibitory on its own than that of CARD9. The linker region together with the inhibitory domain (ID) are required to prevent constitutive activation and maintain CARD11 in an autoinhibitory state. Disruption of the inhibitory domain (ID) region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments
The N-terminal domain may have an alkylhydroperoxide reductase activity
The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. The two transmembrane clusters are necessary and suficient for the plasma membrane targeting and oligomers assembly (PubMed:11856299). The N-terminal and C-terminal domains interact at rest as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain; the binding is specifically inhibited by fully calcium-saturated calmodulin, resulting in activation of AC8 (PubMed:19305019)
The basic domain (B) allows nucleolar localization in the absence of GTP. The intermediate domain (I) inhibits nucleolar localization by the B domain and is required for exit from the nucleolus. Exit from the nucleolus to the nucleoplasm requires both the I and the acidic (A) domains, and may be triggered by GTP hydrolysis (By similarity)
The extracellular domain assumes a distinct boomerang shape when not bound to IZUMO1R/JUNO. Interaction with IZUMO1R/JUNO triggers a conformation change, so that the IZUMO1 extracellular domain assumes an upright conformation
The cytoplasmic C-terminus region is not essential for fertilization. It is however required for protein stability
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (MET) domain that transfers methyl groups to the growing polyketide; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (Probable). Lacks an active enoyl reductase (ER) domain that reduces enoyl groups to alkyl groups, and biosynthesis of fusarielins relies on the trans-acting enoyl reductase FSL5 (Probable)
The N-terminal domain (64-250) is required for the deaminase activity
The Glu-rich region mediates histones interaction
The Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are required for the association with nuclear receptor ESR1
The C-terminal domain is essential for the homodimerization and the interaction with CBL. While the interaction with CBL is apparently mediated via the hydrophobic region of this domain, the highly charged region is apparently required for the homodimerization (By similarity)
Inactive Dennd3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-940 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards Rab12
The CCHC FOG-type zinc fingers 1, 2, 3 and 5 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is essential for the interaction with GATA-type zinc fingers (By similarity)
The NPC motif is essential for oligomerization and water permeability function
DOMON domain could bind catecholamines and thereby could regulate the cytochrome b561 domain function (PubMed:15022831). DOMON domain could bind one heme b (PubMed:19386804)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (318-348) inactivates kinase activity under calcium-free conditions (By similarity)
The first C2 domain mediates Ca(2+)-dependent phospholipid binding (PubMed:7961887)
The second C2 domain mediates interaction with Stonin 2. The second C2 domain mediates phospholipid and inositol polyphosphate binding in a calcium-independent manner (PubMed:7961887)
(Microbial infection) Binding to BoNT/B induces formation of an alpha-helix in the membrane-proximal extracytoplasmic domain (PubMed:17167418, PubMed:23807078)
The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG
XynA is a modular enzyme. The number of CBM6 (carbohydrate binding type-6) domains varies between strains. The polymeric substrate can interact with several of these CBM6 domains
The WH2 motif at the C-terminus binds to actin monomers
Each subunit is composed of an apical domain, an intermediate domain and an equatorial domain (PubMed:26553853). The two hinges that connect the equatorial and intermediate domains (EI hinge) and the apical and intermediate domains (AI hinge) play a significant role in the chaperonin activity (PubMed:26553853). The N-terminus is important in determining the oligomerization status (PubMed:22834700)
The C-terminal effector region is sufficient for its activity within the host cell
The predicted NLS is not required for its function to suppress CRN63- or NIP-derived cell death
The C-terminal domain called the BARA domain is dispensable for the construction of both VPS34 PI3-kinase complexes, but is specifically required for autophagy through the targeting of complex I to the pre-autophagosomal structure (By similarity)
The CFEM domain is involved in heme-binding. It contains 8 cysteines and is found in proteins from several pathogenic fungi, including both human and plant pathogens
Contains an N-terminal DNA-binding domain and a C-terminal helicase domain. The helicase domain plays an important role in high affinity and stable binding of PriA to forked DNAs
The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AFX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage
Has three domains, each of which is closely related to a corresponding domain in the delta' stator, despite the 2 proteins having only 6-8% sequence identity. Interacts with the beta sliding clamp via domain 1 (residues 1-140, in particular residues 61-74), fitting into a cleft between domains 2 and 3 on the surface of the beta-clamp (PubMed:11525728). Residues 61-74 move about 45 degrees and 5.5 Angstroms in the beta-delta versus gamma-delta-delta' structure to contact respectively the beta or delta' (PubMed:11525728)
Each subunit of the homooctameric enzyme folds into a two-domain structure characteristic of a metal dependent amidohydrolase, with a twisted TIM (triosephosphateisomerase)-barrel and a smaller beta-sandwich domain
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (MT) domain responsible for the incorporation of methyl groups; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The Pro/N-degron targets the protein for proteasomal degradation when cells are shifted to glucose-containing growth medium
The eIF2A-like region shares sequence similarity with eIF2A and mediates the interaction with the 40S ribosomal subunit and the 48S preinitiation complex
The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin)
The CxxC motif may bind a [4Fe-4S] cluster
In IrtA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. In addition, IrtA contains an N-terminal siderophore interaction domain (SID) that binds FAD
The monomer is folded into a right-handed spiral of four turns, followed by two small domains which are involved in trimerization
Contains an N-terminal adenylation domain, an internal peptidyl carrier domain and a C-terminal domain that is homologous to nicotinamide-dependent dehydrogenases
The extracellular N-terminus has 4 domains; the first 3 are structurally similar to fusogens from plants, C.elegans and viruses, while the fourth domain is unique to archaea. Domains I and II are discontinuous. The fusion loop in domain II is stabilized by a Ca(2+) ion so that it protrudes from the molecule
Light induces structural changes; in the dark protein is compact and resistant to exogenous protease, in the light protein is less compact while protease treatment generates an N-terminal fragment corresponding to approximately residues 14-156 (the LOV domain)
The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin. Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer
Contains two independently folding units, the N-terminal transmembrane domain (residues 1-205) and the ABC-core domain (206-842) are respectively responsible for the lysosomal targeting and the ATPase activity
The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions. The FYVE domain is required for its function in regulating TLR3 signaling
Forms the trimeric core subcomplex IFT122:IFT140:WDR19 via the C-terminal region, whereas it interacts with IFT43:WDR35 via the N-terminal region containing the WD repeats
Gln-144 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Although it shares weak sequence similarity with sua7/TFIIB, displays a similar subdomain organization as sua7/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds
The UEV domain is required for the interaction of the complex with ubiquitin
The coiled coil domain may interact with stathmin
The testis-specific N-terminal extension mediates tight association with the cytoskeletal fibrous sheath of the spermatozoa flagellum, possibly via interchain disulfide-bonding of Cys-21 with sheath components
Mediates binding to H3K9me2 via N-terminal region, while ability to exclude TET3 from the maternal pronucleus requires the C-terminal part
Has the canonical EER motif, but lacks the canonical translocation motif RxLR, which characterizes most oomycete effectors identified so far. The EER motif is not required to trigger an RPP5-dependent immune response
Consists of the cap domain (residues 35-76) and LRR repeat region (77-213) and an Ig-like region (207-297), where the latter 2 overlap slightly (PubMed:17057330). The LRR repear region interacts via its concave face with host DNMBP (Tuba) (PubMed:24332715)
The Ig-like V-type domain is necessary and sufficient to mediate interaction with JAM3 and integrin alpha-4/beta-1
Has 2 alpha-helices that are important for interaction with cognate toxin HEPN; deletion of helix 2 (residues 52-65) or the C-terminus of helix 4 (residues 114-125) reduces antitoxin function about 100-fold, while deletion of the N-terminus of helix 4 (residues 98-113) reduces antitoxin function over 1000-fold
The C-terminal part (659-707) contributes to MTREX RNA helicase activity, in part, by enhancing its RNA-dependent ATPase activity
The number of the intragenic tandem repeats varies between different S.cerevisiae strains. There is a linear correlation between protein size and the extend of adhesion: the more repeats, the stronger the adhesion properties and the greater the fraction of flocculating cells. The Ser/Thr-rich repeats are also important for proper cell wall targeting of the protein
The BC, DE and FG loops form a tripartite wedge that blocks the substrate-binding site of target cysteine proteases (PubMed:17561110, PubMed:17502099, PubMed:18515357, PubMed:19143838). The BC loop interacts with the catalytically active cysteine and histidine residues of the of the protease catalytic center (PubMed:17561110, PubMed:17502099, PubMed:18515357, PubMed:19143838)
Consists of a surface-exposed C-terminal sphingomyelinase domain and a putative outer membrane-spanning N-terminal channel domain able to mediate glucose and phosphocholine uptake across the outer membrane
Binding of an external ligand to the heme located in the N-terminal sensory domain displaces the Met-104 distal heme ligand, triggering a conformational change that activates the C-terminal DNA-binding domain
The N-terminal extension probably forms a projection that reaches into the active site of cognate toxin Tre1-Pp where it occludes the active site
Deletion of amino acids 23-168 led to effector-independent expression of NorB1, a downstream gene, i.e. the need for an NO-induced signal has been bypassed
The two activities reside in distinct domains (N-terminal amidase and C-terminal synthetase). The two domains expressed independently are folded and functional; liberation of the amidase domain from the synthetase domain highly activates the amidase activity
The poly-Pro domain may confer substrate specificity
Possible isomerization of Pro-318 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA
The ArfGAP1 lipid packing sensor (ALPS) motif is a membrane-binding motif that is sensitive to curvature
The PTS EIIC type-4 domain forms the PTS system translocation channel and contains the specific substrate-binding site
The Ras-associating domain interacts with Ras
The leucine-zipper domain is essential for its localization in the caveolae and for its interaction with CAV1 and EPS15L1
The 6 S1 motif domains are not equivalent; the first 2 no longer bind rRNA but instead are involved in protein-ribosome and protein-protein interactions. Binds to the 30S ribosomal subunit via its N-terminal fragment (190 residues, the first 2 S1 motifs) and allows translation by S1-free ribosomes (PubMed:7003157, PubMed:15340139). The same fragment represses its own translation (PubMed:2120211). The first 3 S1 motifs do however bind to mRNA pseudoknots in the 5'-UTR of at least 1 mRNA (rpsO); deletion of S1 motifs 1-3 but not motifs 4-6 is not viable, although a deletion of motifs 4-6 grows slowly and is cold-sensitive (PubMed:24339747). In case of infection by bacteriophage Qbeta the same N-terminal fragment is necessary and sufficient to form the Qbeta virus RNA-dependent RNA polymerase, although in vitro (-) strand RNA synthesis from the (+) strand genomic RNA also requires the third S1 motif (residues 1-273) (PubMed:6358207, PubMed:25122749). The third S1 motif is required to bind mRNA, tmRNA and viral M-site RNA but requires cooperation with other S1 motifs (PubMed:15340139, PubMed:25122749)
The C-terminal proline-rich region mediates binding to the SH3 domain-containing protein GRB2
Unlike homologous domains of MprF and LysX that are positioned in the cytoplasm, the MprF-like domain of LysX2 is in the extracytoplasmic region
The lumenal domain contains two regions of approximately 650 AA that exhibit 20% identity. The cytoplasmic domain may serve as a Golgi retention/recycling signal
The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type beta/beta. The C-terminal, non-coiled coil regions mediate heterodimerization type beta/alpha and interaction with S100A4 (By similarity)
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes
The nuclear localization signal is required for the localization into the host nucleus and the ability to induce host cell death
The GOLD domain is essential for giantin binding
The effector region mediates interaction with DEF6
Is homologous throughout its length with the C-terminal 3 domains of the pentafunctional AROM protein. The function of the 2 C-terminal domains may be to act as a molecular sensor that detects the presence of quinate pathway intermediates as a prerequisite for the presumed conformational changes necessary for the control of transcription regulation
Contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold. Transmembrane domain 1 functions as a signal for Golgi targeting
The pLxIS motif constitutes an IRF5-binding motif: following phosphorylation, the phosphorylated pLxIS motif of TASL recruits IRF5
The PWWP domain specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and adopts a five-bladed beta-barrel fold with an extended C-terminal alpha-helix, with a conserved H3.3K36me3-binding aromatic cage formed by Phe-291 and Trp-294 of the beta1-beta2 loop and Phe-310 of the beta3-beta4 loop. Specific recognition of H3.3 histone is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains
The N-terminal region contains several LVIVD repeat domains, which are often found in proteins that localize to the cell surface. The C-terminal region contains a NifU-like domain, originally discovered in proteins involved in nitrogen fixation
The disordered N-terminal region is required for the diacylglycerol O-acyltransferase activity and may regulate enzymatic function via its interaction with the MBOAT fold
The MBOAT fold forms a reaction chamber in the endoplasmic reticulum membrane that encloses the active sites. The reaction chamber has a tunnel to the cytosolic side and its entrance recognizes the hydrophilic CoA motif of an acyl-CoA molecule. The chamber has separate entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-glycerol
The PWWP domain is essential for targeting to pericentric heterochromatin
The PX domain binds phosphatidylinositol 3-phosphate which is necessary for localization to the endosomes
Modular protein made up of an N-terminal effector binding GAF-type domain and a C-terminal wHTH DNA binding domain, separated by a helical linker (PubMed:16488888, PubMed:28011634). The GAF domain is involved in the formation of homodimers (PubMed:28011634). Amino acid binding to the GAF domain is associated with drastic but localized changes in structure (PubMed:19500589). Structural changes upon isoleucine binding may lead to increased affinity of Ile-bound CodY for its target DNA (PubMed:28011634)
The C-terminal part interacts with the N-terminal part of histone H3 and promotes acetylation of histone H3 'Lys-9'
The extracellular domain (1-1412) is sufficient to inhibit bdl function
The N-terminal sterile alpha motif (SAM) domain, but not the Ras-associating (RA) domain, is essential for the function
Seems to consist of two fused copies of the CbiX domain, resembling CbiK arrangement
The C-terminal disordered region mediates non-specific DNA-binding
The N-terminal domain (about residues 1-140) is an archaea-specific tRNA-editing domain (PubMed:26113036) that has a highly similar structure to Dtd (D-aminoacyl-tRNA deacylase). Editing of incorrectly charged L-seryl-tRNA(Thr) by this domain is tRNA catalyzed (PubMed:26113036)
Xin repeats bind F-actin
The CRN proteins have modular architectures that include a signal peptide, a conserved N-terminus, and highly diverse C-terminal domains. The conserved CRN N-terminus harbors a distinct LXLFLAK motif, which is followed by the conserved DWL domain. A highly conserved HVLVXXP motif marks the end of the CRN N-terminal domains and forms a junction where diverse C-terminal effector domains are fused. The conserved CRN N-terminus mediates the translocation into the plant host cells
The N-terminal domain is physically isolated from the rest of the protein and may serve to anchor the protein to the carboxysome shell or to RuBisCO; in PDB:2FGY the N-terminal domain binds Zn(2+) which is thought to be non-physiological. The central domain bears the catalytic Zn(2+), while the C-terminal domain is structurally similar to the central catalytic domain but cannot bind Zn(2+)
The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P
The N-terminus has marked structural similarity to the mammalian gasdermin N-terminal domain. The C-terminal region wraps around the twisted beta sheet core, probably stabilizing the inactive state
The N-terminal region is involved in phosphatidylethanolamine-binding and is required for atg8-PE conjugation
The flexible region (FR) is required for atg7-binding
The C-terminal region mediates the interaction with microtubules and is able to nucleate and bundles microtubules in vitro
The centrosome localization domain (CLD) region mediates the localization to centrosomes and homooligomerization
Contains an N-terminal catalytic domain fused with a RAM (Regulation of Amino acid Metabolism) domain at the C-terminus. The mutant enzyme lacking the RAM domain is insensitive to inhibition by lysine, indicating that the RAM domain is responsible for enzyme allosteric regulation
The Tudor domain may not recognize methylation marks, but rather bind unassembled free histone H3
The sterile alpha-motif (SAM), but not the Ras-association domain, is important for its interaction with MCK1 and responses to cell wall and oxidative stresses
The BEACH-type PH domain (1556-1653) is required for interaction with GFS12
The N-terminus (residues 1-115) forms a head domain that is structurally related to those of XRCC4, XLF/NHEJ1, and SASS6
The PPIase domain enhances mitochondrial targeting
Has a helicase-type domain in its N-terminus and an endonuclease-type domain in its C-terminus. AMP lies in a cleft in the helicase domain
LIM zinc-binding domain 1 is required for self-association. LIM zinc-binding domain 1 and LIM zinc-binding domain 2 both are required for optimal actin-bundling activity (By similarity). LIM zinc-binding domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates binding to SPTB (PubMed:9234731, PubMed:10751147)
Folds into three domains: the FAD-binding domain, the capping domain and the C-terminal helical domain
The coiled coil domain is required for homodimerization and regulates the enzymatic activity
The predicted NLS is required for its function to induces cell death in plant host cells
The PHD-type domain binds histone H3 when trimethylated at 'Lys-4' (H3K4me3) in combination with a nearby acetylation (K9ac, K14ac and/or K18ac), but not H3K4me3 alone
The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides
A 68 amino acid island between the 20th and the 21th LRR is essential for the binding of brassinosteroids
The FF ER export motif at the C-terminus is not sufficient to support endoplasmic reticulum exit, and needs assistance of Gln-508 for proper recognition of COPII coat components
Contains two overlapping leucine-zipper-like motifs at the C-terminal region, which might serve as a site for protein-protein interaction. In this domain, a slightly degenerated ERF-associated amphiphilic repression (EAR) motif seems to be involved in the activity of transcriptional repression
The polybasic region (PBR) is responsive to the binding to phosphoinositides (PtdInsPs), including phosphatidylinositol 5-phosphate (PtdIns(5)P)
An expressed fragment (residues 194-362) hydrolyzes an artificial lysozyme substrate 4-methylumbelliferyl-beta-D-N,N',N''-triacetylchitotrioside (MUF tri-NAG)
Both the N- and C-terminal regions are required for interaction with him-18
The C-terminal coiled-coil domain mediates homotrimerization of CNGA subunits
The coiled coil domain is necessary for the homodimerization
While ADP, ATP, ITP, TTP and UTP can be crystallized in the enzyme in approximately the same place as CTP, it is their phosphate tails that anchor them to the enzyme, their nucleoside moieties do not bind in the same way CTP does
N-terminal amphipathic alpha helix form a funnel-shaped structure that is required for the plasma membrane association of the resistosome complex, cell death triggering, and disease resistance
The numerous interruptions in the triple helix may make this molecule either elastic or flexible
Botulinum neurotoxin A light chain: Has protease activity
Botulinum neurotoxin A heavy chain: Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol. The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 77 and 101
The EGF-like region is specific to this family of proteins and seems to consist of the C-terminal of an EGF-like domain fused to the N-terminal of another one
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif also mediates interaction with ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs) (By similarity)
The YTRF endocytosis motif engages the clathrin-mediated endocytic machinery through adapter protein-2
The C-terminal proline-rich domain possesses a significant intrinsic transcriptional activity. This activity is inhibited by the N-terminus in the full-length protein
The SP-RING-type domain mediates interaction with SMAD3 and SMAD4
The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates
Neuropeptide gamma contains alpha-helical structures at the C-terminus which may be required for interaction with a cognate receptor
The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen
Probably exists in a closed and an opened conformation due to interaction of the C-terminal RAB-binding domain (RBD), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, with the N-terminal calponin-homology (CH) domain. The conformational change is regulated by RAB13 and may modulate MICALL1 interactions with functional partners
The PDZ domain mediates binding to a subset of proteins containing a PDZ-binding motif at the C-terminus: the specificity for PDZ-binding motif is provided by the 2 residues located upstream of the canonical PDZ-binding motif. The PDZ domain also mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B)
The PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes
The C-terminal region of ATG1 responsible for ATG13-binding comprises six alpha-helices which fold into two antiparallel three-helix bundles resembling each other (By similarity)
The C-terminal SGF11-type zinc-finger domain together with the C-terminal catalytic domain of not/nonstop forms the 'catalytic lobe' of the SAGA deubiquitination module
The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity (By similarity). Essential for glycosylation of FGF23 (By similarity)
The EGF-like region drives the cytokine specificity for ALKAL2
The heparin-binding region binds heparin glycosaminoglycan. Heparin-binding is required for ALKAL2-driven activation
The A.T hook DNA-binding domain is required for the interaction with MAPK14
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full-length protein
The proline-rich site binds the SH3 domain of the p85 subunit of PI3-kinase
Binds heme b via the PAS-like domain
The PHD-type domain binds specifically histone H3 tri-methylated at 'Lys-4' (H3K4me3), thus promoting binding to chromatin
The SET domain does not bind the methyl group donor S-adenosyl-L-methionine and histone 3 H3K4 peptide as a large loop prevents the docking of the 'Lys-4' side chain
The C-terminus domain is responsible for the localization to the centrosome during mitosis
The PTB domain mediates receptor interaction
The GRAS domain is involved in DNA-binding
The C-terminal region is required for the early endosomal and mitochondrial localization
Lacks the C-terminal WD repeats
This inhibitor contains three inhibitory domains
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain. DNM1 binding abolishes autoinhibition
The cytoplasmic C-terminus is involved in the gating mechanism
The mature peptide (59-84) forms alpha-helices which probably disrupt target cell membranes
The C-terminal PTS1-type tripeptide peroxisomal targeting signal is required for the import into peroxisomes
The uracil deoxyribose moiety interacts with the protein through Ile-79 and Tyr-83, which discriminate against the ribose form of the nucleotide
The jas domain (343-367) is required for interaction with COI1
The N-terminal ubiquitin-like domain is required for proteasome association and UBP6 activation at the proteasome
Deletion of the PDZ domains leads to dis-inhibition of protease activity and almost complete loss of RseA even under non-inducing conditions
The C-terminal domain (416-599) is not required for the reductase activity while the non-functional deaminase domain (21-150) is necessary
The C-terminus (residues 351 to 560) is required for efficient SNF1 pathway signaling
The TIR domain is a signaling domain involved in cell death induction (PubMed:19132868). It is involved in homo- and heterodimerization, but other domains also contribute to the interaction (PubMed:24744375). The LRR domain may interact directly with pathogen-derived elicitors (PubMed:10571887)
Binds calcium via its EF-hands
The C-terminal CBM-CenC domains mediate the binding of XynA to microcrystalline cellulose. CBM-CenC 2 alone can also promote cellulose binding
The N-terminus of the protein, including the glycosyltransferase 1 domain (residues 1-171), is required but not sufficient for full formation of the stable GtfA-GtfB complex; the complex of GtfA with truncated GtfB has intermediate N-acetylglucosaminyl transferase activity
Some isoforms lack the first Ig-like domain which may confer homophilic adhesion activity. However, they can bind and activate FGFR1
The zinc finger domains are essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain
The cysteine framework is I (CC-C-C). Alpha5/5 pattern
The equipotent ability to inhibit alpha-7/CHRNA7 nAChR subunit by both the globular and ribbon toxin arise mainly from the insertion of an additional residue in the first loop and partly from residues in the termini
C-terminal 700 AA are mainly in alpha-helices and beta-sheets
The LIM domain specifically interacts with the Pit-1 POU domain and is required for synergistic interactions with Pit-1, but not for basal transcriptional activation events
The autoinhibitory domain is involved in regulating enzyme activity through autophosphorylation and possibly, through heparin binding
Domain IV is globular
The leucine-rich repeat (LRR) domain is disrupted by a non-LRR region, resulting in the formation of two LRR solenoid structures shaped like the Arabic number '7'. This is strikingly different from the horseshoe structures of the canonical LRR proteins
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (321-351) inactivates kinase activity under calcium-free conditions (By similarity)
Has 2 forms, fold switches to a thioredoxin-like fold (KaiB(fs)) when bound to KaiC, KaiA or CikA (PubMed:26113641, PubMed:28302851). The KaiB(fs) form binds faster to KaiC than its alternate form, so less fully phosphorylated KaiC forms; the KaiB(fs) form activates signaling through CikA and inhibits signaling through SasA (PubMed:26113641) (Probable). The C-terminal region may confer species specificity; C-terminal hybrids do not all rescue deletions in S.elongatus PCC 7942 (PubMed:16227211)
The RLR CTR domain controls homooligomerization and interaction with MAVS/IPS1. In the absence of viral infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through intramolecular interactions with the RLR CTR domain. Upon binding to viral RNA and ubiquitination by RNF135, a conformational change releases the autoinhibition promoting further homooligomerization, interaction of the CARD domains with the adapter protein MAVS/IPS1 and activation of the downstream RIG-I signaling pathway
The helicase domain is responsible for dsRNA recognition
The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton
The second CARD domain is the primary site for 'Lys-63'-linked ubiquitination
The EGF-like domain and the SXC (ShKT) domain are essential for the biological activity of the protein. May function as protein interaction domains
The PH 1 domain mediates the oligomerization in a calcium dependent manner, and the association with the phosphatidylinositol 4,5-bisphosphate
The SU domain binds calmodulin in a calcium-dependent manner (By similarity). It contains actin-binding sites
The N-terminal zinc fingers are involved in sequence-specific DNA binding
C-terminal zinc fingers mediate homodimerization
In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (By similarity). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity)
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3 (By similarity). IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines (By similarity)
The N-terminus is required for efficient association with MHC class I molecule and for a stable interaction between MHC I and calreticulin. Binding to TAP is mediated by the C-terminal region (By similarity)
The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinomas cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading
Interaction between the motor domain and the tail leads to an inactive, monomeric conformation. Phospholipid binding via the PH domains leads to the formation of the active, dimeric form of the protein and strongly increases actin-dependent ATPase activity and motor activity
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (PubMed:25122759). It can refold after extension suggesting an in vivo force-dependent function (PubMed:25122759). An anti-parallel coiled coil is located C-terminal to the SAH domain and mediates dimerization (PubMed:27276269, PubMed:27580874)
The N-terminal domain (39-56) is necessary and sufficient for thylakoid binding
Each G (guanine nucleotide-binding) domain has activity on its own; domain 1 is twice as active as domain 2. The G domains do not interact, instead each contacts the C-terminal KH-like domain which lies between them
Binds target DNA via the HMG box domain
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (PubMed:14700635). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:14700635). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) or reductase domain (R) that releases the newly synthesized peptide from the enzyme (PubMed:14700635). LpsC is composed of only one module which is required for the activation of D-lysergic acid activation and its incorporation in the final ergot alkaloid (PubMed:19139103)
The structure of the N-terminal domain remains unchanged upon phosphorylation
Contains two direct repeats of 7 amino acids in the N-terminus
All KH domains contribute to binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute (PubMed:29476152). The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules
The Clp repeat (R) domain probably functions as a substrate-discriminating domain, recruiting aggregated proteins to the ClpB hexamer and/or stabilizing bound proteins. The NBD2 domain is responsible for oligomerization, whereas the NBD1 domain stabilizes the hexamer probably in an ATP-dependent manner. The movement of the coiled-coil domain is essential for ClpB ability to rescue proteins from an aggregated state, probably by pulling apart large aggregated proteins, which are bound between the coiled-coils motifs of adjacent ClpB subunits in the functional hexamer
Is exclusively composed of 4 tightly packed alpha helices (no beta strand is present)
The region A, also named N-term, mediates the interaction with DDX6/RCK and is required for cytoplasmic mRNA processing body assembly
The F-box domain is essential for the formation of SFC(COI1) complexes
The Leu-rich domain is involved in the interactions with RBCS-1B and RPD3B
Contains 4 domains, connected by flexible linkers. In the active conformation, the domains are in an extended conformation, each making extensive interactions with the RNA polymerase catalytic core
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (PubMed:19903881, PubMed:21829166). This domain is probably also responsible for interaction with Crp (PubMed:10860740)
Although both SET and pre-SET domains are present, the absence of the post-SET domain may alter the methyltransferase activity
These proteins have 2 BMC domains which evolve independently of each other, giving the term pseudohexamer to the trimerized subunit. Although the homotrimer fills the approximate space of a BMC hexamer protein, the BMC-T trimers are more compact. Their universal presence in BMCs indicates their structural importance. The homohexamers form pores of at least 5 Angstroms in diameter; in the stacked homohexamer both pores are closed (PubMed:28642439). In the BMC the inner pore is fully or partially closed while the outer pore is closed (PubMed:30833088)
N-terminus residues are involved in complex formation with CCL5. A N-terminal derivative peptide composed of residues 37-54 inhibits CCL5 activity in monocyte migration assays, suggesting that Evasin-4 derivatives could be used as a starting point for the development of anti-inflammatory drugs
The C-terminal part is necessary for the interaction with the PRP19C/Prp19 complex/NTC/Nineteen complex
The KH domains mediate RNA-binding
The beta subunit contains the carboxyl transferase (CT) domain
The C-terminal part (437-563) is required for the association with the endoplasmic reticulum lumen membrane
The cysteine framework is C-CC-C
The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, by interacting with phospholipids. Has affinity for phosphatidylserine, and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P, PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3
The bipartite nuclear localization signal (bNLS) and Ala-rich (alanine-rich; ARR) regions are involved in DNA-binding
Has three main structural domains: an N-terminal FERM domain, a central alpha-helical domain and a C-terminal actin-binding domain
The FERM domain is organized in a clover-shaped structure that comprises three subdomains identified as F1 (residues 2-82), F2 (residues 96-198), and F3 (residues 204-296). In the active form, the subdomain F3 adopts two mutually exclusive conformational isomers where a row of four phenylalanine side chains (Phe250, Phe255, Phe267 and Phe269) must point in the same direction. In the autoinhibited form, the F3 subdomain interacts with the C-terminal domain (residues 516-586) and stabilizes the structure, selecting only one possible arrangement of phenylalanine side chains. The FERM domain mediates binding to membrane lipids and signaling molecules
The central alpha-helical domain is composed of two alpha helices (residues 326-406 and 417-466) connected by a linker. It protrudes from the FERM domain forming a coiled coil structure where the linker can have either a loop or a helix conformation. The monomer is predicted to form an intra-molecular helix-loop-helix coiled coil structure. Whereas the dimer adopts an elongated dumbbell-shaped configuration where continuous alpha helices from each protomer are organized in a antiparallel coiled coil structure that connect FERM:C-terminal domain swapped complex at each end. The dimer is predicted to link actin filaments parallel to the plasma membrane
The U-box domain mediates interaction with E2 ubiquitin ligases and is required for the ubiquitin-protein ligase activity
The first 11 amino acids are essential for phosphorylation and exclusive nuclear localization
The coiled-coil domain (557-589) and the WD-repeat domain are sufficient for SPA1 function. The coiled-coil domain is necessary and sufficient for interactions with HFR1 and COP1. The protein kinase domain may play a role in promoting destabilization of SPA1 under far-red light. The DWD box is required for interaction with DDB1A (By similarity)
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with smc4 forming a V-shaped heterodimer
The C-terminal 65 amino acids are required for catalytic activity
The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 or PEX20 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex
The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3)
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA)
The N-terminal periplasmic domain encodes a plug that inserts into the 22 beta-strand barrel, the extracellular loops extend up to 60 Angstroms away from the outer membrane. Part of the plug (the plug loop, resides 121-139) interacts with transferrin (TF), as does the L3 helix finger in extracellular loop 3 (residues 351-361). When the L3 helix finger inserts into TF it disturbs the conformation of TF and its coordination of iron 2. Electron microscopy suggests that in the TbpA-TbpB-TF complex, TF is captured directly above the loop domain of TbpA in a chamber of about 1000 Angstroms(3) formed by the 3 proteins, where interactions between the proteins serve to abstract iron 2 from TF
The entire WD repeat region is required for the interaction with ORC complex components, as well as for association with chromatin and for binding to histone H3 and H4 trimethylation marks H3K9me3 and H4K20me3
Sequence analysis combined with the expression of constructs corresponding each to two or three adjacent TSP type-1 domains suggests the presence of 21 TSP type-1 domains; not all of these are detected by standard bioinformatic tools
The D-RWD region contains a double-RWD domain which is involved in the interaction with other kinetochore proteins
The C-terminal residues 721 to 760 are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12; and the C-terminal 17 residues are required for the ATG8 lipidation (By similarity)
Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins
The C2H2 domain is necessary for the transcriptional repression
The 2 guanylate cyclase domains fold into a pseudo-dimeric structure
Binds DNA via the 2 GATA-type zinc fingers
The N-terminal ABC transporter domain (positions 161 to 410) contains degenerated Walker A and B ATP-binding motifs, suggesting that it may be less efficient in ATP binding or not functional at all. This is a distinctive feature of the PDR subfamily
The unusual length of the two extracellular loops at positions 686 to 774 and 1408 to 1476 is another specific feature of the PDR subfamily which may have an important role for function
Contains four C-X9-C motifs that are predicted to form a helix-coil-helix structure, permitting the formation of intramolecular disulfide bonds
The BH3 motif is essential for pro-apoptotic activity
The cadherin 1 domain is required for binding to CDHR5
The PDZ domain mediates interaction with ROPN1
The overall structure is basket-shaped, with a large substrate-binding cavity at the center of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. The central cavity functions as the binding site for a wide range of substrates
The N- and C-terminal halves of this hexokinase contain a hexokinase domain (PubMed:9493266, PubMed:9735292, PubMed:10574795). The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus (PubMed:9493266, PubMed:9735292, PubMed:10574795). Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule (PubMed:9493266)
Has protease activity (PubMed:1331807)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (PubMed:10932256). HC forms channels in bilayers at low pH (PubMed:3856850). The N-terminal belt of the TD wraps an extended belt around the perimeter of the LC; it is shorter than in BoNT/A and does not block the active site (PubMed:10932256). The belt may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:17907800)
Contains a unique C-terminal C-plug that plays an important role in substrate transport. The C-plug forms a folded domain and completely blocks the path to the putative substrate-binding site. Under neutral or basic pH, the C-plug probably remains closed and prevents substrate transport (PubMed:22407317, PubMed:23589309). At acidic pH, the C-plug may be displaced, allowing influx of Glu and efflux of GABA (PubMed:23589309)
The BAR domain mediates the interaction with the coiled coil domain of AMOT, leading to its recruitment to tight junctions
The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-54 and Tyr-101/Phe-102
The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif locates to a long loop in the arm domain called the bowtie tail. Integrin-binding stabilizes an alternative conformation of the bowtie tail. Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as ltbp1, lrrc32/garp and/or lrrc33/nrros), resulting in distortion of the prodomain and release of the active TGF-beta-1
Contains 4 domains, connected by flexible linkers. In the active conformation, the domains are in an extended conformation, each making extensive interactions with the RNA polymerase catalytic core (PubMed:12000971)
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble (By similarity). The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (PubMed:12000971)
Shares weak sequence similarity with ubiquitin family, but contains an 'ubiquitin superfold' and the C-terminal Gly is required for isopeptide linkage
The tight homopentamer forms a pore with an opening of about 3.5 Angstroms in diameter which is positively charged
The extensive loop region (ELR) is specific for fungal secreted chorismate mutases and is required for the interaction with the host defense kiwellin KWL1
The ROQ region is required for CDE RNA-binding. It may also be involved in localization to stress granules
The RBD-FIP domain mediates the interaction with Rab11 (RAB11A or RAB11B)
Contains a N-terminal winged-helix DNA-binding domain and a regulatory C-terminal forkhead-associated (FHA) domain, which mediates binding to a Thr-phosphorylated site in the cognate kinase
Both the N-terminus (1-33) and the C-terminus (38-70) of the mature peptide form alpha-helices which probably disrupt target cell membranes. The linker region (34-37) probably derives from a processing quadruplet motif (PQM), found in propeptides of many zodatoxins, hinting at a fusion of two originally separate membrane-active peptides
Loop 1 (residues 17-28) effects catalytic activity while recognition of the ACA cleavage site is influenced by loop 2 (residues 53-61). Alterations of loop 2 generate new cleavage sites in addition to retaining the original cleavage site
The N-terminus (1-116) is sufficient for plasma membrane localization. VWA domain fragments interfere with the function of the full-length protein, triggering a lesion-mimic phenotype
The interaction with myosin V is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades
Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and, at least in part, functionally redundant (By similarity)
The regions responsible for dimerization and for DprA-RecA interaction partially overlap, it is suggested that when RecA interacts with the DprA-ssDNA NPC it rearranges or disrupts the DprA dimer, leading to nucleation of RecA on ssDNA (PubMed:22904190)
The 244-aa domain between residues 633 and 876 is the primary occludin (Ocln)-binding site and is required for stable association with the tight junction (By similarity)
The C-terminal region (residues 1151-1372) is an actin-binding region (ABR) that interacts directly with F-actin and plays an important role in the localization of Tjp1 at junctions (By similarity). The ABR is also required for the localization to puncta at the free edge of cells before initiation of cell-cell contact (By similarity). The ABR is also necessary for Tjp1 recruitment to podosomes (By similarity)
The second PDZ domain (PDZ2) mediates homodimerization and heterodimerization with Tjp2 and Tjp3 (By similarity). PDZ2 domain also mediates interaction with Gja12 (PubMed:15183511)
The tight homopentamer forms a pore with an opening of about 4 Angstroms in diameter which opens into a wider tunnel at the base of the truncated pyramid. The pore is positively charged
The Glu-rich acidic region in C-terminus is essential for FACT activity
The KRAB domain mediates interaction with TRIM28 and is required for transcriptional repressor activity
The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-terminus of the protein
Has been proposed to contain 7 WD repeats. This prediction could not be reproduced
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (Probable)
The pG1 pseudoGTPase domain does not bind GTP
The protein kinase domain 2 is predicted to be catalytically inactive
Composed of 3 distinct structural domains: the N-terminal domain, which has a mononucleotide binding fold typical for the P-loop NTPases, followed by a pronounced alpha-helical coiled coil domain and the C-terminal domain, which may be involved in RNA binding
The cytosolic domain interacts with sigma factor SigF
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase. Cpf1 has the following architecture: A-T-C-T-C-T-C
The first transmembrane domain may act as a type I signal anchor (PubMed:15385547). The catalytic loops is exposed toward the lumen (PubMed:15385547). The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family (By similarity)
PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1 and EPHB2 and with the C-terminus of PPFIA1 and PPFIA4. PDZ 4 and PDZ 5 mediate interaction with PRLHR (By similarity). PDZ 4 and PDZ 5 mediate interaction with the C-terminus of GRIA2 and GRIA3. PDZ 4, PDZ 5 and PDZ 6 mediate homomultimers. PDZ 7 mediates interaction with PDZ domain of GRASP1. PDZ 7 domain binds CSPG4. PDZ 6 mediates interaction with the C-terminus of liprins-alpha. PDZ 1, PDZ 2 and PDZ 3 mediate interaction with the PDZ-binding motif of FRAS1
The region downstream of Arf-GAP domain is essential to GAP activity in vivo. This region may be required for its targeting to Golgi membranes
The phospho-regulated basic and hydrophobic (PRBH) motif is sufficient and important for interaction with phospholipids permitting cortical localization (PubMed:26481050). Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane (PubMed:26481050, PubMed:32579558)
Contains an N-terminal module that displays cellulase activity (CtCel5C), a central type I dockerin module (Doc) that facilitates the integration of the enzyme into the cellulosome, and a C-terminal module, CtCE2, which displays dual activities: it catalyzes the deacetylation of plant polysaccharides and also potentiates the activity of its appended cellulase catalytic module through its non-catalytic cellulose binding function
In IrtB the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
Fragments of the mature protein (residues 77-96, 97-116 and 117-136) prevent uptake of M.tuberculosis by a human macrophage-like cell line (PubMed:25041568)
The N-terminal domain mediates glycosyltransferase activity
The C-terminal domain that mediates lysyl hydroxylase activity is also important for homodimerization
The cryptic mitochondrial transit peptide is revealed after cleavage by caspase upon oxidative stress and cell death. It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria
The His-rich (HRR) region contains approximately 12 tandem internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR binds heparan sulfate and possesses antiangiogenic, antibacterial and antifungal properties through binding Candida cells, and preferentially lysing the ergosterol-containing liposomes at low pH. The tandem repeats also bind divalent metal ions and heme
The cystatin domains can also bind heparan sulfate. Binding is enhanced in the presence of zinc ions
Consists of three domains: the CORE domain which forms the binding site for nucleotides, the LID domain which closes over the active site upon ATP or shikimate binding, and the substrate-binding domain which functions to recognize and bind shikimate
The two basolateral sorting signals (BLSS) in C-terminal cytoplasmic tails direct SLC16A8 to the basolateral membrane
Perforin consists of three domains: (1) the MACPF domain, which includes the central machinery of pore formation, (2) the EGF-like domain, which forms a 'shelf-like' assembly connecting the MACPF and C2 domains, and (3) the C2 domain, which mediates calcium-dependent binding to lipid membranes. The C2 domain is critical for initial calcium-dependent interaction with lipid membranes of the target cell: calcium-binding causes a significant structural rearrangement, leading to oligomerization and deployment of the two transmembrane beta-strands (named CH1/TMH1 and CH2/TMH2) that enter the membrane as amphipathic beta-hairpins. The third calcium-binding site (Ca(2+) 3), which constitutes the weakest affinity site, triggers structural rearrangements in the C2 domain that facilitate its interaction with lipid membranes
Contains a catalytic N-terminal domain and a C-terminal regulatory domain, linked together by a flexible region (PubMed:18498255, PubMed:19351325). The catalytic domain consists of a TIM barrel flanked by an extended C-terminal region. The active site is located at the center of the TIM barrel near the C-terminal ends of the beta-strands and is composed of conserved residues of the beta-strands of one subunit and the C-terminal region of the other (PubMed:18498255)
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol. It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL
Full-length protein is required for specific association with the 50S ribosomal subunit
Displays a distorted and non-productive active site that probably switches to a fully productive state only upon association with TRMT10C/MRPP1, HSD17B10/MRPP2 and pre-tRNA substrate
The cysteine cluster which is probably involved in the coordination of the [4Fe-4S] cluster is located at the C-terminal part of the protein
The RETICULON domain is partial in comparison with the other paralogs
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; an enoyl reductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P)
The enzyme consists of two functional domains, a catalytic core joined to a carbohydrate-binding domain (CBM) by a serine-, threonine-, and proline-rich, highly glycosylated linker sequence (Probable). The CBM binds to cellulose but not to mannan, and increases the mannan-hydrolysis of complex substrates (PubMed:12523968)
The N-terminal HD domain has ssDNase activity (PubMed:27105119). The C-terminal GGDEF domain has the cOA synthesis activity (PubMed:28663439)
Cluster B is an all-cysteinyl-liganded 4Fe-4S cluster; cluster C is a mixed Ni-Fe-S cluster which is the active site of CO oxidation. Cluster D is also an all-cysteinyl-liganded 4Fe-4S cluster that bridges the two subunits of the CODH dimer
The N-terminal zinc-fingers 2 and 3 are required for DNA binding as well as for targeting IKFZ1 to pericentromeric heterochromatin
The C-terminal zinc-finger domain is required for dimerization
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The N-terminus is necessary for its recruitment to DNA damage sites
Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (PubMed:30846601). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity)
D-box [RxxLxxxN] motif functions as a recognition motif for the ubiquitination machinery
The functional J domain is required for the release from histone-dependent chromatin-binding
Contains 122 imperfect repeats of a consensus octapeptide A-G-Y-G-S-T-L-T; further on a 16-residue and a regional 48-residue periodicity is superimposed
The C-terminal region is necessary for depolarization-induced and calcium-dependent transcription activation
The TPR 1 repeat interacts with the C-terminal of HSC70. The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8 and 9 repeats (also called TPR2B domain) interact with HSP90
The PCI domain is necessary and sufficient for the interactions with other CSN subunits of the complex
The N-terminal part (1-211), which is not required for deneddylating activity and CSN complex formation, is nevertheless essential for other aspects of CSN complex function
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). AclP has the following architecture: T-C-A-T-C (PubMed:25302411)
The N-terminal DNA-binding domain (residues 1-929) is a ssDNA-dependent ATPase and has ATP-dependent 3'-5' helicase function; both are stimulated in the presence of RecC, suggesting this domain interacts with RecC. Holoenzyme reconstituted with this RecB N-terminal fragment has no nuclease activity (PubMed:9448271). The C-terminal domain (residues 928-1180) has weak ssDNA endonuclease activity as an isolated fragment (PubMed:9790841) (PubMed:10518611). RecD probably interacts with this domain. The C-terminal domain interacts with RecA, facilitating its loading onto ssDNA. Interaction is decreased by ATP (PubMed:16483938). The RecB helicase domains change conformation upon nucleotide binding. As ssDNA is unwound and fed to the RecD subunit the latter transmits conformational changes through each subunit to activate the RecB nuclease (PubMed:15538360)
The holoenzyme may undergo conformational shifts upon DNA binding: the nuclease domain of RecB may swing away from the DNA exit tunnel in RecC. When Chi DNA binds to the RecC tunnel, the nuclease domain may then swing back to its original position (that seen in crystal structures), allowing it to nick the DNA 3' of the Chi site and then rotate to load RecA. At high Mg(2+) the nuclease domain may swing back more frequently, explaining differences seen in assays performed at high Mg(2+)
The extracellular region contains three distinct subdomains: a membrane proximal alpha domain, a central beta domain and a C-terminal gamma domain. The alpha domain might serve as a chaperone that stabilizes FtsL. The gamma domain is required for interaction with other divisomal proteins. The beta domain might modulate protein-protein interactions of the flanking alpha and gamma domains
The RabBD domain mediates interaction with RAB27A
The jas domain (259-284) is required for interaction with COI1
The PTB domain is necessary for the inhibition of MAP3K7IP2-mediated activation of NF-kappa-B
The TIRT domain mediates interaction with e2f4 and tfdp1
The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. The two transmembrane clusters are necessary and suficient for the plasma membrane targeting and oligomers assembly. The N-terminal and C-terminal domains interact at rest as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain; the binding is specifically inhibited by fully calcium-saturated calmodulin, resulting in activation of AC8
The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 2 are occupied, designated as sites 2 and 3 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Site 3 can bind either AMP, ADP or ATP (AMP, ADP or ATP 2). Site 2 binds specifically ADP (ADP 1) and is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of ADP (PubMed:22019086)
The BC, DE and FG loops form a tripartite wedge that blocks the substrate-binding site of target cysteine proteases (PubMed:32731033). The BC loop interacts with the catalytically active cysteine and histidine residues of the protease catalytic center (PubMed:32731033)
The C-terminal part of the protein seems to be involved in the cyclization step(s) required for the synthesis of pinene
The EF3-like region is necessary and sufficient for interaction with GCN20 (PubMed:9234705)
The RWDBD (RWD-binding domain) region mediates binding to RWD domain-containing proteins, such as GCN2
The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain. The Prospero-type homeodomain is essential for repression of RORG transcriptional activator activity
AF-2 (activation function-2) motif is required for recruiting coregulators containing the LXXLL motif, such as NCOA1, and control the transactivational activity
Contains an N-terminal PPIase domain and an IF (Insert in the Flap) domain
The antiaggregation activity resides in the serine-rich region and the C-terminus
The phosphatase sequence motif I (including Arg-125) and II (including His-169) are part of the cytoplasmic loop 2 and phosphatase sequence motif III (including His-223) is part of the cytoplasmic loop 3
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 476, which is replaced by an Asn residue
The SRX domain is sufficient for interaction with GTP-bound SRP102/SR-beta
The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity
The Abraxas-interacting region (AIR) mediates the interaction with ABRAXAS1
Consists of an N- and C-terminal catalytic domains linked to a middle reiterated domain. Only the C-terminal catalytic domain is active
The PH domain binds to phosphoinositides and is essential for podosome formation
The C-terminus is necessary for localization to the cell membrane (PubMed:26578515)
The lectin-like LINK domain is responsible for hyaluronan binding
Contains a Gln-rich C-terminal domain which could correspond to the transactivation domain
Domain G is globular
The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity (By similarity)
EWS activation domain (EAD) functions as a potent activation domain in EFPS. EWSR1 binds POLR2C but not POLR2E or POLR2G, whereas the isolated EAD binds POLR2E and POLR2G but not POLR2C. Cis-linked RNA-binding domain (RBD) can strongly and specifically repress trans-activation by the EAD
The jas domain (170-194) is required for interaction with COI1
The DRBM 3 domain appears to be the major RNA-binding determinant. This domain also mediates interaction with XPO5 and is required for XPO1/CRM1-independent nuclear export
The extracatalytic C-terminal part is highly rich in proline residues
The di-lysine motif confers endoplasmic reticulum localization
OAS domain 3 is catalytically active. OAS domain 1 has no catalytic activity but is essential for recognition of long dsRNAs
The Ras-associating domain is necessary for the Rap guanine nucleotide exchange activity. The N-terminal regionis necessary for cAMP-binding. The PDZ domain is necessary for its targeting to the cell membrane (By similarity)
Contains an N-terminal DNA-binding domain and a large C-terminal effector-binding domain. Contains two distinct sugar-binding sites with different affinities
The central cytoplasmic loop (residues 295 to 350) is critical for the function, but unlike other homologous proteins, has no apparent role in imparting substrate specificity or in the recruitment of the transporter protein
The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs
The N-terminal domain is required for interaction with FtsZ. The C-terminal domain efficiently binds peptidoglycan and is required for septal localization. Both domains are required for MapZ cellular function
The N-terminal transmembrane domain is involved in interaction with TolA and TolQ, while the central and C-terminal domains are involved in dimerization. The C-terminal domain is also involved in interaction with TolA and in association with the membranes (PubMed:10419942). May undergo large scale structural remodeling, where the N- and C-terminal sequences unfold in order for the protein to both reach and bind the peptidoglycan layer around 90 Angstroms away from the inner membrane (PubMed:26354441)
Adhesive and proteolytic functions of tsh lie in different domains of the protein
The coiled-coil domain mediates tetramerization
The C-terminal assembly domain promotes self-interactiona; allows functional channel
The C-terminal coiled-coil domain interacts with a single CALM molecule via the first two membrane-proximal helical regions, with CALM forming a clamp-like structure. Binding of CALM C-terminus to the first helical region is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to the second helical region is calcium-dependent and regulates electrophysiological activity of the channel
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation (PubMed:19549836). Autoinhibition of these functions is mediated by an interaction between the SH3 and F-BAR domains (PubMed:20188097, PubMed:23236520). The F-Bar domain also mediates the binding to the cell actin cytoskeleton through the interaction with CAV-1 (By similarity)
(Microbial infection) The SH3 domain is required for the cell-to-cell spreading of HIV-1 virions
The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded
The N-terminal domain likely catalyzes substrate activation by formation of an initial acyl-AMP intermediate, the central region contains the phosphopantetheine attachment site, and the C-terminal domain catalyzes the reduction by NADPH of the intermediate thioester formed from the attack of the phosphopantetheine thiol at the carbonyl carbon of acyl-AMP (By similarity). Large-scale domain motions occur between the adenylation and thiolation states. Phosphopantetheine binding alters the orientation of a key Asp, resulting in a productive orientation of the bound nicotinamide. This ensures that further reduction of the aldehyde product does not occur (PubMed:28719588)
The C-terminal (1113-1447) part mediates the histone acetyltransferase (HAT) activity
Contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors. LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro
Modular protein that contains an adenylation domain which activates the glutamate residue into an aminoacyl-AMP ester, a methyltransferase domain, a first peptidyl carrier protein domain which bears a phosphopantetheinyl arm to attach the activated L-glutamate, a condensation domain involved in the condensation of this amino acid with a second amino acid bound at the carrier protein domain of another module, a second peptidyl carrier protein domain which bears a phosphopantetheinyl arm to attach a L-alanine activated by AmbB and a thioesterase domain that may release the newly synthesized peptide from the enzyme
The PH domain is sufficient for the nuclear export of the oncogenic N-terminal truncated form. The relocalization is not affected by the Leu-492 mutation
The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation
The rhodanese domain is sufficient for RNF41-binding
Glu-127 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-202 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group
The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex (PubMed:16109376, PubMed:16109377). It is also required for maintenance of higher-order chromatin structure (PubMed:22334664)
The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-433, respectively (PubMed:20871596). The exact combination of modified histone tails required to recruit BRD4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3 (PubMed:22464331). A number of specific inhibitors bind competitively to acetyl-lysine-binding residues Asn-140 and Asn-433, promoting removal from acetylated histones. Many of these inhibitors are benzodiazepine derivatives (PubMed:22137933, PubMed:22136404, PubMed:23517011, PubMed:23530754)
Consists mainly of membrane-spanning sided beta-sheets. 19 strands distributed along the entire VDAC protein, have the potential to adopt transmembrane beta pleated sheet structures, which rolled together may form a 'beta-barrel' type structure, possessing pore dimensions
Consists of a soluble N-terminal domain and C-terminal probable beta-barrel in the outer membrane with 14 predicted beta-strands
The structure is significantly stabilized upon cofactor binding
C-terminus (307-412) is necessary for binding to liposomal membranes as assessed by phosphatidylinositol-4,5-bisphosphate (PIP2)-containing giant unilamellar vesicles (GUVs), models of biological membranes
The CaMBD domain (358-373) is required for calmodulin binding
The GBeta-binding domain (577-584) is required for GB1 binding
The transmembrane domain 1 and 2 function as a signal-anchor and stop-transfer sequence, respectively, generating a double-spanning integral membrane protein with a N- and C-terminal cytoplasmic orientation. Transmembrane domain 1 and 2 are probably sufficient to mediate membrane translocation and topology formation in a N-myristoylation-independent manner. Transmembrane domain 2 is sufficient to block the protein secretion pathway. The two coiled-coil domains are necessary for its endoplasmic reticulum (ER) three-way tubular junction localization. The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation
The N-terminal zinc fingers are involved in sequence-specific DNA binding and heterotypic associations with other family members
The SPOR domain is important for normal localization, but not for cell division or rod shape
The transcriptional activation domain 3/TA3 does not participate in the direct transcriptional activity of RELA but is involved in the control by RELA of the accessibility of target gene promoters. Mediates interaction with ZBTB7A
The transcriptional activation domain 1/TA1 and the transcriptional activation domain 2/TA2 have direct transcriptional activation properties (By similarity). The 9aaTAD motif found within the transcriptional activation domain 2 is a conserved motif present in a large number of transcription factors that is required for their transcriptional transactivation activity (PubMed:17467953)
The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. It mediates both barbed-end actin capping and actin bundling activities. The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (By similarity)
The fibrinogen C-terminal domain is sufficient to mediate endothelial cell adhesion
The DRBM domain is required for binding to guide RNAs (gRNA) and mRNAs which facilitates the association with the GRBC complex
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger (PubMed:21532592, PubMed:23707686). The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate (PubMed:21532592, PubMed:23707686)
The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site (PubMed:23707686)
Amino acids 201-225 are sufficient for specific binding of phosphatidic acid
The putative coiled-coil domain is necessary for interaction with TSC2
XTBD domain is necessary for interaction with xrn-2
The C-terminal four TSP1-like repeats are necessary and sufficient for binding COMP
The GoLoco domain is necessary for interaction with GNAI1, GNAI2 and GNAI3
In the disassembly complex (PDB:6P8V) Cap6 (this protein) crystallizes as a right-handed spiral; the top 4 subunits bind ATP while the bottom 2 do not. A CdnC monomer lies along the surface of the hexamer at the interface of subunits 5 and 6, with Cap7 (also called HORMA) at its tip, over the central hexamer pore. The N-terminus of Cap7 extends into the pore, contacting 5/6 Cap6 subunits
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). It is required for IRS1 ubiquitination and subsequent proteasomal degradation
Both zinc fingers are required to induce development
The N-terminus is probably essential for channel affinity
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction affinities. The UBA-like domain mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin ligation to DCUN1D1
The protein structure shows 2 N-terminal domains, the central catalytic and C-terminal domain (PubMed:10319817). The C-terminal domain recognizes the anticodon region of the tRNA while the acceptor arm is sandwiched between the N-terminal domains and the catalytic domain (PubMed:10319817). The N-terminal also contributes to the precise recognition of tRNA(Thr) (PubMed:10319817). The editing domain encompasses approximately residues 62-224; when it is removed the protein mischarges tRNA(Thr) with L-serine (PubMed:15079065, PubMed:11136973)
This protein has four EF-hand domains, two of which may be functional calcium-binding sites
The C-terminus forms an amphiphilic helix that targets the protein to the periplasmic side of the inner cell membrane
The ETGE motif, and to a lower extent the DLG motif, mediate interaction with KEAP1
The NEAT domain binds Fe(3+) heme iron. Reduction of the high-spin Fe(3+) heme iron to high-spin Fe(2+) results in loss of the heme from the binding site of the protein due to the absence of a proximal histidine
Has a remarkable domain of repetitive pentameric units sometimes followed by a tripeptide spacer, it may separate two functional basic and acidic domains
The Arg/Lys-rich basic domain functions as a tripartite nuclear localization signal
The PDZ domain contains the signal for export from the nucleus (By similarity). The N-terminal region including the PDZ domain is required for the formation of Cajal bands on myelinated nerves (By similarity)
The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides
The YTH domain mediates RNA-binding
The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3)
Has the canonical EER motif, but lacks the canonical translocation motif RxLR, which characterizes most oomycete effectors identified so far
The RING-type zinc-finger domain is required for E3 ubiquitin ligase activity
The CUB domain is important for the interaction with the cholesterol-anchor of SHH. The CUB domain regulates protease recruitment and activation during SHH shedding
Both DRBM domains are required for efficient binding to pri-miRNA. The region between residues 276 and 498 has an autoinhibitory function on pri-miRNA processing activity
Peroxisomal targeting signal 1 (PTS1) is a tripeptide located at the C-terminus of more than 95% of all peroxisomal matrix proteins. The prototypical PTS1 is the terminal tripeptide SKL (serine-lysine-leucine) but the consensus of PTS1 is defined as [S/A/H/C/E/P/Q/V] [K/R/H/Q] [L/F]. However, this description of the PTS1 consensus must probably be expanded beyond the terminal tripeptide
The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365 (By similarity)
The UBZ3-type zinc finger domain and the PIP-box mediate the interaction with ubiquitinated PCNA and are both necessary for the enzymatic activity in translesion synthesis
The C-terminal residues are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12
The PH domain mediated binding to phospholipids with phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate
The chorein N-terminal domain mediates lipid transfer activity
Heparin-binding motifs (HBM) are characterized by an XBBXBX or XBBBXXBX sequence, where X is any neutral amino acid and B is a positively charged basic amino acid, and are defined as the consensus sequence necessary for protein-heparin interactions. HBM motifs may be involved in spore adherence to host cells
The PDZ-binding motif is required for cell surface expression, neurite outgrowth promotion (By similarity). This motif is also involved in DLG1-, DLG3- and DLG4-binding
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (Probable)
The UIM (ubiquitin-interacting motif) is required to engage the NEDD8 modification on cullins
The UBX domain mediates interaction with VCP/p97
The UBA domain is required for binding ubiquitinated-protein substrates
Comprises six structurally related gelsolin-like (G1-G6) domains, that, in a calcium-free environment, are packed together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur (PubMed:19666512). Binding calcium may release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently (PubMed:12460571, PubMed:19666512). G1 and G4 bind two Ca(2+) in a type I and in a type II manner (PubMed:12460571, PubMed:19666512). G2, G3, G5 and G6 bind only one Ca(2+) in a type II manner (PubMed:12460571, PubMed:19666512). Type I Ca(2+) binding sites are shared between actin and gelsolin-like repeats G1 and G4 (PubMed:12460571, PubMed:19666512). Type I binding governs the strength of interactions between gelsolin and actin by direct participation at the binding interface (PubMed:12460571, PubMed:19666512). Ca(2+) binding to G2 and G6 disrupts the interactions between G2 and G6, releases the C-terminal tail, and induces large interdomain rearrangements that result in the exposure of the F-actin-binding site on G2 and contributes to the activation of gelsolin (PubMed:12460571, PubMed:19666512). Binding to phosphoinositides may inhibit the severing and capping properties of gelsolin (Probable)
The N-terminal region (2-281) contains the glycosylase and lyase activities
The N-terminal half is highly basic
The BTB/POZ-like domain may mediate the interaction with some component of ubiquitin ligase complexes
Exhibits a tripartite organization, with its C-terminal part forming a homotrimeric 28-stranded OM beta-barrel (OMBB), its central part forming a long trimeric coiled coil that can traverse the large periplasmic space, and the extreme N-terminal part forming an SLH domain trimer that can interact with the PG layer
The C-terminal region of isoform 5 mediates its intracellular retention
The coiled coil domain may mediate the interaction with dystrophin
The proline-knot motif (81-90) may be involved in targeting to lipid bodies
The C-terminal extension (CTE) is used to better adjust the substrates into the active sites and mediates in vivo subcellular localization of the protein (PubMed:19801656, PubMed:24970891). It also modulates expression levels of Rv0805 in mycobacteria (PubMed:24970891)
The C-terminus is necessary for the co-dependent secretion, for maintaining the EsxA (ESAT-6) cellular levels, and for interacting with EsxA
Domains close around the active site upon filament formation, which probably enhances nucleotide hydrolysis (PubMed:27821762). Nucleotide-binding also probably induces domain movement (Probable)
The N-terminus is necessary for nuclear localization. The C-terminus is necessary for transcriptional activity (By similarity)
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (By similarity). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer (By similarity)
The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and 'Thr-4827' phosphorylated HERC2 (PubMed:18001824). This domain is required for proper recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent (PubMed:23233665)
Domain VI is globular
The RBM1 (RPA1-binding, also named RPA70N-binding) motif mediates interaction with RPA1. The RBM2 (RPA2-binding, also named RPA32C-binding) motif mediates interaction with RPA2
The ATR-activation domain (AAD) motif is required to bind and activate ATR
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (354-384) inactivates kinase activity under calcium-free conditions
The LIM zinc-binding domains and the Cys-rich region mediate interaction with GATA6
The RRM domain mediates integration into cytospeckles
The extracellular domain forms gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization
A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes
The Asp-Xaa-Asp-Asp-Thr-Ala (DXDDTA) and Gln-Xaa-Xaa-Asp-Gly-Ser-Trp (QXXDGSW) motifs are expected to bind to Mg(2+)
The SWIRM domain may act as an anchor site for a histone tail
The HrcQb-C domain interacts with the HrcQa C-terminal domain
The PHD-type zinc fingers mediate the interaction with E(z)
In contrast to vertebrate homologs (PHF1, PHF19 and MTF2), the Tudor domain does not bind H3K36me3 (PubMed:23104054, PubMed:23142980)
The N-terminal domain is followed by a GAF (phytochrome-like) domain that lacks the conserved Cys residue for ligand binding, a histidine kinase domain and a C-terminal response regulator domain without the conserved Asp residue that is phosphorylated (pseudo-receiver domain, PsR)
Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions (PubMed:22464331). Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) (PubMed:22901802). The bromo domains also recognize and bind a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (By similarity)
Adopts a seahorse-like shape and consists of four domains: head, neck, body, and tail
The C-terminal basic cluster region, which consists mainly of lysine residues, is important for the formation of a stable RFC-PCNA-DNA complex, although it is not critical for loading PCNA onto DNA in vitro (PubMed:16172520). An 11-mer corresponding to the PIP-box inhibits DNA synthesis by Pol I (pol)
The proline-knot motif may be involved in targeting to lipid bodies
The coiled coil domain (residues 44-77) is essential for membrane-targeting in cardiomyocytes
The third RNA recognition motif, called PUMP domain in PubMed:10606266, is atypical and may rather mediate protein-protein interactions
Is organized in two protein domains. The N-terminal domain has a fold similar to that of desulforedoxin and contains a mononuclear Fe(3+) ion, center I. The second domain contains a different mononuclear iron center, center II, with a Fe(2+) ion (By similarity)
Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix
The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions (By similarity)
The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins (PubMed:22966849). The two C2 domains bind independently to planar membranes, without interdomain cooperativity (PubMed:25437758). Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins (PubMed:26322740, PubMed:26333120)
The C-terminal domain interacts with histones H1 and H3, and may be responsible for condensin complex targeting to mitotic chromosomes. This domain is independent from the bipartite nuclear localization signal, although they are contained within the same region (By similarity)
The transmembrane domain mediates interaction with KIDINS220
The extracellular domain mediates interaction with NGFR
The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (By similarity)
The poly-Gln domain is involved in the interaction with BECN1 and subsequent starvation-induced autophagy (PubMed:28445460)
Contains an N-terminal coiled-coil domain and a C-terminal TPR domain, separated by a flexible linker
Contains an N-terminal CZB (chemoreceptor zinc binding) domain and a C-terminal GGDEF domain
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (PubMed:24373768). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (PubMed:23791178)
The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (PubMed:24847877)
The C-terminal half (89-105) of the Ser/Pro-rich region and the transmembrane domain are necessary and sufficient for membrane integration
The TPR region (238-373) interacts with TIC110
The STI1 2 domain (386-425) has a stimulatory effect on HSP93 ATP hydrolysis
The F-box-like region is required for the interaction with SKP1
The CARD domain mediates a direct interaction with CRADD
Consists of two distinct domains, a catalytic domain and a coenzyme-binding domain
Contains a C-terminal domain similar to that of the C-terminal section of MAP3K7
The LIM zinc-binding 2 (LIM 2) interacts with TBX4
The LIM zinc-binding 3 (LIM 3) domain provides the structural basis for recognition of tyrosine-containing tight turn structures. This domain is necessary and sufficient for interaction with TBX5 (By similarity)
The BCB domain mediates the interaction with CUL3
The N-terminal domain is not required for catalytic activity, but it is involved in substrate binding
The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition
The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates
The C-terminus domain (aa 502-621) mediates interaction with MTMR9
The PTS2-type peroxisomal targeting signal, which mediates interaction with PEX7 and localization to peroxisomes, is cleaved following import into peroxisomes
DMA domain may interact with ubiquitin
The EF-hand domains are unfolded in the absence of Ca(2+) and fold upon Ca(2+) addition
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (PubMed:22329759)
The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-terminus of the protein (PubMed:23368695)
The N-terminus (residues 1-69) is thought to form 2 alpha-helices that allow dimerization and probable hexamerization; this region inhibits DAC activity of the rest of the protein (PubMed:24939848)
Although it shares some sequence similarity with SRS2 yeast helicase, does not contain a functional ATPase domain suggesting it has no helicase activity
The EIID domain, with its homologous EIIC domain, forms the PTS system translocation channel and contains part of its specific substrate-binding site
The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved. Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity. In addition, the conserved Cys-314 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination
The 4 amino acid insert at the 'A' site is required for efficient binding of heparin
The NtA domain, absent in TM-Agrin, is required for binding laminin and connecting to basal lamina
Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC4, forming a V-shaped heterodimer
Has the CSbeta/beta fold, which comprises anti-parallel beta-sheets stabilized by three or four disulfide bonds
Macro domains 1 and 2 may be involved in the binding to poly(ADP-ribose) (PubMed:28525742, PubMed:26479788). Macro domain 2 is required for recruitment to DNA damage sites (PubMed:23230272). Macro domains 1 and 2 are probably dispensable for the interaction with STAT1 and DTX3L and for STAT1 phosphorylation (PubMed:26479788)
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. Pum2 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine
The SH3 domain mediates the stable interaction with Cas
The RRM domains are necessary but not sufficient for binding to APOB mRNA. Additional residues in the pre-RRM and C-terminal regions are required for RNA-binding and for complementing APOBEC1 activity (By similarity)
The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, by interacting with phospholipids (PubMed:24001019). Has affinity for phosphatidylserine, and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P, PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3 (PubMed:24001019)
the PDZ-binding motif mediates interaction with PDZ domain-containing proteins and is required for is required for synaptic localization in photoreceptors
Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity
AAA-cassette D1 is required for interaction with PEX6. ATP-binding in AAA-cassette D2 is required for interaction with PEX6. ATP-binding and hydrolysis in AAA-cassette D2 is required for proper function in PEX5 dislocation
The GGQ domain interacts with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis
The M-domain stimulates the interaction between CPFTSY and the chloroplast signal recognition particle (cpSRP)
The C-terminal residues (539-564) are required for interaction with CAO/cpSRP43
The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin. Swapping with the UBP-type zinc finger from USP5 restores ability to bind unanchored ubiquitin and subsequent activation of the protein (PubMed:22216260)
The PDZ-binding motif mediates interaction with GOPC
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (332-362) inactivates kinase activity under calcium-free conditions (By similarity)
The cysteine-rich C-terminus is involved in its granular distribution in the cytoplasm (By similarity)
The cysteine-rich domain CRC binds zinc in vitro
The C-terminal part is necessary for interaction with szy-20
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (450-480) inactivates kinase activity under calcium-free conditions (By similarity)
Both the N-terminal (up to position 79) and the C-terminal (from position 304) sequences are required for interaction with SSX2
Contains two distinct DNA-binding domains. One is located in the N-terminal region and binds to the 5'-CAACA-3' motif. The second is located in the C-terminal region and binds to the 5'-CACCTG-3' motif
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the trimerized C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface. The passenger domain is probably exported as a hairpin structure, with all 3 strands of the trimer in the pore simultaneously
The PHD domains mediate specific binding to histone H3 unmethylated at 'Lys-4' and may preferentially recruit the protein to transcriptionally inactive genes
The chromo domains mediate specific binding to histone H3 trimethylated at 'Lys-27' (H3K27me3) and may be required in neuron differentiation for proper gene regulation
Two EF-hand domains are present. However, only EF-hand 1 (and not EF-hand 2) binds calcium
The C2 domain mediates membrane localization and substrate selection
The ubiquitin-like domain mediates interaction with the E3 ubiquitin-protein ligase RNF126 which is responsible for the BAG6-dependent ubiquitination of client proteins. SGTA also binds this domain and competes with RNF126 to antagonize client protein ubiquitination and degradation. The ubiquitin-like domain also mediates the interaction with USP13
Contains an 'insertion' sequence of 42 residues which is not present in other ferritins
Is composed of four functional domains: the N-terminal 5'-deoxyadenosylcobalamin binding region that is homologous to the small subunit of ICM (IcmB), a middle P-loop GTPase domain (MeaI) that likely acts as a chaperone for ICM, a structured linker region involved in dimer formation, and a C-terminal part that is homologous to the large substrate-binding subunit of ICM (IcmA)
The alternatively spliced domain I3 corresponding to amino acids (636-669) of isoform 4 is an EPB41 binding site mediating association to membranes in polarized and non-polarized cells
The L27 domain may regulate DLG1 self-association. The N-terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization
The first 16 AA of the protein contain topogenic information that is able to direct a reporter protein to the ER
The tify domain is required for homo- and heterodimerization and for the interaction with other TIFY proteins
The jas domain (302-326) is necessary and sufficient for the hormone dependent interaction with COI1 and the hormone independent interaction with MYC2
May have three functional domains: one for interaction with CheB and CheY, a second for regulating phosphorylation and controlling the stability of the protein, and a third for receiving input signals regulating CheA activity
Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure
RRM1 and RRM2 domains preferentially target UGU(U/G)-rich mRNA elements
The C-terminus (residues 341-390) is not required for either 50S ribosome subunit association nor 70S ribosome dissociation
The PINc domain confers endonuclease activity and is expected to bind the catalytic metal ion
Consists of a biotin carboxylase (BC) domain at the amino terminus and a biotinyl-binding/biotin carboxyl carrier(BCC) domain at the carboxyl terminus
Recognition of anti-sigma-G factor Gin (csfB) occurs via the first 71 residues (PubMed:18208527)
The FM region is required for binding smad2/smad4 complexes. FM2 is more effective than FM1 and only interacts with phosphorylated smad2 that is in an activated smad complex (By similarity)
The PIP-box mediates the interaction with PCNA, while the RanBP2-type zinc finger mediates binding to 'Lys-63'-linked polyubiquitin (PubMed:22704558, PubMed:22705370, PubMed:22759634)
All seven C2 domains associate with lipid membranes in a calcium-dependent manner. Domains C2 1 and 3 have the highest affinity for calcium, the C2 domain 1 seems to be largely unstructured in the absence of bound ligands. The C2 domain 1 from isoform 14 does not bind calcium in the absence of bound phospholipid (PubMed:24239457, PubMed:24461013)
The cholinesterase-like (ChEL) region is required for dimerization and export from the endoplasmic reticulum
The C-terminal 40 residues are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12; and the C-terminal 17 residues are required for the ATG8 lipidation
One side of the hexamer is concave which is lined by hydrophobic residues, the other side has a slightly protruding, 6-stranded beta-barrel
Contains LRR and Ig-domains that can mediate low-affinity interaction with EGFR. The LRRs and the Ig-domains are each sufficient for EGFR/ERBB1 binding. This interaction is abolished only when both the LRRs and the Ig-domains are deleted
The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors. CAPRIN1 molecules in the condensed phase are neutral. mRNA-binding promotes phase separation. Moderate concentrations of ATP enhance phase separation by reducing the electrostatic potential of CAPRIN1, thereby promoting intermolecular interactions. In contrast, high concentrations of ATP invert the electrostatic potential of CAPRIN1, so that CAPRIN1 molecules become negatively charged, lead to inhibition of phase separation
Contains an extra C-terminal sequence (ECTS), which contains a highly conserved PEP binding motif
This trifunctional enzyme consists of two major domains: a N-terminal part, containing the methylene-THF dehydrogenase and the methenyl-THF cyclohydrolase activities and a larger formyl-THF synthetase domain
The C-terminal EF-hand is necessary for the binding to RAD4 and for efficient nucleotide excision repair (NER)
The SET domain is required for methyltransferase activity and ectopic effect on plant growth
Binds different substrates in the same active site (PubMed:18295794, PubMed:22178925). Binding of the substrate induces conformational changes of EmrE (PubMed:18295794, PubMed:20551331, PubMed:22178925). The asymmetric antiparallel homodimer exchanges between inward- and outward-facing states that are identical except that they have opposite orientation in the membrane (PubMed:22178925, PubMed:24448799). The conserved C-terminal tail is strongly coupled to EmrE's drug-binding domain and participates in secondary gating of EmrE-mediated proton/drug transport, occluding the binding pocket of fully protonated EmrE in the absence of drug to prevent dissipative proton transport (PubMed:30287687)
Each subunit is composed of an apical domain, an intermediate domain and an equatorial domain (PubMed:32808291). The apical domain is sufficient for substrate recognition (PubMed:21094166). Contains a characteristic histidine-rich C terminus which is essential for copper binding (PubMed:32808291). Copper binding causes conformational rearrangement (PubMed:32808291)
The cytoplasmic region is required for interaction with FtsA (PubMed:24750258). The periplasmic region is composed of a membrane-proximal region containing three short partially formed helices (H1, H2 and H3), followed by an unstructured glutamine-rich linker, and a C-terminal globular SPOR domain (PubMed:15101973, PubMed:19684127). Essential function of FtsN is accomplished by a small region of at most 35 residues that is centered about the H2 helix (PubMed:19684127). The SPOR domain, which exhibits a ribonucleoprotein (RNP) fold, binds peptidoglycan and is a strong septal localization determinant, but it seems not essential for cell division (PubMed:15466024, PubMed:19684127, PubMed:24056104)
The MIT domain is involved in interaction with CdvB
The N-terminal signal peptide is necessary for IDL1 function
The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich C-terminal domain interacts with F-actin
Contains three extended channels that together form a T-shaped, three-channel nexus (PubMed:27815501). Contains an active site base originating from the second monomer of the dimer (PubMed:29025976)
The 6 amino-acid N-terminal tail displays a well-defined structure and plays a role in stabilizing the peptide
The Ig-like V-type (immunoglobulin-like) domain mediates binding to PtSer involving a Ca(2+) ion
The N-terminal domain is sufficient to bind to viral RNAs and promote their degradation. The second and fourth zinc fingers are involved in binding to specific viral RNAs. Contains a divergent PARP homology ADP-ribosyltransferase domain which lacks the structural requirements for NAD[+] binding. It is therefore inactive
The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes
The PDZ-binding motif is required for neurite outgrowth promotion and for DLG1-, DLG3- and DLG4-binding
The PH domain of FAPPS binds the small GTPase ARF1 and phosphatidylinositol-4-phosphate (PtdIns4P) with high selectivity, and is required for recruitment of FAPPs to the trans-Golgi network (TGN)
The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins
The UBL domain mediates association with RNF31 via interaction with its UBA domain
The transmembrane domains are sufficient for localization in the cilium. The cytoplasmic tails are necessary for localization in cell bodies and anchoring at the ciliary base. Cytoplasmic tails also regulate sensory function
Intramolecular interaction between the zinc finger domain and the CAP-Gly domains may inhibit interaction with tubulin
The N-terminal region is required for cytoplasmic localization
The ANK repeats and the SH3 domain are required for specific interactions with p53/TP53
Truncation of 30 residues from the C-terminus results in a temperature-conditional defect in protein sorting
Deletion of the C-terminal 'ferric reductase' domain (residues 444-645) phenocopies the deletion mutant; makes a magnetosome with normal crystals sandwiched between flake-like crystals
The 27 C-terminal residues (residues 237-263) are absolutely required for enzymatic activity; a deletion mutant lacking this C-terminal region shows a complete absence of enzymatic activity
The ring domain is sufficient for the interaction with NAC19
Contains 3 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which are usually required for the association with nuclear receptors
The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding
The N-terminal domain binds DNA and the C-terminal domain is involved in dimerization. Both domains are required for transcriptional activity and for ESX-1 function
Consists of three domains. The N-terminal SAF domain, which forms a beta-clip fold, is likely involved in the substrate recognition. It is connected by a long unstructured linker to the second domain, which serves as a dimerization interface between two monomers. The C-terminal domain represents the catalytic core of the protein and probably contains the metal binding site
Mutagenesis suggests that interactions with P1- and P4-phosphate are minimum indicating the enzyme may have a wide substrate range
The glutamine-rich domain might function in activating gene expression
The MBOAT fold forms a reaction chamber in the endoplasmic reticulum membrane that encloses the active sites (PubMed:32433611, PubMed:32433610). The reaction chamber has a tunnel to the cytosolic side and its entrance recognizes the hydrophilic CoA motif of an acyl-CoA molecule (PubMed:32433610). The chamber has separate entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-glycerol (PubMed:32433610)
The N-terminal region, including the PHD-type 1 and 2 zinc fingers and the C2HC pre-PHD-type zinc finger, is required for binding to histone H3
Has 3 domains that are structurally very similar to those in BoNT/A; light chain (nLC, equivalent to the light chain, residues 1-408), N-heavy chain (nHN, residues 409-829) and C-heavy chain (nHC, residues 830-1193) (PubMed:22363010)
Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain
The C-terminal region contains 1 L, 2 W and 2 Y motifs. W, Y and L motifs are present in at least half of the identified oomycete RXLR-dEER effector candidates and W and Y are critical for the functions of the very large number of predicted oomycete effectors that contain them
The ASD2 domain mediates the interaction with ROCK1 and is required for apical constriction induction
Contains a chimeric signal that facilitates targeting of the protein to both the endoplasmic reticulum and mitochondria. A 12 amino acid sequence between 33 and 44 functions as a putative mitochondrial-targeting signal. The removal of the first 4- or 32-amino acid residues from the intact protein positions the mitochondrial targeting signal for efficient binding to the mitochondrial import receptors. The membrane-free P4501A1 seems to be more sensitive to proteolysis
Has an N- and C-terminal domain; kanamycin binds in the cleft between the 2 domains
The YEATS domain specifically recognizes and binds crotonylated histones
The Z-binding domains recognize and bind left-handed double-stranded Z-RNA structures, but not A-RNA, the right-handed double-stranded RNAs that are structurally very different from Z-RNAs. The second Z-binding domain (also named Zalpha2) acts as a molecular switch regulating pyroptosis, necroptosis and apoptosis (PANoptosis). The second Z-binding domain is essential for sensing influenza A virus (IAV) Z-RNAs
(Microbial infection) The RIP homotypic interaction motif (RHIM) mediates interaction with the RHIM motif of the herpes simplex virus 1/HHV-1 protein RIR1/ICP6 to form hetero-amyloid structures
Lacks the ATP-binding domain
Contains 2 BMC domains, trimerizes to give a hexamer. Each trimer forms a pore with an opening of about 13 Angstroms in diameter; depending on the conformation of conserved residues Glu-69 and Arg-70 the pore is open or closed. Dimerization of the trimers forms a small barrel-like compartment, accessible via the pore. Barrels with one open and one closed pore or with 2 closed pores have been seen. A pocket that is the right size to loosely bind RuBisCO substrates and products is found between the 2 BMC domains in each monomer
The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact respectively with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively
The RNA-binding domains RRM2 and RRM3 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer (PubMed:32610138, PubMed:33106659). Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9A-containing vesicles, thereby enabling growth into autophagosomes (PubMed:33106659)
The extracellular domain (ECD) region specifically binds trypsin
The C-terminal domain of Avr1 comprises three motifs (W1, W2, and Y), two linker regions (ln1 and ln2), and at the very end the T-region. The T-region of AVR1 is important but not sufficient to trigger R1-mediated HR and W1, W2 and Y are equally important for recognition by R1
Amino acids 23-36 of the EF-hand-like domain are necessary catalysis but not for binding to lipid vesicles
Forms a U-shaped beta-half-barrel with a large hydrophobic cavity (3549 Angstroms(3)). The cavity is opened when amphipathic helices 2, 3 and 9 move away from helices 7 and 8 (PubMed:21965687). Has 5 potential amphipathic helices (P1 to P5, residues 56 to 63, 155 to 162, 194 to 202, 240 to 250, and 270 to 279 respectively); P2, P3 and P5 form helices in the presence of lipid vesicles (PubMed:16159783)
Both the BIR and NACHT domains are essential for effective inhibition of pro-CASP9 cleavage. BIR3 domain binds to procaspase-9 and the NACHT domain interacts with the NACHT domain of APAF1 forming a bridge between pro-CASP9 and APAF1 (By similarity)
Contains six tetratricopeptide (TPR) protein-protein interaction motifs (PubMed:23547883, PubMed:16403447, PubMed:18776008). TPR1-TPR4 form the minimal region required for secretin assembly and function (PubMed:23547883)
The coiled coil domain can form antiparallel homodimers and mediates dimerization with the coiled coil domains of ATG14 or UVRAG involved in the formation of PI3K complexes
The C-terminal evolutionary conserved domain (ECD) contains poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent with structural docking models revealing two highly scored poly-Gln-binding pockets in the ECD. As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3
The first transmembrane domain may act as a type I signal anchor. The catalytic loops is exposed toward the lumen. The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family
The BEN domain 4 is necessary and sufficient for the localization of BEND3 to heterochromatic regions
The C-terminal domain is involved in RNA binding
The N-terminal guanylate cyclase domains are required for enzyme activity. Fragments containing the first 470 amino acid residues are fully active
The N-terminal alpha-hairpin extension is required for pectinmethylesterase inhibitor activity
The DRBM 3 domain appears to be the major RNA-binding determinant. This domain also mediates interaction with XPO5 and is required for XPO1/CRM1-independent nuclear export (By similarity)
Contains 4 domains, connected by flexible linkers. In the active conformation, the domains are in an extended conformation, each making extensive interactions with the RNA polymerase catalytic core (PubMed:11931761, PubMed:12016306)
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (PubMed:11931761, PubMed:22136875)
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (PubMed:11931761)
Isoform v1 and isoform v2 of this protein have four functional EF-hand calcium-binding domains. Isoform v3 and isoform v4 have the third EF-hand domain interrupted by an insert
The SH2 2 domain is required for interaction with FBXL2 and PTPN13
The JAZ-interaction domain (JID) (82-141) is sufficient for interaction with MYB proteins and most of the TIFY/JAZ proteins (PubMed:21335373, PubMed:23943862)
Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs (PubMed:11118454). One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (By similarity). Binds calmodulin in a calcium-dependent way (PubMed:11118454)
The N-terminus is cytoplasmic and the C-terminus is extracellular, contrary to what is observed for G-protein coupled receptors. Unlike G-protein coupled receptors, transmembrane helices are not kinked or tilted relative to the plane of the membrane
The fibronectin type-III-like domains bind BPAG1 and plectin and probably also recruit BP230
The N-terminal putative ATP-binding domain is required for function. The C-terminal region contributes to both localization and function in cellulose synthesis
The BAR domain is necessary and sufficient for mediating homotypic and heterotypic interactions; associates with cytoplasmic membrane structures; mediates interaction with TBC1D1 and ADIPOR1 (By similarity). The PH and PID domains mediate phosphoinositide binding. The PID domain mediates phosphatidylserine binding and allows localization to cytosolic membrane structures and nucleus. The PH domain allows localization to the plasma membrane, cytosolic vesicles and distinct nuclear and perinuclear structures and is sufficient for RUVBL2 interaction (By similarity)
The C-terminal SR-rich domain is required for interactions with SR proteins and the splicing regulators TRA and TRA2, and the N-terminal domain is required for formation of the U2AF1/U2AF2 heterodimer
The PHA domains are required for interactions with ERF7 and HDA19
Contains four structural/functional domains: the FAD-binding domain, the NAD(H)-binding domain, the copper-binding domain and the domain of anchorage to the membrane at the C-terminus
Each MAP domain contains a 31-residue subdomain that shares striking sequence homology with a segment present in the peptide binding groove of the beta chain of the MHC class II proteins from different mammalian species
The positively charged inner surface of the NAC-A/B domain is crucial for NACA localization in the nucleus and DNA-binding. This region is blocked from binding nucleic acids in the heterodimeric complex by a helix region in the beta-subunit, it also displays much higher affinity for RNA than DNA (By similarity)
Both the N-terminal docking peptide and the catalytic core domain must bind the uba3-nae1 complex simultaneously for optimal transfer of nedd8
The N-half (TM1-TM4) and C-half (TM5-TM8) domains are connected by an intracellular loop. Each domain is formed from four-helix bundles and they align in a pseudo twofold symmetry manner. The N-half domain is the substrate-heme binding domain and the C-half domain is the cofactor heme binding domain
Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix
The phosphatase sequence motif I (including Arg-143) and II (including His-189) are part of the cytoplasmic loop 2 and phosphatase sequence motif III (including His-235) is part of the cytoplasmic loop 3
Has two high-affinity metal-binding sites, one in the N-terminal region and another in the transmembrane region. Both sites are able to access and bind metal ion independently of each other. The N-terminal metal-binding site is not strictly necessary for activity and metal selectivity, but is needed for maximal activity and may be involved in regulation. The metal-binding site in the transmembrane region is essential for activity of the pump
The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction
Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases
Homotypic interactions mediated by the BTB (POZ) domain of this protein may promote the clustering of distant insulator complexes into nuclear insulator bodies
N-terminal region is required for phagocytosis of Gram negative bacterium
The LRR repeats are required for the interaction with the PCGF1-BCORL1 heterodimeric complex
The JmjC domain mediates demethylation activity (PubMed:17994099). It is also required for repression of ribosomal RNA genes (PubMed:17994099)
The F-box domain mediates interaction with UBB
In the autoinhibited state, the SH3 domains are bound to the concave surface of the F-BAR domain and prevent promiscuous membrane binding
Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions (PubMed:23761074, PubMed:26686642). Contrary to F-BAR domains from other proteins, causes membrane flattening on giant unilamellar vesicles (in vitro) (PubMed:23761074, PubMed:26686642). Binds to membranes enriched in phosphatidylserine and phosphatidylinositides, such as phosphatidylinositol 3-phosphate, phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate (PubMed:23761074, PubMed:26686642, PubMed:27601635)
The F-box domain is required for the interaction with SKP1A and SKP1B
Consists of three domains: an N-terminal alpha/beta domain, a split beta-barrel with a similar fold of a family of flavin reductases and a C-terminal alpha/beta domain with a topology characteristic for the UbiD protein family
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (418-448) inactivates kinase activity under calcium-free conditions (By similarity)
The PDZ-binding motif mediates interaction with the CFTR, NHERF1/EBP50 complex and probably with USH1C
Contains an N-terminal domain that binds non-specifically to RNA and a C-terminal domain that binds specifically and tightly to hairpin 92 of 23S rRNA
The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1
This protein is glycine-rich and contains several repeats of the motif (G/S)1-4(Y/F) like structural proteins from insect egg shells, egg cases and vertebrate cytokeratins
FhuD interacts with a periplasmic and a transmembrane/cytoplasmic region of FhuB. The transmembrane region may be part of a pore through which a portion of FhuD inserts into the cytoplasmic membrane during transport
DOMON domain could bind catecholamines (PubMed:15022831). DOMON domain could bind one heme b (PubMed:19386804)
The horseshoe-shaped TROVE domain is built with 7 helical HEAT-like repeats, and is closed by the VWFA-like domain giving rise to a ring-shaped monomer. Single-stranded RNA is bound in the positively charged central cavity
The MIDAS-like motif in the VWFA-like domain binds divalent metal cations
The MYFF motif is functionally important for stabilization of the overall ClpPR complex
Interacts with p70-S6K via its PDZ domain
The PP1 binding region is natively unstructured, upon PP1 binding, it acquires structure, blocks a substrate-binding site, and restricts PP1 phosphatase specificity to a subset of substrates
The J-like region, although related to the J domain does not stimulate ATPase activity of mtHSP70. It nevertheless mediates the heterodimerization with the J domain of PAM18 and is therefore essential for PAM complex function (By similarity)
The 329-DSEL-332 motif is involved in the recycling of PTGDR2 to the cell surface after agonist-induced internalization. This motif seems to be required for GRK2 and GPRK5/GRK5 to promote agonist-induced internalization (By similarity). Thr-351 is a major site for PKC-induced internalization of the receptor (By similarity)
The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore (PubMed:35768507). The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex (PubMed:35768507)
The ankyrin repeats are necessary and sufficient for NEK8-binding
The SAM domain mediates interaction with the SAM domain of ANKS3
The C-terminal PEST domain is a region rich in proline, glutamic acid, serine and threonine residues that is required for the light-dependent regulation of development and secondary metabolism
The Kringle domain is dispensable for larval growth and axon regeneration after injury
The PAN domain is required to maintain gonad structure and thus fertility. Dispensable for larval growth
The first 5 zinc fingers, but not the last one, are required for DNA-binding and transcriptional activity
Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity
The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling. Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation. The activating sterol is likely to be cholesterol. The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH
Comprises six structurally related gelsolin-like (G1-G6) domains, that, in a calcium-free environment, are packed together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur (By similarity). Binding calcium may release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently (By similarity). G1 and G4 bind two Ca(2+) in a type I and in a type II manner (PubMed:24743229, PubMed:28695858, PubMed:31199804). G2, G3, G5 and G6 bind only one Ca(2+) in a type II manner (PubMed:12742020, PubMed:24743229, PubMed:28695858, PubMed:31199804). Type I Ca(2+) binding sites are shared between actin and gelsolin-like repeats G1 and G4 (PubMed:24743229, PubMed:31199804). Type I binding governs the strength of interactions between gelsolin and actin by direct participation at the binding interface (By similarity). Ca(2+) binding to G2 and G6 disrupts the interactions between G2 and G6, releases the C-terminal tail, and induces large interdomain rearrangements that result in the exposure of the F-actin-binding site on G2 and contributes to the activation of gelsolin (By similarity). Binding to phosphoinositides may inhibit the severing and capping properties of gelsolin (By similarity)
The C-terminus (residues 95-191) binds DNA (PubMed:21085634)
The acidic C-terminus and the basic N-terminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components (By similarity)
The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved (Probable). Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity (PubMed:29911972). In addition, the conserved Cys-314 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination (Probable)
Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and hematopoietic system
Compared to higher eukaryotes TAF1, yeast TAF1 lacks the C-terminal bromodomains and C-terminal kinase activity. The TFIID interacting proteins BDF1 and BDF2 may substitute for these domains
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of pan2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs
The N-terminus (residues 1-113) forms a head domain that is structurally related to those of XRCC4, XLF/NHEJ1, and SASS6
The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex (By similarity). The BRCT 5 and 6 domains function as a single module and are necessary and sufficient for in vitro phospho-specific binding (substrates phosphorylated by the kinases ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) in response to gamma irradiation). In contrast, in vivo two pairs of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more efficiently
The thioredoxin domain is inactive
The C-terminal region contains a general transcription activation domain. The N-terminal region, comprising a basic and a Gln-rich domain, confers transcriptional potency and specificity by mediating association with the MADS box of SRF. The basic domain may be required for nuclear localization. The SAP domain is important for transactivation and ternary complex formation
The C-terminus (424-433) is important for catalytic activity or for enzyme stability. The N-terminus (1-78) appears to be dispensable for enzymatic activity
The pentapeptide insert motif is required for the stabilization of the apo-enzyme in an active closed conformation, independently of Mg(2+) binding (PubMed:19268421, PubMed:25787157). The motif is also required for homodimerization (PubMed:19268421, PubMed:25787157). This motif is only present in Apicomplexa and plant enolases (Probable)
The DKSLVK motif binds to the lysine-binding Kringle domains of plasminogen from various mammalian species (By similarity). This motif is present only in enolases of plant and several microbial pathogens including Plasmodium species (By similarity)
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core
In an autoinhibited form the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site
The C-terminal SGF11-type zinc-finger domain together with the C-terminal catalytic domain of USP22 forms the 'catalytic lobe' of the SAGA deubiquitination module
Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain
Binds double-stranded DNA via the SANT domain. The SWIRM domain does not bind double-stranded DNA (By similarity)
The lack of conserved catalytic residues in the ER domain supports the fact that nectripenoids retain an alkene at C2-C3
Arg-186 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The extreme C-terminus is essential for localization to the membrane and the Z ring, self-interaction and activity
The SPOR domain binds septal peptidoglycans and is required to target DedD to the septal ring
The C-terminal 24 residues of isoform 2 are required for its function
The two SXIP sequence motifs mediate interaction with MAPRE1; this is necessary for targeting to growing microtubule plus ends
Has 4 domains; N-terminal, PAZ, Mid and PIWI. The N-terminal, Mid and PIWI domains form a crescent-shaped base with a stalk rising from the end of the N-terminal domain that holds the PAZ domain above the cresent. A groove is present in the center of the crescent closed off by the PAZ domain, in which the putative active sites are found. The PIWI domain assumes an RNase H fold and has the catalytic residues
Both EF-hands are required for function
The DRBM 3 domain appears to be the major RNA-binding determinant
The HEAIGH motif probably functions as the active center of the metalloprotease
The large luminal loop 5 is essential for mannosyltransferase activity but not for PMT1-PMT2 complex formation
The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3))
Consists of 3 PA2-type domains
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils. Four skip residues (Skip1-4) introduce discontinuities in the coiled-coil heptad repeats. The first three skip residues are structurally comparable and induce a unique local relaxation of the coiled-coil superhelical pitch and the fourth skip residue lies within a highly flexible molecular hinge that is necessary for myosin incorporation in the bare zone of sarcomeres
The EF-hand domain 1 cannot bind calcium due to the presence of a Lys instead of an Asp at position 427 and a Gln instead of a Glu at position 434 preventing calcium binding (By similarity). The EF-hand domains 3 and 4 probably bind calcium constitutively when calcium levels are low, while the EF-hand domain 2 binds calcium following an increase in calcium levels (By similarity)
Contains an N-terminal domain that mediates interactions with the hexameric ring, a central S1 domain and a C-terminal zinc-ribbon domain
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). ACTTS4 has the following architecture: C-A-T-C (Probable)
KRAB domain is not required for nuclear targeting or for DNA binding
Zinc finger region is involved in nuclear targeting and DNA-binding
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tim10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The NET domain could serve as an interface to localize different proteins or complexes to chromatin
Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands. The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity
Consists of two domains: an N-terminal catalytic domain and a C-terminal domain, not required for activity, that is predicted to form a beta-propeller-like protein-protein interaction domain
The RING finger domain, in addition to its role in ubiquitination, functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite nuclear localization signal (NLS)
The WD40 domain (386-731) is necessary and sufficient for TRIB1 binding
The PTB domain is required for interaction with trim-21
Has good structural similarity to 2-oxoglutarate-dependent dioxygenases of the TET and the alkB families, in spite of very low overall sequence similarity
The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane (By similarity). It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain
The C-terminal part of the protein is important for tillering. Mutant moc1, in which the last 124 amino acids are missing, is mono culm
Composed of an N-terminal response regulatory domain joined by a flexible linker to the C-terminal DNA-binding domain; the relative conformation of the 2 domains alters upon phosphorylation
The IMD domain forms a coiled coil. The isolated domain can induce actin bundling and filopodia formation. In the absence of G-proteins intramolecular interaction between the IMD and the SH3 domain gives rise to an auto-inhibited state of the protein. Interaction of the IMD with RAC1 or CDC42 leads to activation
The RRM domain is required for the formation of the ASAP complex
The CULT domain binds thalidomide and related drugs. Thalidomide binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, while no such change is observed in rodents
The coiled coil domain is essential for the resistance to AvrRpt2; the cultivars that do not display resistance showing specific variations in this region
As opposed to other villin-type headpiece domains, supervillin HP (SVHP) doesn't bind F-actin due to the absence of a conformationally flexible region (V-loop)
The N-terminal regulatory domain is required for peptidase activity in vitro
The N-terminal region (amino acids 35-623) is able to catalyze the release of phosphate from 2',3'-cyclic nucleotides, but not from 5'-nucleotides
KH domains KH 3 and KH 4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of degradation
The CAAX motif is a signal for prenylation and required for endosomal colocalization with Rab8 and Rab10
The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms)
The poly-Lys disordered region (352-356) mediates the formation of liquid-liquid phase separation (LLPS), an essential step for nucleation and formation of the NLRP6 inflammasome complex
Consists of an N-terminal domain that binds the heme c cofactor, followed by a long linker segment, and a C-terminal region that exhibits an eight-bladed heme d1-binding beta-propeller domain
Composed of one catalytically active A module and three R modules
The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding (PubMed:19864432). The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides (PubMed:25256292)
The membrane-association motif is essential for the localization to membrane of Golgi stack. According to some authors, it is a transmembrane domain; the existence of a transmembrane region is however unproven
The DOCKER domain may mediate the GEF activity
The 3 cNMP binding domains are required for localization to the endoplasmic reticulum. The cNMP binding domain 3 is involved in the binding to lipid droplets
Within the cytoplasmic CTD, an enhancer domain, limited to residues 428-441, upregulates substrate translocation via the MEP2 hydrophobic core, while an autoinhibitory domain, comprised within the 450-485 region and including the NPR1-target serine Ser-457, counteracts the action of the enhancer domain (PubMed:32069286). In between, a linker domain, limited to residues 442-449, appears required for optimal activity when the kinase is present but dispensable when the kinase integrity is altered (PubMed:32069286)
The WY domain contains 3 alpha-helices and is required for the interaction with a host MAP kinase
The C-terminus is involved in oligomerization and is essential for membrane association. The NAB domain, also called NAB (NET actin-binding) domain, is involved in F-actin binding
The ice-binding site may be formed by 7 T/S-X-T motifs
The N-terminal response regulatory domain inhibits DNA-binding by the rest of the protein, in its absence the protein binds specifically to the nrsRS-nrsBACD (slr0793-slr0796) intergenic region
The N-terminal region does not contain a typical signal sequence but is required for secretion (By similarity). It also determines exosomal location (PubMed:26845719)
RRM domain 2 has moderate RNA-binding affinity. RRM domains 3 and 4 may facilitate RNA looping when binding to two appropriately separated binding sites within the same target pre-mRNA (PubMed:23782695)
The dsRNA binding domains (dsRBDs) 1 and 2 are sufficient for the function in miRNA precursors processing and mature miRNA generation
Both CSM and C-box motifs are required for binding to the anaphase promoting complex/cyclosome (APC/C)
Each CNA-B domain is able to independently mediate adherence to the substrate
The extracellular domain is required to protect against axon degeneration (PubMed:19158290, PubMed:26335717). The first three Ig-like domains mediate interaction with RTN4R and RTN4RL2, but are not sufficient to inhibit neurite outgrowth (By similarity). The two C-terminal extracellular Ig-like C2-type domains are required for inhibition of axon longitudinal growth. Besides, the two C-terminal extracellular Ig-like C2-type domains are required for protection against apoptosis after nerve injury (PubMed:26335717)
RS domain directs localization of proteins to the speckled subnuclear compartment and the purpose of this localization is to allow colocalization and co-concentration of components of the splicing and splicing regulatory machinery to permit relatively high rates and/or efficiencies of reaction and interaction
The amino acids 79-83 in the C-terminal region of are important for binding to host calmodulin
2 residues (Tyr-62 and Arg-65) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
Winged-helix (WH) domain directly recognizes and binds unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove of DNA
Contains at least 2 actin-binding domains, one on each side of the LIM domain. Both domains bind actin monomers and filaments. The C-terminal domain binds filaments more efficiently than the N-terminus (By similarity)
The N-terminal kinase domain produces inositol polyphosphates. The C-terminal acid phosphatase-like domain binds inositol polyphosphates and negatively regulates their accumulation. The C-terminal domain reduces the amount of inositol pyrophosphates in a dose-dependent manner in vitro
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity
The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions
Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in protein binding. In Arabidopsis thaliana, EB1A and EB1B possess an acidic C-terminal tail that has autoinhibitory function, but EB1C has a tail region with patches of basic amino acid residues required for nuclear targeting
Only isoform a is thought to bind DNA. Zinc fingers 3, 4 and 5 are the most important for DNA binding; removal of finger 5 almost abolishes DNA binding and prevents the selection of binding sites
The second BPTI/Kunitz inhibitor domain is able to inhibit trypsin. It has however no activity toward chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator
The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (PubMed:11852086, PubMed:12060745, PubMed:12560340, PubMed:19074135, PubMed:24901643). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits (PubMed:24901643). The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells. The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons (By similarity)
Oligomerization seems to be mediated by the histidine kinase domain (residues 142-386) which forms tetramers and hexamers. The DHp subdomain (dimerization and phosphotransfer, residues 142-270) forms hexamers and octamers. NaCl treatment reduces the histidine kinase domain to tetramers and the DHp domain to hexamers, suggests the DHp domain senses NaCl
Composed of two domains (I and II) organized with a C-clamp shape
Contains a C-terminal catalytic domain, and an N-terminal region which modulates catalytic activity (PubMed:2991277, PubMed:9760239). The N-terminal domain is not essential for catalysis (PubMed:2991277)
The ATP-cone domain may function to recruit ATP/dATP to elicit a conformational change in NrdR that is necessary for binding
Contains two distinct classes of F-actin-binding domains. Although both can each bind F-actin, the 2 are required to bundle actin filaments
The different N-terminus extensions of isoform 1 and isoform 4 determine their respective subcellular localization and differentiel effect on myoblast fusion and accumulation of muscle-specific proteins. The different N-terminus extensions of isoform 1 and isoform 4 are not essential for their catalytic activity
Gate loop 1 and gate loop 2 regions are adjacent to the S-adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction
The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1
The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway
Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate. The PH domain is necessary and sufficient for plasma membrane relocalization (By similarity)
The coiled coil domain is involved in interaction with CCDC120
The SPRY domain mediates the interaction with MET, AR, and CDC2L1
Has two distinct domains: an N-terminal nucleotidyltransferase (NT) domain responsible for UTase activity, and a HD domain that encodes UR activity (By similarity). Lacks the two C-terminal ACT domains found in GlnD orthologs, that seem to have a role in glutamine sensing
The cysteine framework is C-C-C-C-C-C-C-C-C
Consists of three main regions, an N-terminal coiled-coil domain (residues 1-77) that probably binds to protein Pup and functions as a docking station, an interdomain (residues 78-227) involved in Mpa hexamerization, and a C-terminal ATPase domain of the AAA type (residues 228-533)
The PHD-type zinc-finger domain is required for interaction with LRSAM1 and negative regulation of autophagy
The acetyl-CoA-binding domain mediates crotonyl-coA hydratase activity (By similarity). The acetyl-CoA-binding domain is required for recruitment to sites of DNA double strand breaks and for binding to poly (ADP ribose) moieties (By similarity)
The C-terminus forms a beta-barrel with 8 anti-parallel strands
The linker region, also named autoinhibitory interface, is required to prevent constitutive activation and maintain CARD9 in an autoinhibitory state. Disruption of this region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS7 has the following architecture: A-T-C-A-T-C
The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns(3)P). While full-length protein is unable to bind PtdIns(3)P in vitro, it is assumed that the binding to the ATG5-ATG12 conjugate exposes the PH domain, allowing the association with PtdIns(3)P (PubMed:22342342)
DhaK and DhaL domains have differential roles, individually DhaK is inactive and DhaL displays cyclase but not kinase activity
The tight homohexamer forms a pore with an opening of about 5 Angstroms in diameter and is positively charged
The hemerythrin-like region acts as an oxygen and iron sensor by binding oxygen through a diiron metal-center. In absence of oxygen and iron, the protein is ubiquitinated and degraded
The substrate-binding pocket is formed by two protein molecules (PubMed:33292448). When compared to other Bdh enzymes, SmBdh contains a shorter alpha6 helix, which provides more efficient entry and exit of molecules from the active site, thereby contributing to enhanced substrate turnover (PubMed:33292448)
The 3D-structure of the Fe2OG dioxygenase domain is similar to that of the Fe2OG dioxygenase domain found in the bacterial DNA repair dioxygenase alkB and its mammalian orthologs, but sequence similarity is very low. As a consequence, the domain is not detected by protein signature databases
Substrate DNA-binding induces large structural changes that generate a surface for DNA-binding across the Cas2 dimer and formation of an optimal catalytic site (PubMed:26478180)
Consists of an N-terminal FAD-binding domain with a Rossman fold, a substrate-binding domain and a C-terminal helix that bridges the 2 domains close to the antibiotic-binding site. This last helix is flexible, is not found in TetX of Bacteroides species, and may contribute to their different substrate specificities
The homotrimer is held together by an extended N-terminal coiled coil, which leads into three separate globular C-terminal domains of beta-sandwich topology
The PID domain mediates binding to the TrkA receptor
AFL adopts the six-bladed beta-propeller fold and contains six binding sites per monomer, each located between two adjacent blades (By similarity). The six binding sites that are non-equivalent, and owing to minor differences in amino-acid composition they exhibit a marked difference in specific ligand recognition (By similarity)
Myelin regulatory factor: The peptidase S74 domain, also named Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecular Chaperone Domain (ICD), has protease activity and mediates autocatalytic processing of the protein to generate the Myelin regulatory factor, N-terminal active transcription factor and the Myelin regulatory factor, C-terminal components
The PDZ-binding motif specifically binds the PDZ domain of SNX27: the specificity for SNX27 is provided by the 2 residues located upstream (Glu-388 and Ser-389) of the PDZ-binding motif (PubMed:17828261, PubMed:21422294)
Mutations that delete the second laminin EGF-like repeat impair only dorsal migrations of mesodermal cells and axons
Contains a lipid-binding SYLF domain which is essential for activity
Neither C2 domains mediates Ca(2+)-dependent or -independent phospholipid binding
The matrin-type zinc finger domain is required for localization to nuclear speckles
The domain architecture includes starter unit:ACP transacylase (SAT), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), product template (PT), acyl-carrier domain (ACP), and thioesterase/Claisen cyclase (TE/CLC) domains (PubMed:17086560). The SAT domain receives a C6-fatty acid starter unit and transfers it onto the ACP for chain elongation. The KS accepts the hexanoyl-ACP unit and subsequent malonate extender units are loaded onto the ACP from the MAT domain for chain extension to generate the linear poly-beta-keto ACP-bound intermediate. The linear intermediate is then cyclized and aromatized in the PT domain. The resulting bicyclic intermediate is ultimately transferred from the ACP to the TE/CLC domain and undergoes Claisen-type C-C bond cyclization to release the product norsolorinic acid anthrone (noranthrone), which spontaneously oxidizes in vitro to norsolorinic acid (PubMed:17086560, PubMed:18403714, PubMed:19847268, PubMed:20332208)
The C-terminal domain is necessary for the RFX complex formation
The propeptide is required for localization to the gonad basement membrane
The disintegrin domain is required for distal tip cell migration and partially for mig-17 localization to the gonad (PubMed:17491590). Required for the control of pharynx length (PubMed:26994289)
The PLAC domain is required for distal tip cell migration but not for gonadal localization
The PH domain is required for localization to the membrane
Contains many imperfect repeats of a consensus octapeptide A-G-Y-G-S-T-X-T; further on a 16-residue and a regional 48-residue periodicity is superimposed
Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs 1 and 2 are essential for the association with nuclear receptors, and constitute the RID domain (Receptor-interacting domain)
Contains a protease-associated domain of unknown function
Heparin-binding motifs (HBMs) are characterized by an XBBXBX or XBBBXXBX sequence, where X is any neutral amino acid and B is a positively charged basic amino acid, and are defined as the consensus sequence necessary for protein-heparin interactions. HBM1 motif is necessary for spore adherence to host cells
The N-terminus is required for targeting to the BMC; 42 residues target GFP to the BMC, although 98 residues give better targeting
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (364-394) inactivates kinase activity under calcium-free conditions
(Microbial infection) The bromodomain mediates binding to HIV-1 Tat
Consists of 16-stranded beta-barrel sheets, with large surface-exposed loops, that form a transmembrane pore at the center of each barrel. The pore is partially ocluded by a peptide loop that folds into the pore lumen (By similarity)
Alternative way of activation involves binding the proline-rich motif to the SH3 domain of SHO1
The RS domain (871-946) is required for phytochrome B signal transduction through alternative splicing regulation
Both the cytoplasmic and the extracellular domain are required for normal trafficking to the cell surface, and thus for fertilization (PubMed:25655701). The extracellular domain can insert itself into lipid membranes, probably as a trimer (PubMed:28235200). The extracellular domain has structural similarity to class II viral fusion proteins
The long form contains a basic insert which acts as a cell retention signal
The C-terminal activation region (AD) is used for downstream signaling. Seems to be essential for coactivator function with nuclear receptors and with the aryl hydrocarbon receptor
The N-terminal activation region (AD) is necessary and sufficient for synergistic activation of LEF1-mediated transcription by CTNNB1. Contains a EP3000 binding region which is important for synergistic cooperation
RAP domain is required for TBRG4 function in mRNA stability and translation
Is organized in two protein domains. The N-terminal domain has a fold similar to that of desulforedoxin and contains a mononuclear Fe(3+) ion, center I. The second domain contains a different mononuclear iron center, center II, with a Fe(2+) ion
The SRCR domain 3 mediates calcium-sensitive interaction with hemoglobin/haptoglobin complexes
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds
The PINIT domain of PIAS3 is required for STAT3-PIAS3 interaction and for translocation to the nucleus
Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position
Regions C1 and C2 can either interact with nucleotide-free CDC42, or interact together, depending on the phosphorylation state of Ser-1443. When Ser-1443 is not phosphorylated, C1 and C2 interact, which prevents binding of nucleotide-free CDC42 and promotes binding of GTP-bound CDC42. Phosphorylation of Ser-1443 prevents interaction between C1 and C2, which opens the structure of the C-terminus and allows binding and sequestration of nucleotide-free CDC42 on both C1 and C2
The N-terminal part acts as a polyketide synthase and includes a ketosynthase (KS) domain that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) domain that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The C-terminal part acts as an NRP synthetase composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. PytA contains one module and terminates in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme
The fifth SH3 domain mediates binding with ADAM12, ADAM15 and ADAM19
Three specific residues, Phe-177, Leu-180 and Asn-196 are conserved between non-primate mammals whereas the respective residues are serine, phenylalanine and threonine in primates (PubMed:19056333). The two residues at positions 177 and 180 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil (PubMed:19056333). The presence of an asparagine at position 196 is important for the maintenance of the quaternary structure resulting in stability at cold temperature and improved catalytic activity toward retinal (PubMed:19056333)
The C-terminus domain (aa 540-655) mediates interaction with MTMR9
The HIN-200 domain mediates interaction with MDM2
The DDXXD motifs are important for the catalytic activity, presumably through binding to Mg(2+)
The HARE HTH-type domain recognizes and binds N(6)-methyladenosine methylated DNA (m6A)
The 4 C2H2-type zinc fingers are required for DNA-binding, but dispensable for the H3K27me3/2 demethylase activity
The macro domain alone is sufficient to neutralize DarT from non-cognate T.aquaticus in E.coli, DarT in M.bovis, and to de-ADP-ribosylate DNA in vitro
The C-type lectin domains, also called carbohydrate-recognition domains or CRDs, 1-3 have at most very weak affinity for carbohydrates. C-type lectin domain 4 shows the highest affinity binding and has multispecificity for a variety of monosaccharides. At least 3 C-type lectin domains (4, 5, and 7) are required for high affinity binding and endocytosis of multivalent glycoconjugates
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a acyl carrier protein (ACP) domain, a methyltransferase domain (CMeT) and a reductive NADPH-binding domain that is required for NADPH-dependent product release (Probable). The CMet adds methyl groups as check-point tags, which are recognized by KS, such that a lack of methylation causes release of immature products at the triketide stage (By similarity)
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (PubMed:19307175). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (PubMed:19307175)
The IMD domain consisting of an antiparallel dimer of three-helix bundles, featuring on one side a positively charged. The N-terminal alpha-helix inserts into the lipid bilayer. Also forms homodimers and homooligomers. The residue Trp-141 is essential for oligomer formation (By similarity)
The N-terminal domain has binding sites for ComK and ComS and probably for unfolded/aggregated proteins; the C-terminal domain interacts with ClpC
The N-terminal cytochrome b5 heme-binding domain is essential for catalytic activity
RRM4, together with the C- and N-terminal regions, is sufficient for RNA-binding. RRM 1 has no RNA-binding activity itself, but improves discrimination between poly(A) and poly(U) in combination with the other repeats
The RING domain mediates ubiquitination and the neurite outgrowth inhibitory activity
The FERM domain binds phospholipids and mediates lipoprotein receptors recognition at the plasma membrane through their cytoplasmic tails
The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes
The PWWP domain mediates the interaction with nucleosomes
The ANK repeats mediate the interaction with the MCM complex and histones, while the LRR repeats mediate the interaction with MMS22L
The LITAF domain is stabilized by a bound zinc ion (By similarity). The LITAF amphipathic helix region (68-90) is necessary for plasma membrane localization
Both N-terminal (1-47) and C-terminal (114-134) domains are sufficient for the interaction with MIEL1 or with the N-terminal domain of LSD1
The LITAF domain (48-113) is not involved in the interaction with LSD1
The two DNA binding domains are required for binding to the E2 site
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF6, the motif is inactive
The N-terminal (1-23) and C-terminal (66-84) Cys-rich domains are both involved in zinc binding
The LIR motifs (LC3-interacting regions) are required for the interaction with ATG8 family proteins (PubMed:31722778, PubMed:27791457, PubMed:28668392, PubMed:28395732). The LIR motifs 1 and 2 at the N-terminus bind one ATG8 protein and the LIR motif 3 at the C-terminus binds another ATG8 protein (PubMed:31722778, PubMed:27791457). Among ATG8 proteins, the LIR motif 3 has preference for host GABARAP (GABARAP GABARAPL1, GABARAPL2) compared to LC3 (MAP1LC3A, MAP1LC3B, MAP1LC3C) (PubMed:31719622)
The membrane targeting (MT) region binds phosphatidylinositol 3-monophosphate (PI3P) (PubMed:26343456). The MT region, together with the alpha-3 helix promote localization to high-curvature membranes, intimating localization to highly curved domains in autophagosome intermediate membranes (PubMed:26343456). The alpha-3 helix is involved in extraction of the phosphatidylethanolamine (PE) moiety and docking of the acyl chains into the lipid-binding site (PubMed:28395732)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tim-9/tin-9.1 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
Two module-bearing peptide synthase with a C-terminal epimerization domain, which is probably inactive. Each module incorporates one amino acid into the peptide product and can be further subdivided into domains responsible for substrate adenylation, thiolation, condensation (not for the initiation module), and epimerization (optional). At the N-terminus, contains a N-formyltransferase domain that is probably responsible for the formylation of the first incorporated amino acid
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases (PubMed:20530286). Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases (PubMed:20530286). ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases is required for HIV-1 binding/entry and virus infection (PubMed:20530286)
The cytoplasmic domain is necessary for the regulation of neurite-like outgrowth
The C-terminal domain (508-668) is necessary and sufficient for Golgi targeting
The proline-knot motif (113-122) may be involved in targeting to lipid bodies
Consists of 2 homologous sesquiterpene synthase domains. The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for the catalytic activity, presumably through binding to Mg(2+)
The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. The I-domain is necessary and sufficient for interaction with ICAM1 and F11R
The BC-box, which mediates binding to the elongin BC complex, has the consensus [APST]-L-x(3)-C-x(3)-[AILV]
The chaperone domain provides a folding template for proper folding of the beta-propeller (BP) domains of LRP5/6
The escort domain ensures LRP5/6 safe-trafficking from the ER to the Golgi by preventing premature ligand-binding
Contains 3 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant (By similarity)
Both HotDog ACOT-type hydrolase domains are required for efficient activity
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins (By similarity). The WPRW motif is also required for the inductive function, independent of a transcription regulation activity
The C2 domain 1 associates with lipid membranes in a calcium-dependent manner
The coiled-coil domain is sufficient to localize to apical junctions
Arg-289 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Interactions with CASP8 and CASP10 are mediated by the DED domain
Consists of two alpha-helical lobes, each of which contains one c-type heme
The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity. This domain is catalytically active as a dimer
Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL), a transcriptional binding motif, which mediates interaction with PPARA
The proline-knot motif (71-80) may be involved in targeting to lipid bodies
The C2 and Ras-GAP domains constitutively bind to MAP3K5 and facilitate the release of 14-3-3 proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY motif, are crucial for its cell membrane localization and neuronal migration function. The PH domain is necessary but not sufficient to activate the JNK signaling pathway through ERN1 (By similarity). Exists in a closed inactive form by an intramolecular interaction between the N- and the C-terminal domains. The proline-rich motif is critical both for PI3K-AKT activity inhibition and MAP3K5 activation. The PH and C2 domains are necessary for the binding to phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its tumor-suppressive function
The PDZ-binding motif is required for neurite outgrowth promotion (By similarity). This motif is also involved in DLG1-, DLG3- and DLG4-binding
The MID/MTR4-interacting domain is necessary and sufficient to mediate interaction with MTREX
RRM 1 and RRM 2 recognize preferentially RNAs containing the core motif GGUG. The atypical C-terminal RRM domain (RRM 3) does not interact with RNA/DNA, but is crucial for interaction with the THO/TREX complex
The DOCKER domain mediates interaction with small GTPases like RAC1 and is required for their activation
In IrtB the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused (PubMed:32296173). The IrtAB transporter assumes an inward-facing conformation, which may represent the low-affinity state after mycobactin release towards the SID and the cytoplasm (PubMed:32296173)
The KA1 domain mediates binding to phospholipids and targeting to membranes
The DNA-binding nuclear receptor domain and the NR LBD domain are required for binding of the RARB/RXRA heterodimer to both DR1 and DR5 DNA elements
The core amyloid fragment (CAF) represents the amyloidogenic unit of melanosomal fibrils. It is predicted to form a beta-solenoid structure comprising four coil right-handed beta strands with Tyr-151 and Trp-160 residues pi-stacking against each other to confer stability
The Asp-Xaa-Asp-Asp (DXDD) motif is important for the catalytic activity through binding to Mg(2+)
The region which spans amino acids 42-49 is required for enzymatic activity and contributes to the formation of a potentially important antigenic determinant
The N-terminus (up to about residue 249) has mART activity, as well as NADase activity. The C-terminal 41 residues are required for internalization by HeLa cells and for vacuolization (PubMed:24948331). The C-terminus (residues 266-591) is required for interaction with annexin A2 (PubMed:25139904). Has 3 structural domains, the N-terminal mART domain (mono-ADP ribosyltransferase, residues 1-205), D2 (residues 273-439) and D3 (residues 440-591). mART is joined to D2 by a linker (residues 257-272) which has a disulfide bond. The 3 domains assemble into an isosceles triangle, where the probable active site and NAD(+)-binding site are occulded. Enzyme activity will require either a conformation change or proteolytic processing. Domain D2 and D3 together bind lipids, domain D3 is at least partially responsible for binding to and internalization by host cells (PubMed:25848012). A C-terminal fragment (residues 273-591) is capable of inducing vacuolization upon incubation with HeLa cells (PubMed:34078958)
Binds DNA via the 2 GATA-type zinc fingers. Each zinc finger may bind either adjacent sites in a palindromic motif, or a different DNA molecule allowing looping and long-range gene regulation (By similarity)
Putative metalloprotease with an atypical HExxxH zinc-binding motif instead of HExxH, which interrupts the active site-containing helix without affecting the integrity of the catalytic site arrangement
Contains an N-terminal nucleotide-binding domain (NBD) and a C-terminal regulatory domain (RD)
Contrary to Nlrp1b alleles 1, 2, 3 and 5, allele 4 is missing a CARD domain, which has been shown in other alleles to be involved in the interaction with CASP1 and CASP4/CASP11. It is thus unclear if this allele is able to promote inflammasome assembly
The FIIND (domain with function to find) region may be involved in homomerization, but not in CASP1-binding (PubMed:16429160). In allele 4, the FIIND region is truncated and hence does not contain the activating cleavage reported for allele 1 (PubMed:16429160). Consequently, it may not undergo autocatalytic cleavage in this region (PubMed:16429160)
Consists of a N-terminal RlmL domain and a C-terminal RlmK domain, linked by a highly flexible loop
N-terminal part (1-266) has GTPase activity. Required for proper cellular localization
This multifunction enzyme is comprised of two structurally and functionally independent domains (PubMed:1548230, PubMed:8692863). Contains a highly conserved interior pocket (PubMed:18388203). The size, shape and composition of the pocket are important to orient and specifically fold the polyketide chain (PubMed:18388203). The accessibility of the hydrophobic cavity is regulated by a dynamic equilibrium between open and closed states (PubMed:34139289)
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and MAP1LC3A
The ROQ region is required for CDE RNA-binding (PubMed:27010430, PubMed:25026077, PubMed:23663784). Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites are important for mRNA decay (By similarity). ADE RNA-binding involves an extended binding surface on the ROQ region with a number of additional residues compared with the CDE RNA (PubMed:27010430). It may also be involved in localization to stress granules (PubMed:20412057, PubMed:23583642)
The RING-type zinc finger may be required for proper localization to stress granules, but not to P-bodies
Contains multiple repeats consisting of single amino acids (e.g. Gly, Ser, His, and Asn) and pairs of amino acids (e.g. Gly-Val)
The C2 domain is a non-calcium binding domain (PubMed:31492901). Cooperates with the PH domain in the binding to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:31492901)
The PH domain cooperates with the C2 domain in the binding to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2)
Possesses a PD-(D/E)XK-like nuclease domain
The Plant immunity suppression domain is sufficient to retain the ability to suppress immunity-associated responses
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (365-395) inactivates kinase activity under calcium-free conditions (By similarity)
The PPxY motif 1 mediates interaction with NEDD4 (By similarity). The PPxY motif 2 is required for the coactivation function (PubMed:16772533)
The PWI domain binds nucleic acids with significant help from its N-terminal flanking basic region. It has an equal preference for binding to single- or double-stranded species, and it contributes to RBM25 role in modulation of alternative splicing, maybe by mediating RNA-dependent association with LUC7L3 (By similarity)
PETase retains the ancestral alpha/beta-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases
The SH3 domain mediates the stable interaction with Cas and is involved in establishing tight junctions in epithelial cells
The N-terminal domain has phosphatase activity. The C-terminal domain has epoxide hydrolase activity
ZAS2 domain binds DNA as dimers, tetramers, and multiple of tetramers and readily forms highly ordered DNA-protein structures
The C-terminal region of isoform 4 mediates its intracellular retention
The C-terminal Glu-rich acidic region is essential for FACT activity
Repression domain 1 (RD1) is involved in transcriptional repression (By similarity). RD1 is necessary for its interaction with PML (By similarity)
The tight homohexamer forms a pore with an opening of about 2 Angstroms in diameter which is positively charged
DNA photolyase domain is sufficient for light detection and phototransduction
Consists of an N-terminal kinase domain, a transmembrane domain, and a C-terminal domain containing four repeats of the PASTA signature sequence (Penicillin-binding protein and Ser/Thr protein kinase associated domain). The PASTA domain binds to peptidoglycan (PGN) subunits (shown in strain Rx / Cp1015), is essential for StkP activation and substrate phosphorylation, and is required for cellular targeting to midcell
Cys residues in the pre-SET domain normally bind 3 zinc ions that are arranged in a triangular cluster, but here these Cys residues are only partially conserved, suggesting that the pre-Set domain may not bind a zinc cluster
Contains an 'insertion' sequence of 109 residues which is not present in other G-protein alpha chains
The Pru (pleckstrin-like receptor for ubiquitin) domain mediates interactions with rpn-2 and ubiquitin. Preferential binding to the proximal subunit of K48-linked diubiquitin allows ubh-4 access to the distal subunit
The C2H2-type zinc finger 1 has a major repressor function
Contains an N-terminal DNA-binding domain and a C-terminal ligand-binding regulatory domain
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and 3 acyl-carrier protein (ACP) domains that serve as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The C-terminus contains a key domain which is responsible for the RNA digestion activity (By similarity)
When BTB domain is deleted, growth-suppressing properties are lost
Binding to ERLEC1 is mediated by the oligosaccharides linked to the kringle domain
Contains two helicase domains. The N-terminal helicase domain has catalytic activity by itself, contrary to the C-terminal helicase domain that may have a regulatory role and enhance the activity of the first helicase domain
Sequence consists of two domains: the C-terminal glutamine amide transfer (GAT) domain catalyzes the hydrolysis of glutamine; the N-terminal synthase domain catalyzes the amination of UTP (PubMed:3514618, PubMed:3298209). Structure shows each subunit consists of three distinct segments: the N-terminal amidoligase (ALase) domain, which mediates oligomerization and contains the ALase active site where ATP and UTP substrates bind, and an interrupted helical interdomain linker segment that connects the ALase domain to the Type I glutamine amidotransferase (GATase) C-terminal domain, which generates ammonia via glutamine hydrolysis (PubMed:15157079). A gated channel that spans 25 Angstroms between the glutamine hydrolysis and amidoligase active sites provides a path for ammonia diffusion; the channel is accessible to solvent at the base of a cleft adjoining the glutamine hydrolysis active site, providing an entry point for exogenous ammonia (PubMed:15157079)
The tyrosine-based internalization signal may be involved in trafficking at the trans Golgi network (TGN)
Contains 6 A-type repeats and 11 B-type repeats similar to those found in maize, rice and barley dehydrin and rab proteins
Has a basic N- and C-terminal and an acidic central domain
The FHA domain mediates interactions with threonine-phosphorylated MELK
The C-terminal tandem repeats are not required for the procoagulant activity
The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs. The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias)
The C-terminal domain (CTD) helps bind DNA, is required to complement a gene deletion
Binds ubiquitinated proteins via its RanBP2-type zinc finger
The BTB (POZ) domain is atypical and mediates the formation of a homopentamer instead of a homotetramer (By similarity). Homopentamerization is due to the presence of 4 residues in the BTB (POZ) domain: Leu-56, Gly-100, Val-112 and Ala-118 (By similarity)
Composed of a compact central beta-barrel domain with long alpha-helical extensions that form a three-pronged structure around an internal cavity. Substrate proteins may be bound in this cavity
The P4M (PtdIns(4)P-binding) region mediates binding to PtdIns(4)P and membrane attachment
The C-terminus (residues 376-404) is important for interaction with IscU
The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain
The MH1 domain is required for DNA binding (By similarity). Also binds zinc ions which are necessary for the DNA binding
The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import (By similarity)
The N-terminal HD domain has ssDNase activity. The C-terminal GGDEF domain has the cOA synthesis activity
The DWD box is required for interaction with ddb1
Interblade loops of the WD repeat region mediate most of the interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA minor groove and mediates recognition of lesions and separation of the damaged and undamaged strands
Interblade loops of the WD repeat region mediate most of the interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA minor groove and mediates recognition of lesions and separation of the damaged and undamaged strands (By similarity)
Contains an N-terminal DNA-binding domain and a C-terminal ligand-binding regulatory domain (PubMed:26396194). The C-terminal regulatory domain can bind saturated fatty acids (PubMed:26396194)
The SH3 domain is essential for its targeting to activated CD28 costimulatory molecule
Contains two target DNA recognition domains (TRD), each specifying recognition of one of the two defined components of the target sequence (Probable). The TDRs show high structural similarity and each forms a globular structure. The two TDRs are separated by 2 long, conserved antiparallel helices that form a coiled coil structure (PubMed:16038930)
Efficient dihydrouridine synthesis requires the presence of both the catalytic domain and the C-terminal RNA-binding DRBM domain
The nuclear localization signal is both required for nuclear localization and palmitoylation
There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is involved in catalytic reaction and UDP-Gal binding
The alpha subunit loop in the ricin B-type lectin domain regulates substrate specificity and modulates the substrate access to the active site. In isoform A, the alpha subunit loop is composed of positively charged residues and acts on negatively charged substrates. In isoform B, the alpha subunit loop is composed of negatively charged residues and acts on positively charged substrates
The polyhistidine repeat acts as a targeting signal to nuclear speckles
Ig-like V-type domain mediates binding to lymphocyte
The proline-rich muscle-specific exon 3 contains eighteen approximate 23-AA repeats
The propeptide region is both necessary and sufficient for bmp-inhibitory activity. The propeptide region and the N- and C-terminal thirds of the mature protein are necessary for neural induction activity. Although cleavage doesn't appear essential for activity, residues surrounding the cleavage site are necessary for activity (By similarity)
One chain folds into a compact single domain composed of repeating units, five beta-beta-alpha-beta modules, which surround the central active site
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA (By similarity)
Is a green cupredoxin able to bind a maximum of three Cu(2+) ions: a green copper site (CuT1.5), a type 2 copper binding site (T2) located in the N-terminal region, and a third site with a yet unidentified location
The C-terminal part is necessary for interaction with atx-2
The SUZ domain is necessary for RNA binding
The DIX domain mediates self-interaction and interaction with dishevelled and axin1
Domain I shares an identical polypeptide fold with the beta subunit ETFB though there is no sequence similarity
Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain (By similarity)
The 377 first amino acids might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P)
Between 2 and 19 copies of the INQS repeats are to be found in different strains; these are thought to serve to generate phase-variable expression of this gene
The coiled coil is required for interactions with ced-1, ced-6 and ubc-21
Helix VIII may act as a gatekeeper for either suppression or activation of the receptor, depending on post-translational modifications and interactions with various receptor partners (PubMed:28379944). Helix VIII is found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G-proteins or beta-arrestins (PubMed:28379944). Upon switching to a membrane-bound conformation, helix VIII can support the recruitment of G proteins and beta-arrestins (PubMed:28379944)
Conformational changes take place in the N-terminal and the winged-HTH (wHTH) domain on ligand or DNA binding. SA and PAS stabilize a conformation of Rv2887 incompatible with DNA binding. Rotation of the N-terminal plays a key role in the dimerization
The homeobox domain binds to double-stranded DNA
The Z-binding domains recognize and bind left-handed double-stranded Z-RNA structures, but not A-RNA, the right-handed double-stranded RNAs that are structurally very different from Z-RNAs (PubMed:32200799). The second Z-binding domain (also named Zalpha2) acts as a molecular switch regulating pyroptosis, necroptosis and apoptosis (PANoptosis) (PubMed:32350114, PubMed:33109609). The second Z-binding domain is essential for sensing influenza A virus (IAV) Z-RNAs (PubMed:28607035, PubMed:28716805, PubMed:32350114)
The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels (PubMed:24503055). It is unclear which EF-hand binds calcium as none of the 4 EF-hand domains seem to contain a canonical calcium-binding site
The Pocket domain binds to the threonine-phosphorylated domain C, thereby preventing interaction with heterodimeric E2F/DP transcription factor complexes
Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself (By similarity)
The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels. It is unclear which EF-hand binds calcium as none of the 4 EF-hand domains seem to contain a canonical calcium-binding site
The G protein domain (about resides 1-184) binds GDP faster and with higher affinity than GTP and releases GTP much faster than GDP. Release of bound nucleotide causes a rearrangement of GTP-binding domain G5, which may transmit information about the nucleotide-bound state from the G-domain to the transmembrane region of FeoB and effect Fe(2+) transport
The Leu-lock (Leu-115) site inserts into a hydrophobic pocket in XRCC4
The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 2 are occupied, designated as sites 2 (or A), and 3 (or B) based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Site 3 can bind either AMP, ADP or ATP (AMP, ADP or ATP 2). Site 2 binds specifically ADP (ADP 1) and is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of ADP
Contains a first dinucleotide binding domain, which harbors FAD, a second dinucleotide binding domain, which interacts with NADH and C-terminal domain that provides anchoring to the membrane (PubMed:28801048). A long discussion has taken place about whether NADH and the quinone bind to the same or to different sites. Structural studies clearly indicate the presence of distinct binding sites for the two substrates (PubMed:26172206, PubMed:28181562)
The L/FRRG motif is essential for the cytoplasm to vacuole transport (Cvt) pathway, for the recruitment of apg-6/atg8 and atg16 to the PAS in nutrient-rich medium, and for its recruitment to and dissociation from the PAS under starvation conditions
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS9 has the following architecture: C-A-T-C
The Asp-Asp-Xaa-Xaa-Xaa-Asp (DDXXXD) and Asn-Xaa-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Glu (NSE) motifs are important for the catalytic activity, presumably through binding to Mg(2+)
The coiled coil domain mediates the interaction with FLNA leading to its recruitment to lamellae
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (PubMed:17464044). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:17464044). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (PubMed:17464044). Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (PubMed:17464044). GliP has the following architecture: A-T-C-A-T-C-T (PubMed:17154540, PubMed:17464044)
The Gly/Pro-rich domains may be required for an unusual geometry of interaction with ligand or substrates
BRCT domain 1 is required to prevent abnormal chromosome condensation. It binds directly to the SWI-SNF chromatin remodeling complex (By similarity)
BRCT domains 2 and 3 recognize phosphoserine/phosphothreonine marks on proteins with high selectivity, and mediate interaction with phosphorylated CDC27. They also mediate the dual recognition of phosphoserine and phosphotyrosine in the C-terminal tail of histone H2AX (By similarity)
2 residues (Tyr-74 and Arg-77) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
Contains three distinct domains: an adenylation (A) domain that activates the substrate amino acid which is subsequently covalently linked as a thioester (aminoacyl-S-PCP) to the 4'-phosphopantetheine prosthetic group of the second domain, the peptidyl carrier protein (PCP) domain, as well as a reductase (R) release domain
The jas domain (177-202) is required for interaction with COI1
The N-terminal region and all three C3H1-type zinc fingers are necessary to induce transcriptional repression
Lacks the zinc protease domain of other FtsH proteins. Also much longer in both the N- and C-termini
Composed of four fascin beta-trefoil domains
The first DRADA repeat binds Z-DNA
The third dsRNA-binding domain (DRBM 3) contains an additional N-terminal alpha-helix that is part of a bi-partite nuclear localization signal, together with the sequence immediately C-terminal to DRBM 3. The presence of DRBM 3 is important to bring together the N-terminal and the C-terminal part of the bi-partite nuclear localization signal for import mediated by TNPO1. RNA binding interferes with nuclear import
The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (PubMed:12560340, PubMed:18463252, PubMed:19690160). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits (PubMed:12954870, PubMed:19219384). The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells (PubMed:8978827, PubMed:10719893). The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons (PubMed:16407566)
The cholesterol-binding site is formed by transmembrane helices TM1, TM7 and TM13
The N-terminal region is an inactive protease, the C-terminal region may have transporter activity which could contribute to its function in proteolysis by MamE
12 dinuclear ferroxidase centers are located at the interfaces between subunits related by 2-fold symmetry axes. The lysine-rich N-terminus is required for self-aggregation as well as for dps-driven DNA condensation
The KA1 domain is required for the control of asymmetric neuroblast division
Domains throughout the protein, and not only the N-terminus, are required for secretion and translocation. Both N- and C-terminal domains are also required for formation of tubules
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide back- bone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (By similarity)
Contains 3 histidine repeat motifs between the 4th and 5th transmembrane, exposed to the cytoplasm, that may be involved in the binding site of zinc
The GRAM domain is required for localization to the plasma membrane
The myotubularin phosphatase domain is required for localization to the plasma membrane
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Tim10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The N-terminal domain (1-802) but not the C-terminal domain (755-1330) is essential for interaction with SPO11-1
Rho-GAP domain is required to promote GRIA1 exocytosis from recycling endosomes. Rho-GAP and BAR domains are necessary for the control of long-term potentiation in hippocampal neurons (By similarity). In dendrites, BAR domain mediates the recruitment to patches where plasma membrane is deformed by acto-myosin mediated contractile forces (By similarity)
The ROQ region is required for CDE RNA-binding (PubMed:25504471, PubMed:25026078). Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites are important for mRNA decay (PubMed:25026078). ADE RNA-binding involves an extended binding surface on the ROQ region with a number of additional residues compared with the CDE RNA (By similarity). It may also be involved in localization to stress granules (By similarity)
An acidic domain (AC) contains three highly conserved tyrosines that are involved in the autoinhibition of GEF activity
The second LIM zinc-binding domain interacts with KDM5A
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (By similarity). It can refold after extension suggesting an in vivo force-dependent function (By similarity). An anti-parallel coiled coil is located C-terminal to the SAH domain and mediates dimerization (By similarity)
The FH2 and MBD domains are essential for its function in regulating Golgi ribbon formation
The EAL domain (residues 532 to 799) is a cyclic dinucleotide di-GMP (c-di-GMP) PDE hydrolyzing c-di-GMP to 5'pGpG; it has no activity on cAMP
Binding of an external ligand to the heme located in the N-terminal sensory domain displaces the distal heme ligand from Met-87 to the ligand and triggers a conformational change that regulates the activity of the C-terminal catalytic domain
The heme-PAS domain (residues 1-139) forms homodimers
The Inka box (also named iBox or inca box) binds and inhibits PAK4 by binding a substrate-like manner
The C3H1-type zinc finger domain and C-terminal region are necessary for pre-miRNA binding (PubMed:22055188). The C-terminal region and proline-rich domain are necessary for oligomerization (PubMed:22055188)
(Microbial infection) The C3H1-type zinc finger domain is necessary for JEV and DEN viral RNA-binding and antiviral activity (PubMed:23355615)
Consists of a fusion of two distinct domains: an N-terminal sugar phosphate isomerase-like domain associated with DSD activity and a C-terminal hydroxyphenyl-pyruvate dioxygenase-like domain. This C-terminal domain does not show any 4-hydroxyphenylpyruvate dioxygenase (HPPD) or protocatechuate dioxygenase (PCD) activity, but appears to be important for optimal DSD activity of QuiC1 in vivo
Contains an N-terminal subtilisin domain and a C-terminal P-domain
Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A
L27 domain is required for targeting to postsynaptic density
The C-terminus (residues 101-190) is required for ribosome-binding; deletion of the last 42 residues partially decreases ribosome-binding
Interacts with different set of proteins thanks to 3 different hydrophobic pockets. Hydrophobic pockets 1 and 2, which mediate interaction with PDCD6IP, are largely formed by residues from EF-hand 3 (EF3) to 5 (EF5), as well as by Tyr-180 (EF5) of a dimerizing molecule (Pocket 1) and from EF-hand (EF2) to 4 (EF4) (Pocket 2). Hydrophobic pocket 3, which mediates interaction with SEC31A, is mainly formed by residues from EF-hand 1 (EF1) to 3 (EF3)
EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium-binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity. A one-residue insertion in the EF5-binding loop prevents the glutamyl residue at the C-terminal end of the loop from serving as the canonical bidentate calcium ligand (By similarity). EF5 acts as a high-affinity magnesium-binding domain instead (By similarity). Magnesium, may affect dimerization (By similarity). EF5 may bind either calcium or magnesium depending on the context (By similarity)
The CCHC FOG-type zinc fingers probably directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is probably essential for the interaction with GATA-type zinc fingers (By similarity)
The FYVE-type zinc finger domain contributes to vacuolar localization
LIAT1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas LIAT1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in LIAT1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human LIAT1, respectively
The N-terminal intrinsically disordered region (IDR) facilitates its liquid-liquid phase separation (LLPS) in the nucleolus. In the IDR, the lysine-rich domain mediates self-association and targeting to the nucleolus
The CRC domain mediates DNA-binding (PubMed:19725879, PubMed:27465258). It contains two CXC subdomains (joined by a flexible linker) which are both required for efficient association with target DNA (PubMed:27465258). Each CXC subdomain coordinates three Zn(2+) ions (PubMed:27465258)
The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA. The interdomain linker (564-579) acts as a hinge to fix the relative orientation of the 2 RRMs. The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs. Unlike in CPEB1, a continuous polar interface is formed between the 2 RRMs
In human, and in contrast to mouse protein, the SAM domain is not required for deoxynucleoside triphosphate (dNTPase) activity and ability to restrict infection by viruses
The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association
A penicillin-binding domain is found between residues 420-820
The DZC domain is necessary and sufficient for dimerization. A C-terminal fragment containing both DZC domains is able to rescue the short root phenotype. The N-terminal part (1-57) promotes BRX membrane association and is required for efficient degradation in the nucleus
Has a modular structure: a carbohydrate esterase catalytic module at the N-terminus, a linker rich in serines and threonines, and a C-terminal carbohydrate-binding module (CBM). The genes for catalytic modules and CBMs seem to have evolved separately and have been linked by gene fusion
The cytoplasmic N-terminus is important for tetramerization and for interaction with the beta subunits that promote rapid channel closure
Contains one leucine-zipper motif and two pairs of conservatively spaced Cys (Cys pair 1 and 2) involved in forming heterodimers
A 70 amino acid island between the 21th and the 22th LRR is essential for the binding of brassinosteroids
The JM domain (815-883) is a positive regulator of kinase activity and is required for Tyr phosphorylation
A guanylyl cyclase domain (1021-1134) having an in vitro activity is included in the C-terminal kinase domain
Interacts with FliW via its C-terminal alpha helices (approximately 44-57 and 63-74)
The C-terminal region is required for transcriptional activation
C-terminus is required for spindle assembly
The ubiquitin-like domain is required for HRD1 trans-ubiquitination and degradation. Reported to be involved in ERAD-M but not ERAD-L function (PubMed:20005842). However, a contradictory report states that it is not required for either ERAD-L or ERAD-M function (PubMed:19940128). Reported to be required for HRD1 oligomer formation (PubMed:19940128). However, a contradictory report does not observe any defects in oligomerization following deletion of the domain (PubMed:21074049)
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils. Four skip residues (Skip1: Thr-1187, Skip2: Glu-1384, Skip3: Glu-1581 and Skip4: Gly-1806) introduce discontinuities in the coiled-coil heptad repeats. The first three skip residues are structurally comparable and induce a unique local relaxation of the coiled-coil superhelical pitch and the fourth skip residue lies within a highly flexible molecular hinge that is necessary for myosin incorporation in the bare zone of sarcomeres
CAHS proteins contain 2 repeats of 19-mer peptides designated as CAHS-motifs that comprise each two octapeptides connected by a tripeptide (PubMed:27649274)
The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of SYT1, SYT2, EPS15, EPS15R and ITSN1
Has three domains with a flexible linker between the domains II and III, and assumes an 'L' shape. The position of domain III with respect to the tetramer is variable
The N-terminal domain (1-230) determines the lipid droplet size
The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids (By similarity)
DNA binding is primarily driven by the H-T-H domain, but requires full-length protein for maximum affinity
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of apg-7/atg9-containing vesicles, thereby enabling growth into autophagosomes
The ubiquitin-like region is necessary for its localization to stress granules (SGs) in a VCP-independent manner. The AN1-type 1 and 2 zinc finger domains are necessary for the recruitment of the 26S proteasome to SGs. Both the AN1-type 1 and 2 zinc finger domains and the ubiquitin-like region are necessary for efficient SGs clearance upon specific arsenite-induced responses
The CARD domain mediates interaction with APIP
The monomeric form is autoinhibited in a closed conformation through a bound ADP at the nucleotide binding site. Exchange of ADP for ATP and binding of cytochrome c trigger a large conformational change where the first WD repeat region swings out, allowing the NB-ARC domain to rotate and expose the contact areas for oligomerization (By similarity)
The Ripply homology domain and the WRPW motif are both necessary for its transcriptional corepressor activity on the transcription activator TBX1
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tim8 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The N-terminal region (1-98) is sufficient for induction of SAR of N.tabacum to TMV infection. The C-terminal region (99-155) is sufficient for eliciting HR in N.tabacum
The N-terminal domain interacts with LptC, at the inner membrane, and the C-terminal domain interacts with LptD, at the outer membrane
The ATPase domain dimerizes on its own via its dimerization region, the Toprim (topoisomerase/primase) domain does not. The Toprim domain has Mn(2+)-dependent nuclease activity on linear and supercoiled dsDNA. It faces away from the dimerization domain
The bromo domain mediates the specific interaction with acetylated histones
The SGF29 C-terminal (also named tudor-like) domain mediates binding to methylated 'Lys-4' of histone H3 (H3K4me)
The Calponin-homology domain mediates its binding to microtubules
The disordered region is required for activation of the CARD8 inflammasome
The C-terminal part of CARD8 oligomerizes to form the core of the CARD8 inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments. The UPA region reduces the threshold needed for filament formation and signaling. Directly recruits and polymerizes with the CARD domain of caspase-1 (CASP1) through the favorable side of the growing filament seed
The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (311-341) inactivates kinase activity under calcium-free conditions
The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR
The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation (By similarity)
The UBA domain binds both poly- and mono-ubiquitin
ARM repeats 1 to 5 mediate interaction with cadherins
Consists of two domains that are separated by a deep cleft, in which the Zn(2+) ion is bound
The extracellular domain carries the Vel antigen
The N-terminal first 50 residues are required for inhibition by the substrate adenylyl sulfate
The mature peptide (64-97) probably forms alpha-helices which disrupt target cell membranes
The PIP-box mediates interaction with PCNA and localization to replication foci
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm; a C-methylation (C-Met) domain; and a C-terminal reductase (R) domain (By similarity). Methylation occurs during the processive construction of the carbon backbone, directly after the second extension at the triketide stage (By similarity). The C-terminal R domain is involved in a reductive release mechanism, reducing the thiolester intermediate to the observed aldehyde and concomitantly releasing the free holo-ACP thiol (By similarity)
The PH-like region is similar to the PH domain but is not detected by Pfam and PROSITE prediction tools. It is unclear whether it is a real PH domain
The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns(3)P)
The first five extracellular Ig-like domains are required for correct localization of syg-1
The cytoplasmic domain is necessary for syg-2 subcellular localization
Zona pellucida domain may enable to form filaments
The N-terminal amphipathic alpha-helix (81-100) is essential, but not sufficient, for the thylakoid membrane targeting
The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs that include MIA2, MIA3 but also SEC31A. These interactions are probably competitive
The myosin tail domain mediates binding to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) and binds to membranous compartments. It is required for recruitment to Fc-gamma receptor (Fc-gamma-R) phagocytic cups
The penta/hexapeptides repeats form a proline-rich acidic domain. In addition, a part of this region contains a perfect direct repeat
The JmjC domain mediates demethylation activity. It is also required for repression of ribosomal RNA genes (By similarity)
The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival (By similarity)
The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins (PubMed:23201271). The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities (PubMed:23201271)
The low charge region mediates the transcriptional activation activity
The catalytic SET domain binds histone H3 (PubMed:27474439, PubMed:28256625). It is also able to bind oncogenic histone H3 K36M/I found in a number of cancer types, in which histone H3 'Lys-36' is replaced by a Met or an Ile residue. When binding the oncogenic variant histone H3 K36M/I, the SET domain undergoes dramatic conformational change to accommodate the histone H3 peptide, leading to sequester and inhibit SETD2 activity and block global H3K36 methylation (PubMed:27474439, PubMed:28256625)
the 9aaTAD motif (residues 862 to 870) is a transactivation domain present in a large number of yeast and animal transcription factors
The horseshoe-shaped TROVE domain is built with 7 helical HEAT-like repeats, and is closed by the VWFA-like domain giving rise to a ring-shaped monomer. Single-stranded RNA is bound in the positively charged central cavity (By similarity)
Apo-AcpS adopts different conformations depending upon the pH conditions of the crystallization solution
The N-terminal region seems to be responsible for association with chromosomes, thus excluding any involvement of the Zn finger in this process
Contains a C-terminal transmembrane helix, three copies of tyrosine-based sorting motifs, and an NPxY eukaryotic motif, which binds phosphotyrosine-binding domains present on signaling and adapter eukaryotic proteins (PubMed:33563829). The NPxY eukaryotic motif is essential for ER-mediated remodeling and lysosomal evasion by the LCV (PubMed:33563829)
Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs. One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (PubMed:29472584). Binds calmodulin in a calcium-dependent way (By similarity)
The C-terminal R3 domain contains 3 tandem repeats required for the binding to insoluble chitosan
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Ala and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins
The DARXP motif is also sometime designated as G6 region
The N-terminal domain binds DNA and the C-terminal domain is involved in metal-binding and dimerization
The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs. The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region
The K-loop region occludes the S-adenosyl-L-methionine-binding pocket. Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding
the 9aaTAD motif (residues 1034 to 1042) is a transactivation domain present in a large number of yeast and animal transcription factors
The Rab-GAP TBC domain lacks GTPase activator activity but is necessary for interaction with ARF6
The cell attachment motif mediates the attachment to chondrocytes. It mediates the induction of both the IAP family of survival proteins and the antiapoptotic response
The TSP C-terminal domain mediates interaction with FN1 and ACAN
Each of the eight TSP type-3 repeats binds two calcium ions. The TSP C-terminal domain binds three calcium ions
The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (PubMed:23118222). The N-terminal palmitoylated peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195)
The N1 region (38-149) is sufficient for re-targeting to the inner membrane and proper insertion. The N2 region (150-269) may act as a start transfer signal, but it cannot direct proteins to the inner envelope
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain 2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (By similarity)
The 4 repeats act cooperatively in the binding of G actin
The C2H2-type zinc fingers determines the hotspot localization through its binding to specific DNA sequences. Variations in their sequence affects affinity towards DNA-binding motif
The Kazal-like domains mediate the serine protease inhibitor activity
The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs (PubMed:28525753). The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region (PubMed:32266935)
The K-loop region occludes the S-adenosyl-L-methionine-binding pocket (PubMed:30197297). Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding (PubMed:30197297)
The N-terminal domain (EF-hands 1 and 2) is required for localization to the phagocytic cup, G-actin binding and activation of kinases
The C-terminal domain (EF-hands 3 and 4) is required for G-actin binding but is dispensable for localization to the phagocytic cup and activation of kinases
The central linker region between EF-hands 2 and 3 is required for the interaction with F-actin
Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant
The propeptide domain acts as an intramolecular chaperone for the folding of the catalytic domain (By similarity). Also acts as an inhibitor of the catalytic domain thereby regulating SUB2 activity during secretion (By similarity)
The transmembrane domain is required for SUB2 progression through the secretory pathway
The cytoplasmic domain is required for the correct redistribution at the merozoite surface and posterior capping but is dispensable for its progression through the secretory pathway
Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per monomer. ATP binding to NBD1 triggers binding of polypeptides and stimulates ATP hydrolysis at NBD2. Nucleotide binding to NBD2 is crucial for oligomerization (By similarity)
The C-terminal extension is involved in oligomerization
The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding (By similarity)
This protein consists of an immunoglobulin-like seven-stranded antiparallel beta-barrel domain linked to a subdomain composed of two beta-hairpin ribbons
In photoreceptor cells the DEP domain is essential for targeting RGS9 to the outer rod segments
Cleavage by CASP8 liberates a C-terminal fragment that promotes apoptosis and inhibits the activation of NF-kappa-B in response to TNF signaling
The C3H1-type zinc finger domain and C-terminal region are necessary for pre-miRNA binding. The C-terminal region and proline-rich domain are necessary for oligomerization
The carbohydrate binding modules (CBM) mediate starch-binding
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box
Residues 60 to 82 are required for the interaction with host plant binding immunoglobulin proteins (BiPs) and subsequent virulence
The macro domain mediates non-covalent poly(ADP-ribose)-binding and recruitment to DNA damage sites (PubMed:19661379, PubMed:29220652, PubMed:29220653). Mediates auto-inhibition of ATPase activity by interacting with the N-terminal ATPase module, encompassing the helicase ATP-binding domain and helicase C-terminal domain (PubMed:29220652, PubMed:29220653). Binding to poly-ADP-ribosylated histones upon DNA damage releases the auto-inhibition by the macro domain and trigger ATPase activity (PubMed:34486521, PubMed:34874266). Does not bind monomeric ADP-ribose and mono-ADP-ribose fails to release the auto-inhibition of the ATPase module by the macro domain (PubMed:29220653)
The histidine box motifs may contain the active site and/or be involved in metal ion binding
The N-terminal 134 amino acids are necessary for homodimerization and RNA-binding. The N-terminal 298 amino acids are sufficient to interact with KCNMB4 and to regulate presynaptic action potential (AP) duration in neurons. The two agenet-like domains are necessary for binding to histone H3 in a methylation-dependent manner. The KH domains are necessary for mediating miRNA annealing to specific RNA targets. The KH 2 domain is necessary for binding to kissing complex (kc) RNA ligands. The RGG box domain is necessary for binding to mRNA targets that contain G-quadruplex structures. The RGG-box domain is necessary for binding to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the superoxide dismutase SOD1 mRNA. The RGG box domain is necessary for binding to its own mRNA. The RGG-box domain is necessary for binding to homomer poly(G)
The KRAB domain is responsible for the transcriptional repressor activity
The GAT domain and the VHS domain are required for the interaction with polyubiquitinated proteins
The VHS domain binds to phosphatidylinositol monophosphates (By similarity). The KRKK motif within the VHS domain is required for binding to phosphatidylinositol monophosphates, with a preference for phosphatidylinositol 5-phosphate (PtdIns(5)P) (By similarity)
The C-terminus is required for transcriptional repression and mesoderm induction
Consists of 3 structural domains. The pH-responsive N-terminus inhibits the adenylyl cyclase (AC) activity of the C-terminal catalytic domain. The length of the linker segment (aa 192-206) is decisive for regulation
Is a multimodular protein that comprises seven distinct domains. The catalytic glycoside hydrolase domain resides in domain 3 (residues 602-893). Possesses four potential carbohydrate-binding modules (CBMs)
The KVTF motif (residues 138 to 141) is required for the interaction with the PP1c family proteins PP1c-1, PP1c-2 and PP1c-3
The tight homohexamer forms a small pore which is positively charged
Its N-terminus, which contains the proline-rich repeats, is highly immunoreactive
The ARM-repeat containing C-terminal region is required for the binding to the Kinesin-12 members
The tyrosine-protein phosphatase 2 domain (D2) mediates dimerization. The extreme N- and C- termini of the D2 domain act to inhibit dimerization and removal of these sequences increases dimerization and inhibits enzyme activity
The Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. Within this motif, the conserved Lys is essential for transport activity mediated by the heterodimer with ABCG8
Consists of three different domains. The central region of the enzyme is the catalytic domain. The N-terminal region contains cenC-type cellulose-binding domains and seems to act as a thermostabilizing domain: a derivative lacking this region shows a lower optimum temperature for activity (35 degrees Celsius) than the full-length enzyme, and a reduced thermal stability that results in a complete inactivation of the enzyme after 2 hours incubation at 55 degrees Celsius. The C-terminal region contains family 9 carbohydrate-binding modules
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2
The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2
Removal of the transmembrane regions (residues 1-156) has no effect on csrB translation, however removal of either the HAMP-like region, EAL or GGDEF domains obviates the activity of CsrD
Domain B contains 29.5 X 9 AA tandem repeats, and 2 X 14 AA repeats
The tight homohexamer forms a pore with an opening of about 4 Angstroms in diameter which is positively charged
The N-terminal domain mediates intranuclear attachment to the nuclear pore complex. The C-terminal domain mediates its nuclear import
Has a GGDEF domain (residues 173-310) preceded by a PAS-like domain (residues 84-149) which together have ATPase activity, followed by a region with a DHH (339-496) and a DHHA1 (591-646) domain (PubMed:19901023). The combined GGDEF, DHH and DHHA1 domains have c-di-AMP phosphodiesterase activity (residues 150-659) that is 10-fold enhanced by inclusion of the PAS-like domain (84-149); PDE activity may only require the DHH/DHHA1 domains (PubMed:19901023). The PAS-like domain is important for heme b-binding (PubMed:21257773)
The Asp-Asp-Xaa-Xaa-Xaa-Glu (DDXXXE) and Ser-Xaa-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Glu (SSE) motifs are important for the catalytic activity, presumably through binding to Mg(2+)
CAHS proteins contain 2 repeats of 19-mer peptides designated as CAHS-motifs that comprise each two octapeptides connected by a tripeptide (PubMed:22937162)
Contains 3 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motif 2 is essential for the association with nuclear receptor EcR
The MEINOX domain (33-138) is sufficient for interactions with BELL proteins (PubMed:18398054). The BP-interacting domain (BPID, 1-32) is necessary for interactions with KNOX proteins (PubMed:18398054)
Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane (PubMed:27161523). Each cadherin domain binds three calcium ions (PubMed:27161523)
The SWIM-type zinc finger is required for ubiquitination activity
The TOG (tumor overexpressed gene) domains are arranged in the N-terminal region with each domain composed of six (for the most part non-canonical) HEAT repeats and forming a oblong paddle-like structure. 3D-structure analysis shows the presence of additional HEAT repeats that are not detected by sequence-based prediction programs. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice
The extracellular domain (25-427) is sufficient for male and female gametophyte development before double fertilization, but not for early embryogenesis. The cytoplasmic domain (507-593) is necessary for correct early embryogenesis and mediates homodimer formation at the plasma membrane
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (336-366) inactivates kinase activity under calcium-free conditions (By similarity)
Contains 24 transmembrane helices (TM) that form four homologous functional repeats connected by intracellular linkers. Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments represent the voltage-sensor. S4 transmembrane segments lack some of the charged residues (K and R) found at every third position in the S4s of the NaV, CaV, and KV channels. Pore-forming loops (P loops) between S5 and S6 of each domain form an EEKE sodium- ion selectivity filter a mixture between the EEEE found in the CaVs and the DEKA of NaVs. Voltage-sensing domains (VSDs), formed by S1 to S4 of each domain, detect changes in membrane potential and induce the opening or closing of the ion-conducting pore domain, formed by S5 and S6
The NPF repeat domain is involved in EPS15 binding
The DPW repeat domain is involved in AP-2 and clathrin binding
The jas domain (186-210) is required for interaction with COI1 and Pseudomonas syringae HopZ1a
Has an N-terminal glycoside hydrolase 36 domain with a probable carbohydrate-binding domain in the C-terminus. The C-terminus is not required for activity on soluble substrates but increases efficiency of cleavage in red blood cells
While it shares structure similarities with CGAS, it also features a number of differences. The crystal structure is in inactive conformation and the enzyme would require a conformational change to be active. The nucleotidyltransferase activity is therefore unclear
The catalytic domain (residues 1-190 and 303-408) adopts a typical 'prim' fold structure formed by two three strand beta-sheets that line the inside of the lower and upper parts, each surrounded by alpha-helices on the outside (PubMed:24043831, PubMed:24239947). It comprises a highly conserved catalytic triad, a structural zinc-binding motif and the nucleotide-binding motifs. The Asp-109, Asp-111 and Asp-306 catalytic triad binds two Mn2+ or Mg2+ ions which activate for nucleophilic attack the 3'-hydroxyl of the growing RNA primer or of the first NTP bound at the initiation site (PubMed:24043831, PubMed:24239947, PubMed:25550159, PubMed:26975377). The nucleotide-binding motifs coordinate the phosphates, the ribose and the base of a NTP molecule (PubMed:24043831). The interaction between O2' of the initiating NTP and Asp-306 stabilizes the ribose during the di-nucleotide synthesis (PubMed:26975377). It is proposed that the first nucleotide binds to the elongation site, followed by binding to the initiation site of a second NTP, which will become the 5'-terminal nucleotide of the primer (PubMed:26975377)
The leucine-rich repeat domain is sufficient for guiding both axon projection and neuronal migration, in vitro
The six transmembrane regions are tightly packed within each subunit without undergoing domain swapping. Transmembranes TM1-TM3 are positioned on the inner circle of the channel tetramer and participate in inter-subunit interactions that are central to the assembly of the ion conduction pore. The RxxxFSD motif within transmembrane TM1 coordinates a network of specific inter- and intra-subunit interactions with other conserved residues on TM2 and TM3 and plays a key role in the tetrameric assembly of the channel. Transmembrane TM4-TM6 are positioned on the periphery of the channel and do not contribute to contacts with neighboring subunits. Transmembranes TM1 and TM2 are linked by an extended strand-like tail and two short helices (H1 and H2) which protrude outwards from the main body of the transmembrane domain and enclose the external open entrance of the ion conduction pore in the channel tetramer. Transmembrane TM1 forms the pore-lining inner helix at the center of the channel, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three hydrophobic residues on the C-terminal half of the TM1 helix form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Ile-17 is probably responsible for channel selectivity
Is composed of an N-terminal sensory globin-fold domain that binds heme and oxygen, and a C-terminal GGDEF diguanylate cyclase domain
The N-terminal 10-AA residues are absolutely required for enzymatic activity
The cysteine framework is VI/VII (C-C-CC-C-C). Has the PXY motif between the first and the second Cys residues
The toxin-channel complex has a triskelion-like shape with one toxin heterodimer radiating from each ASIC1 subunit. Toxin subunits protrude from the edges of the channel trimer, with each heterodimer interacting almost exclusively with a single subunit
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex (By similarity). The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer, upon arginine binding (PubMed:33296665). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (PubMed:33296665)
The binding of TAF10 and TAF11 requires distinct domains of TAF13
The alpha-NTD is essential for RNAP assembly and basal transcription, whereas the alpha-CTD is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity). The alpha-NTD recognizes upstream AT-rich elements and the alpha-CTD interacts with the transcriptional activator Fis in reconstitution assays in E.coli
Forms a funnel-like structure. Contains three Zn(2+) binding sites, two of which could be involved in Zn(2+) transport
The C-terminal domain not found in other pectate lyase-like protein is required for PMR6 function since the pmr6-2 mutation confers resistance by introducing a frameshift in the mature mRNA which eliminates the C-terminal domain
May negatively modulate calmodulin/cmd-1 expression via a negative feedback loop in which the IQ domains bind to calmodulin
The C-ter coiled-coil domain is sufficient for localization and homodimerization
The BTB domain is required for interaction with CUL3
Each subunit has 12 transmembrane (TM) helices; TM1 and TM6 are interrupted by short non-helical Gly-rich loops in the middle of their transmembrane spans. TM11 and TM12 provide most of the homodimerization interface. Each subunit has a central cavity which probably binds substrate
The BH3 motif is required for the interaction with Bcl-2 proteins and cytotoxicity
The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding
The extracellular domain may be shed following protease cleavage in some cell types
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins. The WPRW motif is also required for the inductive function, independent of transcription regulation activity (By similarity)
The PH domain mediates binding to phosphatidylinositol 4,5-bisphosphate
The C-terminal domain (CT) has toxic activity, which can be exchanged between N-terminal sections from different toxin molecules
The BRCT domains 1 and 2 are required for intramolecular interaction, but not for intermolecular oligomerization (PubMed:15545273). The BRCT domains negatively inhibit its GEF activity in interphase cells (PubMed:15545273, PubMed:31888991). The same BRCT domains may act as a positive regulatory motif for the completion of cytokinesis after the breakdown of nuclear membrane during mitosis (PubMed:15545273)
The docking domain is responsible for the weaker heterodimerization with H2B
An intact death domain is needed for apoptosis
The catalytic charge relay system lies at the bottom of a deep cleft which probably accounts for its substrate specificity (PubMed:17024087, PubMed:23921389). The C-terminal A2 domain (approximately residues 322-347) penetrates into the central pore of the SubB pentamer, making different contacts with each SubB subunit (PubMed:23921389)
The fibrinogen C-terminal domain mediates binding to carbohydrates
The N0, N1, N2 and N3 domains are periplasmic, while the secretin and S domains form a channel that is partially inserted in the outer membrane. The N1, N2 and N3 domains each form a periplasmic ring; the N0 domain was present but not resolved by electron microscopy. The secretin domain forms a double beta-barrel structure; the outer barrel has a diameter of about 140 Angstroms while the inner barrel forms the central gate with a small pore in the closed state (PubMed:29042496). Isolated N-terminus (domains N0, N1 and N2) assembles as a hexamer of dimers (i.e. dodecamers). The N0 domain probably moves during export (PubMed:29042493). It has been suggested that the C15 symmetry of the C-terminus may transit to a C6 symmetry by displacement of 3 of the N-terminii (Probable)
Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain
The N-terminus (residues 1-164) forms a trimer with a partially blocked channel forms at the trimer interface (PubMed:20133749). The C-terminus has 4 domains that resemble the small subunit of RuBisCO (rbcS) joined by flexible linkers; the first one (CcmMS1) has been crystallized and folds much like RbcS. CcmMS1 binds to holo-RuBisCO (RbcL(8)-RbcS(8)), a CcmMS1-CcmMS2 constructs binds about 10-fold better, while the entire C-terminus with all 4 CcmMS domains binds with an intermediate affinity. CcmMS1 binds to a different region of RbcL than does RbcS, up to 5 CcmMS1 domains can bind to the intact holo enzyme (PubMed:30591587)
The TPR domain is essential for ubiquitination mediated by UBE2D1
The SP-RING-type domain is required for promoting EKLF sumoylation
N-terminal domain is required and sufficient for targeting to the septal ring
The PCI domain is not sufficient to efficiently mediate CSN complex assembly and for biological activity
Its C-terminal domain interacts with TAL1
All KH domains contribute binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute. They are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules
Has 2 zinc-ribbon domains (N-ZR and C-ZR); functionally important residues Asp-94 and Glu-95 are probably located at the tip of a domain that extends from C-ZR into the RNAP active site. The nature of these residues determines if the protein is involved in stalled transcript cleavage and thus activation (Asp and Glu residues in this protein, TFS1) or in RNAP inhibition (Lys residues in TFS4)
The MBT repeat 2 specifically recognizes and binds monomethylated and dimethylated proteins. In contrast, it does not bind trimethylated proteins. The MBT repeat 1 does not bind methylated peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence context
The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu residue
The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Tim9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF8, the motif is inactive
The EF-hand is necessary for the colony survival activity to protect cells from death induced by exposure to DCA
The GRAM and PH domains are required for the localization of ATG26 to the preautophagosomal structure (PAS) and are involved in autophagy (PubMed:27696999)
The mushroom-shaped heptamer is composed of a cap domain (comprising 7 beta sandwiches and the amino latches of each protomer), 7 rim regions whose protruding strands may interact with the membrane bilayer, and the stem domain (52 Angstroms in length, 26 Angstroms in diameter) which forms the transmembrane pore
The PH 1 domain and amino acids 619-780 (a region called TSS; otherwise known as CC-Ex) are necessary for membrane localization. PH 1 and TSS domains are necessary for Rac1 activity. The PH 2 domain is engaged in the enhancement of the catalytic activity of the adjacent DH domain. The PH 1, TSS and DH domains are necessary to induce neurite-like structure
The N-terminus (1-130) is determinant for the chain length specificity. Region I (76-96) and region III (201-229) are involved in the recognition of both substrates in a coordinated manner
Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A (By similarity)
The cysteine framework is II (CCC-C-C-C)
The C-terminal evolutionary conserved domain (ECD) contains poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent with structural docking models revealing two highly scored poly-Gln-binding pockets in the ECD (PubMed:28445460). As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3 (PubMed:28445460)
The leucine-zipper domain is required for its dimerization and activation
The 244-aa domain between residues 633 and 876 is the primary occludin (OCLN)-binding site and is required for stable association with the tight junction (PubMed:9792688)
The C-terminal region (residues 1151-1372) is an actin-binding region (ABR) that interacts directly with F-actin and plays an important role in the localization of TJP1 at junctions (PubMed:9792688, PubMed:12354695, PubMed:20930113). The ABR is also required for the localization to puncta at the free edge of cells before initiation of cell-cell contact (PubMed:12354695). The ABR is also necessary for TJP1 recruitment to podosomes (PubMed:20930113)
The second PDZ domain (PDZ2) mediates homodimerization and heterodimerization with TJP2 and TJP3 (PubMed:9792688, PubMed:17928286)
The UBX domain lacks key residues critical for VCP binding
The HEAT repeats have been determined based on 3D-structure analysis of the D.melanogaster ortholog and are not detected by sequence-based prediction programs
Is folded into two distinct domains, an N-terminal ATPase domain and a C-terminal Rossmann-fold domain, which are joined by a flexible linker
The N-terminal region mediates interaction with MARCHF6, leading to SQLE ubiquitination and proteasomal degradation when cholosterol levels are high. The first part of the N-terminal region contains a hydrophobic region that inserts into the membrane; contrary to predictions, there are no transmembrane helices. The second part contains a region that can form an amphipathic region that associates with membranes. This region is ejected from the membrane by high cholesterol levels and becomes disordered in an aqueous environment. This is critical for cholesterol-dependent proteasomal degradation. Additional parts of the N-terminal region are predicted to be disordered and contribute to flagging the protein for proteasomal degradation already under basal conditions
The conserved PP2C phosphatase domain (257-736) is interrupted by an insertion of approximately 200 amino acids
The PB1 domain mediates interactions with MAP2K5
The PDZ domain mediates the interaction with CRB3
Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors (By similarity)
(Microbial infection) Binding to BoNT/B induces formation of an alpha-helix in the membrane-proximal extracytoplasmic domain (PubMed:17167421)
The cysteine framework is C-C-C-C-C-C-C-C-C-C-CC
The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer
Consists of two discrete domains, an N-terminal cytochrome b domain and a C-terminal flavin-binding domain. The cytochrome b domain is required for efficient cytochrome c reduction
The BAR domain mediates interaction with the exocyst components EXOC4 and EXOC8 and is required for the function in cell migration (PubMed:21658605). It also mediates the interaction with PLXND1 (PubMed:24841563)
The BAR-like domain displays limited similarity to other BAR domains
Contains a dimerization domain which shares similarity with the LIM-binding domain of animal transcription coregulators
The integrin-binding motif mediates the binding to integrin alpha-5/beta-1 (ITGA5:ITGB1) and integrin alpha-V/beta-3 (ITGAV:ITGB3) and is required for the function in integrin-mediated cell-cell adhesion
The dityrosine basolateral targeting motif mediates localization to the basolateral membrane in polarized cells
Lacks the EPN motif and the presence of Gln instead of Glu at amino-acid position 114 may explain its inability to bind peptidoglycan
The protein contains a weakly acidic N-terminal transactivation domain (TAD) followed by a second TAD rich in proline, serine and threonine. Each of these domains may be required for transcriptional activation of a subset of target genes (By similarity)
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, a motif known to be important for the association with nuclear receptors
The PDZ domain mediates binding to a subset of proteins containing a PDZ-binding motif at the C-terminus: the specificity for PDZ-binding motif is provided by the 2 residues located upstream of the canonical PDZ-binding motif (PubMed:17828261, PubMed:21422294). The PDZ domain also mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B)
The PBZ-type zinc fingers (also named CYR) mediate non-covalent poly-ADP-ribose-binding (PubMed:18474613, PubMed:18172500, PubMed:30104678). Specifically recognizes branched poly-ADP-ribose chains generated by PARP2 (PubMed:30104678). Poly-ADP-ribose-binding is dependent on the presence of zinc and promotes its recruitment to DNA damage sites (PubMed:18474613, PubMed:18172500)
The serine protease 1 and 2 domains are catalytically active, whereas the serine protease 3 domain lacks the essential Ser residue of the catalytic triad at position 1015 and is predicted to be inactive
The second proline-rich region may interact with actin targeting the kinase to a specific location in the cell
The C-terminal is cytoplasmic and is important for interaction with ZO-1. Sufficient for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction (By similarity). The first extracellular loop participates in an adhesive interaction
The MBD domain is necessary for chromocentric localization
Composed of two similar domains
Binds a calmodulin chain via each of the two IQ domains. IQ domain 1 mediates interaction with calmodulin both in the presence and in the absence of Ca(2+). IQ domain 2 mediates interaction with calmodulin in the presence of Ca(2+)
The TH1 domain is required for activity in complementing zebrafish defects in Kupffer's vesicle lumen size
The ARID domain is required to target the PRC2 complex to its target genes
The GSGFP motif is required for the interaction with SUZ12
Contains a R/KLFGV repression motif, which may be involved in the activity of transcriptional repression
The ESA1-RPD3 (ER) motif is common to ESA1 and RPD3 and is required for ESA1 histone acetyl-transferase (HAT) activity and RPD3 histone deacetylase (HDAC) activity
The proline-rich region is required for PFN1 interaction
Modular protein that contains an aryl carrier protein (ArCP) domain which bears a phosphopantetheinyl arm to attach the activated salicylic acid, a condensation/cyclization domain involved in the formation of the oxazoline ring, an adenylation domain which activates the serine or threonine residue into an aminoacyl-AMP ester, a peptidyl carrier protein (PCP) domain which bears a phosphopantetheinyl arm to attach the activated serine or threonine, and a terminal thioesterase domain which assists in the transfer of intermediates from MbtB to ACP1 in MbtD
Only Ras-associating 1 domain is involved in the binding to let-60
Has 2 endonuclease domains. The discontinuous RuvC-like domain cleaves the target DNA noncomplementary to crRNA while the HNH nuclease domain cleaves the target DNA complementary to crRNA (Probable)
Contains three structural domains: an N-terminal TRAM domain, a central domain containing an iron-sulfur cluster, and a C-terminal domain that displays the typical SAM-dependent methyltransferase fold
The SANT domains may bridge the nucleosomal substrates and the demethylase KDM1A
The two PDZ domains mediate the interaction with phosphatidylinositol 4,5-bisphosphate (PIP2) and target SDCBP2 to the plasma membranes and nucleoli, PIP2-rich regions
The N-terminal regulatory domain is not required for peptidase activity in vitro
Contains an activation domain in the C-terminal region
Contains a N-terminal NAI2 domain (474-759)
The Asp-Xaa-Asp-Asp-Thr-Ala (DXDDTA) and Arg-Xaa-Xaa-Asp-Gly-Ser-Trp (RXXDGSW) motifs are expected to bind to Mg(2+)
The SEC7 domain is sufficient for nucleotide exchange activity
Essentially unstructured in the absence of calcium ions. Requires calcium ions for folding
Arg-345 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Displays an autoinhibited conformation: Tyr-97 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9
The NTE (N-terminal extension) motif is a structural component of the catalytic domain and thus contributes to activity
The C-terminal 30 residues are probably required for function in DNA repair
Acidic motifs (DDEEE) in the C-terminal domain are necessary and sufficient for efficient transport to the contractile vacuole
The C-terminal domain recognizes the anticodon bases but the N-terminal contributes also to the precise recognition of tRNA(Thr) by ThrRS
The SPX domain has very high affinity for inositol polyphosphates, such as myo-inositol hexakisphosphate and 5-diphospho-myo-inositol pentakisphosphate (5-InsP7), and moderate affinity for inorganic pyrophosphate. Its affinity for inorganic phosphate is 2 to 3 orders of magnitude lower (Probable). SPX domains may integrate inositol pyrophosphates (PP-InsP)-dependent signaling to adapt cytosolic phosphate concentrations to different metabolic situations (Probable)
The ANK repeats at the N-terminus recognize and bind host caspases (CASP3, CASP7, CASP8 and CASP9)
The Ras-GEF domain and the N-terminal Ras-GEF domain mediate Ras activation
The IQ domain is dispensable for the Ras-GEF activity
The DH (DBL-homology) domain is required for rac1 activation
The transmembrane domain (TM) is the major site of interaction with slc51a. The extracellular-membrane interface is absolutely required for transport activity. The intracellular-membrane interface is necessary for establishing the correct membrane orientation that is essential for the heterodimer Ost-alpha/Ost-beta complex formation and transport activity at the cell membrane surface (By similarity)
The Gln- and His-rich domain may mediate protein-protein interactions
The C-terminal region from residues 107 to 136 is important for BAK1/SERK3-binding and the host cell death suppression
The N-terminal conserved region (G2B region) is required for the interaction with gls2 and its translocation to the endoplasmic reticulum, whereas the C-terminal conserved region (MRH region) is involved in the recognition of N-glycans bearing from 5 to 9 mannose units
The RCC1-like repeats assemble into a circular seven-bladed beta propeller structure. Each blade is composed of four antiparallel beta-strands with loops between each strand
The SPRY domain mediates the interaction with MET
Consists of an N-terminal kinase domain, a transmembrane domain, and a C-terminal domain containing four repeats of the PASTA signature sequence (Penicillin-binding protein and Ser/Thr protein kinase associated domain). The PASTA domain binds to peptidoglycan (PGN) subunits, is essential for StkP activation and substrate phosphorylation, and is responsible for cellular targeting to midcell (By similarity)
The first transmembrane domain may act as a type I signal anchor (PubMed:12077416, PubMed:15385547). The PAL motif is required for normal active site conformation (By similarity)
Binds calcium via its EF-hands. Calcium-binding mediates a conformational change. Can also bind magnesium (By similarity)
Adding an N- or C-terminal His-tag to this protein prevents it forming BMCs (PubMed:27450681). One side of the hexamer is concave and lined by hydrophobic residues, the other side has a slightly protruding, 6-stranded beta-barrel (By similarity)
Contains a C-terminal (513-598) carbohydrate-binding domain (CBM)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). InpA has the following architecture: C-A-T-TE (PubMed:18804170)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM12 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The C-terminus (463-494) binds calmodulin in a calcium-dependent fashion
The PDZ-binding motif is required for cell surface expression, neurite outgrowth promotion and interaction with DLG1, DLG3 and DLG4
A Cys-rich motif in the N-terminus (residues 207-221) may bind a metal cofactor or iron-sulfur cluster and be responsible for sensing redox or other signals
The RP domain (arginine/proline-rich) is involved in the recognition of substrates such as cmk-1
Contains the CKS-17 immunosuppressive domain present in many retroviral envelope proteins. As a synthetic peptide, it inhibits immune function in vitro and in vivo (By similarity)
The architecture of ATPKS is the following one: adenylation (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain, and thioester reductase (TE) domains
Has 2 domains, the N-terminal GT8 domain that binds UDP and Mn(2+) and a C-terminal domain that assumes a Rossmann-like fold. The GT8 domain has UDP-galactose hydrolysis activity but no galactose transferase activity (PubMed:28246170). The C-terminal domain probably binds the partially glycosylated protein acceptor in a continuous, surface-exposed groove that can possibly bind proteins with varying degrees of glycosylation (Probable)
The N-terminal 153 residues are responsible for the prion properties of NEW1
A tripeptide motif (FDE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
The WD repeats mediate interaction with ubiquitin
The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with CDC48 C-terminus
The VWFC domain mediates the covalent links between monomers throught disulfide bridges. Ig-like C2-type domains are required to sulfilimine bond formation. The VWFC domain is not required for trimerization. The LRR domain mediates high affinity binding to laminin-1
The RBM1 (RPA1-binding, also named RPA70N-binding) motif mediates interaction with RPA1 (PubMed:27601467, PubMed:27723720, PubMed:27723717). The RBM2 (RPA2-binding, also named RPA32C-binding) motif mediates interaction with RPA2 (PubMed:27601467, PubMed:27723720, PubMed:27723717)
The ATR-activation domain (AAD) motif is required to bind and activate ATR (PubMed:27723720, PubMed:27723717)
Mutagenesis of amino acids 147 to 164 and 155 to 164 lead to a major cytoplasmic localization, with only minor localization in the nucleus
The DWD box is required for interaction with DDB1
The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins) (PubMed:30948426). Both motifs are required for binding and activation of alpha subunits (PubMed:30948426)
Possesses a two-domain structure consisting of an N-terminal ATPase domain belonging to the AAA(+) superfamily and a C-terminal protease domain. The ATPase domain likely acts as a molecular chaperone functioning in the unfolding of protein structures, along with ATP hydrolysis
The N-terminal WD repeats are involved in ubiquitin-binding
The first seven ANK repeats at the N-terminus (1-242) are essnetial for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons
The 330-DSEL-333 motif is involved in the recycling of PTGDR2 to the cell surface after agonist-induced internalization. This motif seems to be required for GRK2 and GPRK5/GRK5 to promote agonist-induced internalization. Thr-347 is a major site for PKC-induced internalization of the receptor
The atypical PHD domain functions as a negative modulator of cofactor binding
Contains a basic DNA-binding region at the N-terminus which is usually found in bZIP transcription factors, but does not contain the characteristic leucine zipper domain (PubMed:25058475). Instead, four C-terminal ankyrin repeats were identified that were shown to confer protein-protein interaction of regulatory proteins (PubMed:25058475)
The fungal-differentiation regulator (Fungal-DR) domain is only found in fungal regulator of G-protein signaling (RGS) proteins that regulate differentiation pathways. It is required for function
The extracellular domain is necessary for conferring apical characteristics on the salivary gland membrane (PubMed:24718992). Necessary for regulating salivary gland membrane expansion and tube length, but is not required for cell rearrangement during tube elongation (PubMed:24718992). Sufficient to promote the outgrowth of follicle cell microvilli and the formation of microvilli bundles (PubMed:16260500, PubMed:24718992) Sufficient to promote formation of microvilli-like structures in the salivary glands and the follicle cell microvilli bundles (PubMed:16507588, PubMed:24718992). Dispensable for apical localization (PubMed:24718992)
The cytoplasmic domain is necessary for the formation of uracil-induced endosomes
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain (By similarity)
The N-terminal S1 motif binds RNA, and can also bind single-stranded DNA (in vitro). The C-terminal region interacts with the other degradosomal components
Contains a C-terminal autotransporter domain that integrates into the outer membrane and enables the translocation of the catalytic N-terminal domain to the bacterial cell surface
The EAL domain is required for c-di-GMP PDE activity, and the degenerate GGDEF domain is required for full PDE activity of the EAL domain (PubMed:18227161). The GG(D/E)EF motif in CdpA is degenerate, having the sequence GVGEW
The propeptide is required for multimerization of vWF and for its targeting to storage granules
The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2
The C-terminal region contains a general transcription activation domain. The N-terminal region, comprising a basic and a Gln-rich domain, confers transcriptional potency and specificity by mediating association with the MADS box of SRF. The basic domain may be required for nuclear localization. The SAP domain is important for transactivation and ternary complex formation (By similarity)
Two regions important for regulation and RNA-binding are found in the N-terminus (residues 2-7) and middle (residues 40-47). Both are part of the intercalated beta-strands that form the hydrophobic core of the protein; region 1 from one monomer contacts region 2 of the other. The homodimer has 2 distinct RNA-binding regions on opposite, solvent-exposed surface of the protein
The C-terminal 33 residues are required to neutralize cognate toxin VapC2 (PubMed:27672196)
The PH and FYVE domains may be important for TNF-induced localization to the endoplasmic reticulum and for enhanced cellular sensitivity to TNF-induced apoptosis. The FYVE domain is important for binding to the endosomal membrane (By similarity)
Neither ATP binding nor ATP hydrolysis is required for SSZ1 function
Does not seem to bind unfolded protein substrates, as its C-terminal putative peptide-binding domain is not required for its function
The ATG8 interaction motif (AIM) mediates interaction with proteins of the ATG8 family including GABARAP
The Kelch repeats mediate interaction with TIAM1, a CUL3(KBTBD6/7) E3 ubiquitin ligase substrate
The UIM domains specifically bind 'Lys-48'-linked ubiquitin polymers (PubMed:18467495, PubMed:26876100). The UIM domains mediate interaction with polyubiquitinated proteins (PubMed:18467495, PubMed:26337389)
This glycosomal PGK has a C-terminal extension of 38 AA which is not present in the cytosolic isoenzyme. This domain most likely serves as topogenic signal to direct the glycosomal PKG to the glycosome
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. NRPS9 has a reduced A-T architecture
Contains 3 N-terminal periplasmic polypeptide transport-associated (POTRA) domains and a C-terminal 16-stranded beta-barrel transmembrane region. The beta-barrel is closed on the extracellular face by loop 6 (residues 456-495), while the C-terminal beta-strand forms an inward kink which may act as a gate for substrate access from the periplasm. This kink weakens the beta-strand pair between the first and last strands which may contribute to gating and substrate translocation
The DMAP1-binding domain mediates substrate recognition. It specifically recognizes a conformation-dependent protein determinant present in acid hydrolases
Recognizes phosphatidyl serine via its epidermal growth factor-like domains
Has the canonical dEER motif, but lacks translocation RxLR motif, which characterizes most oomycete effectors identified so far
The beta-propeller contains long interblade connector loops, and mediates interaction with DDX19B
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which may be required for an association with nuclear receptors
The coiled-coil domain mediates interaction with MAP3K4 and inhibition of AXIN1-mediated JNK activation through MAP3K4
The DIX domain mediates interaction with AXIN1 and inhibition of AXIN1-mediated JNK activation through MAP3K1. Mediates interaction with DVL2; this interaction is required for activation of Wnt signaling
This cytosolic PGK lacks a C-terminal extension of 38 AA which is present in the glycosomal isoenzyme
Intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of cleavage by inflammatory caspases CASP1 or CASP4/CASP11 (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:29576317, PubMed:31097341). The linker helix loop inserts into the N-terminal domain (By similarity). The intrinsic pyroptosis-inducing activity is carried by Gasdermin-D, N-terminal, that is released upon cleavage by inflammatory caspases (PubMed:26375003, PubMed:26375259, PubMed:26611636)
Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane. The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation
Contains about 100 repeats of the sequence DGENNQ or DGGENNQ
The PH domain binds the small GTPase ARF1 and phosphatidylinositol-4-phosphate (PtdIns4P) with high selectivity, and is required for its recruitment to the trans-Golgi network (TGN)
Has 3 domains; a discontinuous peripheral domain (P, 13-39, 76-133, 221-254), an elongated loop (E, 53-73) and the discontinuous axial domain (A, 137-216 and 259-263). The E-loop forms contacts between two subunits, while the A domain mediates contacts in the 5-fold interface (PubMed:19172747). Pores are formed by residues 184-189, pore size can be modified by mutagenesis (PubMed:30376298, PubMed:33769792)
The TAP-C domain (also known as UBA domain) mediates the interaction with Panx
The RIIa domain mediates interaction with AKAP3
(Microbial infection) The TIR domain is structurally mimicked by the TIR domain of B.melitensis protein TcpB
The RUN domain is required for the interaction with RAB1A and RAB1B
The DOCKER domain is necessary for the GEF activity. The DOCKER domain mediates interaction with activated CDC42 in conjunction with residues 66-126
The homeobox DNA-binding domain is necessary for its nuclear localization, transcriptional and erythroid differentiation activities (PubMed:14671321)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase. AcrB has the following architecture: C-A-T-TE
Repression domain 1 (RD1) is involved in transcriptional repression (PubMed:11062467, PubMed:30599067). RD1 is necessary for its interaction with PML (PubMed:22002537)
Both the DNA unwinding and positive supercoiling activities require the cooperation of both domains. The cooperative action between the helicase-like and the topoisomerase domains is specific. The helicase-like domain probably does not directly unwind DNA but acts more likely by driving ATP-dependent conformational changes within the whole enzyme, functioning more like a protein motor. The 'latch' region of the N-terminal domain plays a regulatory role in the enzyme, repressing topoisomerase activity in the absence of ATP and therefore preventing the enzyme from acting as an ATP-independent relaxing enzyme; it also helps to coordinate nucleotide hydrolysis by the ATPase domain with the supercoiling activity of the topoisomerase domain (By similarity)
The PHD-type zinc finger mediates the binding to H3K4me2 and H3K4me3
The N-terminal section (alone) shows no toxic effect when injected into the host. This section may function in stabilizing the catalytic part of the protein, or in directing it to specific target sites of action (PubMed:19320760)
A C-terminal domain (245-347) is required for dimerization
The first RRM (RNA recognition motif) domain is essential for binding to AU-rich elements
Contains a remarkable run of alternating Gly-Thr residues which is polymorphic in length. At least three types of Gly-Thr length exist in the natural population, (Gly-Thr)23 (shown here), and two major variants (Gly-Thr)17 and (Gly-Thr)20. This Gly-Thr stretch is implicated in the maintenance of circadian period at different temperatures. Deletion of the repeat leads to a shortening of the courtship song cycle period, and thus could be important for determining features of species-specific mating behavior
Mutations in the PAS domain result in longer circadian rhythms and courtship song (PERL mutation) or makes the flies arrhythmic (PER01 mutation)
Residues at positions 150 and 232 are important for type of reaction catalyzed, using identical substrate (PubMed:29317628). Both ausE and prhA accept preaustinoid A1 as a substrate to form divergent products through dynamic skeletal rearrangement. AusE (containing Leu-150 and Ser-232) first desaturates at C1-C2 to form preaustinoid A2,followed by rearrangement leading to the formation of the spiro-lactone in preaustinoid A3 (PubMed:29317628). In contrast, prhA (containing Val-150 and Ala-232) first desaturates at C5-C6 to form berkeleyone B, followed by rearrangement of the A/B-ring to form the cycloheptadiene moiety in berkeleydione (PubMed:29317628)
The cytosolic domain is involved in S100A9 interaction
The cysteine framework is C-C-C-C-C-C-C-C-C-C-C-C
The second PHD-type zinc finger mediates binding to histone H3K4Me3
The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another rad50 molecule, thereby forming a V-shaped homodimer
Contrary to other WD repeat Groucho/TLE family members, does not contain any identifiable Q, GP, CcN or SP domains. Only the C-terminal WD-repeat domain is conserved
The first Ig-like domain is necessary for localization to the primary synapse region of HSNL motor neurons
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of smc-6, forming a V-shaped heterodimer
The proline stretch works as a part of the transcriptional activation domain
The SH3 domain mediates interaction with SHANK2, SHANK3 and PRAM1
The carbohydrate binding module (CBM) binds to insoluble beta-1,3-xylan, but not to insoluble beta-1,4-xylan, beta-1,4-glucan, beta-1,4-mannan, curdlan, chitin, or soluble polysaccharides
Multidomain protein in which the components of the entire signal transduction cascade for SigF regulation appear to be encoded in a single polypeptide. Contains an N-terminal PAS sensor domain, followed by an adjacent PAC (PAS domain-associated C-terminus) region, a phosphatase domain, an anti-sigma factor kinase domain, and a C-terminal anti-anti-sigma factor domain (or substrate domain) (Probable). Phosphorylation at Ser-600 leads to a change in the overall shape of the dimer (PubMed:19700407)
The PX and BAR domains mediate association with membranes and are required for membrane tubulation
LIM domains are necessary for transcription activation
Deletion of amino acids 30-164 allows induction of NO reductase activity even in the absence of NO, i.e. the need for an NO-induced signal has been bypassed
The extracellular and guanylate cyclase domains are essential for chemosensory responses
The LEM domain is required for GIY-YIG domain-mediated DNA cleavage and induction of DNA damage response
The C-terminal domain (318-476) binds to actin
Contains two carnitine binding sites, a primary binding site at the center of the protein and a secondary binding site at the bottom of the intracellular vestibule (PubMed:20357772). Contains two gamma-butyrobetaine binding sites, one in the central transport site, the other in an extracellular binding pocket (PubMed:20829798). Binding of both butyrobetaine molecules is cooperative, indicating that the extracellular site is regulatory (PubMed:20829798). The occupied regulatory site may increase the binding affinity of the transport site and initiates substrate translocation (PubMed:20829798). Both L-carnitine and gamma-butyrobetaine are able to dissociate completely from their primary site into the cytoplasm (PubMed:22843728). Substrate molecules initially located at the secondary sites dissociate even faster into the extra- or intracellular regions (PubMed:22843728)
The CSD domain is required for function in muscle differentiation
The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members
The channel is composed of 4 repeated units, each containing a transmembrane pore part and a gating ring part. The gating ring is composed of eight identical RCK (Regulators of K conductance) domains, in an alternating arrangement of one domain from each of the four subunits and four from the intracellular solution. Two protein interfaces between dimers of RCK domains from the pore-forming subunit and from the intracellular solution hold the ring together. One is called the fixed interface and the other the flexible interface. The flexible interface forms a cleft where calcium binds. Upon calcium binding the gating ring undergoes a conformational change that enables it to pull open the inner helices of the pore, allowing ion conduction
The TPR region (103-213) is necessary for interaction with HSP70-1 while the linker domain (214-530) facilitates selective recognition of chloroplast precursor complexes
C2H2-type zinc finger 4 is a ubiquitin-binding zinc finger (UBZ) and required for polyubiquitin binding, possibly binding the proximal ubiqutin, and for catalytic activity (PubMed:29576528) (Probable). C2H2-type zinc fingers 1-3 are required for localization to sites of DNA damage (PubMed:29576528)
U-box 1 is critical to the ubiquitin ligase activity, and U-box 2 mediates interaction with host CLK1
The 25 C-terminal region may carry the signal responsible for translocation into the host cell
The coiled-coil domain is required for the induction of autophagy during endoplasmic reticulum (ER) stress
The RING-type zinc finger is required for auto-polyubiquitination
The PX domain mediates interaction with membranes enriched in phosphatidylinositol phosphate. Has high affinity for phosphatidylinositol 4,5-bisphosphate, but can also bind to membranes enriched in other phosphatidylinositol phosphates
The GSGFP motif is required for the interaction with SUZ12 (PubMed:20064375). The ARID domain specifically binds to the CCGCCC motif and is required for the lysine-specific histone demethylase activity. The PHD-type 3 zinc finger is required for the interaction with histone H3 di- and trimethylated at 'Lys-4' (By similarity)
The Ras-associating domain is necessary for the Rap guanine nucleotide exchange activity. The N-terminal regionis necessary for cAMP-binding. The PDZ domain is necessary for its targeting to the cell membrane
The LIR motifs (LC3-interacting region) are required for its interaction with lgg-1 and lgg-2
Contains a deeply buried active site and two entrances from the surface of the protein into the active site
Four regions are important for the activity: the C-terminal loop, the last three C-terminal residues, the stretch of seven N-terminal residues and residues 8-9 are necessary for the antifungal activity and dispensable for antibacterial activity
The longin domain is essential for the vacuolar and subcellular targeting
The first 14 N-terminal residues form the YfgM degron, which directs the protein to FtsH for proteolysis
The C-terminus (270-280) is essential for tRNA binding and processing activity
The length of the linker region between residues 387-394 which separates two alpha-helices regulates the size of the glycogen particles synthesized but plays no role in the interaction with gsy-1
The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12
The N-terminal FAP motif (residues 11 to 13) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates
The heat repeats and the C-terminal domain are necessary for impairing GCN1 function on ribosomes, and hence preventing GCN2 kinase activity in amino acid-starved or repleted cells (PubMed:22888004)
The acidic C-terminal extension is essential for the cell cycle function
The C4-type zinc finger mediates a competitive interaction with UFSP2 and ligand-bound nuclear receptors. It also mediates interaction with the transcriptional coactivators and the basal transcription machinery
The N-terminal coiled-coil domain is required for both nuclear pore complex (NPC) and spindle matrix localization
The C-terminal domain is required for interchromosomal localization during interphase (PubMed:15356261). The C-terminal domain is sufficient for localization to the nuclear lamina as well as for spindle localization (PubMed:15356261)
N-terminal residues are not required for inhibitory activity
Probably exists in a closed and an opened conformation due to interaction of the C-terminal RAB-binding domain (RBD), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, with the N-terminal calponin-homology (CH) domain. The conformational change is regulated by RAB13 and may modulate MICALL1 interactions with functional partners (By similarity)
The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity
The C-terminal B30.2/SPRY domain interacts with the first N-terminal CARD domain of RIGI
One-module-bearing peptide synthase with a C-terminal epimerization domain. Each module incorporates one amino acid into the peptide product and can be further subdivided into domains responsible for substrate adenylation, thiolation, condensation (not for the initiation module), and epimerization (optional), and N methylation (optional)
The first two EGF domains mediate the interaction with DAF. A third tandemly arranged EGF domain is necessary for the structural integrity of the binding region (By similarity)
The protein has mostly an alpha helical conformation similar to myosin heavy-chain tail that might adopt a coiled-coil conformation
The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin) (PubMed:27411375)
The cytoplasmic N-terminal domain is important for ArgO function in vivo, but not the periplasmic C-terminal region. A pair of conserved aspartate residues, located near the opposing edges of the cytoplasmic membrane, may play a pivotal role in facilitating transmembrane arginine flux
The C-terminal cytoplasmic domain plays a significant role in normal function and it might also mediate co-operativity between the three subunits (PubMed:17453422). The C-terminal cytoplasmic domain is also required for interaction with the T-loop of GlnK (PubMed:11847102, PubMed:17190799)
The N-terminal region contains three independent domains that are capable of mediating transcriptional repression (RD1, RD2 and RD3)
The C-terminal region contains two separate nuclear receptor-interacting domains (ID1 and ID2), each of which contains a conserved sequence referred to as the CORNR box. This motif is necessary and sufficient for binding to unligated nuclear hormone receptors, while sequences flanking the CORNR box determine the precise nuclear hormone receptor specificity (By similarity)
Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain. NC1 domain mediates hexamerization of alpha chains of type IV collagen (By similarity)
Adopts the classical GT-B fold containing the N-terminal and C-terminal domains that accommodate the sugar acceptor and UDP-glucose, respectively (PubMed:33310191, PubMed:33152360). The spacious sugar-acceptor binding pocket might be responsible for the broad substrate spectrum (PubMed:33310191)
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC2, forming a V-shaped heterodimer
The DPW repeat domain is involved in AP2A2 and clathrin binding
The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction with the AP-2 complex subunit AP2B1
The joining helix is required for stability of the light-adapted state
Contains a defective C-terminal cyclic-di-GMP phosphodiesterase EAL domain, which lacks key amino acids required for phosphodiesterase activity. Restoration of consensus amino acids in the degenerate EAL domain does not restore phosphodiesterase activity and reduces ability to antagonize BluR
RI-alpha binding site, predicted to form an amphipathic helix that is required for binding to Prkar1a
The C2 and the RGS domains are both required for its inhibitory effect on G-protein signaling
The N-terminal disordered part (1-148) binds unspecifically dsDNA and expands the binding and moving range of CGAS on dsDNA (By similarity). The disordered and positively charged residues enhance CGAS-DNA phase separation by increasing the valencies of DNA-binding. The N-terminus is required to sense chromatin and its phosphorylation blocks its activation by chromatin DNA (By similarity). When the N-terminal part (1-148) is missing the protein bound to dsDNA homodimerizes (By similarity)
The N-terminal acidic repeat region mediates, in part, the glycosaminoglycan-accelerated thrombin inhibition
Consists of three main regions, an N-terminal coiled-coil domain (residues 1-96) that binds to protein Pup and functions as a docking station, an interdomain (residues 97-245) involved in Mpa hexamerization, and a C-terminal ATPase domain of the AAA type (residues 246-609)
The coiled coil region mediates dimerization
Contains a unique periplasmic sensor domain (SD) and lacks a cytoplasmic linker domain between the second transmembrane helix and the dimerization and histidine phosphotransfer (DHp) domain, indicating that this system may utilize a potentially unique signal sensing and transmission mechanism (PubMed:33753465). Detection of the signal via the periplasmic sensor region may induce conformational changes of the dimer and close the transmembrane helices TM1 and TM2 and subsequently the cytoplasmic DHp domains in a scissor-like mechanism, which changes the activation status of kinase domains (PubMed:33753465)
Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal (PubMed:26375003). The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain (PubMed:26375003)
Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane (PubMed:33883744). The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744)
Two regions, an N-terminal (aa 96-107) and a C-terminal (aa 274-311) are required for binding FGF2
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full-length protein (By similarity)
Interaction of FYVE-type domain with phosphatidylinositol 3-phosphate (PtdIns(3)P) is necessary for targeting to the membranes of the late endocytic pathway
The kinesin motor domain binds to microtubules with high affinity and has a robust ATPase activity but a very slow motility. The kinesin motor domain protects microtubules from cold depolymerization. Binds to each tubulin heterodimer resulting in a microtubule complexes. Binds at the tubulin intradimer interface, at the crest of the protofilament, and orients slightly toward the next protofilament
Contains an N-terminal DNA-binding domain, a linker region and a C-terminal effector binding domain. Dimerization is mediated via the C-terminal domain
Consists of three domains. The N-terminal dimerization domain has the same fold as the IIA domain of the mannose transporter of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS). The middle domain is similar to HPr and the C-terminus is similar to the N-terminal domain of enzyme I (EI) of the PTS. The IIA domain of DhaM (via phospho-His-9), instead of ATP, is the phosphoryl donor to dihydroxyacetone (Dha). The phosphoryl flow likely involves HPr ('His-15') -> DhaM (His-432 -> His-170 -> His-9) -> DhaL-ADP -> Dha. The HPr-like domain of DhaM cannot efficiently substitute for the general carrier protein HPr
Contains a small N-terminal 3-helix bundle domain and a large C-terminal TPR domain, connected by a linker region (PubMed:22215984, PubMed:23526880). The 3-helix bundle domain and the linker region form the ComA binding surface (PubMed:22215984, PubMed:23526880). A RapF surface mimics DNA to block ComA binding to its target promoters (PubMed:22215984). Interacts with PhrF via the TPR domain (PubMed:23526880)
The SOCS domain mediates the interaction with ELOB and ELOC, while the NHR domain may be involved in ubiquitination substrate binding
Two helices (H2 and H8) are predicted to insert into membranes and form pores by assembling into tetramers. The helices are contained within a helical bundle domain that undergoes significant conformational changes during pore formation to allow exposure of the transmembrane helices and transition of the toxin from a soluble monomer to a transmembrane tetramer
The protein kinase active site is incompatible with ATP binding and is inactive (PubMed:26455797)
The C-terminus (351-372) is required for interaction with COP1 (PubMed:27041596)
The COP1-binding motif (355-360) is required for regulation activity (By similarity)
The MYND-type zinc finger is essential for the ubiquitin-dependent degradation of RPN4
Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds
The tight homhexamer forms an irregular pore with an opening about 4.8 X 6.5 Angstroms
the ligand-binding domain (LBD) contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. NR4A2 lacks a 'classical' binding site for coactivators (By similarity)
Contains 2 sites/pockets that bind histamine with different affinities. Site H (high affinity) is indicated here as binding to histamine 1, and site L (low affinity) is indicated as binding to histamine 2
Forms a U-shaped beta-half-barrel with a small hydrophobic cavity (933 Angstroms(3)) which is large enough to hold a single diacylated glycolipid molecule
Has 2 BMC domains which can evolve independently of each other (Probable). Two ethanolamine molecules bind in the interface between these 2 domains. Ethanolamine 1 binds on the cytoplasmic side, while ethanolamine 2 binds on the lumenal side of the BMC (PubMed:25752492)
Lacks a cytoplasmic PDZ-binding motif, which has been implicated in function of related LRFN proteins
The ubiquitin-like domain mediates interaction with MJD
The Asp-Asp-Xaa-Xaa-Glu (DDXXE) motif is important for the catalytic activity, presumably through binding to Mg(2+)
N-terminal zinc-fingers recognize and bind to the consensus Ikaros target site (5'-GGGA-3'), found in the promoter regions of immunologically relevant genes
C-terminal zinc fingers mediate homodimerization and heterodimerization
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. Hkm10 contains an amino acid adenylation domain (A), a peptidyl carrier protein (PCP) domain with a phosphopantetheine prosthetic group, and a short-chain dehydrogenase/reductase terminus (R), but it does not have an identifiable condensation (C) domain required for the formation of peptide bonds during non-ribosomal peptide synthesis
The rod domain contains six 100-residue motifs that appear to have a cross-beta conformation
2 residues (Tyr-73 and Arg-76) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
Consists of two related domains. The catalase-peroxidase activity is associated with the N-terminal domain but no definite function has been assigned to the C-terminal domain, although it may play a role in substrate binding
The isolated charged lumenal magnetite-interacting component (MIC, residues 298-314) binds Fe(2+)
Amino acids 31-34, 96-99 and 246-249 are necessary for interaction with the Importin alpha/Importin beta receptor. The first 18 amino acids, amino acids 69-76 and 179-182 are necessary for interaction with TNPO3. Amino acids 31-34, 96-99 and 246-249 are necessary for nuclear localization (By similarity)
Each monomer contains 2 structurally homologous domains with high sequence similarity connected by a short five-amino acid residue linker. Intriguingly, a water-filled channel is observed between the 2 monomers
The N-terminus has several structural domains; the ATPase domain (about residues 1-265), the transducer domain (about 266-428) and the toprim domain (455-572) (PubMed:25202966). Comparing different structures shows ATP hydrolysis induces domain shifts in the N-terminus that are probably part of the mechanism of DNA cleavage and rejoining (PubMed:25202966)
AtaP has the domain architecture (T1-C1-A1-T2-C2) (PubMed:23586797). The single adenylation (A) domain in ataP suggests that one specific substrate, L-Phe, is loaded onto the T (carrier) domains of ataP (PubMed:23586797)
The molecule is in a coiled coil structure
Binding of RbcS probably induces a conformation change that displaces RbcX2 and triggers the final mature conformation
Has an FMN-binding N-terminal domain (NTD), an FAD-binding C-terminal domain (CTD), and a 4Fe-4S cluster between the two domains. CTD is the main contributor to the iron-reduction activity, and NTD and the 4Fe-4S cluster are not directly involved in such activity
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (330-360) inactivates kinase activity under calcium-free conditions
Peptide exit pores open in the compressed state; in this conformation the active site residues move apart and the protease cannot be active
Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-305) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation (By similarity)
In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif (5'-ATGAAAT-3')
The N-terminal domain (1-265) is necessary for binding to KU80
The C-terminal part (169-201) is essential for male fertility and correct chromatin compaction in mature sperm
This protein differs from the typical myosin heavy chain structure in having head and tail domains but no discernible neck domain
The N-terminal domain (1-205) is necessary and sufficient for proper localization and function of this protein, and for its interaction with MmpL3
The N-terminal part (residues 1 to 452) is intrinsically disordered but moderately compact and is able to demixe into liquid droplets at concentrations far below its concentration in cytokinesis organizing centers (also called nodes); these physical properties are appropriate for scaffolding other proteins in nodes (PubMed:31243991). The N-terminus has the ability to associate faintly with the medial cortex and is sufficient to form tight rings (PubMed:15572668, PubMed:22427686). This domain is responsible for oligomerization that may contribute to the activity of mid1 as a scaffold for other proteins in cytokinetic nodes and contractile rings (PubMed:22918954)
The C-terminus contains a cryptic lipid-binding C2 domain and a PH domain, and is involved in the anchorage to membranes, which stabilizes cytokinetic ring position
The nuclear localization sequence (NLS) is required for nuclear import, whereas both leucine-rich nuclear export sequences NES1 and NES2 are required for nuclear export
Helix VIII may act as a gatekeeper for either suppression or activation of the receptor, depending on post-translational modifications and interactions with various receptor partners. Helix VIII is found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G-proteins or beta-arrestins. Upon switching to a membrane-bound conformation, helix VIII can support the recruitment of G proteins and beta-arrestins
Intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of cleavage by inflammatory caspases CASP1, CASP4 or CASP5 (PubMed:26375003, PubMed:29898893, PubMed:28928145, PubMed:29576317). The linker helix loop inserts into the N-terminal domain (PubMed:28928145). The intrinsic pyroptosis-inducing activity is carried by Gasdermin-D, N-terminal, that is released upon cleavage by inflammatory caspases (PubMed:26375003)
Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane (PubMed:33883744). The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18) (PubMed:33883744). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744)
The Ras-associating domain plays a central role in the activation of Ral-A GDP/GTP exchange activity
The C-terminal domain interacts with lipid membranes containing acidic phosphoinositides and is required for location at the midbody
The MIT domain interacts with the MIT-interacting motifs of several components of the ESCRT-III complex
DNA-binding occurs via the first 2 N-terminal domains, which are also responsible for ATPase
The central region (432-645) which is structurally composed of 2 domains (432-500 and 501-645) is necessary for helicase activity
The C-terminal region (646-704) inhibits ATPase and helicase activity
Recognizes the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex substrate, PIK3R1, through the 4 tandem C-terminal Kelch domains
Consists of two globular domains connected by a flexible linker. ATP binds in a cleft at the interface between the N- and C-terminal domains and its binding induces significant local conformational changes
Interacts with EnvZ through its soluble periplasmic region
The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion
The DIX domain mediates interaction with dixdc1
Possible isomerization of Pro-334 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA
The SAP domain is necessary for binding to the stem-loop structure of histone mRNAs and to form the ternary complex with SLBP, but not for 3'-end histone mRNA exonuclease activity
The N- and C-terminal halves of this hexokinase contain a hexokinase domain. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus
The presence of the HAMP domain is required for dimerization and catalysis
The C-terminal region is necessary for the channel activity stimulation
Contains about seven structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a superhelical structure with a solenoid shape (By similarity)
Belongs to monofunctional group I BPL as it lacks the N-terminal helix-turn-helix (HTH) DNA-binding domain
The regulatory domain (RS) also called auto-inhibitory domain (AID) inhibits kinase activity of the protein kinase domain (KD) (PubMed:19474788)
The chaperone-containing TCP1 (CCT) domain is essential for the interaction with the scaffold protein VAC14
Contains five HAMP domains, three at the N-terminus and two at the C-terminus, separated by a PAS-sensing domain (PubMed:20399181). The PAS domain binds penta-coordinated b-type heme and is likely responsible for sensing the gases (PubMed:21255112, PubMed:28167524). Binding of oxygen induces conformational changes in the PAS-heme domain (PubMed:34383467). The N-terminal HAMP domains facilitate the O(2)-dependent shift of PAS to the signal-on conformation (PubMed:34383467). Signals propagate from the PAS domain to the C-terminal HAMP domains via a conserved DxT motif (PubMed:34383467). PAS and HAMP domains do not directly interact but are arranged in a linear fashion (PubMed:23274111)
The box 1 motif is important for association with JAKs
The proline-rich region is not required for host mitochondrial association (HMA)
Gln-208 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The PMEI region may act as an autoinhibitory domain and prevent untimely PME activity during transport. The PMEI region is cleaved by SBT6.1 (S1P) in the Golgi apparatus prior to cell wall targeting
The N-terminus binds DNA, the C-terminus (residues 83-239) is responsible for dimerization (PubMed:9388199). The C-terminal domain binds acyl-CoA (PubMed:7836365, PubMed:11296236)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (345-375) inactivates kinase activity under calcium-free conditions (By similarity)
The POU domain controls nuclear translocation
The Death domain mediates the interaction with PIDD1 and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn probably recruit 7 CASP2 to form the PIDDosome (PubMed:17289572). The Death domain mediates a direct interaction with the Death domain of RIPK1 (PubMed:9044836)
The CARD domain mediates a direct interaction with CASP2
Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains. The KxGQ motif completely occludes the typical substrate binding pocket. Nucleotide-binding opens the substrate binding pocket and flips the active site from inside the hydrophobic core into a catalytically competent, solvent-exposed posture
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissembling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis
Composed of one catalytically active A module and one R module
The active site is important for FtsI localization
Lacks a classic transcription activation domain and instead possesses an N-terminal region capable of inhibiting heterologous activators
The C-terminal CBM-CenC domains mediate the binding of XynA to microcrystalline cellulose. CBM-CenC 2 alone can also promote cellulose binding (By similarity)
The N-terminal domain (residues 1-62) is required for interaction with SocA and targeting of SocB for degradation by ClpXP
The PDZ-binding motif is required for TLE4-binding
The Grh/CP2 DB domain is required for direct DNA-binding (PubMed:26906118). The Grh/CP2 DB domain is essential to maintain the undifferentiated state of embryonic stem cells (By similarity)
The SAM-like domain is required for homohexamerization (PubMed:26906118)
The C-terminal evolutionary conserved domain (ECD) contains poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent with structural docking models revealing two highly scored poly-Gln-binding pockets in the ECD (By similarity). As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3 (By similarity)
A central prokaryotic signal-sequence-like domain may be used to export the protein to the chloroplast envelope after import into the stroma
The peripheral subunit binding domain (PBSD), serves as a selective binding site for other domains of the E1 and E3 subunits
The C-terminal catalytic domain catalyzes the transfer of acetyl groups and acetyl-CoA synthesis
The loop element facing inside the core cavity formed by residues Val-405 to Trp-420 is potentially critical for the organization of the PDH complex core scaffold
The SEC7 domain is sufficient for stimulation of nucleotide exchange on myristoylated yeast ARF2
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 131 and 155
The PPIase activity resides only in the second parvulin domain. The N-terminal region and the C-terminal tail are necessary and sufficient for the chaperone activity of SurA. The PPIase activity is dispensable for SurA function as a SurA protein with a deletion of the parvulin domains is almost completely functional in vivo. The N-terminal region and the C-terminal tail are also required for porin recognition
Domain I contains three cation-binding sites: the ligand-integrin-binding site (LIMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent to MIDAS site (ADMIDAS). In the absence of a ligand or in calcium-dependent binding, only ADMIDAS is occupied. In magnesium-dependent binding all three sites bind metal ions. LIMBS positively modify ligand binding whereas ADMIDAS negatively modify ligand binding
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family protein GABARAPL1
The C-terminal CBM20 domain is required for the interaction with glycogen and glycogen-associated proteins
The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization (PubMed:17560374). The second BIR domain is sufficient to inhibit CASP3 and CASP7, while the third BIR is involved in CASP9 inhibition (PubMed:11257231, PubMed:12620238). The interactions with DIABLO/SMAC and HTRA2/PRSS25 are mediated by the second and third BIR domains
The cytoplasmic domain appears to play a critical role in proapoptosis and tumor suppressor activity in NSCLC
Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain. NC1 domain mediates hexamerization of alpha chains of type IV collagen (PubMed:22842973)
Forms a 10-stranded antiparallel beta-barrel structure able to accommodate a hydrophobic ligand in its interior (Ref.4). In fact, this fold hosts the heme group, which is located in a wide surface cleft (PubMed:32295384)
The N-terminal region (1-20) is the minimal region necessary for ubiquitination and further proteasomal degradation
The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24171105). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (By similarity). The activating sterol is likely to be cholesterol (By similarity). The extracellular site is required for shh-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of shh (By similarity)
The monomer consists of a 16-stranded antiparallel beta-pleated sheet barrel (171 residues), three short alpha-helices (18 residues) and 13 hydrogen-bonded reverse turns (26 residues)
The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself. The WXXF motif 1, which is preceded by an acidic residue and has a glycine in second position mediates specific interaction with AP-1. The WXXF motif 2, which is followed by the C-terminal carboxyl group negative charge, allows specific interaction with AP-2 (By similarity)
Binds to WAS within the N-terminal region 170, at a site distinct from the CDC42-binding site
The TEK-boxes are required for 'Lys-11'-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue
The SPOR domain is dispensable for cell division, but it consolidates the position of FtsN at the cell division site and the cell pole
the N-terminal beta-strand formed by residues 99-104 is essential for the function
The three two-fingered repeats tightly encircle spi, providing the basis for it's sequestration. The first repeat harbors a 120 AA insert specific to drosophilidae
The 9aaTAD motif (residues 261 to 269) is a transactivation domain present in a large number of yeast and animal transcription factors
The cysteine framework is CC-CC-C-C-C-CC-C-C-C-C
Consists of two distinct domains: a typical methyltransferase domain and a unique substrate binding domain
The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity (By similarity). The TIR domain alone is active and (slowly) produces 2'cADPR (PubMed:36048923)
It is unknown whether the acidic chain located at the N-terminus is functional or whether it represents a propeptide
The NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding
The C6H2-type zinc finger recruits ZNG1, promoting zinc cofactor transfer in the peptidase domain of METAP1
Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds
Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR
Comparison of drug-sensitive and drug-resistant protein structures shows the active site is highly flexible
Has 2 endonuclease domains. The discontinuous RuvC-like domain (approximately residues 1-62, 718-765 and 925-1102) recognizes and cleaves the target DNA noncomplementary to crRNA while the HNH nuclease domain (residues 810-872) cleaves the target DNA complementary to crRNA (PubMed:22745249, PubMed:24529477)
Has a bilobed architecture with a recognition lobe (REC, residues 60-718) and a discontinuous nuclease lobe (NUC, residues 1-59 and 719-1368) (PubMed:24529477, PubMed:24505130). The crRNA-target DNA lies in a channel between the 2 lobes (PubMed:24529477, PubMed:26841432). Binding of sgRNA induces large conformational changes further enhanced by target DNA binding (PubMed:26113724, PubMed:26841432). REC recognizes and binds differing regions of an artificial sgRNA in a sequence-independent manner. Deletions of parts of this lobe abolish nuclease activity (PubMed:24529477)
The PAM-interacting domain (PI domain, approximately residues 1099-1368) recognizes the PAM motif; swapping the PI domain of this enzyme with that from S.thermophilus St3Cas9 (AC Q03JI6) prevents cleavage of DNA with the endogenous PAM site (5'-NGG-3') but confers the ability to cleave DNA with the PAM site specific for St3 CRISPRs
The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats
Binds calcium, probably via its EF-hands
The KRAB domain is required for function as transcriptional repressor
Zinc fingers 2 and 3 mediate recognition of the target element, ZF2 interacting with the 5' half (TGC) and ZF3 interacting with the 3' half (CGC)
Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (By similarity). Its contribution to the mechanism confering the myosin movement on actin filaments is debated (By similarity)
The death domain mediates interaction with RANBP9 (By similarity). It also mediates interaction with ARHGDIA and RIPK2 (PubMed:26646181)
The extracellular domain is responsible for interaction with NTRK1
The glycoprotein is arranged on a p6 lattice with a lattice constant of 16.8 nm. It forms 4.5 nm high, dome-shaped, morphological complexes with a narrow pore at the apex opening into a 'funnel' towards the cell membrane (PubMed:16453843)
A short peptide sequence (termed the Stachel sequence) in the C-terminal part of the extracellular domain (ECD) functions as a tethered agonist. Upon structural changes within the ECD, e.g. due to extracellular ligand binding or mechanical movements, this intramolecular agonist is exposed to the 7 transmembrane region, triggering G-protein activation
The apo form can adopt multiple conformations (PubMed:22365933). The beta5-alpha11 loop near the active site is a flexible region that can adopt a variety of conformations in the acylated state of PBPA and appears important for acylation (PubMed:22365933)
PEST motif is known to mediate rapid protein degradation
The PDZ domain probably binds peptides ending with C-terminal Tyr-X-Phe sequences, which activates proteolysis. In the absence of OMP peptides the PDZ domain inhibits peptidase activity (By similarity)
In CydC the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused
Consists of an N-terminal domain, which is sufficient for the localization to the septal ring and is required for cell division, followed by a linker domain, and a C-terminal domain, which forms the translocation motor involved in chromosome segregation. The C-terminal domain can be further subdivided into alpha, beta and gamma subdomains. The alpha and beta subdomains multimerise to produce a hexameric ring, contain the nucleotide binding motif and form the DNA pump. The gamma subdomain is a regulatory subdomain that controls translocation of DNA by recognition of KOPS motifs and interacts with XerD recombinase
The N-terminal region and C-terminal zinc-finger RNA-binding domain are both necessary for interaction with SNAPIN
The PHD-type zinc finger mediates binding to histone H3 methyllysine at position 4 (H3K4me3)
Zinc fingers 3,4 and 5 are required for DNA binding and for interaction with SPI1
Its N-terminal half (200 amino acids) is sufficient for maximum enhancement of YY1 DNA binding and a portion of this sequence is responsible for binding YY1
The BAR domain is able to sense membrane curvature upon dimerization (PubMed:19816406). Membrane remodeling seems to implicate insertion of a N-terminal amphipathic helix (AH) in the membrane (Probable)
A single nitrate molecule is bound to a site on the dimer symmetry axis
The X-ray structure in complex with crRNA and target RNA shows a crRNA-recognition lobe (REC, residues 1-360) which anchors the crRNA repeat and a nuclease lobe (NUC, residues 361-1159) which binds the spacer crRNA-target RNA duplex and cleaves target RNA (PubMed:28757251). The target ssRNase active sites are within the 2 HEPN-like folds, which interact in vivo to form the functional active site (PubMed:26593719, PubMed:28757251). The N-terminal region and HEPN-like fold 2 play a role in pre-crRNA processing (PubMed:28475872). Binding of target RNA to the Cas13a-crRNA complex induces conformational changes that include bringing the 2 HEPN-like domains together to form the target cleavage active site, widening the channel that binds the crRNA-target RNA duplex, facilitating contact between the NUC lobe and the RNA duplex, and altering the conformation of the crRNA (PubMed:28757251)
The MPN (JAB/Mov34) domain mediates interaction with TSSC4 and SNRNP200 (PubMed:35188580). Has structural similarity with deubiquitinating enzymes, but lacks the residues that would bind the catalytic metal ion
The VHS domain binds to phosphatidylinositol monophosphates (PubMed:25588840). The KRKK motif within the VHS domain is required for binding to phosphatidylinositol monophosphates, with a preference for phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:25588840)
The PASTA domains interact with peptidoglycans and are required for PknB localization
The C-terminal domain (743-867) is required for binding of RPD3I and RBAP1
The mature protein contains tandemly repeated, identical sequences
In the N-terminus possesses a conserved domain OCA for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif
The jas domain (183-205) is required for interaction with COI1 and Pseudomonas syringae HopZ1a
Has 4 structurally distinct domains; N-terminal, PAZ (binds the 3'-end of gDNA), Mid (binds the phosphorylated 5'-end of gDNA) and PIWI (binds near the 5'-end of gDNA) arranged in a bilobal manner (PubMed:28319084). Upon binding of gDNA the PAZ and Mid domains separate, opening a channel probably for tDNA-binding; a smaller channel also opens between the N-terminal and PIWI domains (PubMed:28319084). The N-terminal and PAZ domains undergo further major rearrangement when the binary Ago-guide DNA complex binds tDNA; the PAZ domain binds the 3'-end of gDNA in the absence of target, upon ternary complex formation it is probably the N-terminal domain that binds that end of the dsDNA (PubMed:24442234). The PIWI domain assumes an RNase H fold and has the catalytic residues (PubMed:28319084)
The RING finger region is required to block Wnt signaling and is also required for endosomal localization
The C3H1-type zinc finger domain and C-terminal region are necessary for pre-miRNA binding (By similarity). The C-terminal region and proline-rich domain are necessary for oligomerization (By similarity)
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The GTPase domain dimerizes and forms the BDLP tube surface, the middle and GED domains are elongated and involved in self-assembly, while the paddle region inserts into the outer leaflet of the membrane, possibly promoting membrane curvature
The cyclic nucleotide ligand binds in the C-terminal SAVED domain. DNA binding requires the extreme N-terminus
Has protease activity (PubMed:7578132)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD). Upon trypsin digestion the isolated TD forms channels in bilayers when the cis side is acidic/oxidizing and the trans side is pH 7.0/reducing (PubMed:2446925, PubMed:17666397, PubMed:19096517). The RBD rotates 140 degrees around the TD in the presence of NTNHA (PubMed:22363010). The 3 major domains each serve as a chaperone for the other 2 to ensure they act only in the correct host cell context (PubMed:19096517). In BoNT/A structures the LC is separated from the RBD by the TD; the belt wraps around the perimeter of the LC, protecting Zn(2+) in the active site (PubMed:18032388, PubMed:19351593, PubMed:22363010). The belt region (449-545) may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:17907800)
Contains 5 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. These motifs are not required for interaction with PPARG
PAZ domain provides a major contribution for nucleic acid recognition. PAZ binds oligonucleotides of different lengths and has a strong preference for single-stranded nucleic acids (ssRNA or SSDNA) or RNA duplexes with single-stranded 3' overhangs. Can bind the characteristic two-base 3' overhangs of siRNAs, indicating that it may contribute to the specific and productive incorporation of siRNAs and miRNAs into the RNAi pathway
The Flo11 domain contains aromatic residues that form two hydrophobic bands on the surface of the protein that confer homophilic binding (PubMed:32286952, PubMed:25960408, PubMed:22129043). The hydrophobic bands are lined by stretches of acidic residues that may sensitise the protein to environmental pH (PubMed:25960408). The domain is required for biofilm formation (PubMed:25960408). The domain does not interact with mannose or calcium ions (PubMed:22129043, PubMed:25960408)
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and LC3A
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 99 and 126
The CARD domain mediates LPS recognition and homooligomerization
Microtubule binding occurs via a basic patch in the central spectrin-like domain and requires also the unstructured C-terminal domain
Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity. Two major calcium-sensitive sites are involved in conformational changes and determine separate functional properties: the first site (Glu-25, Asp-44 and Glu-74) regulates the actin-capping and actin-severing activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates only the actin-severing activity (By similarity)
The UIM domain is required for protective effect on PP2A
The transmembrane domain (TM) is the major site of interaction with SLC51A. The extracellular-membrane interface is absolutely required for transport activity. The intracellular-membrane interface is necessary for establishing the correct membrane orientation that is essential for the heterodimer Ost-alpha/Ost-beta complex formation and transport activity at the cell membrane surface
The BTB domain is required for growth-suppressing properties
Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing and alternative polyadenylation (APA)
The C-terminal region (about 633-690) acts as a brake for ATP hydrolysis (PubMed:17991488) and interacts with RPA (PubMed:21195035)
DNA-binding domain 1 interacts with the repeated motifs encoded by the RTS1 element as well as the elements enhancer region. DNA-binding domain 2 has only a weak DNA binding activity
Adopts an inhibitor cystine knot (ICK) fold. Is defined as a knottin (one disulfide bond crosses the macrocycle formed by two other disulfide bonds)
The N-terminal domain determines nucleotide recognition and specific binding, while the C-terminal domain determines the specific binding to the target protein. When the N-terminal domain of MobA is fused to the C-terminal domain of MocA, comparable kinetic constants as wild-type MobA are obtained with GTP, and the activity with CTP is completely lost. Consistent results are obtained when the N-terminal domain of MocA is fused to the C-terminal domain of MobA: the kinetic constants with CTP are comparable with the ones found for wild-type MocA, although no activity with GTP is detected
The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and 'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin chains. Also binds monoubiquitin
PH (probe helix) motif serves as a DNA recognition helix
Consists of an N-terminal FAD-binding domain with a Rossman fold and a C-terminal substrate-binding domain
The N-terminal region is not required for secretion and hemolytic activity, but is involved in phagosomal escape of bacteria in infected cells and is critical for bacterial virulence. This region contains a PEST-like sequence, which does not mediate proteasomal degradation, but controls listeriolysin O production in the cytosol
The extracellular domain may not be directly implicated in the detection of volatile odorants
Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself (By similarity). Interacts with IGF1R (By similarity)
Contains a predicted C-terminal beta-barrel porin domain and a N-terminal periplasmic superhelical domain containing tetratricopeptide repeats, which may mediate protein-protein interactions, perhaps with PgaB
The N-terminal domain shows evolutionary conservation with that of PEX1, and is able to bind phospholipids with a preference for phosphatidylinositol mono- and bisphosphates
The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31
The two NEAr transporter (NEAT) domains act in concert to bind, extract, and transfer heme from hemoglobin to downstream Isd proteins
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which is essential for the association with nuclear receptors
Consists of an N-terminal ligand-binding domain that encloses a wide aqueous vestibule and a transmembrane domain that forms a narrow channel
Contains 1 EAR motif required for the interaction with TPL and TPRs
The C-terminal region (366-485) is required for transactivational activity. The N-terminal region (92-128) is important for nuclear localization
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation
Is composed of three domains: an FAD-binding domain (residues 2-107 and 223-297), an NADH-binding domain (residues 108-222), and a C-terminal domain (residues 298-379)
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro (PubMed:23932717). The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs (By similarity)
The critical DXXE motif connecting the transmembrane regions forms a pentameric barrel that constitutes the mouth of the pore. Inside the barrel, two acidic residues are in position to form two carboxylate rings
Although it contains a rhodanese domain, does not display phosphatase activity, suggesting that the protein is enzymatically inactive
The Leu-lock (Leu-120) site inserts into a hydrophobic pocket in XRCC4
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. BenZ as the following bimodular architecture: A1-T1-C1-A2-T2-C2
Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity. Two major calcium-sensitive sites are involved in conformational changes and determine separate functional properties: the first site (Glu-25, Asp-44 and Glu-74) regulates the actin-capping and actin-severing activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates only the actin-severing activity
The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK3 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them (By similarity). The POLO box domains mediates localization to the centrosome
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gln residues in position and 65, which is replaced by a Leu residue, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins
The N-terminal disordered region does not act as a key DNA-binding domain. The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage
The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins
The KEN box and D-box 3 are required for its ubiquitination and degradation
The N-terminal domain exerts an inhibitory effect on the helicase ATP-binding domain in such a manner that its ATPase activity is restricted (By similarity). Phosphorylation at Ser-158 promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (By similarity)
The Pro-rich region is important for the interaction with RAC guanine nucleotide exchange factors and the subsequent activation of RAC1, which then promotes lamellipodia formation
The intracellular domain of LINGO1 interacts with MYT1L
2 residues (Tyr-56 and Arg-59) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The PHD-type zinc finger mediates interaction with SCE1, GTE3 and GTE5 and is required for E3 activity
The DOCKER domain is necessary for the GEF activity (PubMed:25851601, PubMed:15710388). The DOCKER domain mediates interaction with activated CDC42 in conjunction with residues 66-126 (PubMed:16968698)
Rho-GAP domain is required to promote GRIA1 exocytosis from recycling endosomes. Rho-GAP and BAR domains are necessary for the control of long-term potentiation in hippocampal neurons (PubMed:23739967). In dendrites, BAR domain mediates the recruitment to patches where plasma membrane is deformed by acto-myosin mediated contractile forces (By similarity)
Contains an N-terminal amino acid kinase (AAK) domain and a C-terminal PUA domain. The AAK domain is responsible for catalyzing the reaction and for proline and ADP inhibition. The PUA domain modulates the catalytic and regulatory functions of the AAK domain
The EIIA domain is phosphorylated by phospho-NPr on a histidyl residue
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain (By similarity)
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. Its contribution to the mechanism confering the myosin movement on actin filaments is debated
In the N-terminus has a gamma-class carbonic anhydrase-like domain (CA), while the C-terminus has 3 repeats that are similar to the small subunit of RuBisCO (rbcS), called SSUL. The SSUL are connected by flexible linkers. The N-terminal domain forms a scaffold on which CA and maybe other carboxysomal proteins assemble, while the C-terminus binds RuBisCO (PubMed:8491708) (Probable). At least 2 SSUL domains are required for initiation of carboxysome assembly (PubMed:24267892). Isolated reduced and oxidized CcmM35 binds holo-RuBisCO (RbcL(8)-RbcS(8)) but neither subunit octamer alone; RuBisCO has a higher affinity for reduced M35 (PubMed:30675061)
Contains an alpha-helical IF rod domain organization with three coiled coil-forming segments (coil 1A, coil 1B, and coil 2) (PubMed:26840051)
The SH3 domain mediates interaction with CLNK (By similarity). The SH3 domain also mediates interaction with RALGPS1 (By similarity)
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 106 and 130
The His-85 and His-275 residues facing the outside of the cell are involved in pH sensing
The catalytic domain (residues 1-190 and 303-408) adopts a typical 'prim' fold structure formed by two three strand beta-sheets that line the inside of the lower and upper parts, each surrounded by alpha-helices on the outside. It comprises a highly conserved catalytic triad, a structural zinc-binding motif and the nucleotide-binding motifs. The Asp-109, Asp-111 and Asp-305 catalytic triad binds two Mn2+ or Mg2+ ions which activate for nucleophilic attack the 3'-hydroxyl of the growing RNA primer or of the first NTP bound at the initiation site. The nucleotide-binding motifs coordinate the phosphates, the ribose and the base of a NTP molecule. The interaction between O2' of the initiating NTP and Asp-305 stabilizes the ribose during the di-nucleotide synthesis. It is proposed that the first nucleotide binds to the elongation site, followed by binding to the initiation site of a second NTP, which will become the 5'-terminal nucleotide of the primer
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of a N-terminal amphipathic helix (AH) in the membrane (Probable)
The Ras-associating domain 1 is degenerated and may not bind HRAS (By similarity). The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A and probably RAP2A and RAP2B and recruitment of HRAS to the cell membrane
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containingbinding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3)
The cytochrome b5 heme-binding domain lacks one of the conserved iron-binding His residues at position 100
The dimerization domain also acts as a hinge; changes in its structure probably impact oligomerization and RNA-binding
The RNA-binding RGG-box is required for the recruitment of some P-granule components such as pos-1 and probably mRNA, but is dispensable for granule formation
A highly conserved undecapeptide in the C-terminus has residues important for membrane binding and cell lysis (PubMed:9445384). Mature protein has 3 discontinuous domains; D1, D2, D3 followed by C-terminal D4 (PubMed:15851031, PubMed:26333773, PubMed:26403197, PubMed:27796097, PubMed:28323617). The domains rearrange substantially upon membrane insertion, in particular alpha-helices in D3 refold to form the transmembrane beta-strands (PubMed:15851031, PubMed:28323617). The relative position of domain D4 changes, allowing it to interact with host membranes (PubMed:26333773, PubMed:27796097, PubMed:28323617)
An N-terminal sensor domain binds ornithine already present in the ribosomal exit tunnel; upon ornithine binding the downstream effector domain compacts in the exit tunnel, causing a shift of 23S rRNA U2585 which blocks the action of peptide chain release factor 1 (prfA), causing ribosome stalling
The VYDTAW motif is widely conserved among diterpene cyclases in plants and fungi
The DXDD B-type cyclization motif at positions 328-331 is responsible for the formation of ent-CDP
The DEXXE A-type cyclization motif at positions 664-668 is responsible for the formation of ent-kaurene
The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound form)
The center of the protein is Glu- and Pro-rich
The N-terminal disordered part (1-134) binds unspecifically dsDNA and expands the binding and moving range of CGAS on dsDNA (By similarity). The disordered and positively charged residues enhance CGAS-DNA phase separation by increasing the valencies of DNA-binding. The N-terminus is required to sense chromatin and its phosphorylation blocks its activation by chromatin DNA (By similarity). When the N-terminal part (1-134) is missing the protein bound to dsDNA homodimerizes (By similarity)
Crystallizes with 2 superdomains; the first comprises domains I (residues 1-202, also called the G domain) and II (203-302, also called the beta barrel domain), while the second is composed of domains III (303-385), V (386-482) and a BipA-specific C-terminal domain (CTD, 483-607). Domains I-V are homologous to domains in EF-G and LepA; although the domains are similar, their relative arrangement is different (PubMed:26163516, PubMed:26283392). The structure of isolated superdomain 2 is more compact in the presence of Mg(2+) than in the intact protein (PubMed:26163516). Upon ribosome binding the second superdomain shifts and the CTD assumes a more compact conformation. The CTD binds to the A-site tRNA (PubMed:26283392). Chaperone activity resides in domain I; truncated proteins of 49-607 and 149-607 have no chaperone activity (PubMed:30305394)
The RLR CTR domain is capable of inhibiting dimerization and signaling of RIGI and also facilitates binding of dsRNA
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro (PubMed:23932717). The nucleotide-binding site is juxtaposed to the RNase active site of par-1/pan2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs (By similarity)
The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for par-1/pan2
The A20-type zinc finger directly binds polyubiquitin chains and associates with the 26S proteasome. The zinc-finger A20-type domain is essential for inhibition of NF-kappa-B activation (By similarity)
A conserved motif AVN[ED]CD within the disintegrin-like domain could be involved in the binding to the integrin receptor
The ARID domain mediates the interaction with DNA
The cytoplasmic region mediates interaction with EPB41L1, DLG3, PALS2 and CASK
Members of the RBR family are atypical E3 ligases. They interact with E2 conjugating enzymes such as Ubc10 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate
The glutamine amidotransferase type-1 (GATase) domain hydrolyzes glutamine into glutamate and ammonia where ammonia is then use for the amination of adenyl-XMP intermediate (PubMed:17868038, PubMed:21413787, PubMed:32358899). Upon binding of glutamine, the GATase domain undergoes a conformational change involving an 85 degree rotation, which is required for channeling ammonia from the GATase domain to the GMPS ATP-PPase domain (PubMed:26592566, PubMed:35883427)
The GMPS ATP-PPase domain catalyzes the condensation of XMP with ATP to form the intermediate product XMP-AMP (PubMed:17868038, PubMed:32358899). ATP binds first, and its binding is required for the subsequent XMP binding (PubMed:17868038)
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP binding. Assembling and disassembling the active center during each catalytic cycle provides an effective means to prevent GTP hydrolysis (By similarity)
Consists of two major domains: the N-terminal domain (Kae1-like) is involved in the transfer of carbamoyl from O-carbamoyladenylate to tobramycin or kanamycin; the C-terminal domain (YrdC-like) is involved in the hydrolysis of carbamoyl phosphate and its subsequent adenylation by ATP
The RRM domain and the N-terminal region (15-58) seem to be involved in RNA binding
The N-terminal part of the mature protein (59-100) probably forms an alpha-helix which acts as a membrane-active peptide. It is necessary and sufficient for the toxin's antimicrobial, insecticidal, cytolytic and cytotoxic activity
The C-terminal domain interacts with histones H1 and H3, and may be responsible for condensin complex targeting to mitotic chromosomes. This domain is independent from the bipartite nuclear localization signal, although they are contained within the same region
Protein missing TPR1 (residues 1-41) forms an N-terminal domain of TPR 2-3 and a C-terminal domain with TPR 4-6 which can move with respect to each other, hinged at D-112
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. LIR 1 is also implicated in interaction with retromer; LIR 2 is only implicated in interaction with ATG8 family proteins
Exploits its two major loops and engages more positions in its interaction with V2R (PubMed:35122240). The pharmacophore defined by numerous amino acids positioned in loop 1 (9 to 18) and loop 2 (34, 39 and 44) may be at the origin of the absolute selectivity of this protein for V2R (Probable)
The N-terminal domain mediates dimerization
The C-terminal domain mediates interaction with DNA and nucleosomes (PubMed:11473582, PubMed:25653165). It contains a HTH motif that mediates recognition of the consensus sequence (PubMed:23874396)
Forms a beta-barrel structure that may accommodate hydrophobic ligands
Composed of one catalytically active A module and four R modules
Within the N-terminal cytosolic region appear three 19 amino acid repeated elements containing the M-X-X-M copper-binding motifs
The REP-III motif within the C-terminal cytosolic part resembles a shortened MAC1 copper ion-sensing motif (REP) and plays a role in the CTR1 degradation
The MBT repeat 2 specifically recognizes and binds monomethylated and dimethylated proteins. In contrast, it does not bind trimethylated proteins. The MBT repeat 1 does not bind methylated peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence context (By similarity)
The nuclear export signal 1 (N-NES) negatively regulates its nuclear localization and transcriptional activity
The C-terminus is specifically required for completion of oocyte meiotic divisions
Contains 2 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The first one is essential for the association with ESR1 and ESR2 (By similarity)
The peptide interacts with the surface of DPC micelles by two alpha-helical regions
The zinc finger-like domain binds a zinc ion and is involved in self-association
The RING domain is required for E3 ubiquitin ligase activity
The C-terminal part of HOS1 is involved in the interaction with ICE1
The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (PubMed:19307175). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (PubMed:19307175, PubMed:23204525)
A conserved histidine residue in the third transmembrane domain (His-128) might play an essential role in the pH sensitivity of SLCO2B1/OATP2B1-mediated substrate transport. Transmembrane domain 1 (TM1) may be localized within the substrate binding pocket
Composed of an N-terminal alpha/beta-hydrolase domain and a C-terminal cyclase homology domain (CHD)
The ATP-binding domains (NBD) and the transmembrane domains (TMD) are fused
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of timm13-A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The central ion permeation pathway is formed by the first transmembrane domain from each of the five subunits. Mg(2+) binding strengthens interactions between subunits and leads to the formation of a symmetrical homopentamer surrounding a closed ion permeation pathway. Co(2+) binding also induces a conformation change. Low Mg(2+) concentrations trigger both a conformation change within each subunit and a loosening of the interactions between subunits. This results in an open ion conduction pathway. In addition, this results in a less symmetrical shape of the whole complex
An extended PIP motif (50-69) is sufficient for abscission induction
The N-terminal (AA 44-121) exhibits neurite outgrowth-inducing activity. The C-terminal exposed loop (AA 382-418) is essential for serpin activity
The Fibrinogen C-terminal domain mediates interaction with the TEK/TIE2 receptor
The RGD motif is involved in integrin ITGAV:ITGB3 binding
The C-terminal 40 residues are required for homodimerization
The fungal-differentiation regulator (Fungal-DR) domain is only found in fungal regulator of G-protein signaling (RGS) proteins that regulate differentiation pathways. It is required for function (By similarity)
The Neck region contains 3 internal repeats that are only found in rodents
The phospho-regulated basic and hydrophobic (PRBH) motif is sufficient and important for interaction with phospholipids permitting cortical localization (PubMed:26481050). Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane (PubMed:26481050)
The Myb-extension domain (593-622) is critical for telomere binding
Interacts with RAF-1 via its C-terminal ankyrin repeat domain. The same domain also mediates its homodimerization (PubMed:10329666). The third ankyrin repeat is required for association with the two other RFX subunits; RFX5 and RFXAP. The three central ANK repeats mediate binding to the PxLPxI/L motif of RFX5 (By similarity)
Contains an N-terminal nucleotide-binding domain and a C-terminal acceptor-binding domain
Contains an N-terminal ATP-binding domain, an adjacent helical lid domain, and a C-terminal tetramerization domain
Cys-415 near TM10 is a major determinant of nucleobase transport activity
The HEAT repeats have been determined based on 3D-structure analysis and are not detected by sequence-based prediction programs
Interacts with RAF1 via its C-terminal ankyrin repeat domain. The same domain also mediates its homodimerization (By similarity). The third ankyrin repeat is required for association with the two other RFX subunits; RFX5 and RFXAP. The three central ANK repeats mediate binding to the PxLPxI/L motif of RFX5 (PubMed:20732328, PubMed:22649097)
The N-terminal Gln-rich domain can confer two distinct functional states, a dominant active prion-like aggregated state and a soluble state
The EGF-like domains mediate interaction with CNTN1. The fibronectin type-III domains 3-5 mediate interaction with BCAN. The fibronectin type-III domains 1-2 and 7-9 mediate interaction with SCN2B (By similarity)
The RPEL repeats mediate binding to globular actin (G-actin); each RPEL repeat-binding to one G-actin monomer. In addition, each intervening spacer sequence region can bind one G-actin monomer, to reach a pentavalent complex
Has 4 domains (N-terminal, PAZ, Mid and PIWI). The N-terminal and PAZ domains are joined by linker L1, the PAZ and Mid domains are joined by linker L2. The domains assemble in 2 lobes; the PAZ lobe consists of the N-terminal, L1, PAZ and L2 domains, while the PIWI lobe has the Mid and PIWI domains. The PIWI domain assumes an RNase H fold and has the catalytic residues. Compared to orthologs, the N-terminal domain has a different secondary structure and position. The 5'-end of the gRNA is anchored between the MID and PIWI domains while the 3'-end is in the PAZ domain (PubMed:27035975). In the gRNA:tDNA complex the 5'-end of gRNA remains anchored in the Mid domain and is unpaired with tDNA, while the 3'-end of the gRNA is released from the PAZ domain. Upon release of the 3'-end of the gRNA from the PAZ domain during nucleic acid duplex formation, conformational changes allow Glu-482 to move to complete the active site. An N-lobe rearrangement allows a unique, straight orientation of the hybrid helix not seen in other Ago ternary complexes (PubMed:28520746)
Contains the N-terminal Scar homology domain (SHD), but unlike the genuine SCAR proteins, lacks the C-terminal VCA (verprolin homology/cofilin homology/acidic) domain
The C-terminal region is necessary for nucleus and cytoplasmic localization. The N-terminal region is necessary for nucleus and nuclear bodies localization
The periplasmic domain binds citrate with high affinity. The C-terminal cytoplasmic domain senses reduced conditions using a single Cys in vitro
The C-terminus of isoform A interferes with binding to non-phosphorylated RHO. Interaction with phosphorylated RHO triggers displacement of the C-terminus and leads to a conformation change that mediates high-affinity RHO binding. Isoform B is C-terminally truncated and is therefore already in the optimal conformation for RHO binding
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-46 in the first module and Ile-246 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity
The binding to LHCP occurs through the first ankyrin repeat and the L18 domain of LHCP
Homodimerization occurs through both the third and the fourth ankyrin repeats
Chromo domain 1 may act as a negative regulator of GTP hydrolysis by FFC/cpSRP54. It is unnecessary for targeting complex formation but is required for integration into the thylakoid membrane
Chromo domain 2 is involved in binding to the M domain of FFC/cpSRP54
The N-terminal PX domain interacts specifically with phosphatidylinositol 4,5-bisphosphate
The N-terminus is involved in protein dimerization and in transactivation of transcription
The C-terminus of isoform 2 is necessary for isoform 2 interaction with TBR1
Zinc finger domains are necessary for sequence-specific binding to DNA
The jas domain (182-206) is required for interaction with COI1 and Pseudomonas syringae HopZ1a
Upon tRNA-binding, the alphaC region transforms into a helix, which together with the alpha6 helix secures both ends of the tRNA variable loop (By similarity). The N-terminal disordered region is part of the catalytic pocket and essential for methyltransferase activity: upon S-adenosyl-L-methionine- and tRNA-binding, the N-terminal disordered region becomes ordered, sandwiched between the bound cofactor and the tRNA, and the WDR4 C-terminus attaches to the METTL1 N-terminus to stabilize the bound tRNA together (By similarity). Together with WDR4, which also binds tRNAs, tRNAs undergo bending to facilitate G46 flipping into the catalytic pocket to be modified (By similarity)
The Death domain mediates the interaction with CRADD and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn recruit 7 CASP2 to form the PIDDosome
The LRR repeat-containing domain has a regulatory activity, being autoinhibitory for the activation of NF-kappa-B
The mature protein has a random coil structure at acidic pH, rapidly changing to beta-sheet as the pH rises (examined from pH 3.0 to 10.0); at pH 6.7 and higher forms amyloid fibrils visible by electron microscopy
The PPxY motif 2 mediates interaction with WWOX. Both PPxY motifs mediate interaction with NEDD4 (By similarity)
Contains 2 BMC domains, trimerizes in a staggered manner to give a hexamer; each subunit in one trimer interacts with 2 subunits in the facing trimer. In each stacked hexamer one trimer forms a pore of about 14 Angstroms in diameter; open-closed and open-open trimers are seen in crystals. Glu-120 forms a salt bridge with Arg-121 of the adjacent subunit to close the pore. Dimerization of the trimers forms a channel-like compartment (volume 13,610 Angstroms(3)), accessible via an open pore. This channel may be large enough to accomodate transport of substrates into and out of the carboxysome
The PCNA interacting protein (PIP) box mediates interaction with pcna and recruitment of pcna to DNA single-strand breaks
The GRF-type Zinc-finger domain binds single-stranded DNA (ssDNA) with high affinity and regulates the 3'-5' exonuclease activity (PubMed:29361157, PubMed:28028224). Required for the 3'-5' end resection of oxidative DNA damage and activation of the atr-chek1 DNA damage response pathway following oxidative stress (PubMed:28028224)
Has protease activity (By similarity)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (By similarity). In BoNT/E the domains are arranged differently than BoNT/A and BoNT/B; in BoNT/E the LC and RBD are on the same side of the TD and are in contact, whereas in BoNT/A and BoNT/B the LC is separated from the RBD by the TD (By similarity). The putative transmembrane region is closer to the receptor-binding regions in this toxin, which may explain why it acts faster than BoNT/A and BoNT/B (By similarity). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (By similarity). The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (By similarity)
Side chains of Lys-102, Lys-135 and Lys-165 capture Ser that is misactivated by AARS/AlaRS
Only the C-terminus (residues 321-436) is necessary to interact with MamK; its addition to MCP25 confers the ability to interact with MamK
The 2 Tudor domains recognize and bind methylated histone H3 'Lys-4' residue (H3K4me). Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails. Trimethylated H3 'Lys-4' (H3K4me3) is bound in a cage of 3 aromatic residues, 2 of which are from the Tudor domain 2, while the binding specificity is determined by side-chain interactions involving residues from the Tudor domain 1. The Tudor domains are also able to bind trimethylated histone H3 'Lys-9' (H3K9me3), di- and trimethylated H4 'Lys-20' (H4K20me2 and H4K20me3). Has high affinity for H4K20me2, blocking recruitment of proteins such as TP53BP1 (By similarity)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (337-367) inactivates kinase activity under calcium-free conditions (By similarity)
DNA binding and bending properties of the HMG domains of human and mouse SRY differ form each other. Human SRY shows more extensive minor groove contacts with DNA and a lower specificity of sequence recognition than mouse SRY
The RRM domain interacts with RNA, and is essential for NELF complex function. It is however not required for the NELF complex formation (By similarity)
The LysM domain binds chitin and potentially related carbohydrates, and might be involved in damping host defense
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation (PubMed:20188097, PubMed:20471395). Autoinhibition of these functions is mediated by an interaction between the SH3 and F-BAR domains (By similarity). The F-Bar domain also mediates the binding to the cell actin cytoskeleton through the interaction with CAV-1 (PubMed:21610094)
The PH domain mediates interaction with membranes containing phosphoinositides
The cysteine framework is I (CC-C-C)
Ig-like C2-type domains 7 to 9 are sufficient for interaction with NTN1 and commissural axon outgrowth. The transmembrane domain is necessary for interaction with DCC (By similarity)
Each subunit has a cleft approximately 20-25 Angstroms wide and 20 Angstroms deep, which is sufficient to accommodate dsDNA. Residues thought to be catalytically important (Asp-8, Glu-67, Asp-139 and Asp-142) line this cleft
The Era-type G (guanine nucleotide-binding) domain has GTPase activity, while the C-terminal KH type-2 domain is required for 16S rRNA binding and for membrane localization. Neither rRNA binding nor membrane localization require the N-terminal G domain, and the GTPase does not require the KH domain
May bind to glycans on target cells via the C-terminal beta-prism domain
Three specific residues, Ser-176, Phe-179 and Thr-195 are conserved between primates whereas the respective residues are phenylalanine, leucine, and asparagine in the other mammal enzymes (PubMed:18571493, PubMed:19056333). The two residues at positions 176 and 179 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil (PubMed:19056333). The presence of an asparagine at position 195 is important for the maintenance of the quaternary structure and stability at cold temperature (PubMed:18571493, PubMed:19056333). The absence of an asparagine at position 195 destabilizes the quaternary structure, thereby affecting catalytic efficiency toward some substrates and decreasing stability at cold temperature (PubMed:18571493, PubMed:19056333)
Has 2 domains capable of forming beta amyloid structures, both of which are required for aerial hyphae formation while the N-terminal region is not required for rodlet formation
Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABA-B receptor 1
Only the PABPC1-interacting motif-1 (PAM1) stimulates translation initiation
Loop-1 binds to loop-7, enabling interaction with COPII-coated vesicles (PubMed:27068746). When levels of cholesterol in the endoplasmic reticulum increase, Loop-1 binds to cholesterol instead, thereby disrupting direct binding between the two loops and preventing the SCAP-SREBP complex from exiting the endoplasmic reticulum (PubMed:27068746)
Interacts with phosphatidylinositol 3-phosphate (PI3P) via the FYVE-type domain
The C-terminal short (CTS) helix is essential for catalytic activity (PubMed:34388369). It may be accommodated as a transmembrane helix in the thinned membrane environment of the complex, similarly to the signal peptide in the complex substrates (Probable)
The Pro-rich regions interact with the SH3 domain of CAS family members, such as BCAR1 and NEDD9, and with the GTPase activating protein ARHGAP26
The N-terminal cytosolic domain interacts with sigma-E, and upon overexpression leads to temperature sensitivity above 37 degrees Celsius and cell lysis in stationary phase. After degradation by RseP residues 77-108 bind to SspB, targeting RseA for degradation by the ClpX-ClpP protease
The C-terminal periplasmic domain (residues 169-186) interacts with RseB and is also the target for DegS; RseB and DegS binding sites do not appreciably overlap. Gln-rich regions (residues 162-169, Q1, and 190-200, Q2) contribute to preventing RseP from acting before DegS. Insertion of 8 consecutive Gln residues into a protein lacking Q1 and Q2 restores DegS-dependence of RseP cleavage
The PPxY motifs are required for E3 ubiquitin-protein ligase activation and for ubiquitination
Folds into three domains, i.e. two ACT domains occurring in tandem at the N-terminus followed by the classical phosphatase (PSP) domain. The PSP domain alone is capable of hydrolyzing L-phosphoserine, albeit with much reduced efficacy. The ACT domains are involved in amino acid binding and play an important role in modulating enzymatic activity
The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. Promotes tyrosine phosphorylation of RIPK2
The PH domain has no affinity for phosphoinositides suggesting that it does not interact directly with membranes
The phorbol-ester/DAG-type zinc-finger and the C-terminal coiled-coil domains (606-986) are both important for association with microtubules
The C-terminal ATG8 interacting motif (AIM) is necessary and sufficient to bind ATG8CL and localize to host autophagosomes
Contains 5 tandem repeated WY-domains dispensable for the interaction with ATG8CL and which function has still to be determined
The dimer forms a pocket of about 8 X 15 Angstroms, lined with acidic residues, which may bind 2 Fe(2+) ions
Has 4 domains (N-terminal, PAZ, Mid and PIWI). The N-terminal and PAZ domains are joined by linker L1, the PAZ and Mid domains are joined by linker L2. The domains assemble in 2 lobes; the PAZ lobe consists of the N-terminal, L1, PAZ and L2 domains, while the PIWI lobe has the Mid and PIWI domains. The PIWI domain assumes an RNase H fold but in this bacteria does not have catalytic activities. The gRNA:tDNA duplex lies between the 2 lobes. The 5'-phosphate and first base of the gRNA bind in the Mid domain, the middle of the gRNA binds to the PAZ domain, while the 3'-region of the gRNA strand base-pairs with the 5'-region of the tDNA strand but not to the PAZ domain. The 5'-region of the tDNA strand binds to RsAgo N-terminal domain in the heteroduplex
In the CSD domain, Trp-45 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring
The BAG domain probably mediates direct interaction with HSP70
Contains a single ricin B lectin domain with a characteristic beta-trefoil fold consisting of three repeated subdomains each containing a more or less conserved QXW motif
The N-terminal amphipathic helix (residues 1 to 18) is involved in the membrane recruitment
Contains one Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif essential for phosphatidate phosphatase activity
The ankyrin repeats and the SH3 domain are required for a specific interactions with p53/TP53
The cysteine framework is XIII (C-C-C-CC-C-C-C)
The EF-hand 2 domain within the regulatory N-terminal domain binds one calcium in the mitochondrial intermembrane space. Calcium triggers the binding of the regulatory N-terminal domain to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain (PubMed:25410934). In the absence of calcium, the linker loop domain may close the vestibule and prevent substrates from entering the carrier domain (By similarity)
The BH3 motif is intrinsically disordered in the absence of a binding partner but folds upon binding (PubMed:18589438). Folds when bound to BCL2L1 (By similarity). Also folds when bound to MCL1 (PubMed:18589438)
The TPR repeats mediate protein-protein interactions with substrate proteins, but also autoinhibit PPT phosphatase activity
The N-terminus (residues 1 to 11) forms an amphipathic helix which is required for the association to membrane
The N-terminal half is sufficient for DNA replication
The C-terminal coiled coil part contains the plexin-interacting region
2 residues (Tyr-90 and Arg-93) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute to transcript binding. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full length protein
The SRCR domains mediate binding to bacteria. The minimal bacterial-binding site is an 11-residue repeat of GRVEVLYRGSW where VEVL and W are critical residues
Undergoes significant conformational changes during the full ATP-dependent dicing reaction cycle for processing a 50 bp dsRNA with a 3' two-nucleotide overhang and a 5' monophosphate terminus (PubMed:35768513). At the initial dsRNA binding stage, the helicase and DUF283 domains transition from an extended to a closed conformation, this anchors the bound dsRNA through major and minor groove recognition and forms the ATP- and 5'-phosphate binding pockets required for dicing activity (PubMed:35768513). In the next ATP hydrolysis-driven steps, the dsRNAs is thread through the helicase domain towards the catalytic center (PubMed:35768513). The overall domain configuration is relatively rigid during the translocation process until the dsRNA terminus reaches the Platform-PAZ domains (PubMed:35768513). During the early-translocation stage, in which about 8 bp of the dsRNA duplex is threaded through the helicase domain towards the catalytic center, interactions between the DUF283 and RIIIDb domains prevent non-specific cleavage by blocking the access of dsRNA to the RNase active center (PubMed:35768513). In the mid-translocation stage, in which about 17 bp of the dsRNA duplex is thread towards the catalytic center, the dsRBD domain binds to the dsRNA, in the process bending and pushing the dsRNA towards the PAZ domain (PubMed:35768513). At the end of the translocation stage, around 21 bp of the dsRNA threads through the helicase domain into the PAZ-platform cassette, in the process disrupting the DUF283-RNaseIIIb interaction, allowing the dsRNA substrate to enter the catalytic active center of the RIIID domains for precise cleavage, and thus achieves the fully active dicing conformation (PubMed:35768513). In this structure, a clear breakage of the dsRNA after the dicing near to the catalytic center occurs exactly 21 bp away from the PAZ-domain-binding terminus (PubMed:35768513). During the post-dicing state, the cleaved siRNA is released, and the remaining dsRNA duplex bound by the helicase domain returns to a conformation similar to the early-translocation state, which enables the complex to start the next dicing cycle (PubMed:35768513)
The N-terminal helicase domain, containing the Helicase ATP-binding, Helicase C-terminal and Helicase insertion domains, functions in dsRNA stimulated ATPase activity and RNA translocation during the dicing reaction (PubMed:15066283, PubMed:21419681, PubMed:35768503, PubMed:35768513). Essential for processing endogenous and viral dsRNAs (PubMed:28416567, PubMed:24009507, PubMed:32843367). Binds and hydrolyzes ATP enabling the dicer to translocate along the long dsRNA substrates, and produce siRNAs processively from the end (PubMed:21419681, PubMed:29269422). Some reports suggest the domain is essential for the recognition and initial binding of both blunt (BLT) and 3' overhanging (3'ovr) termini dsRNA substrates (PubMed:35768503, PubMed:35768513). However, another reports found that the helicase domain is only required for binding and correct cleavage of BLT dsRNAs and is dispensable for processing of 3'ovr termini dsRNAs (PubMed:32843367, PubMed:29269422). One of the reports suggest that the helicase domain recognizes dsRNA with BLT termini, and then initiates processive cleavage via a threading mechanism in which the BLT dsRNA is locally unwound and threaded through the helicase domain in an ATP-dependent manner (PubMed:29269422)
The PAZ and platform domain is important for ensuring length fidelity of siRNAs, substrate discrimination, cleavage and anchoring of 3' overhanging (3'ovr) termini substrates, and the positive regulation of Tl (PubMed:26601278, PubMed:27872309, PubMed:29269422, PubMed:35768503). The platform-PAZ domains are important for mediating the ATP-independent cleavage of dsRNAs with 3' overhanging (3'ovr) dsRNAs into 22mer siRNAs (PubMed:29269422). Substrate dsRNAs with blunt termini, are threaded through the helicase domain, cleaved and then the 2-nt 3' overhang of the dsRNA is recognized and anchored by the 5'-pocket in the platform-PAZ domain (PubMed:29269422). The PAZ domain recognizes and anchors the 5'-monophosphate of long dsRNA substrates, positioning the substrate so that the RNase III domain can cleave the dsRNAs 21 nt away from their 5' end (PubMed:27872309, PubMed:35768503). Although it is important for ensuring length fidelity of 21-nt siRNA production, it is not required for efficient siRNA production (PubMed:27872309, PubMed:35768503). Important for substrate discrimination (PubMed:24488111, PubMed:29550490). Inorganic phosphate appears to occupy the same binding pocket in the PAZ domain as the 5' monophosphorylated end of short dsRNAs, pre-miRNAs or hairpin RNA substrates, and so once bound, the inorganic phosphate likely blocks binding and thus cleavage of the dsRNAs (PubMed:24488111, PubMed:29550490). Physiological concentrations of inorganic phosphate inhibit processing of the inappropriate substrates microRNAs (pre-miRNAs) and short dsRNAs, whereas cleavage of long dsRNAs is not inhibited possibly because they are recognized by a different domain/s i.e. the helicase domain and/or the central dsRNA binding domain (PubMed:21419681, PubMed:24488111, PubMed:29550490). This suggests that binding to inorganic phosphate may block binding to nonphysiological substrates, such as pre-miRNAs function to prevent the enzyme from processing nonphysiological dsRNAs substrates (PubMed:21419681, PubMed:24488111, PubMed:29550490). This domain is also important for the ATP-dependent cleavage reaction (PubMed:32843367). The PAZ domain also interacts with the Tl mRNA 3'UTR, and is therefore important for the positive regulation of Tl at the post-transcriptional level, and thus mediating Toll signaling (PubMed:26601278)
The DRBM domain or RNA binding domain (RBD), is important for efficient and high-fidelity production of 21 nucleotide siRNAs, and siRNA loading onto AGO2
Interactions between the DUF283 and RIIIDb domains prevent non-specific cleavage by blocking the access of dsRNA to the RNase active center
The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion (By similarity)
The BH3 motif is intrinsically disordered in the absence of a binding partner but folds upon binding (PubMed:23340338). Folds when bound to BCL2L1 (PubMed:23340338). Also folds when bound to MCL1 (By similarity)
The N-terminal part (1-150) is not required for interactions with the ADA2 proteins
Contains an N-terminal H(2)F420 dehydrogenase domain and a C-terminal dissimilatory-type siroheme sulfite reductase domain
The clip domain consists of 35-55 residues which are 'knitted' together usually by 3 conserved disulfide bonds forming a clip-like compact structure (By similarity). The clip domain interacts with cleaved PPO1 and/or PPO2; the interaction results in PPO1 and/or PPO2 activation (PubMed:16362048)
The periplasmic domain (residues 221-339) binds peptidoglycan (PGN) and diaminopimelate, one of the components of PGN
Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins, vesicles and membranous organelles
In the CSD domain, Trp-62 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring
The SAT domain at the N-terminus facilitates crosstalk between the two PKSs atnH and atnG encoded by the cluster
C2 domain 1 is involved in binding calcium and phospholipids. C2 domain 2 may also play a role in the calcium-dependent targeting to membranes (By similarity)
The C-terminal CBM20 domain is required for the interaction with glycogen
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (352-382) inactivates kinase activity under calcium-free conditions
The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA (PubMed:15282608). It is necessary and sufficient to mediate the localization into centromeres (PubMed:7962047, PubMed:15282608)
C2 domain 1 is involved in binding calcium and phospholipids
The myosin motor domain contains the derminants for the direction of left-right body asymmetry
The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin
The C-terminal region of isoform 1 contains a transactivation domain. The Pro/Ser/Thr-rich region in the C-terminus of isoform 2 inhibits DNA-binding of ARNT-AHR dimers
In the presence of tyrosine-autophosphorylated growth factor receptors, the C-terminus folds into an SH2-like region which promotes the stable recruitment of CCDC88A to the growth factor receptors. The SH2-like region is phosphorylated by the growth factor receptors prior to completion of folding
The C-terminal half (AA 167-370) is able to bind cyclin-B and shows a self-ubiquitination activity (mono-, poly, or multi-ubiquitination) in a HECT-like sequence dependent manner
Has 3 domains, the large (RuvB-L) and small ATPase (RuvB-S) domains and the C-terminal head (RuvB-H) domain. The head domain binds DNA, while the ATPase domains bind ATP, ADP or are empty depending on the state of the subunit in the translocation cycle. During a single DNA translocation step the structure of each domain remains the same, but their relative positions change
The presensor-1 beta hairpin in RuvB-L binds domain III of RuvA (PubMed:36002576)
The PN loop (phosphate-nicotinamide, residues 132-136) moves dramatically upon GDP-binding
The HX repeat motif is a specific pH-dependent interaction motif for ions and/or proteins or other biomolecules. This motif could be involved in the control of embryonic development
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (396-426) inactivates kinase activity under calcium-free conditions (By similarity)
Contains an N-terminal PE domain, followed by a conserved linker region and a C-terminal PGRS domain (PubMed:18028308, PubMed:21081760). The PE domain is responsible for the export and localization to the cell wall (PubMed:15101979, PubMed:18028308, PubMed:22110736). The PGRS domain is required for TNF-alpha secretion and is responsible for the main immunomodulatory properties of the protein (PubMed:17095513, PubMed:24106104). Variations within the PGRS domain alter the levels of TNF-alpha induction and are likely to have an impact on the innate immune response (PubMed:17095513). PGRS domain is also required to mediate cell entry into macrophages (PubMed:26978522). Colocalization to the mitochondria of host cells is dependent on the linker region and the PGRS domain, but not the PE domain (PubMed:21081760)
The SH3 motif may mediate binding to the cytoskeleton
The metalloprotease domain is constituted by the two C-terminal nuclear regions
The eukaryote-specific C-terminal extension harbors a nuclear import signal and delivers the ACL4-uL4/RPL4 complex to the pre-ribosome, triggering uL4 release from ACL4 and incorporation into the 60S ribosomal subunit
An extracytoplasmic domain (residues 26-185, without the lipid-anchor, either periplasmic or extracellular) decreases phagocystosis by macrophages; when added exogenously to the deletion mutant initial bacteria uptake by host (mouse) decreases to wild-type levels. When added exogenously however this region is not sufficient to restore phagosome maturation arrest (PubMed:27220037)
The PGRS region is important for localization and function
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (313-343) inactivates kinase activity under calcium-free conditions
The N-terminal RRM domain binds to nucleic acids including single-stranded DNA and RNA homopolymers poly(A), poly(G) and poly(U), but not to poly(C) nor double-stranded DNA. Binds most strongly to G-rich RNA species
The 39 amino acids in the C-terminus (residues 120 to 158) are sufficient for binding the host BKI1
The beta lactamase-like domain catalyzes the hydrolysis of cGMP
Mutagenesis of different positions (F662L, R741F, Q745E, I810T and V853A) on the C-terminal region of citB gene product shows that even B.subtilis mutant has high aconitase catalytic activity, it is defective in sporulation. The defect is at a late stage of sporulation, specifically affecting expression of sigma-K-dependent genes, many of which are important for spore coat assembly and require transcriptional activation by GerE. It strongly suggests that aconitase RNA binding activity may stabilize gerE mRNA in order to allow efficient GerE synthesis and proper timing of spore coat assembly
The 77 amino acids long, arginine-rich C-terminal domain plays a critical role in tuberculosis pathogenesis (PubMed:30192424, PubMed:33757409). This positively charged helical domain specifically binds phosphorylated phosphatidylinositols and cardiolipin, whereas it is unable to bind other phospholipids (PubMed:33757409)
The lysosomal targeting motif, together with te second PQ-loop mediate targeting to the lysosome
Major conformational changes and local movement around the substrate site occur to accommodate substrate for transport (PubMed:31083648). Active transport requires reversible protonation of both Asp-31 and Glu-118 (PubMed:31083648)
Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) regions. These regions lack the critical Cys residues required for ubiquitination but retain the ability to bind ubiquitin (By similarity)
RNA recognition motifs (RRMs) 1 and 2 bind specifically to the poly(A) tail, whereas RRMs 3 and 4 bind non-specifically to polypyrimidine RNAs and may serve to bind to a different part of the messenger or to other RNAs. RRM 2 also mediates interaction with eIF-4G
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-68 and Arg-71) that bind to malonylated and succinylated substrates and define the specificity
The BTB (POZ) domain is atypical and mediates the formation of a homopentamer instead of a homotetramer (PubMed:19361449). Homopentamerization is due to the presence of 4 residues in the BTB (POZ) domain: Leu-56, Gly-100, Val-112 and Ala-118
The C2 domain binds to calcium and membrane lipids
C2H2-type 5 and C2H2-type 6 mediate homodimerization and heterodimerization
Has 2 structurally independent domains; the N-terminal PINc domain which binds Mn(2+), rRNA substrate and probably has endoribonuclease activity, and the C-terminal zinc ribbon domain which also binds rRNA substrate
The N-terminal (AA 42-139) exhibits neurite outgrowth-inducing activity. The C-terminal exposed loop (AA 380-416) is essential for serpin activity
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 105 and 129
Consists of two highly homologous domains, oriented in a head-to-tail fashion, that catalyze epoxide-opening cascades independently in lasalocid biosynthesis. The N-terminal domain (Lsd19A) recognizes the internal C18-C19 epoxide of the substrate and catalyzes energetically favored 5-exo cyclization, while the C-terminal domain (Lsd19B) recognizes the internal C22-C23 epoxide of the substrate and predominantly catalyzes energetically disfavored 6-endo cyclization
The N-terminus of the RabBD domain is necessary and sufficient for interaction with RAB27A
The protein kinase domain is predicted to be catalytically inactive (By similarity). There is a second N-terminal lobe-like kinase domain at residues 830-1095 that contains functional ATP binding sites (PubMed:31148576)
The release of the polyketide chain from the non-reducing polyketide synthase is mediated by the thioesterase (TE) domain localized at the C-ter of the protein, which accepts the sesquiterpene alcohols as substrate to offload the finished ketide from the PKS assembly line
The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids
The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex (PubMed:30842657). The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template (PubMed:30842657)
The first PH domain mediates interaction with membranes enriched in phosphoinositides
Undergoes conformational changes upon binding of effector molecules
The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis (By similarity)
The unstructured hinge region contains clathrin-binding and an autoinhibitory (DXXLL) motifs
The RIP homotypic interaction motif/RHIM mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3)
(Microbial infection) The RIP homotypic interaction motif/RHIM mediates interaction with the RHIM motif of the herpes simplex virus 1/HHV-1 protein RIR1/ICP6 to form heteromeric amyloid structures
Both the N-terminus (1-33) and the C-terminus (38-69) of the mature peptide form alpha-helices which probably disrupt target cell membranes. The linker region (34-37) probably derives from a processing quadruplet motif (PQM), found in propeptides of many zodatoxins, hinting at a fusion of two originally separate membrane-active peptides
BRCT domains are necessary for its targeting to ionizing radiation-induced nuclear foci (PubMed:22036607)
The kinase-inducible domain (KID, 202-229) is required for interaction with HDA19
The SPX domain is sufficient for inhibition of PHR2 binding to DNA
The N-terminal 22 amino acids are sufficient for vacuolar membrane targeting. The internal domain (109-199) is sufficient for the interaction with MTN1
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 73-105, leaving each N-terminal inhibitory region (residues 22-51) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 22-51) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity (By similarity)
The N-terminal input region plays an essential role in DSF perception. DSF binds with high affinity to a 22-amino acid sensor region at the N-terminus (By similarity). The response regulatory domain, but not the HPt domain, is required for repression of DSF biosynthesis (PubMed:20826346)
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids
The DVD domain (residues 393-413) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation
The D domain (residues 37-73) contains a conserved docking site and is required for the binding to MAPK substrates
Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. FG repeat types and their physico-chemical environment change across the NPC from the nucleoplasmic to the cytoplasmic side: PXFG repeats are especially abundant in NUPs on the cytoplasmic side
The Pro-rich region of rgm1 attached to a heterologous DNA binding domain is able to repress the expression of the target gene
The SH3-binding motifs mediate interaction with SHC1 and GRB2
The PH domain mediates phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate binding
Shares some sequence similarities with the AB hydrolase superfamily
The C-terminal tail could affect ion specificity
Each monomer contains a pocket that accomodates cholesterol (PubMed:29167574). Cholesterol derivatives (such as epicholesterol, epicholestanol, epicoprostenol, or 7-dehydrocholesterol) could also fit in the pocket with minor rearrangement of the side chain (Probable). Since arthropods are unable to synthesize cholesterol de novo, it is likely that a cholesterol ligand would be bloodmeal-derived (Probable)
The Nudix hydrolase domain is dispensable for ADP-ribose-dependent channel activation. May be involved in the regulation of ADP-ribose intracellular levels. Essential to prevent response to oxidative stress
Isoform PlGF-2 contains a basic insert which acts as a cell retention signal
Has an N-terminal sirtuin-like domain (SIR2, residues 1-282) and a C-terminal SLOG (STALD)-like domain (residues 283-473). Dimerizes via the SIR2 domain (PubMed:36048923). The SIR2 domain probably has NAD(+) hydrolase activity (PubMed:36048923) (Probable). The SLOG domain binds 3'cADPR; binding alters the protein conformation, probably allowing NAD(+) to access the active site
The EF-hand domains have high affinity for calcium
The GOLD (Golgi dynamics) domain is predicted to mediate diverse protein-protein interactions
The PH domain weakly binds to phosphoinositides
The OSBP-related domain (ORD) mediates binding of sterols and phospholipids. It displays an incomplete beta-barrel containing a central hydrophobic tunnel that can accommodate a single lipid molecule with a flexible lid covering the tunnel entrance. The ORD can bind two membranes simultaneously. It has at least two membrane-binding surfaces; one near the mouth of the lipid-binding pocket and a distal site that can bind a second membrane. These structural features correlate with the phosphatidylinositol 4-phosphate (PI(4)P)-coupled lipid transport optimized in closely apposed membranes, such as organelle contact sites. The lipid transfer cycle starts from the association of the LTP with a donor membrane, which accompanies conformational changes that uncover the ligand-binding pocket. The tunnel opening is generally mediated by displacement of the lid covering the binding pocket allowing uptake or release of a lipid molecule. The LTPs extract the lipid from the membrane by providing a hydrophobic environment as well as specific interaction. Dissociation from the donor membrane shifts the conformation to a closed form. Then, the LTPs loaded with a cargo lipid diffuse through the aqueous phase. Lid opening may be induced by the interaction of a hydrophobic side of the lid with the target membranes (Probable). The OSH3 ORD does not accept sterols due to the small hydrophobic tunnel (PubMed:23791945)
The ankyrin-repeat region is necessary for ATP-dependent protein disaggregase activity (PubMed:32573439, PubMed:36745679). It plays an important role in stabilizing the substrate-bound homododecamer by mediating contacts between the two homohexamers (PubMed:36170828)
MBT repeats have unique discriminatory binding activity for methylated Lys residues in H3 and H4; the MBT repeats bind mono- and dimethylated H3K9Me1, H3K9Me2, H4K20Me1 and H4K20Me2 but fail to interact with these residues if they are unmodified or trimethylated
The unstructured C-terminal region is required for ribosome binding and peptidyl-tRNA hydrolase activity. The C-terminal tail functions as a sensor to discriminate between stalled and actively translating ribosomes by binding in the mRNA entry channel downstream of the A site between the head and shoulder of the 30S subunit. This allows the N-terminal globular domain to sample different conformations, so that its conserved GGQ motif is optimally positioned in the peptidyltransferase center (PTC) to catalyze the hydrolysis of peptidyl-tRNA. The N-terminal domain of ArfB is bound in the A site of the 50S subunit next to the P-site tRNA
The RPEL repeats mediate binding to globular actin (G-actin); each RPEL repeat-binding to one G-actin monomer (PubMed:19008859, PubMed:21673315). In addition, each intervening spacer sequence region can bind one G-actin monomer, to reach a pentavalent complex (PubMed:21673315)
The LIM zinc-binding domains mediate glucocorticoid receptor coactivation and interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG, TCF3, TCF7L2, SLC6A3 and SMAD3. The LIM zinc-binding 2 and LIM zinc-binding 3 domains mediate targeting to focal adhesions and actin stress fibers. The LIM zinc-binding 3 and LIM zinc-binding 4 domains mediate interaction with TRAF4 and MAPK15. The LIM zinc-binding 4 domain mediates interaction with HSPB1, homooligomerization and targeting to the nuclear matrix. The LIM zinc-binding 3 domain mediates interaction with PTPN12
The number of the intragenic tandem repeats varies between different S.cerevisiae strains. There is a linear correlation between protein size and the extend of adhesion: the more repeats, the stronger the adhesion properties and the greater the fraction of flocculating cells (By similarity). The Ser/Thr-rich repeats are also important for proper cell wall targeting of the protein
Contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria
The N-terminal 21 amino acids are necessary and sufficient for translocation into the host cell. The C-terminal region, composed of several highly conserved proline-rich repeats, interacts with the SH3 domain of BAIAP2 and BAIAP2L1, and the GTPase binding domain (GBD) of WASL/N-WASP and WAS/WASP. The N-terminal translocation signal and two proline-rich repeats are sufficient for triggering actin polymerization, but each additional repeat gives higher activity (By similarity)
Contains 2 BMC domains, trimerizes in a staggered manner to give a hexamer; each subunit in one trimer interacts with 2 subunits in the facing trimer. Each stacked hexamer can form a pore of about 14 Angstroms in diameter. Dimerization of the trimers forms a channel-like compartment, accessible via an open pore. This channel may be large enough to accomodate transport of substrates into and out of the carboxysome
The BURP domain located at the C-terminus has not been identified in non-plant proteins (PubMed:9790599). It is critical for PGL3's role in cell growth (PubMed:26106400)
The 2 bromo domains mediate specific binding to acetylated histones. The exact combination of modified histone tails required to recruit brd4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3 (By similarity)
The C-terminal histidine triad (HIT) motif and the N-terminal domain are required for the decapping activity
The CBM1 domain is essential for optimal xylanase activity
Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to be important for the association with nuclear receptors
Has an N-terminal adenylyltranferase and a C-terminal helical domain, with an ATP-binding cleft between them (PubMed:26527143, PubMed:29871922). Upon ATP binding the two domains reposition, antibiotics bind in this cleft (PubMed:29871922)
The heparin-binding region binds heparin glycosaminoglycan (PubMed:25605972, PubMed:34646012). Heparin-binding is required for ALKAL2-driven activation (PubMed:34646012)
The conserved lumenal (CL) domain (74-154) is present only in some FtsH homologs from organisms performing oxygenic photosynthesis
HMG box 2 mediates pro-inflammatory cytokine-stimulating activity and binding to TLR4 (PubMed:12765338, PubMed:20547845). However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance (PubMed:24474694)
The acidic C-terminal domain forms a flexible structure which can reversibly interact intramolecularily with the HMG boxes and modulate binding to DNA and other proteins (PubMed:23063560)
Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family. Apoptotic members of the Bcl-2 family
The tripartite motif (RBCC; RING- and B box-type zinc fingers and coiled coil domains) mediates dimerization
Associates with microtubules in a manner that is dependent on the C-terminal B30.2 domain
The C-terminal domain called the BARA domain is dispensable for the construction of both vps34 PI3-kinase complexes, but is specifically required for autophagy through the targeting of complex I to the preautophagosomal structure
The C-terminal domain recognizes the anticodon bases
The first Fibronectin type-III domain mediates a specific interaction with Hh protein, in vitro. The second Fibronectin type-III domain is additionally required for in vivo signaling activity
Contains a basic DNA-binding region at the N-terminus which is usually found in bZIP transcription factors, but does not contain the characteristic leucine zipper domain. Instead, four C-terminal ankyrin repeats were identified that were shown to confer protein-protein interaction of regulatory proteins
The homeobox domain binds to double-stranded DNA (PubMed:22849347)
Has a highly hydrophobic core sequence flanked at either side by cationic termini
The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3)
The N-terminal beta-barrel domain (residues 25-184) when reconstituted into lipid vesicles is blocked at both ends
The CRIB domain is involved in the interaction with CDC42
Forms a continuous, solvent-accessible conduit: a 'channel-tunnel' over 140 Angstroms long that spans both the outer membrane and periplasmic space. The periplasmic or proximal end of the tunnel is sealed by sets of coiled helices
The N-terminal domain is required for oligomerization and ATPase activity (PubMed:27770024, PubMed:29595954). The six N-terminal residues are necessary for proper oligomer formation, though their absence does not entirely preclude oligomerization (PubMed:29595954). The extreme N-terminus is also required for interaction with MxiN/SctL (PubMed:29595954). The N-terminal domain, not ATPase activity, is responsible for localization of Spa47/SctN to the injectisome (PubMed:31978132). The binding of ATP induces a conformational change of a highly conserved luminal loop, facilitating ATP hydrolysis (PubMed:30013545)
Domain KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules
The N-terminal domain confers transcriptional repressor activity, while the C-terminal domain mediates transcriptional activation
The C-terminus helps to anchor the porin to the outer membrane
The gene is quite polymorphic, the central region is subject to recombination between internal Glu-Pro-rich repeats (Probable). The polymorphic central region is not required for function, small segments in the N- and C-terminus are however required (PubMed:17601786)
The C-terminus (at least 10 residues, not detailed in paper) targets the protein to the nanocompartment
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (390-420) inactivates kinase activity under calcium-free conditions (By similarity)
This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa
The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex. Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection (By similarity)
The N-terminal domain (1-77) recruits and activates specific immune cells by interacting with CCR3-expressing cells
A conserved histidine residue in the third TMD (His-190) may play an essential role in the pH sensitivity of SLCO4A1/OATP4A1-mediated substrate transport
S100A16 proteins, but not other S100 proteins, have only one functional Ca(2+) binding site per monomer (PubMed:14684152, PubMed:17030513). Upon Ca(2+) binding, undergoes conformational changes leading to the exposure of hydrophobic patches which could be implicated in the Ca(2+)-dependent nuclear export. Binds Zn(2+) (PubMed:17030513). Ca(2+) and Zn(2+) do not bind to the same site (PubMed:17030513). Does not bind Cu(2+) (PubMed:17030513)
PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate ACAP1-binding to PIP2 or PIP3 containing membranes. Only one PH domain of one ACAP1 dimer inserts into the membrane, while the other PH domain acts primaryly to interact with adjacent ACAP1 dimers
The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions
The coiled-coil domain is essential for MVB sorting
The BRO1 domain may be involved in the binding to SNF7
The RING-type zinc finger mediates interaction with SUMO2 and localization to the nucleus. Also required for the E3 ubiquitin ligase activity (By similarity)
The GRIP domain binds to ARF1, which leads to the Golgi localization of RUD3
The CARD domain is involved in the interaction with CASP1 and CASP4/CASP11
The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding (PubMed:22536155). Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated (PubMed:22536155, PubMed:23818853)
The C-terminal part of Nlrp1b oligomerizes to form the core of the Nlrp1b inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments. The UPA region reduces the threshold needed for filament formation and signaling
Has three domains with a flexible linker between the domains II and III and assumes an 'L' shape (PubMed:9774974). Domain III is highly mobile and contacts RuvB
The tail domain binds to the cytoplasmic domain of both integrin beta-1a and beta-1d isoforms. The presence of Ca(2+) ions does not prevent binding of a fragment consisting of the second cysteine rich repeat and the tail domain but prevents the binding of the full-length protein (By similarity)
Residues 89 to 100 and 106 to 125 define the N-terminal activation domain (NTAD) and the central acidic activation domain (CAAD) respectively, which can function independently to promote high-level transcription of the target genes
The two fibronectin type-III-like domains, contained in the N-terminal part, form together a cytokine-binding domain
The Tudor domain recognizes and binds H3K36me3 (PubMed:23228662, PubMed:23273982, PubMed:23142980)
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 74-106, leaving each N-terminal inhibitory region (residues 26-62) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 26-62) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity (PubMed:11742976, PubMed:12923572, PubMed:17895376)
An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface (By similarity)
The longin domain is critical for the vacuolar localization
Homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity
Two distinct active sites are responsible for anti-C5aR and anti-FPR activity. They might be closely spatially related and might be overlapping
The cysteine framework is XXVII (C-C-C-CCC-C-C)
The PDZ domain mediates binding to a subset of proteins containing a PDZ-binding motif at the C-terminus: the specificity for PDZ-binding motif is provided by the 2 residues located upstream of the canonical PDZ-binding motif (By similarity). The PDZ domain also mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B) (PubMed:23563491)
The RRM domains are necessary but not sufficient for binding to APOB mRNA. Additional residues in the pre-RRM and C-terminal regions are required for RNA-binding and for complementing APOBEC1 activity
The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (PubMed:10356400)
The Rho-GAP domain is necessary for inhibiting contractile ring constriction during cellularization
The C-terminal domain (724-998) alone is able to regulate gene expression (PubMed:19343174, PubMed:23355006, PubMed:26339297). The C-terminal domain (724-998) is required and sufficient to maintain high steady-state levels of both sense and antisense RNA transcripts of the tRNA gene-associated retrotransposon TRE5-A (PubMed:21076008)
A.T hook involved in DNA-binding is important for the gene regulatory function in vivo
The proline-knot motif (70-79) may be involved in targeting to lipid bodies
The CTD-like region mediates membrane-binding and incorporation into large protein complexes
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. NanA has the following architecture: A1-T1-C1-A2-T2-C2-T3
MelA has a A-T-TE domain architecture. The adenylation (A) domain recognizes and activates the aryl acid substrates, and loads them onto the thiolation (T) domain. The thioesterase (TE) domain shares the missing condensation (C) domain function, and is responsible for condensation and final product release
Contains a dockerin-like region in addition to its catalytic domains, suggesting that this enzyme forms part of a cellulosome-like multienzyme complex
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA (PubMed:34020957). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (PubMed:34020957). SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (PubMed:34020957)
Has 82 approximate repeats of Cys-x-Cys-x-cys
The PH domain inhibits PKD catalytic activity in the absence of DAG, either by direct steric occlusion or distortion of the PKD catalytic cleft
Is composed of a ring composed by 9 residues, and a tail of 10 residues (Probable). The peptide is threaded when the C-terminal tail is inserted throught the isopeptide-bonded ring (Probable)
The tail domain participates in molecular interactions that specify the role of the motor domain (By similarity). It is composed of several tail homology (TH) domains, namely a putative phospholipid-binding myosin tail domain (also named TH1), an Ala- and Pro-rich domain (TH2), followed by an SH3 domain and a C-terminal acidic domain (TH3). The IQ domain and the TH1 region are essential for hyphal growth and for endocytosis. The SH3 domain together with the TH3 region are required for the organization of the cortical actin
The Pro-rich domain may mediate binding to SH3 domains
Potential homodimerization is mediated by the coiled coil domain
The RNA-binding region is essential for the localization to subnuclear bodies and its function
The SAM-like domain, although only slightly related to the SAM domain, apparently displays a similar function. It is essential for homodimerization, the interaction with ubc-9, and the formation of subnuclear bodies
The BTB domain might play a role in targeting to acrosomal vesicles
Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain (PubMed:12695512). Calcium can also bind, with stronger affinity, to another site beyond the Gla domain (By similarity). Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein (PubMed:12695512)
The region between residues 50 and 110, which contains the predicted coiled coil domain, is essential for interaction with YscY
The seven N-terminal amino acids are important for maintaining proper protein folding and increase temperature stability of the protein
The nuclear localization signals mediate translocation to the nucleus
The LEM domain is required for inner nuclear membrane (INM) localization and contains a BANF1 conserved binding motif which allows localization to chromatin (By similarity). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disk, both the LEM domain and the disordered regions are necessary for localization to the NE core (By similarity)
The disordered regions, also named low complexity domain, confer the ability to phase separate (By similarity). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disks, both the LEM domain and the disordered regions are necessary for localization to the NE core (By similarity). During NE reformation, the proline-arginine-rich sequence within the disordered region binds microtubules, targeting LEM2 condensation to spindle microtubules traversing the nascent NE (By similarity)
The winged-helix (WH) region (residues 403-511) activates the ESCRT-II/ESCRT-III hybrid protein, CHMP7, to form co-oligomeric rings around spindle microtubules to facilitate early nuclear sealing
Contains a negatively charged N-terminus and a positively charged C-terminus, which are both involved in sensing and/or transducing osmotic changes to the domain responsible for the translocation of the substrate glycine betaine (PubMed:9446558). The C-terminal domain is directly involved in K(+) sensing or K(+)-dependent activation of BetP (PubMed:15134432)
A conserved histidine residue in the third TMD (His-115) may play an essential role in the pH sensitivity of SLCO1B2/OATP1B2-mediated substrate transport
The LRR repeat region mediates homodimerization
Four hydrophobic segments are not embedded in the cytoplasmic membrane and form two large cytoplasmic loops
The C-terminus is required for interaction with SSB
The C terminus is necessary to target MCC-specific transporters into MCC and for the formation of the plasma membrane invaginations
The middle domain of ADA2a is sufficient for interaction with the HAT catalytic domain of GCN5
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 661, which is replaced by an Asn residue
Amino acids 110-145 are necessary and sufficient for phosphatidic acid binding, while amino acids 1-80 are only necessary
EF-hand 2 and EF-hand 3 domains are the low-affinity and the high-affinity calcium binding sites, respectively (PubMed:11980481, PubMed:26584024). EF-hand 1 and EF-hand 4 domains do not bind calcium due to substitutions that disrupt their respective Ca(2+) binding loops (Probable). The cooperative binding of calcium to the EF-hand 2 domain following EF-hand 3 domain calcium binding requires myristoylation (PubMed:12686556, PubMed:24189072). Calcium binding to the 2 EF-hand domains induces exposure of the myristoyl group through a protein conformation change, this process known as the calcium-myristoyl switch facilitates binding to photoreceptor cell membranes (PubMed:7630423)
Binds E-box via C2H2-type zinc finger domain
The C-terminus (residues 109-133) is required for stable association with the 30S ribosomal subunit in vitro
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (295-325) inactivates kinase activity under calcium-free conditions (By similarity)
The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif locates to a long loop in the arm domain called the bowtie tail. Integrin-binding stabilizes an alternative conformation of the bowtie tail (PubMed:21677751). Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1 (By similarity)
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). AQPF1 has NPS/NPA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
The N-terminal domain of NC, but not its zinc finger, is required for nucleoprotein complex formation and its chaperone activities
The helicase and foldase activities reside in two separate domains, the helicase in the N-terminus and the foldase in the C-terminus
The 3 X 5 AA repeats seem to be critical for the RNA folding activity
The N-terminal domain of JAKs mediates their interaction with cytokine/interferon/growth hormone receptors. Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 (By similarity)
The PHD-type zinc finger (599-665) binds to unmethylated histone H3 'Lys-4' (H3K4me0)
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone, an acyl carrier protein (ACP) domain, a methyltransferase (CMeT) domain responsible for the incorporation of methyl groups, and a reductive NADPH-binding domain that is required for NADPH-dependent product release
Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro) (By similarity). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro) (By similarity)
The PPxY motif 1 mediates interaction with NEDD4 (By similarity). The PPxY motif 2 is required for the coactivation function (By similarity)
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). FgAQP2 has NPA/NLA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
The CHHC region interacts with the 5' splice site of the U12-type intron
The atypical FHA domain contains a 'wing' insert and mediates binding to threonine-phosphorylated IRAK1
A beta-sheet wrapped around a long alpha-helix. Structurally similar to tubular lipid-binding (TULIP) superfamily proteins (PubMed:36403098). The structure of OrfX1-OrfX3 is very similar to OrfX2 from C.botulinum type A2 (AC C1FUH4, PDB:6EKV). The structure of C.botulinum type A2 P47 (AC C1FUH7, PDB:6EKT) is very similar to OrfX3 in the OrfX1-OrfX3 complex (PubMed:36403098)
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of psm3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable rad21 protein, forming a ring structure (By similarity)
Consists of an N-terminal domain, which is sufficient for the localization to the septal ring and is required for cell division, followed by a linker domain, and a C-terminal domain, which forms the translocation motor involved in chromosome segregation. The C-terminal domain can be further subdivided into alpha, beta and gamma subdomains. The alpha and beta subdomains multimerise to produce a hexameric ring, contain the nucleotide binding motif and form the DNA pump. The gamma subdomain is a regulatory subdomain that controls translocation of DNA by recognition of KOPS motifs and interacts with XerD recombinase (Probable)
Contains large globular domains required for ATP hydrolysis at each terminus and a third globular domain forming a flexible SMC hinge near the middle of the molecule. These domains are separated by coiled-coil structures. The N- and C-terminus interact to make up an ATP-binding cassette-type ATPase domain. The SMC hinge domain mediates dimerization and binds DNA
The C-terminal 21 residues (later called magnetite-interacting component, MIC, residues 112-133) self assemble into multimers up to octamers; this fragment binds Fe(3+) which alters its structure. Also binds Fe(2+)
The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding (By similarity)
May include a tubular lipid-binding (TULIP) domain (residues 2-258)
Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing (PubMed:29276085)
The TPR repeats form 3 domains; the TPR 1 domain is composed of TPR 1, 2 and 3 repeats, the TPR2A domain of TPR 4, 5 and 6 repeats and TPR2B domain of TPR 7, 8 and 9 repeats
The PQA region (for proline, glutamine and alanine-rich) helps stabilize SOX9 and facilitates transactivation (PubMed:31194875). It lacks intrinsic transactivation capability (PubMed:31194875)
This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain
The DH (DBL-homology) domain promotes tyrosine phosphorylation of RIPK2 (By similarity). The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA
Binding to the autoinducer occurs via the N-terminal 170 residues; as E.coli does not produce LuxI autoinducers endogenously it should be able to bind to a number of different AI-1 autoinducers, which would enable it to detect other bacteria. This was shown to be the case
The C2HC MYST-type zinc finger is required for interaction with MCM2 and ORC1
The N-terminus is involved in transcriptional repression, while the C-terminus mediates AR-interaction
AF-2 (activation function-2) motif is required for recruiting coregulators containing the LXXLL motif, such as NCOA1, and control the transactivational activity (PubMed:8816759, PubMed:11689423)
The death domain mediates interaction with RANBP9 (By similarity). It also mediates interaction with ARHGDIA and RIPK2 (By similarity)
The non-canonical Cys-56 facilitates the zinc ion release from the zinc finger domain
The DEP domain is required for cell membrane localization
The C-terminal region binds up to 7 nickel ions in a non-cooperative manner. Can also bind zinc with high affinity, and copper or cobalt with lower affinity. No binding detectable for ferrous, ferric, magnesium and calcium ions. Binding of nickel causes conformational rearrangements in the PPIase domain, modulating its isomerase activity. This region is also important for hydrogenase biosynthesis
The C-terminal putative coiled-coil domain is necessary for interaction with TSC2
Alpha-helical parts of the C-terminal intracellular region may mediate heterodimeric interaction with gbb-2
Several domains are necessary for interacting with OS9. The region in the cytoplasmic tail that is necessary for interaction with OS9, is also required for its transport (By similarity)
The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity (By similarity). Essential for glycosylation of FGF23 (PubMed:31932717)
The DFDF domain is unstructured by itself. It assumes a helical fold upon interaction with DDX6
The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes. In PLD beta, all the calcium-coordinating acidic amino acids are conserved
The F-box-like domain is related to the F-box domain, and also functions to recruit ubiquitin E3 ligase complexes
Is composed of four domains: a catalytic domain, two beta-sandwich domains that may mediate interactions with substrate, and the propeptide domain
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 82 and 124
Consists of 3 domains; the N-terminus (residues 1-112) binds the ribosome, the middle domain (residues 150-246) has PPIase activity, while the discontinuous C-terminus (residues 113-149 and 247-432) binds substrate and has intrinsic chaperone activity on its own
The protein is composed of 2 domains; the N-terminal domain contains the phospholipase C active site (PLC), in a cleft which is also occupied by the 3 zinc ions. The C-terminal domain is a putative phospholipid-recognition domain, which shows structural homology with phospholipid-binding C2-like domains from a range of eukaryotic proteins. The ability to bind membrane phospholipids in a Ca(2+) dependent manner and toxicity is conferred by this C-terminal domain, which also contributes to the sphingomyelinase activity (By similarity)
The atg8 interacting motif (AIM) is required for the interaction with atg8 (PubMed:33138913). The AIM motif is required for atg43 function as mitophagy receptor (PubMed:33138913)
The SH3 and proline-rich domain is required for the interaction with TSPO and the second SH3 domain mediates binding to a proline-rich motif in RIMS1 and RIMS2
The calcium-binding site is essential for the translocation of fructooligosaccharide (FOS) substrates by the transporter
The C-terminal half (AA 167-368) is able to bind cyclin-B and shows a self-ubiquitination activity (mono-, poly, or multi-ubiquitination) in a HECT-like sequence dependent manner
The SAM, Protein kinase and SH3 domains are required for sperm formation
The SAM and SH3 domains are required for localization to clathrin-coated vesicles in spermatocytes
The Pro-rich domains are flanked by Arg/Gly-rich motifs which can be asymmetric dimethylated on arginine residues to give the DMA/Gly-rich regions. Selective methylation on these motifs can modulate protein-protein interactions
Although this has the same function as TubR of B.thuringiensis subsp. israelensis there is little sequence homology and the dimerization interface is different
The N-terminal section (alone) shows no toxic effect when injected into the host. This section may function in stabilizing the catalytic part of the protein, or in directing it to specific target sites of action (By similarity)
The RING-type domain is necessary for E3 ubiquitin ligase activity
The JmjC domain is involved in histone H3 binding
The central Gln-rich region (Q domain) is involved in binding to PI4KB, TBC1D22A and TBC1D22B (By similarity). The C-terminal GOLD domain is essential for giantin binding. The GOLD domain is also involved in homodimerization (By similarity)
The acidic C-terminal domain forms a flexible structure which can reversibly interact intramolecularily with the HMG boxes and modulate binding to DNA and other proteins; may involve Lys-3 and histone H3 'Lys-37' and 'Lys-38'
The seven repeat domain is responsible for dimerization
Contains many imperfect repeats of a consensus octapeptide A-G-Y-G-S-T-L-T; further on a 16-residue and a regional 48-residue periodicity is superimposed
The SH3 domain binds to PtdIns(4)P
Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains (PubMed:15284228). The two ATP-binding domains interact with each other, forming a head-to-tail dimer (PubMed:17036051). Normal ATPase activity requires interaction between the two domains (PubMed:15284228). The first ABC transporter nucleotide-binding domain has no ATPase activity by itself (By similarity)
The R region is intrinsically disordered (PubMed:10792060, PubMed:17660831). It mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation (PubMed:10792060)
Has three domains with a flexible linker between the domains II and III, and assumes an 'L' shape. Domains I and II are responsible for tetramerization and subsequent octamerization. The flexible linker plus domain III (residues 129-191 in this study) interacts with RuvB
The wedge motif stacks with DNA close to the Holliday junction point; Arg-76 interacts with and eventually disrupts the T:A base pair cleavage site, and subsequent to cleavage may prevent their reannealment
Binds a calmodulin chain via each of the two IQ domains (PubMed:12719468, PubMed:15853803). IQ domain 1 mediates interaction with calmodulin both in the presence and in the absence of Ca(2+). IQ domain 2 mediates interaction with calmodulin in the presence of Ca(2+) (PubMed:8034741, PubMed:15853803)
The N-terminal intrinsically disordered region (IDR) facilitates its liquid-liquid phase separation (LLPS) in the nucleolus (PubMed:33443146). In the IDR, the lysine-rich domain mediates self-association and targeting to the nucleolus (PubMed:33443146)
The actin-binding domain 1 (also called ABD1) seems to not bind F-actin alone while the second actin-binding domain (ABD2) can bind F-actin alone. EF-hand domain and the last 65 C-terminal amino acids are not required to cross-link F-actin, but enhance the stability of the binding
A flexible loop interacts with the SHH zinc binding site and contributes to zinc binding
The EEXXXDDL motif at the C-terminus is required for the interaction with atm and its recruitment to sites of DNA damage and promote the phosphorylation of atm substrates, leading to the events of DNA damage response
The coiled-coil domain is required for BECN1- and PIK3C3-binding and for autophagy
The final 80 residues in the C-terminus define a minimum required region for autophagosome binding called BATS
The N-terminal cysteine repeats are required for proper localization to the endoplasmic reticulum
A central region (about residues 21-47) is involved in dimerization, but multimerization requires other residues (PubMed:8755860, PubMed:9398522, PubMed:16650431, PubMed:12460581, PubMed:12592399). The dimerization domain (1-47) also acts as a hinge; changes in its structure probably impact oligomerization and DNA-binding geometries (PubMed:23601147). The N-terminus also interacts with Hha, perhaps via residues 2-18; a well-folded dimer is not necessary for Hha binding (PubMed:16650431). The C-terminus (residues 92-137) binds DNA (PubMed:8913298). Residues in the N-terminus contribute to DNA-binding and to discrimination between curved and non-curved DNA (PubMed:12592399)
In contrast to classical PTS systems, the fructose-specific PTS has no requirement for HPr and Enzyme I; FruB combines a IIA domain with an Enzyme I and a HPr domains
The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGF binding
The acceptor mannose ring localizes in a cavity at the end of a surface-exposed long groove where the active site is located, whereas the palmitate moiety accommodates into a hydrophobic pocket deeply buried in the alpha/beta core of the protein
The cytosolic nudix box binds ADP-ribose and is required for channel activation by ADP-ribose
The PDZ domain is dispensable for protease and chaperone activities
The PP1-binding domain is located between residues 59 and 94. The glycogen-binding domain is located between residues 94 and 257. The PYGL-binding site lies in the C-terminal 16 amino acids
The pyrin domain mediates homotypic interaction with PYCARD/ASC
The HIN-200 domain mediates dsDNA binding via electrostatic interactions
Both the bHLH region and the C-terminal portion are essential for inhibitory function
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of ddp-1/tim-8 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane
The PH domain is responsible for the interaction with the 3-phosphoinositides. The activation loop within the kinase domain is the target of phosphorylation. The PIF-binding region in the kinase domain of PDK1 acts as a docking site, enabling it to interact with and enhance the phosphorylation of substrates containing the PIF motif
The N-terminus is necessary for DNA-binding. The C-terminus is necessary for transcriptional activation (PubMed:11832226)
The CTCK domain mediates interchain disulfide bonds with another molecule of MUC2
The basic N-terminal Arg/Pro-rich binds heparin and heparan sulfate. Binds collagens type I and type II through its leucine-rich repeat domain
ProSAAS(1-180) increases secretion of enzymatically inactive PCSK1
The C-terminal inhibitory domain is involved in inhibition of PCSK1. It corresponds to the probable processing intermediate Big PEN-LEN, binds to PCSK1 in vitro and contains the hexapeptide L-L-R-V-K-R, which, as a synthetic peptide, is sufficient for PCSK1 inhibition
The four C-terminal amino acids of Big LEN are sufficient to bind and activate GPR171
The BRCT domain is required for interaction with RAP74
The jas domain (123-148) is required for interaction with COI1
The interaction with ATN1 is mediated by the coiled domain
The C1 zinc finger does not bind the diacylglycerol (DAG)
The twin Cx9C motifs are involved in the recognition by the mitochondrial mia40-erv1 disulfide relay system and the subsequent transfer of disulfide bonds by dithiol/disulfide exchange reactions to the newly imported protein
The C-terminal wHLH region seems to mediate telomere-specific function
The C-terminal domain is able to act as both DNA-binding domain and a transcriptional activator. The N-terminal domain is also required for transactivation activity on some target genes acting as a discrete activation domain. Neurite outgrowth and expression of genes required for synapse formation are primarily dependent on the C-terminal domain, however the N-terminal domain is required for maximal induction
BRCT domains are necessary for its targeting to ionizing radiation-induced nuclear foci
The Tudor domain 2 mediates reading of dimethyl-lysine residues
The Tudor domain 1 doesn't bind dimethyl-lysine residues, due to an atypical and occluded aromatic cage
Contains an unusual winged helix-turn-helix (wHTH) DNA-binding motif missing the typical third helix
The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins
The periplasmic domain interacts in vitro with purified peptidoglycans
Multidomain protein with an N-terminal glucosyltransferase domain and a C-terminal phosphatidylinositol 3-phosphate-binding domain, which guides the Legionella effector to the surface of the Legionella-containing vacuole. Both domains are essential for the cellular effects on the eukaryotic host
The N- and C-terminal portions are exposed to the cytoplasm. Lacks a typical peroxisomal sorting signal. A region between helical transmembrane domains (TM) 4 and 5 and TM1-TM3 or TM4-TM6 are necessary for the peroxisome-targeting activity
The TBM domain mediates interaction with terf2
G domain binds GTP and has GTPase activity
Arf-GAP domain interacts with G domain and may regulate its GTPase activity
Although both PH domains of isoforms 1 and 2 bind phospholipids, they differently regulate subcellular location. PH domain of isoform 1 directs the protein to the nucleus, but PH domain of isoform 2 directs it to the cytosol. PH domain of isoform 2 is required for binding to AP-1
Contains an helical zipper domain, consisting of five N-terminal helices from each subunit, which forms the molecular dimer axis
The N-terminal domain carries structural determinants essential for agonist and antagonist binding. The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits (PubMed:26416729). The cytoplasmic loop is an important determinant of channel inactivation kinetics
Sushi domains 1 and 2 are required for interaction with Measles virus H protein. Sushi domains 3 and 4 are the most important for interaction with C3b and C4b
The Tudor-like region mediates binding to histone H4 dimethylated at 'Lys-20' (H4K20me2) (PubMed:23209566). Interaction with NUDT16L1/TIRR masks the Tudor-like domain and prevents recruitment to chromatin (By similarity)
The UDR (ubiquitin-dependent recruitment) motif specifically recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15ub). Phosphorylation of the UDR blocks interaction with H2AK15ub
The N-terminal domain possesses xylanase activity, the central region likely has xylan deacetylase activity, and the small C-terminal domain is involved in carbohydrate-binding
Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 is required for Neisseria binding. Sushi domains 3 and 4 are required for interaction with Streptococcus pyogenes M protein and are the most important for interaction with C3b and C4b
Has a penicillin-insensitive transglycosylase/glycosyltransferase (GT) N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (PubMed:10217767, PubMed:12867450, PubMed:22487093). Transmembrane signal-anchor is required for the synthesis of longer, 20-30 disaccharide units containing, glycan chains (PubMed:22487093)
The hinge domain contributes significantly to its chemotactic properties
The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene
The amino terminus contains an intrinsic kinase activity. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins
The RING-type zinc finger domain may be essential for ubiquitin ligase activity
XPG-N, XPG-I,5'-3' exonuclease domains interact with DNA. Contains a chromodomain that acts as additional DNA interaction site and is required for efficient DNA recognition and cleavage
Lacks an FAD-binding domain present in all the other members of the family
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 208, which is replaced by an Asn residue
Composed of 2 N-terminal SH2 domains and a C-terminal kinase domain. The tandem SH2 domains bind to the doubly phosphorylated tyrosine-based activation motif (ITAM) of CD247/CD3Z and the non-canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH (By similarity). The interdomain B located between the second SH2 and the kinase domain contains 3 tyrosines (Tyr-292, Tyr-315, Tyr-319) that are phosphorylated following TCR activation. These sites have been implicated in binding to other signaling molecules including CBL or VAV1. Thus, ZAP70 can also function as a scaffold by recruiting additional factors to the stimulated TCR complex
Segments of the N- and C-terminal domains (residues 19-36 and 515-532, respectively) are predicted to be amphipathic helices and are essential for endoplasmic reticulum membrane association (PubMed:25093817)
The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are propbably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (By similarity)
Residues 1182-1199 comprise a putative nuclear localization signal; nuclear localization is required for the regulation of period length of the circadian clock
The DNA-binding domain (residues 816-954) binds to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and has high affinity for DNA sequences rich in guanine that form G-quadruplex (G4) structures
The C-terminal domain, comprising the DNA-binding domain and the PARP1-binding region, is required for the replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures
The basic motif confers specificity for the CHRNB3 promoter
Formed of E- and discontuous A- and P-loops. A-loops form the main pores while A- and E-loops are the most flexible parts. E- and P-loops of neighboring monomers arrange head-to-tail and form a chainmail topology
The conserved PP2C phosphatase domain (244-663) is interrupted by an insertion of approximately 100 amino acids
The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (By similarity)
The PX domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate
The N-terminal tandem family 41 carbohydrate-binding modules (CBM) are involved in carbohydrate binding. The C-terminal glycosyl hydrolase 13 (GH13) domain is involved in catalysis
Contains a C-terminal (199-277) carbohydrate-binding domain (CBM)
Mature protein (about residues 103 to 571) has 3 discontinuous domains; D1 (residues 103-124, 161-249, 300-345 and 421-444), D2 (residues 125-160 and 445-461), D3 (residues 250-299 and 346-420) followed by C-terminal D4 (residues 462-571)
Isoforms A and C contain and additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties
The C-terminal half of the protein (residues 225-494) is required for interaction with most RNA degradosome partners, whereas dimerization or oligomerization only requires the extreme C-terminus (residues 413-494). Addition of the latter domain to CshB confers on it the ability to interact with Rny
The EVH1/WH1 domain is necessary for cortical localization
The TIR domain mediates NAD(+) hydrolase (NADase) activity. The cyclic nucleotide binds in C-terminal bacterial STING region. Comparison of structures from 2 different bacteria suggests that cyclic nucleotide binding causes domain rotation to form a lid which seals the nucleotide-binding pocket
RI-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer
The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain
The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization
The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity (By similarity)
Contains a N-terminal NAI2 domain (472-772)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (349-379) inactivates kinase activity under calcium-free conditions (By similarity)
Each subunit is composed of three distinct structural regions: an N-terminal polypeptide, a central four-helix bundle that serves as the scaffolding for the catalytic active site, and a C-terminal tail
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (343-373) inactivates kinase activity under calcium-free conditions
The N-terminal sequence (1-53) is sufficient for vacuolar targeting
Gln-155 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (By similarity). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By similarity). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation
The C2 domain 2, but not the C2 domain 1, is necessary for calcium-mediated membrane association. The linker region is necessary for calcium-dependent cell membrane association
Residues 17-29 of LL-37 represent the active core of the antimicrobial peptide (PubMed:32753597, PubMed:35061360). Forms ribbon-like fibrils and exhibits antibacterial activity against Gram-positive M.luteus (MIC=22-25 uM) and S.hominis (MIC=39 uM) (PubMed:32753597, PubMed:35061360). Also exhibits antibacterial activity against Gram-negative E.coli (MIC=47 uM) and P.fluorescens (MIC=136 uM) (PubMed:35061360)
The PCNA interacting protein (PIP) box mediates interaction with PCNA and recruitment to DNA single-strand breaks
The transmembrane domain contains polar residues that mediate the recognition by TUL1
The SPOR domain binds septal peptidoglycans and is required to target RlpA to the septal ring
It seems that PigJ is composed by an active ketosynthase (KS) domain and by a chain length factor (CLF) partner domain that potentially decarboxylates the malonyl group of PigH
Contains two cysteine rich domains (CRD), referred to as the N- and C-terminal CRD's, n-CRD (Cys-303, Cys-310 and Cys-315) and c-CRD (Cys-598, Cys-620 and Cys-629), respectively. Cys-315 is not conserved in orthologs in other yeast species. A nuclear export signal is embedded in the c-CRD, with which the nuclear export protein CRM1/exportin 1 interacts only in the absence of disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or between the c-CRD and the n-CRD
The calcium-binding site is structurally similar to that of EF-hand proteins, but is in two parts, with the last calcium ligand provided by Glu-229
The NLS/NES region (98-121) is necessary and sufficient for interaction with CPK11
The rat light chain has an octopeptide insertion after residue 158 compared with other light chains
Each subunit can be divided into three discernible structural domains: the lid domain, the nucleotide-binding domain, and the C-terminal dimerization domain. PdxB has a unique dimeric structure among NAD-dependent D-isomer specific 2-hydroxyacid dehydrogenases due to the presence of its dimerization domain at its C-terminus
Forms salt bridges between the 2 toxin molecules mediated by Glu-127 Glu-128 on one subunit and Arg-46 Arg-149 on the other
Has a bilobed structure, with the REC lobe (residues 35-526) connected to the NUC lobe (residues 1-35 and 526-1307) by a discontinuous wedge domain (PubMed:27114038, PubMed:27444870). The crRNA-target DNA heteroduplex is bound in the channel between the 2 lobes (PubMed:27114038, PubMed:27444870). One nuclease site is found in the discontinuous RuvC domain which probably cuts target DNA strand in the crRNA-DNA heteroduplex (residues 884-940, 957-1066 and 1262-1307), the other in the NUC domain and probably cuts the non-target DNA strand outside the heteroduplex (residues 1067-1261) (PubMed:27114038). Target DNA binding induces domain movement (PubMed:27444870)
The C-terminal extracellular domain containing the PASTA repeats binds peptidoglycan
The N-terminal 3'-phosphoesterase domain (PE) has 3'-ribonuclease and 3'-phosphatase activities
The central ATP-dependent ligase domain (Lig) functions as an independent domain
The C-terminal polymerase/primase domain (Pol) (PubMed:15520014) adds up to 4 rNTPs in a DNA template-directed fashion (PubMed:15897197)
The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction
The N-terminus (residues 1262 to 1601) functions to regulate both GflB-GEF activity and its localization at the leading edge of cells by binding F-actin directly
Each of the two pore-forming region (also called P-domain or P-loop) is enclosed by two transmembrane segments (2P/4TM) and contains the GYGD signature motif which seems to be involved in potassium selectivity. The C-terminus (328-363) is required for vacuolar targeting
The PWI domain binds nucleic acids with significant help from its N-terminal flanking basic region. It has an equal preference for binding to single- or double-stranded species, and it contributes to RBM25 role in modulation of alternative splicing, maybe by mediating RNA-dependent association with LUC7L3
Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases, including PTPN6/SHP-1, resulting in the dephosphorylation of the downstream protein kinases SYK and BTK
The first 2 SH3 domains are required for WASF1-binding. All 3 SH3 domains can bind independently to PTPN12
The C-terminal part associates with the head of SMC1, while the N-terminal part binds to the head of SMC3
Comprised of three regions: a N-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region
The two catalytic domains appear to be functionally coupled
The C-terminal domain (CTD) is probably responsible for hetero- and homodimerization; it assumes a V-shaped, dimeric metallo-chaperone-like fold that can open and close. Binds up to 3 divalent metal cations (probably iron in vivo); upon binding there is a conformational shift to a tighter dimer
Contains several extensin-like repeats in the C-terminal section
Ths GST-like domain mediates the interaction to eEFB1 and may be responsible for dimerization of the eEF1 complex
The PPIase FKBP-type domain seems to be inactive both for FK506-binding and enzymatic activity
The central coiled-coil region is responsible for association with early endosomes
Consists of 3 domains; the ATPase domain (residues 1-220), the transducer domain (221-392) and the toprim domain (393-804) (PubMed:1646964, PubMed:10734094). ATP-binding is cooperative, and both subunits must be wild-type at residue 103 for supercoiling to occur (PubMed:8621650). Non-hydrolyzable ATP analogs (and ATP-binding) induce dimerization and enhance ATPase activity (PubMed:10734094, PubMed:9657678). ATP hydrolysis induces domain shifts that are probably part of the mechanism of DNA cleavage and rejoining (PubMed:25202966)
The specificity for linear polyubiquitin is given by the 'Glu-16' residue in ubiquitin chain
The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31 (PubMed:24726323, PubMed:24726327, PubMed:27458237). Does not interact with other PUB domain-containing proteins. Phosphorylation at Tyr-56 prevents interaction with RNF31 (PubMed:24726323, PubMed:24726327)
The 'non A-beta component of Alzheimer disease amyloid plaque' domain (NAC domain) is involved in fibrils formation. The middle hydrophobic region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments
The silencing domain, also known as C-terminal effector domain (CED), can act in autonomous repression, including both translational inhibition and mRNA degradation
Contains a novel ssDNA-binding fold, which is structurally and topologically distinct from the OB-fold universally found in standard SSB proteins. The disordered C-terminus of DdrB may mediate interactions with other proteins important for DNA damage recovery
The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins. The two C2 domains bind independently to planar membranes, without interdomain cooperativity. Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (325-355) inactivates kinase activity under calcium-free conditions
The TIR domain alone is active and produces cADPR (residues 134-258). It dimerizes in crystal structures
The PCI domain is necessary and sufficient for the interactions with other CSN subunits of the complex (By similarity). Mediates the interaction with CAPN8
The N-terminal part (1-196), which is not required for deneddylating activity and CSN complex formation, is nevertheless essential for other aspects of CSN complex function, such as repression of c-fos/FOS expression
The CRD1 domain (cell cycle regulatory domain 1) mediates transcriptional repression of a subset of p300 responsive genes; it can be de-repressed by CDKN1A/p21WAF1 at least at some promoters. It conatins sumoylation and acetylation sites and the same lysine residues may be targeted for the respective modifications. It is proposed that deacetylation by SIRT1 allows sumoylation leading to suppressed activity (By similarity)
Contains a proline-rich domain. The insertion of this domain in the DRBM 2 domain is required for stau-oskar mRNA localization
DRBM 3 domain binds optimally to stem-loops containing 12 bp (in vitro)
The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation (By similarity)
The protein kinase domain is predicted to be catalytically inactive. As the kinase activity is required for activation of the endoribonuclease domain, the protein could be inactive
The N-terminus (residues 1-181) is sufficient for the interaction with SCC4 (PubMed:26038942)
The C-terminal cystathionine beta-synthase (CBS) domains can bind different numbers of S-adenosyl-L-methionine (SAM) and S-methyl-5'-thioadenosine (MTA) ligands. Binding of SAM and MTA triggers a drastic conformational change in the protein, which evolves progressively from an open form in the absence of ligands to a closed form when the four sites are fully occupied
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Ser (NPA)
The SlyX motif may be involved in the non-conventional secretion of the protein
The PABA component provides the glutamine amidotransferase activity
The PABB component catalyzes the formation of ADC by binding chorismate and ammonia
Contains many Ser/Thr-rich domain and repeats
The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity
The non-repeat region (NRR, also called binding region, BR) binds to whole cell lysates of wild-type but not bacteria deleted of this gene; it also recognizes whole cell lysates of S.gordonii strain M99 probably via GspB, but not lysates of S.pneumoniae TIGR4 (PubMed:20714350). The NRR is acidic, with a predicted pI of 5.69 in strain ISP479C (PubMed:19202081). The NRR has 4 discrete modules that align end-to-end to form a slightly bent rod. The first is an L-lectin module which binds 1 Ca(2+) ion and N-acetylneuraminic acid (Neu5Ac), and mediates adhesion to human lung epithelial cells (A549 cell line), probably via sialylated receptors. Neu5Ac inhibits binding of A549 cells by the NRR domain. The second beta-grasp module adopts a ubiquitin-like beta-grasp fold which resembles the Ig-binding superfamily, while the 2 other modules resemble cadherins; the cadherin-like modules each bind a Ca(2+). Ca(2+) binding rigidifies the cadherin-like modules and extends the molecule (PubMed:24901708)
The VHS domain mediates high-avidity binding to Lys63-linked and Lys48-linked polyubiquitinated cargos
Macro domains 1 and 2 may be involved in the binding to poly(ADP-ribose). Macro domain 2 is required for recruitment to DNA damage sites. Macro domains 1 and 2 are probably dispensable for the interaction with STAT1 and DTX3L and for STAT1 phosphorylation
The mature protein has 3 domains; a metalloprotease domain (S1, approximately residues 53 to 727) and 2 collagen-binding domains (CBD) (755-872) and (882-991) (PubMed:18937627). The metalloprotease S1 domain is composed of 3 subdomains which together resemble a saddle; an activator domain (residues 57-330), the catalytic peptidase subdomain (340-611) and a helper subdomain (619-731) (PubMed:23703618)
Contains 2 cytoplasmic nucleotide binding domains (NBDs). The N-terminal NBD has ATPase activity. The 2 NBDs are asymmetric and non-exchangeable and the drug efflux by CDR1 involves complex interactions between the two halves of the protein
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). NRPS10 has the foolowing architecture: A-T-C-A-T-C (PubMed:27390873)
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-62 in the first module and Ile-288 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity
Kinase-interacting sequence (KIS) is required for interaction with KIN10 or KIN11
The pore-forming region (also called P-domain or P-loop) is enclosed by two transmembrane segments (1P/2TM) and contains a pseudo GYGD signature motif such as GYFD which seems to be involved in potassium selectivity
C-terminal half (amino acids 134-284) contains cytoplasmic retention domains as well as determinants involved in its stress-induced nucleolar accumulation
The extracellular domain is required for the direct sensing of alkaline pH
Adopts a canonical dual specific tyrosine phosphatase (DUSP) fold, similar to eukaryotic DUSPs (PubMed:25909591). Conformational changes occur upon ligand binding (PubMed:25909591)
Both PH domains are essential for its mitochondrial localization
Although this has the same function as TubR of B.cereus strain ATCC 10987 there is little sequence homology and the dimerization interface is different
The conserved TPR domains are dispensable for ciliary targeting. The N-terminal half is important for cilary localization and/or binding to the axoneme
The N-terminal domain binds DNA and the C-terminal region plays a pivotal role in dimer formation
Forms a right-handed beta-helix with 5 complete coils that stack upon each other
The N-terminal region is required for repressor function
The mature protein is largely unstructured in the absence of a cognate ligand, and has a strong tendency to form fibrillar aggregates
The PH domain is essential for regulated exocytosis and binds phospholipids and plasma membrane. It however does not mediate binding to DCVs
Partially oxidized VKORC1 forms a cysteine adduct with substrates, vitamin K 2,3-epoxide, inducing a closed conformation, juxtaposing all cysteines (S-S or SH) for unimpeded electron transfer (PubMed:33154105). VKOR becomes fully oxidized with an open conformation that releases reaction products, vitamin K quinone, or hydroquinone (PubMed:33154105). Cys-138 and Cys-141 constitute the catalytic redox-active center (PubMed:33154105). Cys-49 and Cys-57 are the cysteine pair that mediates transfer of reducing equivalents during catalysis (PubMed:33154105)
The carbohydrate binding modules (CBM) bind to insoluble beta-1,3-xylan, but not to insoluble beta-1,4-xylan, beta-1,4-glucan, beta-1,4-mannan, curdlan, chitin, or soluble polysaccharides
Two classes of cysteines are involved in transport of acetylcholine. Binding of acetylcholine to VAChT involves one class of cysteine located at the cytoplasmic N-terminus and binding of vesamicol involves both. Organomercurial-mediated modification of two cysteine residues inhibits binding of vesamicol
The N-termimus domain is necessary and sufficient for its targeting to subnuclear cajal and histone locus bodies
S100A16 proteins, but not other S100 proteins, have only one functional Ca(2+) binding site per monomer. Upon Ca(2+) binding, undergoes conformational changes leading to the exposure of hydrophobic patches which could be implicated in the Ca(2+) -dependent nuclear export. Binds Zn(2+). Ca(2+) and Zn(2+) do not bind to the same site. Does not bind Cu(2+)
The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity. It lacks the O helices present in high-fidelity DNA polymerases in the fingers domain (By similarity)
The NG domain region, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the signal recognition particle (SRP) complex subunit SRP54 (PubMed:34020957). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (PubMed:34020957). GTPase induced rearrangement of SR drives SRP-mediated cotranslational protein translocation into the ER (PubMed:34020957)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (Probable)
The N-terminal 16 amino acids are sufficient for the cell membrane targeting of a heterologous protein
The acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules
The TRFH dimerization region mediates the interaction with TINF2
Although this protein contains a RING domain, intrinsic E3 ligase activity has not been proven
The C-terminal region mediates cholesterol-binding
The RKKR polybasic motif mediates binding to acidic phospholipids, such as phosphatidic acid, phosphatidylinositol and phosphatidylserine, inhibiting the ability to mediate lipid droplet fusion
The C-terminal domain is sufficient for glucosyl-1-phosphate transferase activity
Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane. Each cadherin domain binds three calcium ions (PubMed:27161523)
Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that captures N-terminally myristoylated target peptides (PubMed:21642972). Phe residues within the hydrophobic beta sandwich are required for myristate binding (PubMed:22085962)
Instead of having the common DXD motif at the position 130-132, it contains a DTG sequence, which may provide greater metal ion binding flexibility
The RING-type zinc finger domains mediate binding to an E2 ubiquitin-conjugating enzyme
The histidine-N-terminal metal-binding domain (His-N-MBD) seems to have a regulatory role affecting the metal transport rate by controlling the metal release/dephosphorylation rates
Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions
The ANK repeats specifically recognize and bind H3K9me1 and H3K9me2 (By similarity). They also specifically recognize and bind RELA subunit of NF-kappa-B, when RELA is monomethylated at 'Lys-310'
The DIM domain (182-263) is required for heterodimerization
Consits of two domains, an N-terminal domain that resembles the so-called Fe/S A-type scaffold, and a C-terminal domain that shares sequence identity with Nfu-type scaffold proteins. Both domains are important for NfuA to fulfill its function in vivo. The N-terminal domain does not possess the three conserved cysteine residues thought to act as Fe/S cluster ligands in A-type scaffold proteins, but may keep the ability to interact with apoproteins
The PDZ domain is required for interaction with GRID2, PLCB3, SLC9A3 and CFTR
The mechanism appears to be controlled by at least two key structural features of the protein (PubMed:35377837). One of these is the cytoplasmic N-terminal domain, which is crucial for bidirectional translocation of formate across the membrane, suggesting a 'gate-keeper' function controlling anion accessibility (PubMed:33169422). The other structural feature involves two highly conserved amino acid residues: Thr-91 and His-209 (PubMed:35084298, PubMed:35377837, PubMed:35390794). Thr-91 is essential for the ability of FocA to translocate formate in both directions (PubMed:35390794). The centrally located His-209 residue within the pore of FocA is essential for efficient, pH-dependent formate uptake into the cell, but is dispensable for formate efflux (PubMed:35084298, PubMed:35390794). Interplay between Thr-91 and His-209 controls formate translocation (PubMed:35390794)
The C-terminal calcium-binding beta-jelly roll domain (445-562) of the mature domain is not required for folding or activity, but it is required for the hyperstabilization of the protein and possibly for its adaptation to high-temperature environment
The C-terminal region (aa 216-289) represents the dimerization motif
The N-terminal domain is followed by a GAF (phytochrome-like) domain that lacks the conserved Cys residue for ligand binding, a histidine kinase domain and a C-terminal response regulator domain without the conserved Asp residue that is phosphorylated (pseudo-receiver domain, PsR) (PubMed:10926536, PubMed:12626498). Autophosphorylation is dramatically reduced in the absence of the N-terminus (residues 1-183), and lacking in the absence of the GAF domain; removal of PsR increases autophosphorylation 10-fold. Thus PsR may suppress the histidine kinase domain (PubMed:12626498, PubMed:16629668). The GAF and PsR domains are required to complement the deletion strain (PubMed:16629668). The PsR domain is responsible for DBMIB sensitivity and binds quinones directly (PubMed:17088557). A KaiB mutant locked in the KaiB(fs) form binds the CikA PsR domain (PubMed:26113641)
Has 5 domains: N-terminal transmembrane, coiled-coil, KH, HD and an unnamed conserved C-terminal domain (residues 430-520). Both the N-terminal transmembrane helix and C-terminal domain are required for protein function in vivo
The N-terminal 18 residues form an alpha-helix which targets this enzyme and foreign proteins (tested with mCherry, pea ascorbate peroxidase and pyruvate decarboxylase) to the BMC
The two RNA-binding domains (S1 motif and KH domain) are separated by a conserved linker of five amino acids (KYGKL) and can bind RNA independently. Both domains are also needed for RNA degradation and interaction with RRP41, another exosome subunit
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. The C-terminal beta chain translocator domain inserts in the outer membrane via TamA (PubMed:25341963). This domain probably forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage. Finally, the mature protein remains tightly associated with the bacterium (Probable)
The SH3 domain mediates the binding to CBLB, and to HIV-1 Nef
The RRM domain mediates RNA binding; the RNA must have four nucleotides for efficient binding. Mediates the interaction of NEXT complex with promoter upstream transcripts (PROMPTs) and potentially aberrant forms of other non coding RNAs, such as snRNAs. The RRM domain exhibits specificity for polyuridine sequences
The YXXZ (Tyr-Xaa-Xaa-Zaa, where Zaa is a hydrophobic residue) motif mediates the targeting to the lysosomal compartments
The N-terminal lysine-rich domain (112-260) is required for non-specific binding to DNA and for efficient activity on 5-meC
The glycosylase domain (510-1073) is inactive on 5-meC and 5-hmeC excisions but retains residual AP activity. Addition of the C-terminal domain (1077-1393) restored partial base excision activity and increases the AP lyase activity
Consists of two beta-alpha-beta domains with a central cleft in which the amide binds
The B' domain (residues 448-675, Toprim plus a tail domain) forms a dimer; when reconstituted with intact GyrA the complex has ATP-independent DNA relaxation activity (PubMed:19596812). The same fragment (also called TopBK) when reconstituted with intact GyrA or the N-terminus of GyrA (residues 1-502) can catalyze quinolone-mediated DNA breaks (PubMed:20805881)
The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins
The N-terminal domain comprising the first 224 amino acid residues is mostly unstructured
The glycosyl hydrolase-1 3/region III carries the phlorizin hydrolase/glycosylceramidase activities
The glycosyl hydrolase-1 4/region IV carries the lactase activity
The repeats LRR 9, LRR 10 and LRR 11 are involved in binding type I collagen. The poly-Asp region is involved in binding calcium (By similarity). The LRR 5 repeat can inhibit BMP2-induced cytodifferentiation and may be involved in the interaction with BMP2
The N-terminal domain (residues 24-203) is responsible for oligomerization, while the C-terminal domain (residues 222-318) interacts with RseA
The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature, all three interactions rely on F&H motifs, an approximately 12-13 amino-acid sequence centered around Phe and His residues essential for binding (By similarity)
The N-terminal domain (residues 1-142) retains 70% identity to the N-terminal 142 residues of AvrPphD, and is required for translocation into plant cells via TTSS
The histone-fold domain mediates hetero-dimer protein-protein interactions
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (356-386) inactivates kinase activity under calcium-free conditions
The C-terminal coiled-coil domain is involved in oligomerization. The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro)
The PY motif is recognized directly by the WW domains of RSP5
StP/metal binding triggers a notable interdomain conformational change
The basic N-terminus is not necessary for binding to 5S rRNA. It is however required for cooperative binding of L5 and L18 to 5S rRNA as well as for binding of the 5S rRNA/L5/L18 complex to the 23S rRNA
Activated by phosphorylation at the first response regulatory domain, which induces dimerization mediated by the two response regulatory domains and allows the two substrate-binding sites to approach each other and the condensation reaction to occur (Probable). The diguanylate cyclase activity is harbored by the GGDEF domain
The presence of the iron-sulfur cluster is required for assembly of the RNA polymerase complex
The N-terminus contains a number of repeats which contribute additively to bub-1 recruitment to unattached kinetochores. The repeats are not required for localization to kinetochores
Is organized in a condensing KS-AT and a modifying DH-PsiKR-ER-KR region, followed by a flexibly tethered ACP domain
The PH-like region is similar to the PH domain but contains an insert. It is unclear whether it is a real PH domain
The PEST domains are Pro-, Glu-, Ser-, and Thr-rich domains. Proteins with PEST domains are frequently targets of degradation by the ubiquitin proteasome
A short conserved N-terminal region is necessary for the function of this protein (PubMed:21943602, PubMed:26339988). Transient relocalization to microtubule minus ends after neuronal injury also requires this region (PubMed:26339988)
The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA (PubMed:23663784). It may also be involved in localization to stress granules (By similarity)
Is composed of four functional domains: the N-terminal 5'-deoxyadenosylcobalamin binding region that is homologous to the small subunit of ICM (IcmB), a middle P-loop GTPase domain (MeaI) that acts as a chaperone for ICM, a structured linker region involved in dimer formation, and a C-terminal part that is homologous to the large substrate-binding subunit of ICM (IcmA)
The PUA domain plays a role in tRNA recognition through precisely recognizing the CCA end and the D-stem region of tRNA
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Another tyrosine-containing sequence, more C-terminal, accounts for the ability of isoform IIB2 to trigger the phagocytosis of particulate immuno complexes
The coiled-coil region is essential for oligomerization and binding to vacuolar structures
Contains an N-terminal PE domain, followed by a conserved linker region and a C-terminal PGRS domain
The N-terminal 91 amino acids are capable of binding to 5S rRNA and also of displacing full-length protein bound to 5S rRNA. The first 80 amino acids are not sufficient
Tetrapeptide ligand at C-terminus is tethered to inaD by interaction with the second PDZ domain
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. PTPN6 seems to bind predominantly to the first ITIM motif
The MPN domain mediates deubiquitinating activity
Has 3 domains, the helical N-terminus (residues 19-125), a beta-barrel central domain (126-234) and a helical C-terminus (235-409). The C-terminus (410-417) forms part of the substrate-binding pocket with the C-terminal helical domain (PubMed:24975806). The lid loop assumes one of 2 conformations allowing opening and closing of the active site (By similarity)
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol (PubMed:11053434). It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (PubMed:15718238, PubMed:16709157)
The LRR (leucine-rich repeat) domain forms a slightly curved solenoid and may mediate interaction with target proteins. It is involved in autoinhibition of the enzyme activity by interacting with the catalytic domain
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (286-316) inactivates kinase activity under calcium-free conditions (By similarity)
The active phytochrome binding (APB) motif (26-39) is involved in interaction with PHYB and is required for proteasome-mediated degradation
C-terminal domain binds DNA and interacts with MtrB
The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or FCGR2A (PubMed:12690104). It also mediates the interaction with p130Cas/BCAR1 (PubMed:11158326)
The protein kinase domain is predicted to be catalytically inactive as it lacks an expected active site aspartate residue
The Tudor domain recognizes and binds H3K36me3 (PubMed:23142980, PubMed:23228662)
The NAD(+)-binding element stabilizes the ADP-ribosylating turn-turn (ARTT) loop which confers substrate specificity; both domains contribute to ssDNA-binding
A N-terminal domain (80-269) is responsible for the interaction with KU70
The C-terminal domain (464-578) is sufficient for telomere binding
Contains both a transmembrane region and 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. The 2 ITIM motifs of isoform B are required for the inhibition of CLEC1B and GP6:FCER1G signaling and platelet activation
Contains 153 imperfect repeats of a consensus octapeptide A-G-Y-G-S-T-L-T; further on a 16-residue and a regional 48-residue periodicity is superimposed
Binds calcium via its EF-hands (By similarity). Isoform 5 binds calcium
The FERM and PDZ 2 domains are necessary for localization to the basolateral cell membrane. The FERM domain binds to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and is sufficient for membrane localization
The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain (PubMed:23558171). This autoinhibition is released upon competitive binding of an activated GTPase (PubMed:23558171). The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (PubMed:23558171)
The EIIC type-4 domain forms the PTS system translocation channel and contains the specific substrate-binding site
The N-terminal 29 amino acids are essential, but not sufficient, for the interaction with BRI1
The TOG (tumor overexpressed gene) domains are composed of six (for the most part non-canonical) HEAT repeats each. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. Two sets of TOG domains may wrap around a single free tubulin heterodimer accompanied by a open-to-closed conformational change of the STU2 homodimer. Both, TOG 1 and TOG 2 bind curved alpha/beta-tubulin with comparable affinity; the two TOG domains bind noncooperatively to two tubulin heterodimers. Free unpolymerized tubulin-binding is predominantly mediated by TOG 1, association with the microtubules plus ends is mediated by TOG 2 in cooperation with a C-terminal basic domain
The SH3 domain mediates the control of pseudopodium number
The periplasmic region consists of a protease domain (PD) and a PDZ domain, connected by a ten-residue linker (PubMed:30198900). Interactions between the PDZ domain and the catalytic domain lead to an inactive conformation (PubMed:30511675)
Fe(3+) binding by the shorter form (residues 75-133) is inhibited by Ca(2+) and Mg(2+) (PubMed:12496282). The C-terminal 21 residues (magnetite-interacting component, MIC, residues 112-133) self assemble into multimers up to octamers; this fragment binds Fe(3+) which alters its structure (PubMed:23857056). Another paper showed binding of MIC to Fe(2+) via Asp-123, Glu-124, Glu-125, and Glu-127 with a minor contribution from Glu-118 (PubMed:27112228). The isolated lumenal MIC binds Fe(2+) and Ni(2+), Ni(2+)-binding may not be physiological; in this paper binding to Fe(3+) was poor. Although it binds iron the protein fragment has no effect on magnetite crystal formation in an iron co-precipitation experiment, however mutating some of its residues decreases crystal size (PubMed:30405554). Correct subcellular location to the magnetosomes requires the N-terminal 75 residues (PubMed:27481925)
Inhibitory activity is regulated via a pH-induced conformational change of the structure. At pH above 7, Gfh1 is in an inactive flipped orientation that prevents binding to RNAP. At lower pH, Gfh1 switches to an active orientation, which enables binding to RNAP and inhibitory activity
The N-terminal region (1-60) inhibits the arginine N-methyltransferase activity
The PH domain binds phosphatidylinositol phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), and to a lesser extent phosphatidic acid and cardiolipin
The probably cytoplasmic N-terminus cannot be deleted without destabilizing the protein
The Pro-Xaa-Val-Xaa-Leu (PxVxL) motif mediates interaction with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha)
The thioredoxin domain lacks the conserved redox-active Cys at position 417 which is replaced by a Ser residue, suggesting that it lacks thioredoxin activity
Contains three domains displaying pseudo-three-fold symmetry that each contribute a cysteine residue for ligation to a centrally located [4Fe-4S] cluster
The PDZ domain contains the signal for export from the nucleus (By similarity). The N-terminal region including the PDZ domain is required for the formation of Cajal bands on myelinated nerves
Each monomer contains a pocket that accomodates cholesterol. Cholesterol derivatives (such as epicholesterol, epicholestanol, epicoprostenol, or 7-dehydrocholesterol) could also fit in the pocket with minor rearrangement of the side chain. Since arthropods are unable to synthesize cholesterol de novo, it is likely that a cholesterol ligand would be bloodmeal-derived
The N-terminal 134 amino acids are necessary for homodimerization and RNA-binding (PubMed:12950170). The N-terminal 298 amino acids are sufficient to interact with KCNMB4 and to regulate presynaptic action potential (AP) duration in neurons (PubMed:25561520). The two agenet-like domains are necessary for binding to histone H3 in a methylation-dependent manner (PubMed:24813610). The KH domains are necessary for mediating miRNA annealing to specific RNA targets (PubMed:17057366). The KH 2 domain is necessary for binding to kissing complex (kc) RNA ligands (PubMed:15805463). The RGG box domain is necessary for binding to mRNA targets that contain G-quadruplex structures (PubMed:11719189, PubMed:18579868, PubMed:25692235). The RGG-box domain is necessary for binding to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the superoxide dismutase SOD1 mRNA (PubMed:19166269). The RGG box domain is necessary for binding to its own mRNA (PubMed:11532944). The RGG-box domain is necessary for binding to homomer poly(G) (PubMed:14532325)
The C-terminal region contains a Cajal body localization signal at positions 490 through 506 (PubMed:24204304)
Has two distinct conformations in the presence and absence of ferrichrome. The globular N-terminal domain acts a plug that closes the channel formed by the beta-barrel. Binding of ferrichrome at the cell surface induces a conformational change in FhuA, but does not open the channel. Structural changes are propagated and amplified across the plug, and may facilitate binding of FhuA to TonB (PubMed:9865695, PubMed:9353297). TonB binding promotes conformational changes in outer surface-exposed loops of FhuA (PubMed:18653801). Phage T5 is a TonB-independent ligand, and its binding to FhuA results in the formation of high conductance ion channels (PubMed:8617231, PubMed:9353297)
The N-terminal SH3 domains are important for actin cytoskeleton assembly but not for localization
The IQ domains mediate the interaction with calmodulin
Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain
Although 2 transmembrane domains are predicted, PubMed:19269366 showed that it only contains one transmembrane domain. The other predicted transmembrane region is probably a hairpin-type region embedded into the membrane, which does not cross the membrane. It is unclear which of the 2 predicted transmembrane regions is the transmembrane or the hairpin-type region
The BTB domain inhibits the binding to a single consensus binding site, but mediates cooperative binding to multiple binding sites
The N-terminal region (2-283) contains the glycosylase and lyase activities
The N-terminal unstructured half of Pup provides a signal required to initiate unfolding and degradation by the proteasome but is not needed for pupylation, while the C-terminal helical half of Pup interacts with ARC to target proteins to the proteasome (By similarity). The C-terminal 26 residues of PuP also interact with PafA and Dop
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. For SLAMF1 a 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). Binding is mediated by either three 'prongs' (for high affinity binding involving ITSM 1) or a combination of any two also including non-phosphorylated Tyr-288 of ITSM 1 thus providing a positive feedback loop implicating SH2D1A-dependent recruitment of activating FYN. ITSM 2 needs to be phosphorylated on Tyr-335 for SH2D1A binding
The UBZ4-type zinc fingers mediate binding to 'Lys-48'- and 'Lys-63'-linked polyubiquitin
The PIR1/2/3 repeats are required for covalent linkage to the cell wall
The N-terminal TOPLESS domain (TPD)(1-209) binds directly to a 12-amino acid LxLxL EAR motif peptide, but no binding if the leucin residues are replaced
Contains an N-terminal catalytic domain fused with a RAM (Regulation of Amino acid Metabolism) domain at the C-terminus. The mutant enzyme lacking the RAM domain is insensitive to inhibition by lysine, indicating that the RAM domain is responsible for enzyme allosteric regulation. Moreover, the mutant enzyme lacking the RAM domain forms homodimer irrespective of the presence of lysine, which suggests that HCS undergoes changes in its oligomeric state by binding lysine at its RAM domain
Partially oxidized VKORC1 forms a cysteine adduct with substrates, vitamin K 2,3-epoxide, inducing a closed conformation, juxtaposing all cysteines (S-S or SH) for unimpeded electron transfer (PubMed:33154105). VKOR becomes fully oxidized with an open conformation that releases reaction products, vitamin K quinone, or hydroquinone (PubMed:33154105). Cys-132 and Cys-135 constitute the catalytic redox-active center (PubMed:33154105). Cys-43 and Cys-51 are the cysteine pair that mediates transfer of reducing equivalents during catalysis (PubMed:33154105)
C2 domain 1 is involved in binding calcium and phospholipids. According to PubMed:19033398, the C2 domain 2 may also play a role in the calcium-dependent targeting to membranes
The central part (140-272) is important for interaction with MYB30
The HMG domain is essential for CD4 silencing and CD8 activation; mutation of this domain blocks thymus development
The HP domain is important for the localization to actin filament bundles
The three subunits of the retrotranslocation channel (PEX2/prx-2, PEX10/prx-10 and PEX12/prx-12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5/prx-5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex
The zinc fingers are required for transcriptional silencing activity
The catalytic core domain alone is sufficient for the binding to PDRP1 but not for the binding to PDRP2
Is completely devoid of the classical secondary structure elements (alpha-helix and/or beta-strand)
The KA1 domain mediates binding to phospholipids and targeting to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
The N-terminal region is required for targeting to late endosomes/lysosomes. It does not traverse the membrane but contains a membrane-embedded intramembrane domain and interacts with the lipids phosphatidic acid (PA) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (PubMed:26134396). PA and PI(3,5)P2 are required for the protective effect against mitochondrial stress (PubMed:26134396)
The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (PubMed:14695263). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (PubMed:15358149). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation
The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation (PubMed:16934482). It is required for interaction with KCNIP2, and probably other family members as well (By similarity)
A conserved histidine residue in the third TMD (His-113) may play an essential role in the pH sensitivity of SLCO1B2/OATP1B2-mediated substrate transport
Putative ligand binding domain (NR LBD) may be dispensable for import into nuclei and in the development of neurons that control movement
Dimerizes via the C-terminus; dimerization is required for tetramer formation (PubMed:21653318). Binds protein substrate via an exposed loop in the N-terminus (PubMed:25404702)
The third and fourth KH domains are involved in RNA binding and self-association. Stable self-association requires RNA (By similarity)
The GatD/MurT complex has an open, boomerang-shaped conformation in which GatD is docked onto one end of MurT. Both proteins contribute to the catalytic triad
The protein kinase domain is predicted to be catalytically inactive; has lost the main activatory autophosphorylation site and the conserved key residues involved in phospho-substrate. The C-terminal region (containing the POLO box domain) is sufficient for inducing cell cycle arrest (By similarity)
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-43 in the first module and Ile-268 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity
The mature protein is composed of 2 almost identical repeat units
The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase, which methylates Lys-5 in vitro
Composed of two independent domains separated by a small linker. The N-terminal region contains the ssDNA binding site and the C-terminal region contains the nuclease active site
The PH domain does not bind phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate. This lack of binding activity is due to Leu-592, compared to Arg found in other family members
The second RanBP2-type zinc-finger is functional and binds ubiquitin
The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position (PubMed:30810529). Transplantation of the transmembrane segment S4 into HVCN1, generates a functional voltage-activated proton channel (PubMed:30810529)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; a thioesterase (TE) domain that releases the newly synthesized peptide from the enzyme; and 2 acyl-carrier protein (ACP) that serve as the tethers of the growing and completed polyketide via its phosphopantetheinyl arm
The DVD domain (residues 362-385) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation (By similarity)
The D domain (residues 35-50) contains a conserved docking site and is required for the binding to MAPk substrates
The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-45 and Tyr-93/Trp-94
The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs (PubMed:21193640, PubMed:21465557). The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias) (By similarity)
The D-box (destruction box) acts as a recognition signal for association with the APC/C complex, ubiquitination and degradation
The C-terminus is cytoplasmic and is important for interaction with ZO-1. Necessary for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction (By similarity)
Consists of an N-terminal domain, which is sufficient for the localization to the septal ring and is required for cell division, followed by a linker domain, and a C-terminal domain, which forms the translocation motor involved in chromosome segregation. The C-terminal domain can be further subdivided into alpha, beta and gamma subdomains. The alpha and beta subdomains form the DNA pump, and the gamma subdomain is a regulatory subdomain (By similarity). The DNA motor and the gamma subdomain are both required to activate XerS recombinase
The N-terminal region contains a high-affinity nickel-binding site and the C-terminal G-domain contains a low-affinity metal-binding site, which is not selective for nickel and could possibly accommodate other divalent metals (PubMed:16142921, PubMed:18942856). Both metal sites are critical for the maturation of the hydrogenases (PubMed:18942856)
It is unclear whether the potential membrane spanning region near the N-terminus is present as a transmembrane domain in the native protein or serves as a cleaved signal sequence
RNA recognition is mediated by a convoluted intramolecular fold of the TPR repeats (TPR eddy), which scaffolds unique additional helices that form an RNA binding cleft (PubMed:23317505, PubMed:23334420). Undergoes a conformational change upon RNA-binding: unliganded exists in a more open conformation, facilitating RNA entry (PubMed:23334420)
The N-terminus domain is necessary for S/G2 nuclear foci localization
These proteins have 2 BMC domains which evolve independently of each other, giving the term pseudohexamer to the trimerized subunit. Although the homotrimer fills the approximate space of a BMC hexamer protein, the BMC-T trimers are more compact. Their universal presence in BMCs indicates their structural importance. The homohexamers form pores at least 5 Angstroms in diameter; in the stacked homohexamer 1 pore is open and the other is closed (PubMed:28642439). In the BMC the inner pore is fully or partially closed while the outer pore is closed (PubMed:30833088)
Contrary to isoforms 1 and 2, isoforms 3 and 4 do not contain any BH3 motif
Transmembrane domain is required, and the cytoplasmic region conserved between RCR1 and RCR2 is also essential, to endow resistance to Congo red
The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type beta/beta. The C-terminal, non-coiled coil regions mediate heterodimerization type beta/alpha and interaction with S100A4
The BRCT domain 1 and 2 are required for the intramolecular interaction, but not for the intermolecular oligomerization. The BRCT domains negatively inhibit its GEF activity in interphase cells. The same BRCT domains may act as a positive regulatory motif for the completion of cytokinesis after the breakdown of nuclear membrane during mitosis (By similarity)
Ig-like C2-type domains 1 and 2 mediate homophilic interactions
The C-terminal region (residues 79 to 670) consists of seven imperfect tandem repeats, including one W-Y motif (WY1) and six L-W-Y motifs (LWY2 to LWY7) (By similarity). WY1 forms a 3 alpha-helix fold with one hydrophobic core and each L-W-Y motif forms a highly conserved fold consisting of 5 alpha-helices (By similarity). The units contribute differently to the virulence since WY1, LWY2 and LWY6 are important for the ability to suppress the biogenesis of small RNA in host and virulence activity of the pathogen, whereas LWY3, LWY4, LWY5 and LWY7 are dispensable for PSR2 function (By similarity). WY1 and LWY2 are sufficient for association with DRB4, suppress gene silencing and promote infection (PubMed:30595554). These units may function as basic building blocks of Phytophthora effectors to enable virulence activity and accelerate the evolution of novel functions (By similarity)
The C2 domains show Ca(2+)-independent phospholipid binding. None of the C2 domains retains all 5 conserved Asp residues found in calcium-binding C2 domains
The PTS EIIB type-2 domain may serve a regulatory function, through its phosphorylation activity
The PCI domain is necessary and sufficient for interactions with other CSN subunits of the complex
The JAMM motif is required for the deubiquitination and degradation of ubiquitinated substrates
The periplasmic domain is elongated (up to 160 Angstroms long) and forms contacts with the N-terminal POTRA domains of TamA (PubMed:25341963)
The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. In the absence of the extracellular domain, the channel is in a constitutively open conformation (PubMed:23994010). Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore (By similarity)
Folds into a two seven-bladed beta-propeller structure which is required for elongator complex assembly and association with microtubules
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage. Finally, the mature protein remains tightly associated with the bacterium
A 31- to 39-amino-acid region found immediately upstream of the translocator domain is essential for surface expression
The cysteine framework is XXIV (C-CC-C)
Contains two cysteine rich domains (CRD), referred to as the N- and C-terminal CRD's, n-CRD (Cys-265 and Cys-272) and c-CRD (Cys-531, Cys-553 and Cys-562), respectively. A nuclear export signal is embedded in the c-CRD, with which the nuclear export protein CRM1/exportin 1 interacts only in the absence of disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or between the c-CRD and the n-CRD
Is composed of two structurally similar domains arranged face to face
The BTB (POZ) domain mediates dimerization and interaction with a cullin
The TPR repeats and the J domain are required for interaction with Hsp70-type chaperones. The J domain is responsible for stimulating the ATPase activity of the chaperone
Specifically recognizes and binds polyuridylated RNAs via 3 RNA-binding regions (named U-zone 1, U-zone 2 and U-zone 3) that form an open funnel on one face of the catalytic domain, allowing RNA to navigate a path to the active site
The VWFC domain mediates the covalent links between monomers throught disulfide bridges (PubMed:25713063). Ig-like C2-type domains are required to sulfilimine bond formation (PubMed:26178375). The VWFC domain is not required for trimerization (PubMed:31295557). The LRR domain mediates high affinity binding to laminin-1 (PubMed:32485152)
Comprises exclusively 4 tightly packed alpha helices (no beta strand is present)
Made of a minimal module holding ketosynthase (KS), acyltransferase (AT), and C-terminal acyl carrier protein (C-ACP) domains, and additional N-terminal ACP (N-ACP) and C-terminal thioesterase-like domains
The N-terminal region containing the five C3H1-type zinc fingers is essential for endonuclease activity
The C-terminal region containing the two CCHC-type zinc fingers confers a binding preference for RNAs that contain G- and/or C-rich clusters
The 2 domains are closer in the ATP-bound enzyme
The PH domain is required for interaction with PRKCB and its dephosphorylation
The DACHbox-N/DD1 domain forms a structure containing a DNA binding motif similar to that of the forkhead/winged helix domain
The ShKT domain associates with, and blocks several potassium channels in the nanomolar to low micromolar range. The relative affinity is Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4 (By similarity)
The PAM-interacting domain (PI domain, approximately residues 1102-1388) recognizes the PAM motif; swapping the PI domain of this enzyme with that from S.pyogenes Cas9 (AC Q99ZW2) prevents cleavage of DNA with the endogenous PAM site but confers the ability to cleave DNA with the PAM site specific for S.pyogenes CRISPRs
Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to the myosin tail domain (PH-like) present in its tail domain
Contains GGXGXDXUX nonapeptide motifs, which are found in members of the repeat in toxin (RTX) protein family, and which are implicated in Ca(2+) binding. Binds Ca(2+) and shows Ca(2+)-induced reversible conformational changes
N-terminal domain is required for nucleoplasm location and C-terminal domain for nucleolus location
The C-terminal part of the DNA-binding domain may contribute to DNA recognition specificity
The SNF2-like region is essential for localization to DNA replication forks and for promoting underreplication. It is not required for localization to heterochromatin
The CARD domain, rather than the pyrin domain, is involved in the interaction with PYCARD, CASP1 and CASP5
The ZAKalpha motifs are recognized and phosphorylated by isoform ZAKalpha of MAP3K20
The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain. Serves as the predominant binding domain for dsRNA and dsDNA (PubMed:33243852)
The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding (By similarity). Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding (PubMed:22665479, PubMed:22087307). Both N- and C-terminal fragments remain associated (PubMed:22665479, PubMed:22087307)
The pyrin domain mediates an autoinhibitory function, potentially acting as a threshold modulator, which allows NLRP1 to discriminate long from short dsRNA. Inhibits ATPase activity of the NATCH domain
The C-terminal part of NLRP1 oligomerizes to form the core of the NLRP1 inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments (PubMed:33420028, PubMed:33420033). The UPA region reduces the threshold needed for filament formation and signaling (PubMed:33420028, PubMed:33420033). Must recruit the adapter PYCARD/ASC to facilitate CASP1 interaction and polymerization (PubMed:33420033)
Upon dsRNA-binding via its LRR domain, NACHT domain gains ATPase activity which is inhibited by the pyrin domain
The C-terminal part (725-748) is necessary for enzyme activity
The jas domain (117-142) is required for interaction with COI1
The propeptide region is both necessary and sufficient for bmp-inhibitory activity (By similarity). The propeptide region and the N- and C-terminal thirds of the mature protein are necessary for neural induction activity. Although cleavage doesn't appear essential for activity, residues surrounding the cleavage site are necessary for activity
The N-terminal domain (exact residues are not given in the paper) is not required for Cu(+)-binding (when deleted KM for Cu(+) binding is 1.32 uM) nor for ATPase activity, binds 2 Cu(+)/monomer (PubMed:24917681). Contradictory results give a considerable decrease in Cu affinity when residues 1-150 are deleted (KM=31.9 uM for Cu(+)) (PubMed:25899340). The first of 2 N-terminal heavy metal-binding domains (HMA 1, approximately residues 1-70, equivalent to CopA(Z)) has a 5-fold higher affinity for Cu(+) than HMA 2 (residues 71-150) and as a protein fragment can transfer Cu(+) to the ATPase fragment (residues 151-834), suggesting it has a Cu-chaperone function (PubMed:25899340). HMA 2 transfers Cu(+) to HMA 1 but the opposite reaction does not occur in vitro (PubMed:25899340). The HMA 1 fragment complements growth defects in trans, but if its CXXC motif is mutated, or if the remaining CXXC motif in HMA2 is mutated, complementation no longer occurs, showing the 2 HMA domains have different functions (PubMed:25899340). The periplasmic loops of CopA, especially the first half of loop 1, play a large role in binding to CusF (PubMed:24917681). Contradictory results between the various in vitro studies may be due to different levels of protein expression or reconstitution (Probable)
The N-terminal domain interacts with RNAP and the C-terminal domain binds either to Rho or to RpsJ (NusE). Contains an additional, species-specific domain inserted into the N-terminal domain. The N-terminal and C-terminal domains can interact and form a closed conformation
Each GoLoco domain can bind one GNAI3 (PubMed:22952234). In the auto-inhibited conformation, the GoLoco domains interact with the TPR repeat region (PubMed:23665171)
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic of alpha-helical structures. This region is interrupted by a hinge and joined by a nonhelical tailpiece where the regulatory phosphorylation sites reside
Has two ligand-binding domains; the N-terminus has three 101 AA repeats which are responsible for cell wall binding; the C-terminus consists of two blocks of residues with a conserved motif repeated 31 times
Each of the two pore-forming region (also called P-domain or P-loop) is enclosed by two transmembrane segments (2P/4TM) and contains the GYGD signature motif which seems to be involved in potassium selectivity. The C-terminus is not required for transport to the vacuolar membrane
Contains an atypical KH domain with amino acid changes at critical sites, suggesting that it may not bind RNA
The N-terminal region (1-43) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet
Disordered region at the N-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes
The Pro-P-factor precursor carries 4 repetitive units. The second and fourth units generate the major form of the P-factor in the cell. The first and the third units encode slightly different peptides, the fate of which is unclear
In unstressed cells, spontaneous homotrimerization is inhibited (PubMed:7935471, PubMed:7760831). Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation (PubMed:7935471, PubMed:7623826). Furthermore, intramolecular interactions between the regulatory domain and the nonadjacent transactivation domain prevents transcriptional activation, a process that is relieved upon heat shock (PubMed:7760831). The regulatory domain is necessary for full repression of the transcriptional activation domain in unstressed cells through its phosphorylation on Ser-303 and Ser-307 (PubMed:8946918, PubMed:9121459). In heat stressed cells, HSF1 homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity (PubMed:7935471). The D domain is necessary for translocation to the nucleus, interaction with JNK1 and MAPK3 and efficient JNK1- and MAPK3-dependent phosphorylation (PubMed:10747973). The regulatory domain confers heat shock inducibility on the transcriptional transactivation domain (PubMed:7760831). The regulatory domain is necessary for transcriptional activation through its phosphorylation on Ser-230 upon heat shock (PubMed:11447121). 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors (PubMed:17467953)
The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain, selectively bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are propbably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (PubMed:18854321)
Binds to eIF4E1 using a novel tripartite interface in the C-terminal domain comprising a canonical helix which engages the eIF4E1 dorsal surface, a non-canonical helix which engages the eIF4E1 lateral surface and an auxiliary helix that lies anti-parallel to the canonical helix on the eIF4E1 dorsal surface. The tripartite binding mode compromises its ability to compete with eIF4G1 for binding to eIF4E1 but once bound, the complex is very stable and is resistant to competition by eIF4G1
When isolated, the NACHT domain is involved in interaction with CARD8. This interaction is not detected for the full-length protein, maybe due to autoinhibition, this inhibition might by relieved by an inducible change in protein folding
The pyrin domain is necessary and sufficient for suppression of NFKB1 activation induced by TNF and for inducing IL1B secretion in collaboration with caspase-1. It is involved in interaction with PYCARD
Has 3 regions; the N-terminal 8 residues are disordered and not required for toxicity, the central helical segment (residues 9-28) probably crosses the membrane, and the charged C-terminal 2 residues which are required for toxicity
The MIF2 homology domain II targets centromeres and binds the alpha satellite DNA in vivo. The MIF2 homology domain III can induce CENPC dimerization/oligomerization
The two transmembrane domains of the dimer swing out to yield a Y-shaped structure (PubMed:17717154, PubMed:19749753). In each protomer, the cytoplasmic domain adopts a metallochaperone-like protein fold (PubMed:17717154, PubMed:19749753). Each protomer contains three zinc-binding sites: a tetrahedral active Zn(2+) binding site for zinc transport, which is located toward the center of the transmembrane domain, and two cytoplasmic Zn(2+) binding sites that may serve as zinc sensors and regulate activity (PubMed:17717154, PubMed:19749753)
The cytoplasmic domain is required for function in axon guidance
The membrane association is mediated by the calponin-homology (CH) domain
A tripeptide motif (NQE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
The C-terminal domain called the BARA domain is dispensable for the construction of both VPS34 PI3-kinase complexes, but is specifically required for autophagy through the targeting of complex I to the pre-autophagosomal structure
Undergoes an open/closed conformational change upon binding AMP
The N-terminal domain shows evolutionary conservation with that of VCP, and is able to bind phospholipids with a preference for phosphatidylinositol monophosphates
Instead of having the common DXD motif at the position 99-101, it contains a DTG sequence, which may provide greater metal ion binding flexibility
The kelch repeats form a beta-propeller structure involved in protein-protein interaction
The F-box is required for the interaction with SKP1A
The first seven ANK repeats at the N-terminus (1-243) are essnetial for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons
Contains a bacterial GIY-YIG-like domain which can functionally replace the bacterial GIY-YIG domain in the UVRC protein
Contains two distinct classes of F-actin-binding domains. Although both can bind F-actin, the 2 are required to bundle actin filaments (By similarity)
Cooperative binding of CoA and ketopantoate induces a closed inhibited state by interacting with the N-terminal and C-terminal domains, and seems to facilitate the disulfide bond formation
The propeptide functions as an intramolecular chaperone which is essential for the correct folding of the protease domain but is not required for enzymatic function of the folded protein. It is autoprocessed and degraded after completion of the folding process
The GTD-binding domain is sufficient for myosin binding. The transmembrane region (1-61) is sufficient for the membrane targeting
The N-terminal domain has structural similarity with S-adenosyl-L-methionine-dependent methyltransferases, but does not bind S-adenosyl-L-methionine (PubMed:22487307). It is required for correct assembly of the 2 Fe-S clusters (PubMed:27166425)
The galectin domain, in contrast to the one in mammalian ortholog, is a functional carbohydrate-binding galectin
Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 889. These domains are therefore predicted to be inactive
The C2H2-type zinc finger 11 mediates interaction with EHMT1 and EHMT2
The NEAT 1 domain is formed by an antiparallel eight-stranded beta-barrel fold. It binds with higher affinity than the NEAT 2 domain haptoglobin-hemoglobin complexes, haptoglobin and hemoglobin
The MATH domain interacts with ci
The BTB (POZ) domain interacts with gft/CUL3
The HIN-20 domains mediates dsDNA binding via electrostatic interactions
The tight homohexamer forms a pore with an opening of about 5.9 Angstroms in diameter which is positively charged. The C-terminal flexible tail, which is the most variable part of CcmK proteins, seems to be involved in packing of hexamers in layers
The N-terminal region may be required for lipid sulfatide binding
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with mix-1, forming a V-shaped heterodimer
Contains a conserved PPE N-terminal domain and a variable C-terminal domain. The C-terminal region includes a SH3-like region, a leucine zipper DNA-binding motif and a functional nuclear localization signal (NLS)
Contains various tandem pentapeptide repeats in the C-terminal region. The pentapeptide motif is required to efficiently recruit kinesin-1. No position is completely conserved in these repeats, whose consensus sequence is A-[DN]-[FLM]-X-X. The C-terminal 38 amino acid residues, specifically, the C-terminal motif LFNEF, are required for peripheral localization of PipB2 and redistribution of lysosomal-associated membrane protein (LAMP). The N-terminal 225 amino acid residues are sufficient for type III translocation and association with Sifs and SCVs, but not accumulation in peripheral vesicles (By similarity)
The N-terminal region acts as an inhibitor, whereas the C-terminal region carries enhancing activity
The KH-like 3 domain is required for binding to RNA
Consists of two discrete domains, an N-terminal cytochrome b domain and a C-terminal flavin-binding domain. In addition there is an extended C-terminal tail. The cytochrome b domain is required for efficient cytochrome c reduction
The N-terminus cysteine-rich segment may mediate the formation of oligomers. The fibronectin type-III 2-3 mediate the binding to contactin 1. The fibronectin type-III 9 mediates the cell attachment. The fibronectin type-III 2-5 mediate NFASC binding. The fibrinogen C-terminal domain mediates interaction with CSPG5
The region that is important for membrane fusion binds to lipids and can insert itself into lipid membranes. It is unstructured in an aqueous environment and assumes a more ordered, beta-stranded conformation in the presence of lipid membranes
The TIR domain mediates NAD(+) hydrolase (NADase) activity (PubMed:28334607). Self-association of TIR domains is required for NADase activity (PubMed:27671644, PubMed:31278906)
The ARM repeats inhibit the NAD(+) hydrolase (NADase) activity by binding to NAD(+): NAD(+)-binding to ARM repeats facilitates inhibition of the TIR domain NADase through their domain interface (PubMed:33053563). In contrast to classical ARM repeats, the last helix of ARM 6 does not fold back to interact with the first two helices, but instead turns towards the N-terminus of SARM1 (PubMed:33053563). As a result, the two following motifs ARM 7 and ARM 8 reverse their directions and lie perpendicularly (PubMed:33053563). Moreover, ARM repeats interact with different domains not only within each protomer but also of the adjacent ones (PubMed:33053563)
Has an N-terminal cyclic nucleotide-binding domain and a C-terminal transmembrane domain that may also be a Toll/interleukin-1 receptor-like domain (TIR) that might have NAD(+) hydrolase activity
The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively
Residues in the N-terminal region are required for proper localization
Amino acids 60-89 in isoform 2 are necessary for interaction with COPS5, CUL1, CUL3
The tight homohexamer forms a pore with an opening of about 5 Angstroms in diameter
The UBP-type zinc finger domain interacts selectively with an unmodified C-terminus of the proximal ubiquitin. Both UBA domains are involved in polyubiquitin recognition
The C-terminal 38 residues (targeting peptide, TP) are sufficient to target this foreign proteins to the nanocompartment in vivo
The N-terminal region mediates interaction with BRAF (PubMed:29433126). Also mediates membrane localization (By similarity)
The N- and C-terminal halves of the protein contain a hexokinase domain (PubMed:29298880). In contrast to hexokinase-1 and -3 (HK1 and HK3, respectively), both hexokinase domains display catalytic activity (PubMed:29298880). The region connecting the two hexokinase domains is required for the catalytic activity of the N-terminal hexokinase domain (PubMed:29298880). The N-terminal half regulates stability of the whole enzyme (PubMed:29298880)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS3 has the following architecture: A-T-C-A-T-C
The protein has a two-fold symmetry axis, with a central cavity which may be associated with substrate transport. Residues contributed from seven transmembrane helices probably line the substrate transport pathway
Contains a trimerization domain, composed of stacked carbohydrate binding modules, connected by a linker region to the catalytic domain. The trimerization domain appears to be dispensable for UDP-GlcNAc hydrolysis activity, but it may increase poly(RboP) binding affinity
The N-terminal ACP and almost all of the KR domains play an important role in determining the carbon chain length of fatty acids produced
Consists of two domains connected by a short loop, which form a bent shape. The N-terminal domain (residues 32-122) resembles a c-type immunoglobulin (Ig) domain, and the C-terminal contains the catalytic site that is located in a tiny tunnel
The CTBP-binding motifs and the N-terminal group of zinc fingers are required for repressor activity in the pronephros
The C-terminal transmembrane is dispensable for the ubiquitin ligase activity in vitro, but is critical for correct subcellular localization and substrate recognition in vivo
In BmrA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. This is considered to be a half-size transporter that undergoes homodimerization to be functional
2 residues (Tyr-69 and Arg-72) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with XCAP-C, forming a V-shaped heterodimer
The C-terminus, which contains a proline/serine-rich region is involved in nuclear translocation and enzymatic thermostability
The GSGFP motif is required for the interaction with SUZ12 (By similarity). The ARID domain specifically binds to the CCGCCC motif and is required for the lysine-specific histone demethylase activity (PubMed:18270511). The PHD-type 3 zinc finger is required for the interaction with histone H3 di- and trimethylated at 'Lys-4' (PubMed:19430464)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS12 has the following architecture: A-T-C-A-T-C (PubMed:19001367, PubMed:20225828). The activation and loading of antranilate is performed by the first module (PubMed:20225828)
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Both motives are required for full inhibition of FCER1A-mediated degranulation
The ubiquitin-like (UBL) and the UBA (ubiquitin-associated) domains interact intramolecularly in a highly dynamic manner, as each UBA domain competes for an overlapping UBL domain surface. Binding of ubiquitin or proteasome subunit Psmd4 disrupt the UBL-UBA domain interactions and drive Rad23a in to an open conformation (By similarity)
The tail domain participates in molecular interactions that specify the role of the motor domain. It is composed of several tail homology (TH) domains, namely a putative phospholipid-binding myosin tail domain (also named TH1), an Ala- and Pro-rich domain (TH2), followed by an SH3 domain and a C-terminal acidic domain (TH3)
The PX domain binds phosphatidylinositol 3-phosphate which is necessary for peripheral membrane localization of ATG20 to the perivacuolar punctate structures (By similarity)
The N-terminal velvet domain contains a NF-kappa-B-like fold and is involved in DNA-binding (PubMed:24391470)
Amino acids 100 to 347 are sufficient to target SopA to the mitochondria
The ubiquitin-like (UBL) and the UBA (ubiquitin-associated) domains interact intramolecularly in a highly dynamic manner, as each UBA domain competes for an overlapping UBL domain surface. Binding of ubiquitin or proteasome subunit PSMD4 disrupt the UBL-UBA domain interactions and drive RAD23A in to an open conformation (By similarity)
Contains a C-terminal polysaccharide-binding domain which interacts with the phosphatase domain; this interaction is required for glucan phosphatase activity
The C1q domain is commonly called the globular domain
The Ig-like V-type domain 1 mediates interaction with CXADR (PubMed:20813954). The Ig-like V-type domain 2 may also play a role in the interaction (PubMed:20813955)
The C-terminal domain binds to DNA. It is unknown whether binding is specific or non-specific
The conserved active-site motif D(D/E)XX(D/E) is required for coordinating the divalent metal ions that stabilize the PPI moiety of the substrate
Amphipathic peptide that adopts a random coil conformation in water, a beta-sheet structure in methanol, and an alpha-helical conformation in trifluoroethanol-water
The N-terminus (1-130) is determinant for the chain length specificity. Region I (76-96) and region III (201-229) are involved in the recognition of both substrates in a coordinated manner (By similarity)
The PDZ domain mediates interactions with FZD5, FZD8, ASIC3, GRID2, CLCN3 (By similarity). Mediates also interaction with CFTR and ADRB1
The coiled-coil region probably mediates association to membranes, targeting to the Golgi, and interactions with GOLGA3, and STX6. May also mediate interaction with RHOQ (By similarity)
2 residues (Tyr-54 and Arg-57) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The C-terminal domain (residues 450-555) are required for nuclease activity and dimerization
The cysteine framework of the turripeptide OL172 conotoxin-like is C-CC-C
BAC5 sequence consists almost exclusively of X-P-P-Y repeats
The N-terminal region (NRD) inhibits DNA-binding via its interaction with the C-terminal region
The KKXX motif functions as an ER retrieval signal that rationalizes association with PVM and the host cell ER
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site
Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and Olf signaling pathways. C2H2-type zinc fingers 14-19 mediate the interaction with SMAD1 and SMAD4, while zinc fingers 28-30 mediate the interaction with EBF1. zinc fingers 2-8 bind the 5'-CCGCCC-3' DNA sequence in concert with EBF1, while zinc fingers 9-13 bind BMP target gene promoters in concert with SMADs
Consists of an N-terminal kinase domain, a transmembrane domain, and a C-terminal domain containing four repeats of the PASTA signature sequence (Penicillin-binding protein and Ser/Thr protein kinase associated domain). The C-terminal domain binds to synthetic and native peptidoglycan (PGN) subunits and to beta-lactam antibiotics, which mimic the terminal portions of the PGN stem peptide. Deletion of both the transmembrane domain and the PASTA domain negatively affects the stability of the core kinase domain. In contrast, the membrane anchored kinase domain and the full-length form of StkP are stable and capable of autophosphorylation. However, the membrane anchored kinase domain (i.e. StkP lacking the C-terminal PASTA domain) is unable to phosphorylate its substrates, which means that the PASTA domain is essential for StkP activation and substrate phosphorylation. The PASTA domain is also responsible for cellular targeting to midcell (shown in the virulent strain D39). Both the transmembrane and extracellular domains promote dimerization of StkP
Contains 3 EAR motifs associated with active repression of several target genes
The extracellular domain represents the IL4 binding protein (IL4BP)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase. AsrA has the following single module architecture: A-T-C
The C-terminal region (residues 79 to 670) consists of seven imperfect tandem repeats, including one W-Y motif (WY1) and six L-W-Y motifs (LWY2 to LWY7) (Probable). WY1 forms a 3 alpha-helix fold with one hydrophobic core and each L-W-Y motif forms a highly conserved fold consisting of 5 alpha-helices (Probable). The units contribute differently to the virulence since WY1, LWY2 and LWY6 are important for the ability to suppress the biogenesis of small RNA in host and virulence activity of the pathogen, whereas LWY3, LWY4, LWY5 and LWY7 are dispensable for PSR2 function (PubMed:30926664). WY1 and LWY2 are sufficient for association with DRB4, suppress gene silencing and promote infection (PubMed:30595554). These units may function as basic building blocks of Phytophthora effectors to enable virulence activity and accelerate the evolution of novel functions (Probable)
The CBS domains, the R-helix linker (543-562) and the C-terminal domain (833-1001) regulate channel sensitivity to voltage, pH and extracellular chloride concentrations, probably by altering the outer pore structure (PubMed:16500974, PubMed:20581474). The region (738-751) between the CBS domains is essential for channel activation (PubMed:23083714)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (339-369) inactivates kinase activity under calcium-free conditions
The 329-DSEL-332 motif is involved in the recycling of PTGDR2 to the cell surface after agonist-induced internalization. This motif seems to be required for GRK2 and GPRK5/GRK5 to promote agonist-induced internalization (By similarity). Thr-346 is a major site for PKC-induced internalization of the receptor (By similarity)
The coiled-coil domain mediates homodimerization (PubMed:12668758, PubMed:15998640). Also mediates interaction with SBF1/MTMR5 (PubMed:12668758). By mediating MTMR2 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By similarity)
The cytochrome c domains probably enable interaction with the electron transfer chain, possibly by delivering the electrons to a cytochrome oxidase
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (289-319) inactivates kinase activity under calcium-free conditions (By similarity)
The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit caspase-3 and caspase-7, while the third BIR is involved in caspase-9 inhibition. The interactions with DIABLO/SMAC and HTRA2/PRSS25 are mediated by the second and third BIR domains (By similarity)
The UIM domains specifically bind 'Lys-48'-linked ubiquitin polymers. The UIM domains mediate interaction with polyubiquitinated proteins
All EF-hand domains seem to be non-functional
The RUN domain is necessary for NGF induced nuclear redistribution
The C-terminal extension present in isoform 1 and absent in isoform 2 (the F-domain) regulates transcriptional activity by altering the selectivity of binding to cofactors
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, additional domains required for further modifications are also present (Probable). Enniatin synthetase has the C1-A1-T1-C2-A2-MT-T2a-T2b-C3 domain organization (By similarity). The precursors D-hydroxycarboxylic acids and L-amino acids become activated at the A1 and the A2 domains. N-methylation of the amino acid takes place at the MT-domain. The building blocks are transferred from one module to another by means of T-domains and are ultimately stored at the waiting position T2b. Condensation of the building blocks and final cyclization and release from the enzyme is catalyzed by the C-domains (By similarity)
The N-terminal region (1-25) is necessary and sufficient for targeting and anchoring the protein in the chloroplast envelope membrane
The coiled coil domain(123-341) interacts with the plasma membrane and anchors chloroplasts firmly on the plasma membrane
The actin binding motif (346-356) can function in vitro as an actin binding site
The proline-rich domain (648-705) mediates the interaction with profilin
Consists of three domains. The middle domain contains the catalytic site in a wide-open cleft
Two-domain protein with the central portion of the sequence acting as a hinge or connector between the two
Composed of a N-terminal A-region and a number of B-repeats depending on the strain. At the C-terminal end are features required for surface targeting and covalently anchoring to the peptidoglycan. The collagen binding activity is located in the A-region
The LIR motif in the cytosol-facing C-terminal region is involved in the interaction with ATG8 proteins
The disordered region is required for autophagosome binding and reticulophagy, probably via bridging the long distance between endoplasmic reticulum and autophagosome membranes, because ribosomes exist on endoplasmic reticulum membranes that attach to autophagic membranes
The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization
The PH domain binds phospholipids. The PRD1 motif (721-728) is necessary for the interaction with SH3P3
C2 domain is a calcium-binding fold, and the binding promotes the protein association with membranes. A lower affinity toward calcium can be anticipated for PLD alpha due to the absence of two potential calcium ligands (By similarity)
The calmodulin-binding domain (CBD) is located between A-448 and A-496
The CRD1 domain (cell cycle regulatory domain 1) mediates transcriptional repression of a subset of p300 responsive genes; it can be de-repressed by CDKN1A/p21WAF1 at least at some promoters. It conatins sumoylation and acetylation sites and the same lysine residues may be targeted for the respective modifications. It is proposed that deacetylation by SIRT1 allows sumoylation leading to suppressed activity
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of TICAM1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines
The N-terminal region is essential for activation of the IFNB promoter activity
The N-terminal domain (TRIF-NTD) is globular and consists of two alpha-helical subdomains connected by a 14-residue linker. It shares structural similarity with IFIT family members N-terminal regions
Has an N-terminal Jag-N, a linker with a phosphorylated Thr, and 2 RNA-binding domains (KH and R3H) (Probable). A phosphomimetic mutation and mutations that prevent nucleic acid binding are not tolerated in strain R6 (PubMed:28710862). The KH domain of this protein interacts with KhpA (PubMed:30842445). The Jag-N domain is responsible for targeting to the midcell (PubMed:33558392)
The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction (By similarity)
Infrared spectra studies suggest the major structural elements are 47% alpha-helix and 25% antiparallel beta-strands; it is thought the beta-strands make the hydrophobic interior surface (PubMed:21542854)
The guanylate kinase-like domain interacts with the SH3 domain
The region spanning the fifth and sixth transmembrane domains probably forms the pore-forming region
Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs. The Aquifex aeolicus domain can be used in vitro to replace the corresponding domain in E.coli
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (338-368) inactivates kinase activity under calcium-free conditions
The IN box mediates interaction with aurkb/aurora-B
NPXY motif thought to be involved in signal transduction that activates the cell corpse internalization process
The C-terminus (residues 312-335) targets the protein to the type 1 encapsulin nanocompartment
The C-terminal domain (268-393) is organized into 2 subdomains that bear structural similarities to SH3-like domains. Both subdomains adopt a similar 5-stranded beta-barrel-like fold and are connected to each other by a short linker of 5 residues. The 5 beta-sheets are packed at approximately right angles against each other. A highly conserved groove formed at the interface between the 2 subdomains, comprised of Lys residues 302 and 391 and other positively charged residues, may possibly be the site of RNA-binding (By similarity)
Assembles into a propeller-like homotrimer in which each blade contains a GT-B-type glycosyltransferase domain with a typical Rossmann fold. Assembles into a trimer using a novel trimerization domain, termed the HUB domain
A long alpha helix in the N-terminus mediates dimerization, while the earmuff domain is responsible for core histone and dsDNA binding. The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity (By similarity)
The tudor domains recognize and bind to proteins with dimethylated arginine or lysine residues (Probable). Plays an important role in the protein functions through its direct binding to the target proteins (Probable)
The SH3 domain mediates interaction with RALGPS1 (By similarity). The SH3 domain also mediates interaction with CLNK
The YEATS domain specifically recognizes and binds acylated histones, with a preference for histone H3 diacetylated at 'Lys-14' and 'Lys-27' (H3K14ac and H3K27ac)
The C2H2-type zinc finger domain is required for the proper folding of the catalytic domain, but is dispensable for uridylation of single strand RNA substrate
A His-tag on the N-terminus blocks activity, while a C-terminal His-tag does not
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space (By similarity). Then, trimerization and insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface (PubMed:22155776). Presents a lollipop-shaped form which consists of three domains: a C-terminal membrane-anchor domain, a coiled-coil stalk domain and an oval N-terminal head domain. The N-terminal half of the sequence reveals the presence of repeated motifs with the consensus sequence NSVAIGXXS. They form the turns and hydrophobic core of the nine-coiled left-handed parallel beta-roll and trimer structure essential for the collagen-binding activity (PubMed:10931316)
The leucine-zipper domain is required for coactivation activity. When this domain is deleted, the protein is able to stimulate transcription from a number of gene promoters
The WRPW motif is required for binding to tle/groucho proteins and transcriptional repression
The U-box N-terminal domain (UND) confers binding specificity and subsequent ubiquitination
Each HMA domain can bind a copper ion, they are tightly packed and closely interact with each other. Wild-type ATP7B can usually be loaded with an average 5.5 copper atoms per molecule (By similarity)
The mature N-terminus mediates interaction with XIAP/BIRC4
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tim13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The presence of 'disulfide through disulfide knots' structurally defines this protein as a knottin. This toxin contains 2 'disulfide through disulfide knots' that are separated by a short linker (By similarity)
Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface
The SH2 domain interacts with tyrosine phosphorylated forms of proteins
The KEN box is required for the FZR1-dependent degradation of this protein subsequent to ubiquitination
A tandem duplication in the protein fold creates an intact active site between the repeated domains of each monomer
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA (By similarity). Interactions between Sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (PubMed:17803943) (Probable)
The N-terminal region is in a coiled coil structure
The FYVE-type zinc finger mediates the interaction with phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes when not monoubiquitinated at Lys-87
The N-terminus (36-79) resembles a truncated EF hand, the LRR region (80-240) has a curved form, while residues 241-321 form an Ig-like region; the whole region forms a curved tube (PubMed:11575932, PubMed:17662939, PubMed:19900460). The LRR domain alone (31-241) binds mammalian MET and stimulates its Tyr-phosphorylation; the LRR plus Ig-like region (36-321) are required for receptor dimerization; adding the B-repeat allows the protein to scatter host cell colonies, and the GW domains, especially GW2 and GW3, potentiate MET activation (PubMed:17662939, PubMed:21345802). The cap, LRR and Ig-like regions all interact with residues 25-656 of host MET (the Sema, PSI and Ig1 domains) via the interior (concave surface) of the curved tube (PubMed:17662939). Dimerizes via the exterior (convex surface) of the curved tube which probably induces host receptor dimerization; preventing dimerization prevents host downstream signaling (PubMed:19900460) (Probable). The B repeat region crystallizes in a SUMO-like fold. The B repeat region interacts synergistically with N-terminus of InlB, conferring on it the ability to stimulate cell motility; the B repeat does not bind to MET (PubMed:21345802). Deletion of the B-repeat (exact residues are not given) slightly decreased protein activity in host; the authors suggest the B-repeat probably contributes to homodimerization rather than binding another host cell receptor (PubMed:27789707)
The coiled coil region is required for multimerization
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. Is missing the last conserved cysteine
Distinct domains of TAF5/TAFII100 are required for functional interaction with transcription factor TFIIFB (RAP30) and incorporation into the TFIID complex
The mature protein has 2 domains, the N-terminus (residues 21-100) and the C-terminus (residues 126-236) joined by a flexible linker; both domains form beta-barrels. In the crystal structure of the soluble mutant (Ala-21) the N-terminus of 1 subunit interacts with the C-terminus of the other
The autoinhibitory region (AIR) binds to the kinase domain and inhibits its activity
The RK-rich region is required for cAMP responsiveness
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). NPS6 contains a degenerate A domain (dA) in the second module and has the following architecture: A-T-C-dA-T-T-C (PubMed:15755917)
The N-terminus (residues 1-233) has the ADP-ribosylation catalytic domain. NAD(+)-binding or the presence of the linker do not alter the structure of the catalytic domain, however in vitro the presence of the linker masks the DNA- and NAD(+)-binding regions and thus prevents dsDNA-binding by the catalytic domain
The N-terminal domain (residues 1-60) is important for binding to the unfolded mature imported proteins. Residues (47-69) of the cytoplasmic domain interacts with TOMM20 while the C-terminal segment (residues 61-80) binds presequence of preproteins (By similarity). Requires the transmembrane domain (TMD), a short segment (the import sequence) in the cytoplasmic domain localizing separately from the TMD and the C-tail signal in the C-terminal domain for efficient targeting and integration into the TOM complex
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Insertion of the C-terminal translocator domain (beta domain) in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain (alpha domain) to the bacterial cell surface, where IcsA is cleaved by IcsP (SopA) and released into the extracellular medium. This cleavage is important for the maintenance of the sharply polarized distribution of IcsA but is not a prerequisite for intracellular spreading
The N-terminus has 5 copies of an approximately 34 amino acid repeat sequence that are enriched for Gly residues (together called the GRR) (PubMed:8468279). The GRR interacts with the host WASL CRIB domain (PubMed:9582270)
Domain deletion experiments show that amino acids 1-104, and 507-620 are independently sufficient for polar localization for polar localization (PubMed:11481451) and that amino acids 320-433 are responsible for interaction with host ATG5 and IcsB (PubMed:15576571, PubMed:11481451). Other experiments show residues 1-104 are not required for polar targeting (PubMed:8702989, PubMed:18456802). Domain deletion experiments show that residues 103-507 are required for assembly of F-actin and for vinculin binding (PubMed:8702989)
Insertion mutations in the probable autochaperone domain (residues 634-735) alter protein conformation and stability. Insertion mutations in the GRR domain and IcsB-interacting domain are unable to recruit N-WASP and do not form F-actin comet tails (PubMed:18456802). Combined insertion mutations (at residues 149 and 387) decrease adhesion and invasion of host cells but do not affect intercellular spreading once bacteria are inside cells. Thus the adhesion and spreading phenotypes can be separated (PubMed:24721572)
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 712, which is replaced by an Asn residue
The UBX domain is required for interaction with VCP
Contains an N-terminal LytE region, which consists of three consecutive LysM domains, and a C-terminal esterase domain. LytM domains are essential for anchoring protein to the cell wall. The presence of LytM domains results in enhanced rate of protein aggregation at higher temperature
Contains an N-terminal substrate recognition domain and a C-terminal methyltransferase domain, connected by a flexible linker
The conserved, positively charged effector domain (residues 77 to 147), rather than the RXLR domain, is required for binding to phosphatidylinositol monophosphates (PIPs). PIP binding is necessary for accumulation of CMPG1 and Avr3a in host plants
In contrast to Rhodococus, the M.tuberculosis proteasome does not require the propeptide of PrcB for correct folding and assembly
The C-terminal is essential for tetramerization as well as efficient AmrZ-mediated activation and repression of its targets
The periplasmic domain is sufficient to bind MacB. The membrane proximal (MP) region plays a critical role in the stimulation of MacB ATPase activity
The first 350 residues are required for recognition of OmpA
The fibrinogen C-terminal domain mediates calcium-dependent binding to carbohydrates. The domain undergoes a conformational switch at pH under 6.2, and loses its carbohydrate-binding ability
The ubiquitin-like domain is essential for its inhibitory effect on GPCR endocytosis. Mediates its association with the subunits of the proteasome
The UBA domain is essential for its association with microtubule-associated protein 1 light chain 3 (MAP1LC3). Mediates its association with ubiquitinated substrates
The N-terminal domain (about residues 1-143) is an archaea-specific tRNA-editing domain (PubMed:26113036). Catalysis of tRNA editing is performed by the charged tRNA itself (By similarity)
The N-terminal and homeobox regions are together sufficient to bind telomeric DNA
The C-terminal region is required for bending of telomeric DNA
The first 21 residues target foreign proteins (tested with eGFP) to the BMC in E.coli. The cargo is only detected by Western blot in broken shells, strongly suggesting this protein is normally found inside the BMC and not on its exterior
The C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity
The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation
The N-terminal transactivation domain (TAD-A) binds to and is activated by Cbp/p300. The dephosphorylated form contains two unmasked nuclear localization signals (NLS), which allow translocation of the protein to the nucleus (By similarity)
The ligand binding region binds directly to 2 L-amino acids (PubMed:23650915). Binding of GABA induces structural changes of the chemoreceptor (PubMed:31964737)
Is composed of a ring composed by 9 residues, a 5 residue-loop (SVSGQ) and a C-terminal tail (PubMed:26534965). The peptide is threaded when the C-terminal tail is inserted throught the isopeptide-bonded ring. The loop region serves as a recognition element for the isopeptidase AtxE2 (Probable) (PubMed:27998080)
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules
The cyclic nucleotide ligand binds in the C-terminal SAVED domain
Deletion of the C-terminus (residues 835-974) still allows this protein confer phage resistance and act as an antitoxin to PglX
Contains an N-terminal HTH arsR-type DNA-binding domain and a C-terminal rhodanese-like domain
The N-terminal 240 amino acids are sufficient to mediate complex formation
Composed of 3 domains, the NTD (N-terminal domain, residues 1-90), NRD (N-repeated domain, residues 91-197) and DBD (Dmd-binding domain, residues 198-357). The DBD is responsible for dimerization, growth inhibition upon overexpression and recognition of T4 antitoxin Dmd (via residues 327-357) and antitoxin RnlB and subcellular location (PubMed:24112600)
Does not seem to be able to assume a closed conformation, does not bind closure peptide. In the Cap7:Cap8 complex only Cap7 binds a closure peptide
The C-terminal domain (317-395) is responsible for the Golgi localization
C-terminal truncated mutants display increased transactivation
Each protomer consists of two large domains, the substrate-binding domain and the cofactor-binding domain, which are separated by a deep crevice forming the substrate-access channel to the active site, and a small C-terminal oligomerization domain
The C-terminal region (aa 215-288) represents the dimerization motif
The N0, N1, N2 and N3 domains are periplasmic, while the secretin and S domains form a channel that is partially inserted in the outer membrane. The cap gate extends out on the extracellular side of the channel partially closing the channel. The secretin domain forms a double beta-barrel structure; the outer barrel has an outer diameter of about 110 Angstroms while the inner barrel forms the central gate with a small pore in the closed state
The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors (By similarity)
The C-terminal region mediates interaction with the mRNA and polysomes. It is required for translational repression of mRNAs with a 5'TOP motif
The N-terminal region mediates interaction with PABPC1
The leucine-zipper is atypical but could still mediate protein-protein interaction
A linker region between the coiled-coil and PDZ region holds the protein in an inactive state (PubMed:27071417)
The C-terminal part of CARD8 oligomerizes to form the core of the CARD8 inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments (PubMed:33420028, PubMed:33420033). The UPA region reduces the threshold needed for filament formation and signaling (PubMed:33420028, PubMed:33420033). Directly recruits and polymerizes with the CARD domain of caspase-1 (CASP1) through the favorable side of the growing filament seed (PubMed:33420033)
Cys-414 near TM10 is a major determinant of nucleobase transport activity
The pseudo DED region (pDED) mediates the interaction with IFT57
Binds F-actin via the talin-like I/LWEQ domain
The PTS EIIA type-2 domain may serve as a regulatory function, through its phosphorylation activity
The first Z-binding domain binds Z-DNA
The tyrosine-based internalization signal may be essential for its retrieval from the plasma membrane to the TGN
The C-terminal NPFKD sequence is an attractive candidate for either an endocytosis signal acting at the plasma membrane or a retrieval signal acting at the TGN to return the enzyme to the cis/medial-Golgi
Possible isomerization of Pro-305 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA
The zinc knuckle motif binds zinc and is required for the DNA primase activity (PubMed:24682820, PubMed:29608762). It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites (PubMed:29608762)
The RPA1-binding motifs (RBM) mediate interaction with RPA1 and are essential for recruitment to chromatin (PubMed:28534480). The interaction is primarily mediated by RPA1-binding motif 1, which binds to the basic cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding (PubMed:28534480)
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis (PubMed:30889508). Glu-116 is required to stabilize the incoming nucleotide at the 3'-site (PubMed:30889508)
The destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway
The N-terminal and the ALMS motif-containing C-terminal regions are essential for CEP295-mediated centriole elongation
This toxin is amphipathic in nature with a hydrophobic face on one side of the molecule (composed of residues 5-Phe-Met-6 and 27-His--Phe-34) and a hydrophilic (mostly cationic) face on the opposite side (composed of residues 10-Ile--Lys-15 and 18-Arg--Pro-19)
The putative nucleic acid binding region (34-77) coincides with the interaction surface with glutaredoxin
Consists of two tandem immunoglobulin-like Big_5 domains in the N-terminal region (residues 56-145 and 150-250), followed by a L,D-transpeptidase catalytic domain (residues 251-378) and a C-terminal tail (residues 379-408)
The WD repeat domain mediates binding to U1 snRNA and to U4 snRNA. The WD repeat domain also mediates binding to the 7-methylguanosine cap that is found both on mRNA and snRNA molecules. The regions that bind snRNA molecules and the isolated 7-methylguanosine cap overlap at least partially. Besides, the WD repeat domain mediates interaction with the 60S large ribosomal subunit
The exosite polybasic region mediates non-specific RNA-binding, acting as a bridge for RNA-binding target proteins, such as PARP1. The exosite is also required for interaction with non-RNA-binding proteins, such as Hsp90 co-chaperone PTGES3
The coiled coil region may mediate dimerization
DEP domain is required for function, perhaps regulating the apoptotic fate of the Q.pp neuroblast, but appears dispensable for subcellular localization
The BH3-like domain is required for association with BAX and for mediating apoptosis (PubMed:11060313). The three BH domains (BH1, BH2, and BH3) of BAX are all required for mediating protein-protein interaction (PubMed:11060313)
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit srpra. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER
The M domain binds the 7SL RNA in presence of srp19 and binds the signal sequence of presecretory proteins
The loop 2 region is involved in the binding of the 2 ends of resected double-strand breaks and homomultimerization
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with a SMC2 subfamily member, forming a V-shaped heterodimer
The N-terminus (PduON, residues 1-185) has adenosyltransferase activity in vivo and in vitro; it partially complements a deletion mutant for growth on 1,2-PD (PubMed:15547259, PubMed:27446048). The C-terminal domain (PduOC, residues 194-336) is required for full complemention of a pduO deletion (PubMed:27446048)
The C-terminal region is necessary for the kinase activation in response to ABA treatment
The extracellular domain (ECD) region specifically binds trypsin. It is not required for peptide transporter activity
The CRAL-TRIO domain mediates interaction with various inositol phospholipids, such as phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 5-phosphate (PI5P)
This protein is considered an atypical serine/threonine kinase, because it lacks the conventional structural elements necessary for the substrate recognition as well as a lysine residue that in all other serine/threonine kinases participates in the catalytic event (PubMed:12023889). BUD32 has protein kinase activity in vitro, but in the context of the EKC/KEOPS complex, the catalytic subunit KAE1 switches the activity of BUD32 from kinase into ATPase (By similarity)
The conserved PP2C phosphatase domain (244-643) is interrupted by an insertion of approximately 100 amino acids
In the absence of ligand, the homodimer has a V-shaped structure with a large cavity that is accessible from the cytoplasmic side
Has 4 domains (N-terminal, PAZ, Mid and PIWI). The N-terminal and PAZ domains are joined by linker L1, the PAZ and Mid domains are joined by linker L2. The domains assemble in 2 lobes; the PAZ lobe consists of the N-terminal, L1, PAZ and L2 domains, while the PIWI lobe has the Mid and PIWI domains. The PIWI domain assumes an RNase H fold and has the catalytic residues. gDNA lies between the 2 lobes, with its unpaired 5'-end anchored in the Mid lobe while the 3'-end anchors in the PAZ domain in the absence of target or if target nucleic acid has not fully base-paired with the gDNA. The N-terminal, Mid and PAZ domains alter position upon binding different length gDNA, forming and closing DNA-binding channels (PubMed:18754009, PubMed:19092929, PubMed:19812667). The 2 lobes and gDNA move considerably upon formation of the ternary gDNA:target RNA:TtAgo complex to accomodate and base pair the target RNA (PubMed:19092929, PubMed:19812667, PubMed:24374628). Deletions of the N-terminus (residues 1-106 or 1-177) have lost catalytic activity (PubMed:19812667). Upon release of the 3'-end of the gDNA from the PAZ domain during nucleic acid duplex formation, Glu-512 moves about 13 Angstroms to complete the active site (PubMed:24374628)
The CARD domain is involved in the interaction with pycard
The C-terminal part of nlrp1 oligomerizes to form the core of the nlrp1 inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments
The two basolateral sorting signals (BSS) are required to direct SLC16A8 to the basolateral membrane
The C-terminal domain consists of a eight-helix alpha barrel. The eight helices form a pocket that includes a tightly bound phospholipid. The cellular function of this lipid is unknown; it has no significant effect on enzyme activity
Isoform 4 cytoplasmic N-terminal domain participates in the partial inactivation of KCNMA1, possibly by binding to a receptor site
Contains an N-terminal helix-turn-helix DNA-binding domain and a C-terminal domain that binds the effector
The N-terminal domain (1-150) prevents cell death by suppressing caspase-like protease activation
The WRD domain (178-214) is necessary for interaction with MYB108/BOS1
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. It is required for the ubiquitination activity, but dispensable and not sufficient for interaction with MYB108/BOS1 (PubMed:20921156)
The SHP box and the VCP-interaction motif (VIM) are important both together for binding to CDC48. The 2 SUMO interaction motifs (SIM) are each important for binding to SMT3(SUMO)
The coiled-coil domain mediates transient homodimerization with other acetylcholine receptor-bound RIC3 molecules, promoting stepwise ACHR homomeric assembly at the membrane
Is composed of a ring composed by 9 residues, a loop and a C-terminal tail (PubMed:23601645). The peptide is threaded when the C-terminal tail is inserted throught the isopeptide-bonded ring (Probable)
Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-638 has an important role in the selective binding of succinyl-CoA over acetyl-CoA
The ice-binding site is formed by three T-A/G-X-T/N motifs
The characteristic DDXXD motif for binding a trinuclear Mg(2+) cluster is conserved in both the N-terminal terpene cyclase and C-terminal prenyl transferase domains
The Mg(2+)-binding NSE motif in the terpene cyclase domain is not completely conserved, since the asparagine residue in the is substituted with histidine
The potential DNA-binding domain differs in sequence from that of other DP family members and cannot bind DNA
Ig-like C2-type domain 2 mediates specificity through recognition of the Bw4 epitope
Two central helices mediate homodimerization through parallel packing
Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains
The 20s loop, a flexible loop in the active site that permits ligand binding and release in most enolase superfamily proteins, has a four-amino acid deletion and is well-ordered in T.fusca OSBS
The periplasmic C-terminus (residues 87-242) probably binds peptidoglycan
Has two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1 (By similarity)
Comprised of a NH2-terminal actin-binding domain, 24 immunoglobulin-like internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. Filamin repeat 20 interacts with filamin repeat 21 masking the ligand binding site on filamin repeat 21, resulting in an autoinhibited conformation (PubMed:17690686). The autoinhibition can be relieved by ligands like ITGB7 or FBLIM1 (PubMed:21524097). Filamin repeats 19 and 21 can simultaneously engage ligands (PubMed:21524097)
The N-terminal FAP motif (residues 15 to 17) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates
The C-terminus is essential for the function of the protein and it contains two conserved motifs (289-300) and (365-389) of unknown function present in orthologous proteins from various eukaryotes
The C2-domain mediates homodimerization. It is a calcium-sensitive lipid-binding domain with preference for PI(3)P
Has 3 domains that are structurally very similar to those in BoNT/A; light chain (nLC, equivalent to the light chain), N-heavy chain (nHN) and C-heavy chain (nHC)
The RRM1, RRM3 and PABC domains are important for RNA_binding and polar growth (PubMed:17105762, PubMed:19494833). RRM3 recognizes the specific binding motif UAUG of cargo mRNAs (PubMed:30552148)
The cysteine framework is XIX (C-C-C-CCC-C-C-C-C)
The CFEM domain is involved in heme-binding and contains 8 cysteines and is found in proteins from several pathogenic fungi, including both human and plant pathogens (PubMed:12633989). The CFEM domain adopts a novel helical-basket fold that consists of six alpha-helices, and is uniquely stabilized by four disulfide bonds formed by its 8 signature cysteines (By similarity)
Mature protein has 3 discontinuous domains; D1, D2, D3 followed by C-terminal D4; the domains rearrange substantially upon membrane insertion (PubMed:9182756, PubMed:15851031). A highly conserved undecapeptide in the D4 domain has residues important for membrane binding and cell lysis, and penetrates into the upper leaflet of cholesterol-rich bilayers in the pre-pore complex (PubMed:15851031)
Has 2 AAA ATPase type nucleotide-binding domains (NBDs) per monomer, a low-affinity, high-turnover site (NBD1) and a high-affinity site (NBD2) with a 300-fold slower rate of hydrolysis. There is allosteric regulation between the 2 sites. ATP binding to NBD1 triggers binding of polypeptides and stimulates ATP hydrolysis at NBD2. Nucleotide binding to NBD2 is crucial for oligomerization
The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA (PubMed:24990967). The interdomain linker (564-579) acts as a hinge to fix the relative orientation of the 2 RRMs (PubMed:24990967). The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs (By similarity). Unlike in CPEB1, a continuous polar interface is formed between the 2 RRMs (PubMed:24990967)
SRGAP2C is truncated at its C-terminus compared to SRGAP2/SRGAP2A (PubMed:28333212). It only contains an extended F-BAR domain that lacks the last C-terminal 49 amino acids of SRGAP2/SRGAP2A, which are replaced with seven unique C-terminal amino acids (PubMed:28333212). In addition, SRGAP2C acquired a series of unique nonsynonymous base pair mutations selectively targeting five arginine residues compared to SRGAP2B (PubMed:28333212). This truncation and these specific arginine mutations reduce solubility of SRGAP2C and increase its ability to heterodimerize with SRGAP2/SRGAP2A to form an insoluble complex (PubMed:28333212)
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (PubMed:22076378)
The N-terminal part of the mature protein (70-129) is probably involved in the formation of a functional homodimer
Has a short (SR1) and long (SR22) Ser-rich region separated by 2 non-repeats regions (NR1 and NR2). SR2 is comprised of 113 inexact repeats of SASTSASVSASE (PubMed:11854202). SR2 is thought to extend about 0.2 um away from the cell surface (Probable). SR1, NR2 and SR2 are essential for Hsa-mediated hemagglutination and for binding to sialoglycoconjugates (fetuin and NeuAc-alpha-2-3Gal-beta-1-4(Glc)-HSA); removal of the N- or C-terminus of SR2 (residues 448-1459 or 1092-2143 respectively) still allows binding and hemagglutination (PubMed:15213130)
The MAM domain is required for localization at the cell surface
Residues 88-96, 111-125 and 247-283 form flexible loops whose positions are affected on substrate binding
The protein kinase domain is catalytically inactive but contains an unusual pseudoactive site with an interaction between Lys-219 and Gln-343 residues (PubMed:24012422, PubMed:24095729). Upon phosphorylation by RIPK3, undergoes an active conformation (PubMed:24012422, PubMed:24095729)
Has protease activity (PubMed:19476346, PubMed:19543288)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (PubMed:19476346). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (By similarity). The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (PubMed:19476346, PubMed:19650874)
The transmembrane domain mediates interaction with NTRK1
The conserved cystein-rich region (CRR) localized between the zinc fingers is also involved in DNA-binding and transcription repressor activity (PubMed:12484767)
Both the N-terminal and C-terminal zinc fingers are involved in DNA-binding, although the C-terminal finger plays a more important role in the binding (PubMed:10194352)
Dimerizes via the C-terminus; dimerization is required for tetramer formation (By similarity). Binds protein substrate via an exposed loop in the N-terminus (PubMed:25404702)
The N-terminal domain is required for the multimeric binding of laf-1 to RNA
Uses 4 of its 7 zinc finger domains to contact the ZRE. 2 of these (ZF4 and ZF7) dominate the interaction by contacting the essential ACC--GGT ends, while the other 2 (ZF5 and ZF6) contact the 5 basepair central ZRE sequence. 2 zinc finger domains (ZF1 and ZF2) do not contact DNA, and a third ZF3 may be more important for interfinger protein-protein interactions (PubMed:12549926). ZF1 and ZF2 bind zinc in vitro but less stably than zinc fingers involved in DNA binding. ZF1 and ZF2 are critical for zinc regulation of activation domain 2 (AD2) and play a role in zinc sensing and consequent regulation of ZAP1 activity (PubMed:14517251). ZF1-ZF2 interactions stabilize the beta-beta-alpha folded repressed state of the ZF2 activation domain in the presence of cellular zinc excess (PubMed:16720702, PubMed:16483601). DNA binding is inhibited by zinc (PubMed:21799889)
Contains 2 zinc-responsive domains ZRD(AD1) and ZRD(AD2). Zinc binding to residues in ZRD(AD1) and ZRD(AD2) represses the activation function of AD1 and AD2, respectively
Contains 2 activation domains, embedded within larger zinc-responsive domains (ZRDs), designated AD1 and AD2, which are regulated independently by zinc. AD1 plays the primary role in zinc-responsive gene regulation, whereas AD2 is required for maximal expression of only a few target genes (PubMed:21177862). AD2 recruits coactivators less effectively than AD1 and is therefore only functional on some promoters (PubMed:22950018). AD2 is also important for ZAP1 activity under heat stress conditions (PubMed:21177862)
The third and fourth KH domains are involved in RNA binding and self-association. Stable self-association requires RNA
The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis
The DH (DBL-homology) domain may inhibit the Ras-GEF domain, thereby preventing excessive let-60/Ras activation
Contains two domains: a catalytic domain (residues 1-154 and 292-344) and a nucleotide binding domain (residues 155-291) (PubMed:17610898). The active site resides in a deep cleft between the domains (PubMed:17610898)
The central DNA-binding region is composed of 23.5 tandem core repeats with 1 base-specifying residue (BSR residue 13, also called repeat variable diresidue, RVD, residues 12 and 13) each of which recognizes 1 base in the target DNA. The BSR is probably the only residue which contacts DNA in a sequence-specific manner
The activation domain activates transcription of a reporter gene upon expression in planta and in yeast. The 3 putative nuclear localization signals seem to be highly redundant; only mutation of all 3 knocks out the HR
ValRS has two distinct active sites: one for aminoacylation and one for editing. The misactivated threonine is translocated from the active site to the editing site (By similarity)
A region in the N-terminus (residues 55-61) probably interacts with the periplasmic sensor domain of CpxA to inhibit its kinase activity and is also important for CpxP stability (PubMed:16166523). The homodimer has an elongated cradle shape; a hydrophobic cleft on the convex face may interact with periplasmic protein PapE (PubMed:21239493)
The N-terminal domain (residues 1-60) is important for binding to the unfolded mature imported proteins. Residues (47-69) of the cytoplasmic domain interacts with TOMM20 while the C-terminal segment (residues 61-80) binds presequence of preproteins. Requires the transmembrane domain (TMD), a short segment (the import sequence) in the cytoplasmic domain localizing separately from the TMD and the C-tail signal in the C-terminal domain for efficient targeting and integration into the TOM complex (By similarity)
The C-terminal loop (247-313) is required for ferredoxin binding
The N-terminal region interacts with RNAP (PubMed:21922055). The central region is composed of 3 RNA binding domains, S1, KH 1 and KH 2. The C-terminal region contains 2 acidic repeats, AR1 and AR2, which bind to protein N from phage lambda during antitermination. AR2 interacts with SuhB and RNAP alpha subunit C-terminal domain (rpoA); AR2 cannot bind to both simultaneously (PubMed:31020314, PubMed:31127279). SuhB, NusG and the alpha-CTD of RNAP all interact with the AR2 domain and can displace the AR2 domain from the SSK domain (S1, KH1 and KH2) of NusA (PubMed:31127279)
The Trp-rich region is important for the binding to lipid membrane
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-67 and Arg-70) that bind to malonylated and succinylated substrates and define the specificity
The elastin-binding domain is located between residues 13-33 at the surface-exposed N-terminus, whereas the C-terminus, containing the LysM peptidoglycan-binding domain, is not exposed on the surface of intact cells and presumably remains buried within the peptidoglycan. The presence of the TNSHQD sequence, corresponding to residues 18-23, is essential for EbpS activity but not sufficient, additional flanking amino acids in the amino- or carboxy-terminal are required for elastin recognition
Contains an N-terminal domain that mediates interactions with the hexameric ring, a central S1 domain and a C-terminal KH domain
The domain architecture includes starter unit:ACP transacylase (SAT), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), product template (PT), 3 acyl-carrier domain (ACP), and thioesterase/Claisen cyclase (TE/CLC) domains (PubMed:16649078). Although duplicated ACP domains are common, pksA is the only fungal PKS containing 3 ACP domains (PubMed:16649078). The third (C-terminal) ACP is less similar in sequence to the first two and to that of the aflatoxin biosynthetic enzyme aflC (PubMed:16649078). It is possible that the third ACP domain was acquired by unequal recombination and has since diverged into a slightly different form that may have less functionality or altered specificity (PubMed:16649078)
The C-terminal fragment, containing the TAP domain (also called UBA-like domain) and part of the NTF2-like domain, named the NPC-binding domain, mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for its localization to the nuclear rim
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (PubMed:17464044). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (PubMed:17464044). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (PubMed:17464044). Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase (PubMed:17464044). NRPS11 has the following architecture: A-T-C (PubMed:17464044, PubMed:20804163)
The KIEELE motif is required for interaction with downstream signaling molecules
The C-terminal inhibitory domain is involved in inhibition of PCSK1. It corresponds to the probable processing intermediate Big PEN-LEN, binds to PCSK1 in vitro and contains the hexapeptide L-L-R-V-K-R, which, as a synthetic peptide, is sufficient for PCSK1 inhibition (By similarity)
The N-terminal extracellular domain is important for gamete fusion
The transcriptional activation domain 1/TA1 and the transcriptional activation domain 2/TA2 have direct transcriptional activation properties (PubMed:29813070). The 9aaTAD motif found within the transcriptional activation domain 2 is a conserved motif present in a large number of transcription factors that is required for their transcriptional transactivation activity (By similarity)
The EMI and EGF-like domains work in concert to promote self-assembly
Residues in the N-terminus (2-4) and C-terminus (37-44) help recognize the GGA loop in a mRNA stem-loop; recognition mostly occurs via the protein main chain carbonyl oxygens and amides (PubMed:17704818). Similar interactions occur with fragments of sRNA RsmZ; the binding affinity for GGA-containing RsmZ fragments can vary from 10 nM to 3 mM depending on the sequence and structural context (PubMed:24561806)
Consists of three domains: an N-terminal globular domain with diadenylate-cyclase (DAC) activity, a central helical domain and a C-terminal DNA-binding domain
Calcium-binding is structural and does not influence the alkaline phosphatase activity (PubMed:25775211). At very high concentrations, calcium can however substitute for zinc at zinc-binding sites, leading to strongly reduced enzyme activity (PubMed:25775211)
The first seven ANK repeats at the N-terminus (1-242) are essential for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons
The BH3 motif is intrinsically disordered in the absence of a binding partner but folds upon binding (By similarity). Folds when bound to BCL2L1 (By similarity). Also folds when bound to MCL1 (By similarity)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Tim9b/Tim10b from the cytoplasm into the mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across the mitochondrial outer membrane (By similarity)
Contains an N-terminal homodimerization domain, a short linker region and a C-terminal catalytic domain (PubMed:30789718). The N-terminal domain may function in substrate binding by stabilizing the closed conformation (PubMed:30789718). Does not possess the N-terminal Zn(II)-binding cysteine sequence motif found in gamma-butyrobetaine hydroxylases (PubMed:30789718)
The isolated N-terminus (residues 1-80) forms a closed, 6-stranded beta barrel; it probably has the same form in full-length protein (PubMed:17616598). The PRC barrel domain binds ribosomal protein uS19 (By similarity)
The conserved RxLR motif does not seem to be involved in self-translocation into fish cells
The C-terminus (residues 200 to 211) is predicted to form a short helix with charged amino acids and is required for the self-translocation into fish cells
The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation
The N-terminal destruction boxes (D-box 1 and D-box 2) act as a recognition signal for degradation via the ubiquitin-proteasome pathway
Is composed of two domains: an N-terminal catalytic domain (residues 1-242) and a C-terminal tRNA recognition domain (residues 245-309)
The SANT domain and GATA-type zinc finger are required for conversion of the Y rectal cell to the PDA neuron
The TPR repeats are six to seven residues longer than a canonical TPR motif
The HrcQa-C domain interacts with the hrcQb C-terminal domain
The PX domain mediates interaction with phosphatidylinositol 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, unphosphorylated state an intramolecular interaction with the C-terminal SH3 domain precludes phospholipid binding and interaction with CYBA. Phosphorylation disrupts the autoinhibited state
The alpha subunit consists of three domains: an N-terminal domain which includes a six-bladed beta-propeller, a middle domain binding a pentacoordinated c-type heme and a C-terminal domain which harbors a bis-histidine-coordinated c-type heme
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (By similarity). Interactions between sigma-70 factor domain-2 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (Probable)
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic calcium (PubMed:9430701, PubMed:9665851, PubMed:11375391). In the presence of phosphoinositides, regulates phospholipase A2 and lysophospholipase activities in a calcium-independent way (PubMed:12672805)
Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (PubMed:30846601)
Most of the protein is composed of disordered regions. Zinc-binding induces structural rearrangement by promoting molten globule state formation
BON and LysM domains are both required for full K(+) binding. The major K(+) binding site is located in the BON domain and this initial complex is stabilized by interaction with the LysM domain
The homeobox is required for PBX1 nuclear localization and for transcriptional activation of NFIL3
There is conflicting information regarding the regions required for centrosomal localization (PubMed:15784680). One study shows that the region 1591-1671 is necessary and sufficient for targeting to the centrosome (By similarity). Another study shows that a separate region within the coiled-coil domain, 1279-1565, is important for centrosomal localization (By similarity). However, a third study shows that the coiled-coil region (373-1874) is not sufficient for centrosomal localization and instead localizes to cytoplasmic speckles (PubMed:15784680). The observed differences might be due to oligomerization of the longer coiled-coil domain-containing sequence, which would mask the shorter centrosomal targeting sequences (PubMed:15784680)
Contains two domains, a large N-terminal domain encoding a serine protease homologous to subtilisin and a smaller C-terminal domain that possesses unusual sequence features (PubMed:2116590, PubMed:3142851, PubMed:16553828). The C-terminal third of the protein is not required for protease activity but is required for swarming (PubMed:2116590, PubMed:3142851, PubMed:16553828)
The jas domain (105-127) lacks the canonical jasmonoyl-isoleucine (JA-Ile) degron LPIARR that strongly interact with COI1 in the presence of JA-Ile in other TIFY/JAZ proteins (PubMed:22327740). The LxLxL-type EAR (ERF-associated amphiphilic repression) motif (9-13) is required for the interaction with the corepressor TOPLESS (PubMed:22327740). The jas domain (105-127) is required for interaction with Pseudomonas syringae HopZ1a (By similarity)
Consists of a leucine-rich N-terminal half, which is likely to be involved in protein-protein interaction, and a C-terminal half which has high sequence similarity to gelsolin and is therefore likely to be involved in actin-binding
The N-terminal part contains two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1 (By similarity)
The lumenal magnetite interacting component (MIC, residues 36-56) probably binds magnetite
The N-terminal part (1-122) is necessary and sufficient for homooligomerization (PubMed:20832900) and for binding to microtubules while the C-terminal domain is anchored to the plasma membrane (PubMed:20619818)
Contains a substrate-binding domain and an NAD(+)/NADH-binding domain, separated by a deep cleft containing the active site (PubMed:27815281). Several residues in the active site form a hydrophobic cluster, which may be a part of the hydrophobic core essential for protein folding (PubMed:27815281)
Contains a large occluded hydrophilic cavity that spans the entire thickness of the membrane and extends into the intracellular part of the protein. It consists of two connected chambers. The larger chamber is located in the transmembrane domain, and the smaller chamber is formed by the part of the protein that connects the NBDs and transmembrane domains
The N-terminal domain (approximately residues 1-142) is an archaea-specific tRNA-editing domain that hydrolyzes incorrectly charged L-seryl-tRNA(Thr) (PubMed:15079065). Catalysis of tRNA editing is performed by the charged tRNA itself
The CR1 and CR2 motifs mediate sequence-specific DNA binding
The complementarity-determining region CDR1 confers specificity to the peptide antigen. Assumes a loop structure that makes contact with HLA-A*02.01 and contributes to the stability of the TR through interaction with CDR3-beta loop
The complementarity-determining region CDR2 confers specificity to the peptide antigen. Assumes a loop structure that recognizes the peptide-HLA-A*02-B2M complex
The complementarity-determining region CDR3 confers specificity to the peptide antigen. Assumes a loop structure that recognizes the peptide-HLA-A*02-B2M complex
The C-terminal domain is required for association with ATF2
The N-terminal DMA/Gly-rich region (also called GAR domain) is rich in Gly and Arg and functions in nucleolar targeting (By similarity). The central (138-179) and C-terminal (225-281) part of the protein exhibit cooperative RNA-binding activities
An N-terminal fragment (residues 1-523) can be reconstituted with GyrB, but the complex no longer has negative supercoiling or ATP-independent DNA relaxation activities, although it is capable of DNA cleavage; ATP-dependent relaxation is inhibited by novobiocin and non-hydrolyzable ATP analogs (PubMed:8962066). The fragment has ATP-dependent DNA relaxation and 30-fold improved decatenation activities, unlike holoenzyme it preferentially binds supercoiled DNA (PubMed:8962066). This N-terminal fragment becomes a topoisomerase IV-like enzyme; it poorly complements a temperature-sensitive parC mutation (parC is the topoisomerase IV paralog of gyrA) (PubMed:8962066)
The C-terminal domain (CTD, approximately residues 535-841) contains 6 tandemly repeated subdomains known as blades, each of which is composed of a 4-stranded antiparallel beta-sheet (PubMed:15897198). The blades form a circular-shaped beta-pinwheel fold arranged in a spiral around a screw axis, to which DNA probably binds, inducing strong positive superhelicity (about 0.8 links/protein) (PubMed:15897198). The non-conserved, C-terminal acidic tail (residues 842-875) regulates wrapping and DNA-binding by the CTD; deletions within the tail show it is autoinhibitory for DNA wrapping and binding, and couples ATP hydrolysis to DNA strand passage (PubMed:22457353). The GyrA-box is a 7 amino acid motif found in the first blade of the CTD which is discriminative for gyrase versus topoisomerase IV activity (PubMed:9426128). The GyrA-box is required for wrapping of DNA around gyrase, and thus is essential for the DNA supercoiling activity but not DNA relaxation or decatenation activities of gyrase (PubMed:16332690)
The N-terminal domain of the MobA region determines nucleotide recognition and specific binding, while its C-terminal domain determines the specific binding to the target protein
Interacts via the first PHD domain with the N-terminus of histone H3 that is not methylated at 'Lys-4'. Disruption of the first PHD domain has been shown to lead to reduced transcriptional activity and to localization of the protein mainly in the cytoplasm in small granules. While the PHD zinc fingers are necessary for the transactivation capacity of the protein, other regions also modulate this function (By similarity)
The N-terminal HSR domain is required for localization on tubular structures
Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1
The N-terminal and the C-terminal regions are independently capable of directing actinorhodin production
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone, an acyl carrier protein (ACP) domain, and a reductive NADPH-binding domain that is required for NADPH-dependent product release
The N-terminal part (1-106) mediates the nuclear localization, while the fourth zinc finger is required for the localization to M-lines and dense bodies
The DDNN motif is required for targeting to the cell membrane and enzyme activation
The SH3 domain plays a major role in substrate interactions. The SH2 domain of PTK6 plays a role in protein-protein interactions, but is likely more important for the regulation of catalytic activity
The alpha-3 region and to a lesser extent the transmembrane and cytosolic domains regulate surface expression. The alpha-3 region mediates interaction with B2M (By similarity)
The ligand-binding groove is ideally suited to present small organic compounds that can originate from vitamins rather than antigenic peptides
The C-terminus is necessary for localization to the cell membrane
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (348-378) inactivates kinase activity under calcium-free conditions (By similarity)
The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes (By similarity). Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions (By similarity)
The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane
The CTCK domain mediates interchain disulfide bonds with another molecule of MUC5B
Has 16 transmembrane helices and a large cytoplasmic domain that contains the active site
The jas domain (220-244) is necessary and sufficient for interaction with COI1
Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding (By similarity)
Contains an N-terminal DNA-binding domain and a C-terminal dimerization domain
The SH3-binding motifs mediate the interaction with SH3 domain-containing proteins such as PRMT2 and FYN, possibly leading to displace the N-terminal domain and activate the protein
Possesses two phosphotransferase domains. The second one probably contains the catalytic domain (By similarity), while the presence of slight differences suggest a different role for domain 1 (By similarity)
The MH2 domain is sufficient to carry protein nuclear export
A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-143
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase. ApmB has the following architecture: A-T-C-A-T-C
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. LnaA contains an amino acid adenylation domain (A), a peptidyl carrier protein (PCP) domain with a phosphopantetheine prosthetic group, and a short-chain dehydrogenase/reductase terminus (R), but it does not have an identifiable condensation (C) domain required for the formation of peptide bonds during non-ribosomal peptide synthesis
The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity (By similarity)
The N-terminus of RdlA is more highly charged than the same region in RdlB; replacing 3 charged residues by polar residues confers the ability to form amyloid rods to RdlA and allows the mutant protein to form rodlets by itself, which neither RdlA or RdlB can do alone
These proteins have 2 BMC domains which evolve independently of each other, giving the term pseudohexamer to the trimerized subunit. Although the homotrimer fills the approximate space of a BMC hexamer protein, the BMC-T trimers are more compact. Their universal presence in BMCs indicates their structural importance. The homohexamers form pores of at least 5 Angstroms in diameter
The C2 domain is necessary and sufficient to promote melanocyte dendrite outgrowth (PubMed:23999003)
Phe-404 residue probably plays a key role in the activation of the enzyme at the beginning of the catalytic cycle. A conformational change of Phe-404, possibly triggered by the substrate, is central for the activation because it switches KasA to the sufficiently reactive zwitterionic state
The carbohydrate-binding modules (CBMs) are responsible for the affinity to carob galactomannan
The BC2 (basic cluster 2) motif is necessary and sufficient for the nuclear localization and contains the catalytic active site. The localization in the nucleus is however not required for the enzyme activity
The N-terminal domain (residues 1 to 264) is required and sufficient for interaction with the exosome and SKI complexes and for 3'-to-5' mRNA degradation
The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding. In allele 1, autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated (By similarity). It is not known whether this modification occurs in allele 2 (Probable)
The UvrB domain 2 homolog region (UB2H domain) is important for interaction with MltA
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm. Lacks the starter unit:ACP transacylase (SAT) that selects the starter unit
The cysteine-rich C-terminus is involved in its granular distribution in the cytoplasm. The cysteine-rich C-terminus mediates protein-protein interactions, including interaction with HIV-1 Tat, transcription factors, AXIN1, CCNT1 (PubMed:16260749, PubMed:12192039, PubMed:12944466)
The cytoplasmic domain (residues 494-718, expressed as a maltose-binding protein fusion) has c-di-AMP phosphodiesterase activity
In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (PubMed:14633988)
A conserved histidine residue in the third TMD (His-115) may play an essential role in the pH sensitivity of SLCO1B1/OATP1B1-mediated substrate transport
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-105 and Arg-108) that bind to malonylated and succinylated substrates and define the specificity
The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (PubMed:21855799)
Contains an N-terminal coiled-coil domain and a C-terminal TPR domain, separated by a flexible linker. The N-terminal domain forms a stable trimer and controls the oligomeric status. The C-terminal domain, which can also trimerize, is involved in interaction with TolA
All KH domains contribute binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute. The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules
The C-terminal domain may function as glutaredoxin and mediates the interaction of the enzyme with glutathione (GSH). Active in GSH-dependent reduction of hydroxyethyldisulfide, cystine, dehydroascorbate, insulin disulfides and ribonucleotide reductase
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute (PubMed:29476152). The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules
Contains a A-domain and a T-domain. The A-domain is responsible for selection and activation of a substrate, which is then covalently tethered to the T-domain
The protein kinase domain is predicted to be catalytically inactive. Its extracellular domain is capable of promoting cell adhesion and migration in response to low concentrations of ephrin-B2, but its cytoplasmic domain is essential for cell repulsion and inhibition of migration induced by high concentrations of ephrin-B2
The jas domain (164-189) is required for interaction with COI1
The cytoplasmic C-terminal domain is responsible for the racemase activity
Its sequence is related to the DnaJ family but lacks the J domain. The CR-type-like region is similar to CR-type zinc-fingers and was shown to bind zinc (PubMed:21586683)
Gln-174 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The kinase-like region is slightly similar to the kinase domain but does not correspond to a canonical kinase domain and is predicted to be catalytically inactive
The 3'-5' exonuclease activity resides in the C-terminal PHP domain
The N-terminal region is responsible for proper localization to the piliated pole
Contains tandemly repeated, identical sequences of 81 residues
Consists of three domains. The first domain of FRD (Oxidored_FMN, PF00724) carries a non-covalently bound FMN and is used for NADH oxidation. The second, FMN_bind domain (PF04205) contains a covalently bound FMN, that acts as an electron carrier between the two other domains of FRD. The C-terminal FAD_binding_2 domain contains a non-covalently bound FAD and forms a site for fumarate reduction
Its cytoplasmic domain associates with the cytoplasmic domains of tom20 and tom70. Its intermembrane space domain provides a trans binding site for presequences and the single membrane anchor is required for a stable interaction between the GIP complex proteins (By similarity)
The N-terminal region (NR) associates with the endoplasmic reticulum (ER) and is responsible for the formation of the isolation membrane at the PAS
The amphipathic helix in the C-terminal region binds to membranes and facilitates ATG18 binding to PtdIns3P to target the ATG2-ATG18 complex to the PAS
Contains an N-terminal ATPase domain and a C-terminal regulatory domain
The C-terminal cytoplasmic domain seems to be important for SNF3 regulatory function
The N-terminus domain is necessary for its localization to the ER-Golgi intermediate compartment (ERGIC)
The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding. F5/8 domains mediate the recognition and binding to R/KXXR/K CendR motifs (PubMed:19805273, PubMed:33082294)
LIM zinc-binding domain 1 is required for self-association. LIM zinc-binding domain 1 and LIM zinc-binding domain 2 both are required for optimal actin-bundling activity (PubMed:24934443). LIM zinc-binding domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates binding to SPTB (By similarity)
The GAT domain mediates interaction with TOLLIP
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Thr (NPA)
Consists of an N-terminal kinase domain, a transmembrane domain, and a C-terminal domain containing four repeats of the PASTA signature sequence (Penicillin-binding protein and Ser/Thr protein kinase associated domain). The PASTA domain binds to peptidoglycan (PGN) subunits, is essential for StkP activation and substrate phosphorylation (shown in the avirulent strain Rx / Cp1015), and is responsible for cellular targeting to midcell
The Tudor-like region mediates binding to H4K20me2
The extendend C-terminal region contains a kinase-like region, which encodes a catalytically inactive pseudokinase, and an extracellular region reminiscent of carbohydrate-binding proteins
The N-terminus has a gamma-class carbonic anhydrase-like domain (CA), while the C-terminus has 4 repeats that are similar to the small subunit of RuBisCO (rbcS), called SSUL (Probable). The SSUL are connected by flexible linkers. The N-terminal domain forms a scaffold on which CA and other carboxysomal proteins assemble, while the C-terminus binds RuBisCO (By similarity)
The jas domain (185-200) is required for interaction with COI1
The JmjC domain mediates demethylation activity (By similarity). It is also required for repression of ribosomal RNA genes (By similarity)
Contains three distinct domains: an N-terminal catalytic domain that contains a binuclear Zn(2+) cluster, a central dimerization domain and a C-terminal sterol carrier protein type 2 (SCP-2)-like fold domain (PubMed:25066955). Although separated by the dimerization domain in terms of sequence, the N-terminal and C-terminal domains are spatially directly adjacent (PubMed:25066955)
The N-terminal domain is required for the interaction with the WD repeats of TUP1 and for dimerization
The homeobox domain binds to DNA and interacts with the TPR repeats of SSN6
The unstructured, flexible linker domain contains eight residues (Leu-114 to Gln-121), which, in the presence of MCM1, adopt a beta-fold and mediate the cooperative interaction to MCM1
The C-terminal tail domain is disordered in the monomer, even when bound to DNA. In the ternary complex with A1 and DNA, 16 residues (Ile-190 to Leu-205) of the C-terminal tail undergo a conformational change, becoming ordered and contacting the A1 homeodomain
Interacts with different set of proteins thanks to 3 different hydrophobic pockets (PubMed:20691033, PubMed:25667979). Hydrophobic pockets 1 and 2, which mediate interaction with PDCD6IP, are largely formed by residues from EF-hand 3 (EF3) to 5 (EF5), as well as by Tyr-180 (EF5) of a dimerizing molecule (Pocket 1) and from EF-hand (EF2) to 4 (EF4) (Pocket 2) (PubMed:20691033). Hydrophobic pocket 3, which mediates interaction with SEC31A, is mainly formed by residues from EF-hand 1 (EF1) to 3 (EF3) (PubMed:25667979)
EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium-binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity (PubMed:18940611, PubMed:20691033). A one-residue insertion in the EF5-binding loop prevents the glutamyl residue at the C-terminal end of the loop from serving as the canonical bidentate calcium ligand (PubMed:18940611, PubMed:20691033). EF5 acts as a high-affinity magnesium-binding domain instead (By similarity). Magnesium, may affect dimerization (By similarity). EF5 may bind either calcium or magnesium depending on the context (By similarity)
Residues 156 to 543 compose a region conserved in chromatin associated proteins
A fragment of the mature protein (residues 41-60) prevents uptake of M.tuberculosis by a human macrophage-like cell line; lesser effects are seen on bacterial uptake by a human lung epithelial cell line
The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. plk1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them (By similarity)
PDZ 5 mediates the C-terminal binding of GRIA2 and GRIA3. PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1. PDZ 7 mediates interaction with CSPG4
Possesses a three domain structure: the N-terminal 300 residues harbor a clathrin binding site, an acidic middle domain 450 residues, interrupted by an Ala-rich segment, and the C-terminal domain (166 residues)
The N-terminal FleQ domain mediates dimerization and is essential for function
Atypical domain architecture: contains 2 histidine kinase/receiver domain modules
The globular domain exerts a prion-inhibitory effect (in cis) on its own C-terminal prion domain. The het-S globular domain, but not the het-s globular domain, is essential for programmed cell death
The protein contains a prion domain (PrD), but beta-structuring in this domain due to incorporation into a het-s fibril induces a change in its globular domain, generating a molecular species that is incompetent for fibril growth
The C-terminal Solcar repeat is required for association with the TIM22 translocation complex during import
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins (PubMed:25091737). Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain
The core aggregation region, although lacking the prion-typical Gln/Asn (Q/N)-rich domain, is required for the formation of the amyloid-like fibrillar aggregates
C-type lectin domains 3 to 8 are not required for calcium-dependent binding of mannose, fucose and N-acetylglucosamine. C-type lectin domain 2 is responsible for sugar-binding in a calcium-dependent manner
The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell membrane
The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway
The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one hspa5/BiP molecule as a typical substrate of an adjacent hspa5/BiP molecule. hspa5/BiP oligomerization inactivates participating hspa5/BiP protomers. hspa5/BiP oligomers probably act as reservoirs to store hspa5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers
Between 2 and 7 copies of the SINQ repeats are to be found in different strains; these are thought to serve to generate phase-variable expression of this gene. The (SINQ)n peptide may form a random coiled structure that permits appropriate interactions between the N- and C-terminal domains of the protein
Gln-180 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Comprises a single domain but contains five nucleophilic elbows. Each nucleophilic elbow forms a local active site with varied substrate specificities and affinities, thus possessing one or more enzyme activities
The RabBD domain mediates interaction with RAB27A and recruitment on to vesicular structures in cytotoxic T-lymphocytes (CTL)
The C2 1 domain mediates binding to phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2) and localization to the cell membrane
The C-terminus of the protein contains 3 potential CHEK1-binding motifs (CKB motifs). Potential phosphorylation sites within CKB motif 1 and CKB motif 2 are required for interaction with CHEK1
The N-terminal response regulatory domain is atypical as it does not have conserved residues usually found in these domains; it is required for both homodimerization and DNA-binding. The C-terminal domain does not bind DNA alone, nor does it form homodimers. At very high concentrations overexpression of the C-terminal domain has a dominant-negative effect on DNA-binding by the whole protein
Ig-like C2-type 2 mediates neurite outgrowth through binding, induction of phosphorylation, and activation of FGFR
The C-terminal domain may form a component of the hydrophobic substrate-binding site, but in contrast appears not to be directly involved in GSH binding and is not absolutely essential for catalytic activity
The PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). Does not bind phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
The PDF region is required for protein-DNA interaction while the SSB domain is not required for ssDNA binding
The fibrinogen C-terminal domain mediates interaction with CSPG5
The cysteine framework is III (CC-C-C-CC) (Probable). Classified in the M-1 branch, since 1 residue stands between the fourth and the fifth cysteine residues
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; a methyltransferase (CMeT) domain that transfers methyl groups to the growing polyketide; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The KIM (kinase interacting motif) region may be involved in the binding to MAP kinases
The PRB domain is involved in receptor binding, and may be responsible for the cytokine-like growth factor activity due to it's sharing of several structural properties with chemokines
High-affinity binding to heparin/glycosaminoclycan (GAG) is mediated by a large, highly positively charged surface at the interface of dimer's subunits involving approximately residues 30-45, 389-396, and 422-428
The C-terminal domain mediates interaction with DNA and nucleosomes. It contains a HTH motif that mediates recognition of the consensus sequence
The protein has many AA homomeric domains: 21 poly-Gln runs (from 5 to 16 AA in length), 4 poly-Gly (6 to 10 AA), 3 poly-Asn (3 X 5 AA), 1 poly-Ala (10 AA) and 1 poly-Thr (5 AA) runs
The C-terminal segment plays a key role in the formation and stabilization of the octameric configuration, since the short afifavidin (lacking the last 5 amino acids) is only dimeric
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases leading to down-regulation of cell activation (By similarity)
The PH domain binds phospholipids. Binds preferentially phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for phosphatidylinositol-4,5-bisphosphate (PubMed:22030399)
The C2 domains bind Ca(2+) and membranes (PubMed:11823420). Binding to membranes involves Ca(2+)-dependent phospholipid binding (PubMed:11823420). Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins. The two C2 domains bind independently to planar membranes, without interdomain cooperativity. Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins (By similarity)
The Gly-Xaa-Asn repeat domain binds calcium
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins (By similarity). Interacts with shu
The extracellular domain is homologous to the repeating units (of approximately 147 AA) of the cation-independent mannose 6-phosphate receptor
The activation loop within the kinase domain is the target of phosphorylation/activation by upstream protein kinases. The PPI motif mediates the interaction with the ABI (abscisic acid-insensitive) phosphatases. The C-terminal part (309-446) of the protein is required for the phosphorylation of CBL, but is not involved in autophosphorylation
The N-terminal domain (residues 1-84), characteristic of archaeal AMPpases, is essential for enzymatic activity, participating in multimerization as well as domain closure of the active site upon substrate binding. Harbors two dimer interfaces within a single molecule: one by the central domain and the other by the C-terminal domain; these two interactions can continuously occur in a repetitive manner, leading to multimerization
Avian ovomucoid consists of three homologous, tandem Kazal family inhibitory domains. The first domain does not inhibit any tested protease. Domains 2 and 3 inhibit trypsin
This gene contains two large insertion sequences (IS1 and Ceu clpP intein) that divide the clpP gene into three sequence domains. Each insertion sequence forms a continuous open reading frame with its upstream and downstream sequence domains
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (342-372) inactivates kinase activity under calcium-free conditions (By similarity)
the 9aaTAD motif (residues 1054 to 1062) is a transactivation domain present in a large number of yeast and animal transcription factors
The extracellular leucine-rich repeats are required for the specificity of the elicitor protein recognition. Important sequence determinants of Cf-9 function are located in LRRs 10 to 18
The molecule is folded into four functional domains (PubMed:1651334, PubMed:9039918). Each domain is required for a particular step in the toxicity process (PubMed:1651334). Domain 1 contains two calcium ions and the proteolytic activation site (PubMed:1651334). Cleavage of the PA monomer releases the subdomain 1a, which is the N-terminal fragment of 20-kDa (PA-20) (PubMed:8051159, PubMed:11207581, PubMed:9039918). The subdomain 1b is part of the remaining 63-kDa fragment (PA-63) and contains the binding sites for LP and EF (PubMed:8051159, PubMed:11207581, PubMed:9039918). Domain 2 is a beta-barrel core containing a large flexible loop that has been implicated in membrane insertion and pore formation (PubMed:1651334, PubMed:11356563, PubMed:9039918). There is a chymotrypsin cleavage site in this loop that is required for toxicity (PubMed:1512256, PubMed:7961869, PubMed:9039918). Domain 3 has a hydrophobic patch thought to be involved in protein-protein interactions (PubMed:1651334, PubMed:11222612, PubMed:9039918). Domain 4 appears to be a separate domain and shows limited contact with the other three domains: it would swing out of the way during membrane insertion (PubMed:1651334, PubMed:10085028, PubMed:12771151, PubMed:9039918). It is required for binding to the receptor; the small loop is involved in receptor recognition (PubMed:1651334, PubMed:10085028, PubMed:12771151, PubMed:9039918)
Phe-456 residue forms the phi-clamp in the pore and catalyzes protein translocation via a charge-state-dependent Brownian ratchet (PubMed:16051798, PubMed:25778700). During conversion of the heptameric pre-pore precursor to the pore, the seven Phe-427 residues converge within the lumen to generate the narrowest point in the channel lumen (6 Angstroms in width) (PubMed:16051798, PubMed:25778700). To pass through this hydrophobic restriction, substrate proteins LF and EF need to be unfolded prior to translocation (PubMed:25778700)
The alpha-clamp consists in an amphipathic cleft between two adjacent PA protomers, which assists the unfolding of substrate proteins LF and EF (PubMed:21037566, PubMed:32047164, PubMed:32521227). The alpha-clamp binds non-specifically to alpha-helices of substrate proteins LF and EF (PubMed:21037566, PubMed:32047164, PubMed:32521227)
The molecule is in a coiled coil structure that is formed by 4 polypeptide chains. The N-terminal region exhibits a prominent seven-residues periodicity
The translocator domain forms a 12-stranded beta-barrel with a 10 X 12.5 Angstrom channel
Binding of calmodulin to binding site 1 is Ca(2+) dependent, whereas binding of calmodulin to site 2 is Ca(2+) independent
Consists of two structural domains: an N-terminal THUMP domain followed by a C-terminal catalytic Rossmann-like fold MTase domain in a novel arrangement. The two domains are connected by a long loop
The second EGF-like domain is atypical
The EF-hand domain 1 cannot bind calcium due to the presence of a Lys instead of an Asp at position 435 and a Gln instead of a Glu at position 442 preventing calcium binding (PubMed:28746405, PubMed:21287613). The EF-hand domains 3 and 4 probably bind calcium constitutively when calcium levels are low, while the EF-hand domain 2 binds calcium following an increase in calcium levels (PubMed:21287613)
The disordered structure between residues 29 and 65 contributes to the effector function in cell death activation
Consists of two domains: the N-terminal domain, which contains a predicted ribbon-helix-helix (RHH) DNA-binding domain, and the C-terminal domain, which comprises a signature shared by nicking accessory proteins
The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-172) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme
In the dehydrogenase domain, the conserved NAD(P)H-binding sites and sequence similarity to plant dehydrogenases suggest that this protein may have oxidoreductase activity (PubMed:23260659, PubMed:30970244). However, since the active site is not conserved, the dehydrogenase domain seems to serve as a catalytically inert oligomerization module (PubMed:30970244)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (341-371) inactivates kinase activity under calcium-free conditions
The PCI domain is necessary and sufficient for the interactions with other CSN subunits of the complex. Mediates the interaction with CAPN8 (By similarity)
The N-terminus (1-243) is required for interactions with ADO1/ZTL and APRR3
The C-terminus (568-611) is required for efficient NDHH folding, but not for the formation of the chaperonin complex
The N-terminal GAF domain activated by Cl(-)
Contains an N-terminal membrane anchor-containing module, a central non-catalytic domain and a C-terminal penicillin-binding (PB) catalytic domain. The transmembrane region is essential for localization to the septal ring, interaction with FtsW and cell septation
BtyA has an A-T-TE domain architecture (Probable). The adenylation (A) domain recognizes and activates the aryl acid substrates, and loads them onto the thiolation (T) domain (Probable). The thioesterase (TE) domain shares the missing condensation (C) domain function, and is responsible for condensation and final product release (Probable)
The C-terminal dsRNA-binding fold contains a bound zinc ion and is important for normal nuclear retention and function in RNAi-dependent heterochromatin assembly. It binds double-stranded DNA and RNA (in vitro)
Composed of three domains: a modulating N-terminal or AF1 domain, a DNA-binding domain and a C-terminal ligand-binding or AF2 domain
The WH2-domain binds actin monomer and mediated actin bundle assembly
The acidic serine aspartate-rich MEPE-associated (ASARM) motif is sufficient when phosphorylated to inhibit bone mineralization by osteoblasts and cartilage mineralization by chondrocytes by binding hydroxyapatite crystals during the mineralization stage (PubMed:15664000, PubMed:18162525, PubMed:18597632, PubMed:19998030, PubMed:22766095). It can also inhibit dentin mineralization (PubMed:20581062)
The dentonin region is sufficient to promote dental pulp stem cell proliferation (PubMed:15153459). It can also stimulate bone formation, osteoblast differentiation, and activate integrin signaling pathways (PubMed:15040834)
The extracellular domain contains a pattern of cysteine similar to the snail conotoxin Con-ikot-ikot (AC P0CB20), a toxin known to disrupt AMPA receptors (ionotropic glutamate receptor) desensitization
PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate ACAP1-binding to PIP2 or PIP3 containing membranes. Only one PH domain of one ACAP1 dimer inserts into the membrane, while the other PH domain acts primaryly to interact with adjacent ACAP1 dimers (By similarity)
The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions (By similarity)
The protein is composed of 27 tandem core repeats (the BuD domain) with 1 base-specifying residue (BSR, residue 13), which recognizes 1 base pair in the target DNA
The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling (By similarity)
Contains a remarkable run of alternating Gly-Thr residues which is polymorphic in length. At least four types of Gly-Thr length exist in the natural population, (Gly-Thr)23 (shown here), (Gly-Thr)24, (Gly-Thr)25, and one minor variant (Gly-Thr)21. This Gly-Thr stretch is implicated in the maintenance of circadian period at different temperatures. Deletion of the repeat leads to a shortening of the courtship song cycle period, and thus could be important for determining features of species-specific mating behavior (By similarity)
The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of chchd4/mia40 in mitochondria
The coiled-coil domain mediates a strong homo/multidimerization activity essential for core assembly of PML-NBs. Interacts with PKM via its coiled-coil domain (PubMed:18298799)
The B box-type zinc binding domain and the coiled-coil domain mediate its interaction with PIAS1
(Microbial infection) The RING-type zinc finger is necessary for the sumoylation of human cytomegalovirus (HHV-5) immediate early protein IE1
The unique C-terminal domains of isoform PML-2 and isoform PML-5 play an important role in regulating the localization, assembly dynamics, and functions of PML-NBs
The PXLE motif mediates interaction with EGLN1/PHD2
The RRM domain is necessary for interaction with SMAD4. Both the RRM domain and the C-terminus are required for TGFB1/Smad-mediated transactivation activity
Has protease activity (PubMed:8103915, PubMed:8294407)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (PubMed:17173035, PubMed:19476346). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:9783750). The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (PubMed:19476346)
The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are required for PEX5 retrotranslocation and recycling (By similarity). AH2 mediates interaction with lumenal side of the PEX2-PEX10-PEX12 ligase complex, while AH1 is required for extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex (By similarity)
The hemerythrin-like domain might act as a cathion-binding domain since it binds iron in haemerythrin, but can bind other metals in related proteins, such as cadmium or magnesium
The PID domain, truncated by 11 amino acids, as observed in isoform 3, but not full-length, mediates the interaction with RAB6A
The C-terminal domain transmembrane domain is indispensable for the localization to the ER
Has 2 lobes, each of which has an 8-strand beta barrel flanked on their N-terminus by a 4-strand handle domain. Electron microscopy suggests that in the TbpA-TbpB-TF complex, TF is captured directly above the loop domain of TbpA in a chamber of about 1000 Angstroms(3) formed by the 3 proteins, where interactions between the proteins serve to abstract iron 2 from TF
Largely unstructured in aqueous solution
The SH3 domain mediates binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) (PubMed:30092354). It is also required to ensure podocyte integrity while the phosphatase domain is dispensible for podocyte maintenance (By similarity)
Binds DNA through its N-terminal H-T-H motif and binds A-factor via its C-terminal region
Both the BTB domain and C2H2-type motifs are necessary for transcriptional repression activity. The BTB domain is also necessary for oligomerization and efficient sumoylation. The hydrophobic cluster preceding Lys-328 enhanced sumoylation efficiency (PubMed:20797634)
The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-54 and Tyr-101/Tyr-102
Consists of 3 domains; the ATPase domain (residues 1-220), the transducer domain (221-390) and the toprim domain (391-634) (PubMed:11850422). Removal of the N-terminal ATPase domain (residues 2-392) increases ATP-independent DNA relaxation, showing it is not required for DNA binding or cleavage, this enzyme still has some supercoiling activity, but in this case it introduces positive supercoils (PubMed:23804759)
The TPR region (477-578) is not required for assembly into the Toc complex, but interacts with TOC34 only while transferring the preprotein from HSP90 to the Toc core translocon
The amidase region (166-200) is required for the efficient transfer of the preprotein
The tail domain binds to the cytoplasmic domain of both integrin beta-1a and beta-1d isoforms. The presence of Ca(2+) ions does not prevent binding of a fragment consisting of the second cysteine rich repeat and the tail domain but prevents the binding of the full-length protein
The fibrinogen- and elastin-binding sites have been localized to the N-terminal region
CARD is critical for both extrinsic and intrinsic apoptotic pathways (By similarity). CARD domain mediates a protective effect against myocardial ischemia/reperfusion, oxidative stress and TNF-induced necrosis (PubMed:24440909). The C-terminal domain (amino acids 99 to 220) is involved in calcium binding and plays a protective role in calcium-mediated cell death (By similarity)
The N-terminus contains histidine-proline motifs involved in heme binding. Can bind 2 to 3 heme molecules
The PX domain mediates lipid-binding, localization to the plasma membrane and is required for NOX1 activation
The SH3 domains mediate interaction with CYBA/p22phox. Also mediates intramolecular interaction with the proline-rich region
C-terminal transmembrane domain is sufficient for its midcell localization, but not for the full function
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Tim8 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The 169 C-terminal residues are important for deadenylase activity
The uracil deoxyribose moiety interacts with the protein through Ile-81 and Tyr-85, which discriminate against the ribose form of the nucleotide
The linker region, also named autoinhibitory interface, is required to prevent constitutive activation and maintain CARD9 in an autoinhibitory state (PubMed:31296852). Disruption of this region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments (PubMed:31296852)
ApvA has an A-T-TE domain architecture (Probable). The adenylation (A) domain recognizes and activates the aryl acid substrates, and loads them onto the thiolation (T) domain (Probable). The thioesterase (TE) domain shares the missing condensation (C) domain function, and is responsible for condensation and final product release (Probable)
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with cut3, forming a V-shaped heterodimer
Contains an N-terminal mobile Trx domain and four atypical tetratricopeptide repeat (TPR) motifs in the C-terminal region. The Trx domain lacks the canonical Cys-x-x-Cys active site of thioredoxins and is not a functional oxidoreductase
The Asp-Asp-Xaa-Xaa-Asp (DDXXD) and Asn-Xaa-Xaa-Xaa-Ser-Xaa-Xaa-Xaa-Asp (NSD) motifs are important for the catalytic activity, presumably through binding to Mg(2+)
Has 2 similar domains, D1 (approximately residues 1-600) and D2 (approximately residues 601-1193). D1 is able to bind membranes, tether liposomes and cause membrane fusion in the absence of D2; both regions are required for GTPase activity. Possibly the fusion of 2 dynamin-like genes (PubMed:21205012). D1 alone promotes membrane tethering but requires D2 for stable tethering and content mixing (PubMed:31361971)
The deacetylase domain is in the N-terminus, while the C-terminus has a CBM32-type carbohydrate-binding domain that is not required for activity on soluble substrates. The CBM32 domain binds preferentially to repeating N-acetyl lactosamine structures
The N-terminal domain CNT1 (1-489) is sufficient for autophosphorylation and is required for dimerization. The C-terminal domain CCT1 (490-681) of the homodimer binds to COP1
Contains 2 Inka boxes (also named iBox or inca box) (PubMed:26607847). The Inka boxes bind and inhibit PAK4 by binding a substrate-like manner (PubMed:26607847)
The monomer folds into two domains of similar size. The N-terminal domain is the carbamoylphosphate-binding domain; ornithine binds to the C-terminal domain
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of smc5, forming a V-shaped heterodimer
Deletion of the PDZ domain eliminates the heat shock response of the sigma-E regulon, but not the acid stress response
Residues at positions 150 and 232 are important for the type of reaction catalyzed, using identical substrate (PubMed:29317628). Both ausE and prhA accept preaustinoid A1 as a substrate to form divergent products through dynamic skeletal rearrangement (PubMed:29317628). AusE (containing 'Leu-150' and 'Ser-232') first desaturates at C1-C2 to form preaustinoid A2, followed by rearrangement leading to the formation of the spiro-lactone in preaustinoid A3 (PubMed:29317628). In contrast, prhA (containing 'Val-150' and 'Ala-232') first desaturates at C5-C6 to form berkeleyone B, followed by rearrangement of the A/B-ring to form the cycloheptadiene moiety in berkeleydione (PubMed:22234162)
The N-terminal alpha-helix of peptide ECE1-III allows insertion of the toxin into host epithelial cells membranes (PubMed:27027296)
Seems to have a cystatin/monellin-like domain
The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain
The GPS domain is required for signaling
The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain. The FERM domain contains the subdomains F1, F2 and F3. It is preceded by a F0 domain with a ubiquitin-like fold. The F0 domain is required for integrin activation and for localization at focal adhesions (By similarity)
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (PubMed:18511944). Its contribution to the mechanism confering the myosin movement on actin filaments is debated (PubMed:18511944)
The N-terminal domain is essential for interaction with TLR2 and activation of HIV-1 LTR (PubMed:22427668). The PPE region contains the information necessary for targeting and anchorage to the cell wall (PubMed:23469198)
The C-terminal part associates with the head of smc1a, while the N-terminal part binds to the head of smc3
Composed of 2 N-terminal SH2 domains and a C-terminal kinase domain. The tandem SH2 domains bind to the doubly phosphorylated tyrosine-based activation motif (ITAM) of CD247/CD3Z and the non-canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH (By similarity). The interdomain B located between the second SH2 and the kinase domain has been implicated in binding to other signaling molecules including CBL or VAV1. Thus, ZAP70 can also function as a scaffold by recruiting additional factors to the stimulated TCR complex (By similarity)
The loop between transmembrane domains 5 and 6 is flexible and may readily open to the extracellular side to allow water entry into the active site cavity
The N-terminus is responsible for protein export from the bacteria
The central DNA-binding region is composed of 17.5 tandem core repeats with 1 base-specifying residue (BSR residue 13, also called repeat variable diresidue, RVD, residues 12 and 13) which recognizes 1 base in the target DNA; 10.5 or more repeats are required for strong gene expression (tested using an artificial TALE, PubMed:19933107). The BSR is the only residue which contacts DNA in a sequence-specific manner (PubMed:23999294). The number and order of core repeats determines its specificity for different resistance alleles in plants. Deleting and/or swapping core repeats alters the interplay between bacterial avirulence and plant resistance genes. Replacement with repeat domains from other proteins (AvrXa7 or AvrXa10 of X.oryzae pv. oryzae (AC Q56830)) does not elicit the HR in susceptible plants (PubMed:9675896)
An intact NLS2 or NLS3 is required for the plant HR response, whereas NLS1 plays a minor role. Replacement of NLS1-NLS3 or NLS2-NLS3 (residues 1021-1106 or 1067-1106) with the large T-antigen NLS from the SV40 virus fully restores HR activity
The activation domain is necessary for activity in planta
Has 4 domains (N-terminal, PAZ, Mid and PIWI). The N-terminal and PAZ domains are joined by linker L1, the PAZ and Mid domains are joined by linker L2. The domains assemble in 2 lobes; the PAZ lobe consists of the N-terminal, L1, PAZ and L2 domains, while the PIWI lobe has the Mid and PIWI domains. The PIWI domain assumes an RNase H fold and has the catalytic residues. gDNA lies between the 2 lobes, with its unpaired 5'-end anchored in the Mid lobe
Replacement of residues 191-272 by a single Ser residue still protects DNA against digestion by AluI
Composed of two domains: a Mur ligase middle domain containing the canonical ATP binding site and a ribbon-type zinc finger, and a C-terminal Mur ligase domain. The GatD/MurT complex has an open, boomerang-shaped conformation in which GatD is docked onto one end of MurT. Both proteins contribute to the catalytic triad
The PH domain binds phosphoinositides, with a preference for PI(3,4)P2 and PI(3,4,5)P3. The PH domain mediates targeting to the plasma membrane (PubMed:18270267)
The N-terminal region mediates dimerization and homooligomerization (PubMed:28228481). Both the helicase ATP-binding domain and the helicase C-terminal domain form intramolecular interactions with the HRDC domain in a ATP-dependent manner (PubMed:25901030). The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding (PubMed:20639533)
Does not show significant conformational changes upon substrate binding
Has an N-terminal beta-trefoil domain and a C-terminal pore-forming domain. The trefoil domain has barrel and cap subdomains; the cap has 3 possible carbohydrate-binding modules while the barrel is involved in host cell receptor binding. At neutral pH the carbohydrate-binding modules are accessible on the toxin surface but the barrel subdomain is not
The B30.2 domain mediates interaction with GYG1
The SET domain is sufficient for methyltransferase activity
Has the structural arrangement of two alpha-helices stabilized by disulfide bonds (CSalpha/alpha 4(S-S))
The first 18 residues targets this enzyme and foreign proteins (tested with GST and eGFP) to the BMC. The cargo is only detected by Western blot in broken shells, strongly suggesting this protein is normally found inside the BMC and not on its exterior (PubMed:21821773, PubMed:26283792). PduD and PduP compete for encapsulation in BMCs, suggesting PduD also binds to PduA and/or PduJ (PubMed:26283792)
Deletion of the C-terminus (residues 183-272, CTD) suppresses activating mutations in khpB (also called eloR/jag); the deletion no longer interacts with MreD and interacts less efficiently with PBP1b and StkP, CTD deletion leads to increased phosphorylation of KhpB
Domain encompassing residues 35-432 are sufficient for IgM cleavage
Interacts with FliS via its C-terminal domain (residues 537-576), interacts with FliW via its N-terminal domain (residues 1-44). May form a 3-way complex of flagellin, FliS and FliW simultaneously, in which FliS and FliW do not directly interact (By similarity)
The N-terminal domain is followed by a GAF (phytochrome-like) domain that lacks the conserved Cys residue for ligand binding, a histidine kinase domain and a C-terminal response regulator domain (pseudo-receiver domain, PsR)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide back-bone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and 2 acyl-carrier protein (ACP) that serve as the tethers of the growing and complete polyketide via their phosphopantetheinyl arm (PubMed:22492438). At the C-terminus, FSR1 exhibits a reductase (R) domain instead of the canonical TE domain (PubMed:22492438). In contrast to TE and TE/CLC domains, R domains show sequence similarities to the short-chain dehydrogenase/reductase (SDR) superfamily, exhibiting Rossman fold structure and nucleotide binding motifs (PubMed:22492438)
The isolated ATP-binding domain (residues 451-573) crystallized as an asymmetric, domain-swapped dimer without ATP (PubMed:23486471)
The protein surface forms a large groove around the active sites which is larger than homologs, probably to accommodate bulky sterol substrates
In contrast to other poly(A) RNA polymerases, lacks any RNA-binding domain. RNA-binding is mediated through its interaction with gld-3
The CUE domain is required for recognition of misfolded proteins such as mutant CFTR
The VCP/p97-interacting motif (VIM) is sufficient for binding VCP/p97 to form a complex capable of transferring VCP/p97 from the cytosol to microsomes
The C-terminal (153-438) mediates KCNIP3 interaction and the cytoprotective activity (PubMed:17189291). the dileucine motif mediates AP1G1 and AP3D1 interaction (PubMed:15598649)
LIM region interacts with CTNNA1. The preLIM region binds directly actin filaments (By similarity)
LIM-2 and LIM-3 domains mediate the interaction with the N-terminal region of AURKA. The association between LATS2 and AJUBA required the second LIM domain of AJUBA (By similarity)
In mouse, the SAM domain is required for deoxynucleoside triphosphate (dNTPase) activity and ability to restrict infection by viruses. It acts by capping allosteric sites
The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. The presence of the zinc molecules is essential for the translation repression activity of the protein
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins (PubMed:23201271, PubMed:19617556). The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction affinities (PubMed:23201271, PubMed:28581483). The UBA-like domain mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin ligation to DCUN1D1 (PubMed:30587576)
The RRM domain interacts with RNA, and is essential for NELF complex function. It is however not required for the NELF complex formation
Organized into two domains, each containing a covalent c-heme in a structure reminiscent of class 1 cytochromes c. The domains are related by a quasi-twofold axis. The domain interface contains a calcium-binding site with an unusual set of ligands
The N-terminal 20 residues target foreign proteins (tested with eGFP) to the BMC (PubMed:25962918). Formed by 2 beta-barrels, each is capped on both ends by short alpha-helices (By similarity)
The conserved Arg-464 in the Arf-GAP domain probably becomes part of the active site of bound small GTPases and is necessary for GTP hydrolysis
The C-terminus (128-225) is required for transcriptional activation
The extracellular serine/threonine rich region (STR) and the HKR11-MSB2 homology domain (HMH) are essential for MBS2 function, whereas the C-terminal cytoplasmic tail is dispensable for appressorium formation and virulence
The UBAX-like region mediates the interaction with VCP
The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys-11'-linked ubiquitin chains
The NLS interacts with UBE2I
The C-terminal 11 residues (motif 5) is important for function; its removal by trypsin decreases kcat about 40-fold with a less than 2-fold increase in KM for dUTP
PH domain binds phospholipids and is required for nuclear targeting
In the crystal structure alpha helix H1 passes through the middle of the pore with its C-terminus in the periplasm and loop L6 also blocks the channel. Both of the POTRA domains are periplasmic; POTRA stands for polypeptide-transport associated
Apoenzyme contains at least 2 NarJ-binding sites, one interfering with membrane anchoring and another being involved in molybdenum insertion. The first binding-site is a short peptide sequence near the N-terminus that contains a twin-arginine homologous motif
The PDZ domain is required for interaction with ENaC and SGK1, but not for interaction with NEDDL4 and RAF1
The PH domain binds phosphatidylinositol 3,5-biphosphate, phosphatidylinositol 4-phosphate and phosphatidylinositol 3,4,5-trisphosphate in vitro (PubMed:21490059). Required for punctate localization in the cytoplasm and cell corpse engulfment (PubMed:11703939). Required for distal cell tip migration (PubMed:15247908)
The Pro-rich domain is dispensable for endocytosis during the synaptic vesicle recycling, locomotion and for endogenous and evoked excitatory postsynaptic currents (EPSC) at neuromuscular junctions (PubMed:21029864, PubMed:25918845). May play a role together with the SAC domain in targeting unc-26 to synapses (PubMed:25918845)
The SAC domain, but not is catalytic activity, is required for targeting unc-26 to synapses, for locomotion and for normal endogenous and evoked excitatory postsynaptic currents (EPSC) at neuromuscular junctions
Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID)
Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic (By similarity). They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities (By similarity)
Each monomer has two clearly defined domains. The small N-terminal domain (AA 1-161) and the large domain (AA 162-403). Each of the two active sites is made by residues of the large domain of one monomer and some residues of the small domain of the other monomer
The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain, which is unstructured in its native, soluble form, and which forms a parallel in-register beta-sheet in its amyloid form (By similarity). The first 37 residues of this domain are sufficient for aggregation, propagation, and transmission of the [SWI+] prion
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). Lacbi1:307192 has NPC/NSA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
The C-terminal 10 residues are required for the association with ATG9 (PubMed:26565778)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (361-391) inactivates kinase activity under calcium-free conditions (By similarity)
The PXY motifs are required for binding WW domains. PXY1 is required to promote transactivation of beta-globin and for hyperacetylation of histone H3, but not for binding to the HS2 promoter site (By similarity)
The CFEM domain is involved in heme-binding and contains 8 cysteines and is found in proteins from several pathogenic fungi, including both human and plant pathogens (PubMed:12633989, PubMed:22145027, PubMed:25275454). The CFEM domain adopts a novel helical-basket fold that consists of six alpha-helices, and is uniquely stabilized by four disulfide bonds formed by its 8 signature cysteines (By similarity)
The C-terminal CBM6 domain shows calcium-dependent xylo-oligosaccharide and xylan binding. It binds, next to the structural calcium ion, a second calcium ion that, in addition to its coordination sites on the protein, completes its heptacoordination through coordination to the bound xylose moiety
The WW domain is required for autoregulation of FCA expression
The CULT domain binds thalidomide and related drugs, such as pomalidomide and lenalidomide. Drug binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, while no such change is observed in rodents
Eukaryotic orthologs often have inserts compared to cyanobacteria; insertion of a 19-residue sequence from C.merolae into the same position in this protein (at Val-176) has no visible effect on function. An Arg-rich patch composed of 4 residues on the 'top surface' of blades 4 and 5 is important for binding to assembling PSII centers; mutating each Arg residue individually has no phenotype whereas none of the triple mutants grow in high light (90-130 umol photon/m(2)/s), suggesting more than one residue is involved in binding to the lumenal side of assembling PSII centers
Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with RIGI and IFIH1/MDA5 (By similarity)
The transmembrane domain and residues 285-420 are essential for its interaction with DHX58/LGP2
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of MAVS recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines
Each subunit is composed of an N-terminal cytoplasmic domain, a transmembrane domain, a catalytic serine protease domain, and a single C-terminal PDZ domain (PubMed:18479146, PubMed:21445360). The protease domains form the central core of the trimer and the PDZ domains extend to the periphery (PubMed:18479146). PDZ domain is required for protease activity (PubMed:20061478)
Is predicted to have two esterase domains corresponding to distinct carbohydrate esterase families, CE1 and CE6. It can be hypothesized that the release of acetic acid is related to the CE6 domain, while the release of ferulic acid may relate to the CE1 domain
In IrtA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. In addition, IrtA contains an N-terminal siderophore interaction domain (SID) that binds FAD (PubMed:32296173). The IrtAB transporter assumes an inward-facing conformation, which may represent the low-affinity state after mycobactin release towards the SID and the cytoplasm (PubMed:32296173)
The N-terminal zf-AD is an atypical treble-clef like zinc binding domain which enables dimerization, and appears not to have any DNA-binding ability. DNA binding is achieved through the zinc fingers at the C-terminus
The region at residues 254 to 422 is required for stimulation of decapping. The region at residues 422 to 763 is required for PAT1 and LSM1 to accumulate in P-bodies and responsible for translation repression and P-body assembly
The extracellular domain is dispensable for cell growth and survival in vitro (PubMed:25713147). The catalytic activity of PknA is confined within the N-terminal 283 amino acids (PubMed:25665034)
The C-terminus contains the DNA-binding domain (156-218) while the N-terminus contains the transcriptional activation domain (8-82)
AAL adopts the six-bladed beta-propeller fold and contains 5 binding sites per monomer, each located between two adjacent blades (PubMed:14503859, PubMed:12732625). Residues conserved at 5 of the 6 sites, are located on the surface of the AAL and directly contribute to fucose recognition (PubMed:14503859). Because the corresponding residues forming site 6 are not conserved, this site cannot be considered to accommodate fucose molecules (PubMed:14503859). The 5 binding sites that are non-equivalent, and owing to minor differences in amino-acid composition they exhibit a marked difference in specific ligand recognition (PubMed:18493851, PubMed:12732625)
Binding of ATP leads to conformational changes of two loops located outside of the catalytic site. These changes could be critical for interaction with the stalk protein InvI/SctO or with chaperone and effector proteins during type III secretion
WD6 repeat is required for cross-linking by TGM2
Is composed of three domains: a dinucleotide binding domain, a dimerization domain, and a substrate-binding domain
In contract to classical cutinases, possesses a lid formed by two N-terminal helices which covers its active site (PubMed:25219509). The lid opens in the presence of surfactants to uncover the catalytic crevice, allowing enzyme activity and inhibition (PubMed:25219509)
The monomer structure is formed from three repeating units (RUs) that share the same structure as one another. The monomer, the active site and substrate all possess threefold rotational symmetry, to the extent that the active site possesses three potential Ser-Lys catalytic dyads. It is possible that any or all of the three active-site serines may act as nucleophile (albeit only one can do so per catalytic cycle). Mutant, bioinformatic and structural data propose one specific dyad being involved in catalysis
The atypical Tudor domain at the C-terminus contains two large unstructured loops, and doesn't bind methylated residues
The C-terminal domain binds carbohydrates
the ligand-binding domain (LBD) contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. NR4A2 lacks a 'classical' binding site for coactivators (PubMed:12774125)
Contains 29 repeats of the CXXC motif
In contrast to canonical tetrameric potassium channels, lacks the TVGYG selectivity filter motif and presents a completely different structure. The six transmembrane regions are tightly packed within each subunit without undergoing domain swapping. Transmembranes TM1-TM3 are positioned on the inner circle of the channel tetramer and participate in inter-subunit interactions that are central to the assembly of the ion conduction pore. The RxxxFSD motif within transmembrane TM1 coordinates a network of specific inter- and intra-subunit interactions with other conserved residues on TM2 and TM3 and plays a key role in the tetrameric assembly of the channel. Transmembrane TM4-TM6 are positioned on the periphery of the channel and do not contribute to contacts with neighboring subunits. Transmembranes TM1 and TM2 are linked by an extended strand-like tail and two short helices (H1 and H2) which protrude outwards from the main body of the transmembrane domain and enclose the external open entrance of the ion conduction pore in the channel tetramer. Transmembrane TM3 is bent into two segments (TM3a and TM3b) due to the presence of a conserved proline (Pro-102). Transmembrane TM1 forms the pore-lining inner helix at the center of the channel, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three hydrophobic residues (Ile-23, Leu-27 and Leu-30) on the C-terminal half of the TM1 helix form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Ile-23 is probably responsible for channel selectivity
Forms hexameric rings with a central hydrophobic pore via its periplasmic domain, which also binds phospholipids. Contains at least four binding sites
Neither the N-terminal nor the C-terminal are essential for chloroplastic localization of the protein. An internal region (59-Pro-Ala-100) is essential but not sufficient for plastid localization
HD1 motif interacts with SAM domain of PHC1
The BH3 motif is required for pro-apoptotic activity and for interaction with pro-survival Bcl-2 family members
The C-terminal 15-30 residues (cargo loading-peptide, CLP, or targeting peptide) are sufficient to target this protein to the nanocompartment in vivo, while the C-terminal 5 residues suffice in vitro
The C-terminal region mediates association with set9, whereas the N-terminal PWWP domain recognizes H4K20me1
Interacts with FtsZ via its C-terminal region, and with PbpB via two extracytoplasmic loops
The RING-type zinc finger is necessary for ubiquitination and for the IRF3-driven interferon beta promoter activity. Interacts with SKP2 and CUL1 in a RING finger-independent manner (PubMed:18845142). The RING-type zinc finger is necessary for ubiquitination of NMI (PubMed:26342464)
The B30.2/SPRY domain is necessary for the cytoplasmic localization, the interaction with IRF3 and for the IRF3-driven interferon beta promoter activity (PubMed:18845142). The B30.2/SPRY domain is necessary for the interaction with NMI (PubMed:26342464)
The PTS EIIC type-1 domain forms the PTS system translocation channel and contains the specific substrate-binding site
The PTS EIIA type-1 domain is phosphorylated by phospho-HPr on a histidyl residue. Then, it transfers the phosphoryl group to the PTS EIIB type-1 domain
Contains a C-terminal CheY-like regulatory domain where the phosphate can be transferred
The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated further by FLT3LG binding
The polybasic C-terminal domain is not required for membrane localization
The myosin motor domain binds ADP and ATP but has no intrinsic ATPase activity. Mediates ADP-dependent binding to actin
The Grh/CP2 DB domain is required for direct DNA-binding (By similarity). The Grh/CP2 DB domain is essential to maintain the undifferentiated state of embryonic stem cells (By similarity)
The SAM-like domain is required for homohexamerization (By similarity)
The S3b-S4 and S1-S2 loops of repeat IV are targeted by H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b depends on S1-S2 loops of repeat IV (PubMed:27281198)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (Probable). The gsfA PT domain catalyzes the unusual C8-C13 aldol condensation as the first cyclization step in the formation of norlichexanthone (PubMed:23978092). the PT domain, when distorting the polyketide backbone for the aldol cyclization, may also promote the C1-C6 cyclization (PubMed:23978092)
Contains a metal-binding site, which can bind nickel or zinc, with a higher affinity for zinc (PubMed:21239585). His-107 is an essential nickel ligand only in the nucleotide-free state of the protein (PubMed:24338018)
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (PubMed:26656854). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer (PubMed:26656854)
Contains an ATP-binding N-terminal domain and a NrtA-like C-terminal domain, which are connected by a segment containing an abundance of glutamine, alanine and positively charged amino acids (PubMed:8437564). The N-terminal domain is required for activity and the C-terminal domain is involved in regulation of the activity (PubMed:9341163)
Contains an N-terminal PPIase domain, an IF (Insert in the Flap) domain and a C-terminal domain (CTD). The CTD mediates dimerization. Chaperone activity requires both the IF domain and the CTD
The part of the protein spanning the actin filament-binding domain together with the DH domain and the first PH domain is necessary and sufficient for microspike formation. Activation of MAPK8 requires the presence of all domains with the exception of the actin filament-binding domain (By similarity)
Contains an N-terminal region with low similarity to aminopeptidases, an insert domain, and a C-terminal permutated winged helix-turn-helix domain
The C-terminus (339-462) is required for interaction with cpSRP
The active site region is accessed through a large opening that suggests that the enzyme has endopeptidase activity rather than exopeptidase activity
The mariner transposase Hsmar1 region mediates DNA-binding. It has retained some of the nucleases activity but has lost its transposase activity because the active site contains an Asn in position 610 instead of an Asp residue
The nuclear export signal acts as a transcriptional repression domain. The TADI and TADII motifs (residues 17 to 25 and 48 to 56) correspond both to 9aaTAD motifs which are transactivation domains present in a large number of yeast and animal transcription factors
The SH3 domains mediate interaction with CYBA/p22phox
The C-terminal region mediates interaction with the mRNA and polysomes (PubMed:24532714, PubMed:26206669, PubMed:28379136). It is required for translational repression of mRNAs with a 5'TOP motif (PubMed:29244122)
The alpha-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the beta-1 domain of HLA-DRB. Forms hydrogen bonds with the peptide main chain via conserved amino acids (PubMed:8145819, PubMed:9354468, PubMed:9782128, PubMed:17583734, PubMed:29884618). The peptide-bound alpha-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domain of TCR (PubMed:29884618)
The alpha-2 Ig-like domain mediates the interaction with CD4 coreceptor
Composed of two homologous domains
ALT12 encodes a nonribosomal peptide synthetase containing two domains, a peptidyl carrier protein domain and a condensation domain
The PDZ-binding motif mediates interaction with TAX1BP3
The repressor activity is mostly localized to the C-terminal region
The heptad repeat (HR) motif is sufficient for interaction with kinesin heavy (KHL) chains and ODF1. The TPR region is involved in mitochondrial binding (By similarity)
The WW domains mediate interaction with PPxY motif-containing proteins (By similarity). The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2 (PubMed:11042109)
The N-terminal part (1-351) part blocks the association of the tight junction marker TJP1 with the cell-cell boundary when it is overexpressed
The N-terminal 12 amino acids are sufficient for cell membrane targeting of a heterologous protein
The RNA:DNA duplex-binding domain interacts with the template phosphates at positions -2, -1, 1, and 2 positioning its bases -1, 1, and 2 for duplex formation. Interacts only with the beta- and gamma-phosphates of triphosphate moiety of initiating NTP of the primer. The side chain of His-303 mimics a RNA base that would be paired with the template nucleotide at position -1 via a hydrogen bond, thereby facilitating the stacking of the initiating NTP. In the initiating primosome a 'mini RNA:DNA' duplex is formed comprising three template nucleotides at positions -1, 1, and 2 on one strand and His-303, initiating NTP, and incoming NTP on the other strand
The interdomain linker provides flexibility in movement relative to primosome platform composed of PRIM1, the N-terminus of PRIM2, the C-terminus of POLA1 and POLA2. Together with POLA1 interdomain linker, allows for large-scale conformational changes of primosome and coordinated autoregulation of catalytic centers of PRIM1 and POLA1. It is proposed to move the C-terminus of PRIM2 close to PRIM1 during initiation, then move it away with the 5'-end of the nascent primer during elongation. The steric hindrance between the N- and C-terminus of PRIM2 as the RNA primer is elongated limits its length to 9 nucleotides. Ultimately a large rotation of the C-terminus of PRIM2 transfers the primer to POLA1 active site for DNA synthesis
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tim9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
Contains several highly conserved motifs that are important for catalytic activity including the aspartate-rich 'DDxx(x)D/E' motif and the 'NDxxSxxxD/E' motif, both of which are involved in complexing Mg(2+) ions to coordinate the binding of the isoprenyl diphosphate substrate in the active site
This gene contains one large insertion sequence (IS1) that divides the clpP gene into two sequence domains. The insertion sequence forms a continuous open reading frame with its upstream and downstream sequence domains
The protein kinase domain is predicted to be catalytically inactive. Might be required for the negative regulation of the guanylate cyclase domain (PubMed:27062922)
The guanylate cyclase domain is required for thermotaxis responses
The membrane-association motif is essential for the localization to membrane of Golgi stack. According to some authors, it is a transmembrane domain; the existence of a transmembrane region of such is however unsure (By similarity)
The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG (By similarity)
A long alpha helix in the N-terminus mediates dimerization, while the earmuff domain is responsible for core histone and dsDNA binding. The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity
Tudor domains 2 and 3 have higher affinity for arginine-methylated peptides, tudor domain 1 is a poor binder due to an impaired aromatic cage
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-56 and Arg-59) that bind to malonylated and succinylated substrates and define the specificity
The FYVE domain is required for PI3P binding (PubMed:25438943). The N-terminal domain (31-86) is required for the interaction with VPS23A and B (PubMed:25438943). The C-terminal domain (515-601) is required for the binding to ubiquitin (PubMed:25438943). The C-terminal coiled-coil region is required for the interaction with SH3P2 (PubMed:25624505)
Three specific residues, Ser-176, Phe-179 and Thr-195 are conserved between primates whereas the respective residues are phenylalanine, leucine, and asparagine in the other mammal enzymes. The two residues at positions 176 and 179 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil. The presence of an asparagine at position 195 is important for the maintenance of the quaternary structure and stability at cold temperature. The absence of an asparagine at position 195 destabilizes the quaternary structure, thereby affecting catalytic efficiency toward some substrates and decreasing stability at cold temperature
The C2H2 domain is the main region responsible for the transcriprional repression
The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes 'Lys-63'-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin
The GLUE domain (GRAM-like ubiquitin-binding in EAP45) mediates the binding to the 3' UTR of bicoid mRNA
The SMP-LTD domain is a barrel-like domain that binds phospholipids
Composed of antiparallel beta sheets. The strands of the beta sheets run parallel to the fiber axis. Long stretches of silk fibroin are composed of microcrystalline arrays of (-Gly-Ser-Gly-Ala-Gly-Ala-)n interrupted by regions containing bulkier residues. The fiber is composed of microcrystalline arrays alternating with amorphous regions
The CXXC-type zinc-finger domain mediates binding to DNA sequences containing unmethylated cytosine or 5-carboxylcytosine in 5'-CCG-3' DNA sequence motifs (PubMed:26774490). It mediates binding to CpG-DNA (By similarity)
The N-terminus region is necessary for interaction with actin retrograde filament flow and accumulation in neuronal growth cones (PubMed:18519736)
Contains three domains: a FAD-binding domain, a middle domain, and a C-terminal domain (PubMed:27557658). The middle domain forms a cap over the FAD-binding domain and is involved in binding rifampicin (PubMed:27557658)
The cysteine framework is XVI (C-C-CC)
The N-terminal half of KdtA is responsible for determining the number of Kdo residues that are transferred to lipid IVA
Histidine-tagging (His-tagging) at the N-terminus does not impair interaction with H-NS, whereas His-tagging at the C-terminus does impair interaction (PubMed:11790731)
The CBM3 domain binds to cellulose
Both the N- and C-termini are required for chemokine-binding
The N-terminus of the heavy chain associates with the C-terminus of the light chain to form the heterodimer complex. Its C-terminal part of the heavy chain interacts with ESR1 (By similarity)
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex (PubMed:25561175, PubMed:25567906). The cytosolic N-terminus part of the protein destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC (PubMed:32868926). The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer (PubMed:30181260, PubMed:25561175, PubMed:25567906). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (By similarity)
Although predicted to be a GTP-binding protein because of the presence of a Rho-like region, binds and hydrolyzes ATP. In contrast to Rho-like proteins, the conserved Asp residue in position 138 in the G4 region is replaced by an Asn, decreasing the ability to bind GTP
The proline-knot motif (124-133) may be involved in targeting to lipid bodies
The N-terminal velvet domain contains a NF-kappa-B-like fold and is involved in DNA-binding (By similarity)
The leucine-rich repeat domain may reduce the interaction with TMEM173/STING
Can adopt both open and closed states. Full-length closed state protein binds a closure peptide (consensus Glu-Val-Met-Glu-Phe-Asn-Pro). In the Cap7:Cap8 complex only Cap7 binds a closure peptide
The PDZ domain mediates interaction with CRB3
Has a putative N-terminal zinc-finger, a region with homology to RecA with ATPase motifs including the RadA KNRFG motif (approximately residues 60-290), while the C-terminus is homologous to Lon protease (from about residue 290 to the end, the ribosomal S5 domain). In this organism the Lon protease active site Ser-372 is conserved, but not all other bacteria encode Ser at this position (PubMed:1327967, PubMed:8759876). Mutation of Ser-372 has no discernible effect on RadA function, suggesting RadA is not a protease (PubMed:25484163)
The signal sequence is essential in mediating its proper translocation, hyaluronic acid (HA) degradation activity and secretion
The SUMO interaction motif (SIM) is important for binding to pmt3/smt3 (SUMO)
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (Probable). The ER domain was found to be much shorter than those of other fungal RD-PKSs, and in its nucleotide-binding domain (G/AxGxxG), the second glycine is replaced by a serine residue. This suggests that this domain is non-functional and is consistent with the absence of reduction of the double bonds formed by the DH domain in the PKSF products (Probable)
The coiled-coil domain may be necessary for interaction with TRIM21 and for TRIM21-mediated ubiquitination of NMI
The NID domains are necessary for the interaction with IFI35 (By similarity). The NID domain 1 is necessary and IRF7 (PubMed:23956435)
The presence of 'disulfide through disulfide knots' structurally defines this protein as a knottin. This toxin contains 2 'disulfide through disulfide knots' that are separated by a short linker. Bivalence accounts for irreversible toxin action
The KIX domain mediates binding to HIV-1 Tat
The cysteine framework is XXX (C-C-CCC-C-C-C-CC)
AtqA has an A-T-TE domain architecture (Probable). The adenylation (A) domain recognizes and activates the aryl acid substrates, and loads them onto the thiolation (T) domain (Probable). The thioesterase (TE) domain shares the missing condensation (C) domain function, and is responsible for condensation and final product release (Probable)
The PB1 domain provides both positive and negative electrostatic interfaces for directional protein interaction
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (288-318) inactivates kinase activity under calcium-free conditions (By similarity)
Both the N-terminal docking peptide and the catalytic core domain must bind the Uba3-Ula1 complex simultaneously for optimal transfer of Nedd8
The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP. The C-terminal tail is necessary for lysosomal transport
Cysteine residues from the thioredoxin-like domain participate in a series of disulfide-exchange reactions that regenerate the redox-active cysteine residues in the transmembrane domain
The WW domain is sufficient for direct and specific interaction with the phosphorylated CTD of RNAPII largest subunit
The third NHR domain (NHR 3) is required for localization to both mother and daughter centrioles. NHR 1 restricts targeting to daughter centriole (PubMed:22441691). NHR 3 and 4 are required for CCP110/CEP97-binding, but not for HERC2-binding. NHR 5 and 6 are important for HERC2-binding and centrosomal localization (PubMed:22261722)
Contains two cysteine rich domains (CRD), referred to as the N- and C-terminal CRD's, n-CRD and c-CRD, respectively (By similarity). A nuclear export signal is embedded in the c-CRD, with which the nuclear export protein CRM1/exportin 1 interacts only in the absence of disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or between the c-CRD and the n-CRD (By similarity)
The two Pro-rich regions are required for the suppression of AP1 transcription activity
The truncated protein kinase domain is predicted to be catalytically inactive; has lost the main activatory autophosphorylation site and the conserved key residues involved in phospho-substrate. The C-terminal region (containing the POLO box domain) is sufficient for inducing cell cycle arrest
The LIM zinc-binding 3 (LIM 3) domain provides the structural basis for recognition of tyrosine-containing tight turn structures
The second extracellular domain (ECD2, aa 1395-1680) undergoes conformational change in response to its specific interaction with its substrate all-trans-retinal (PubMed:20404325). Nucleotide binding domain 1 (NBD1, aa 854-1375) binds preferentially and with high affinity with the 11-cis retinal (PubMed:23144455)
The C2 domain is a non-calcium binding domain (By similarity). Cooperates with the PH domain in the binding to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) (By similarity)
Contains 2 dsRNA-binding domain (DRBM) (PubMed:9736623). The N-terminus contains the catalytic domain dimerization. The C-terminus binds EIF2S1/EIF2-alpha (PubMed:16179258)
The SOCS box domain is required for IRS1 ubiquitination and subsequent proteasomal degradation
The N-terminus of the heavy chain associates with the C-terminus of the light chain to form the heterodimer complex (By similarity). Its C-terminal part of the heavy chain interacts with ESR1
The HSR domain is important for the nuclear body targeting as well as for the dimerization
Contains a short N-terminal coiled-coil domain and a C-terminal globular domain
The open AAA+ domain (residues 126-400) probably allows nucleotide exchange and has the protease active site, while the closed domain is the active ATPase domain but the protease is inactive
The FYVE-type zinc-finger is necessary for early endosome localization. Recruitment to endosomal membranes via this domain requires the presence of phosphatidylinositol 3-phosphate or other phosphatidylinositides (By similarity)
The PH domain is necessary for localization to the ruffle membrane. Recruitment to ruffle membrane occurs through binding of phosphoinositides by the PH domain. This domain also contributes to the lipid-binding properties of the protein (By similarity)
The DH domain is necessary for its ability to activate JNK1 via CDC42
The PDZ domain contains the signal for export from the nucleus (PubMed:24633211). The N-terminal region including the PDZ domain is required for the formation of Cajal bands on myelinated nerves
Both the PE domain and the non-PGRS C-terminal domain possess independent cell wall localization signals. The PGRS domain is responsible for polar localization of PE_PGRS30 (PubMed:24530527, PubMed:25390359). PE and PGRS domains are necessary for the cytokine-modulating function (PubMed:27129781). The non-PGRS C-terminal domain is not exposed on the surface and is not required for full virulence in vivo (PubMed:22050772, PubMed:25390359)
The C-terminal region (residues 247 to 269) consists of one W motif, a conserved motif found in already well characterized effectors that may be involved in the interaction with host proteins
The CARD domain mediates interaction with CASP1 and NLRC4
The pyrin domain mediates homotypic interactions with pyrin domains of proteins such as of NLRP3, PYDC1, PYDC2 and AIM2
The protein is evolutionarily related to retrotransposon Gag proteins: it contains large N- and C-terminal domains that form a bi-lobar architecture similar to the capsid domain of human immunodeficiency virus (HIV) gag protein. It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells. Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons
The Tudor domain recognizes and binds H3K36me3 (PubMed:23273982, PubMed:23160351, PubMed:23104054, PubMed:23228662). May also bind H3K27me3, with a lower affinity (PubMed:23160351)
The N-terminal domain (1-178) of the short isoform is necessary and sufficient for directing the protein to the endoplasmic reticulum and to spherical structures
The extracellular N-terminus Ig-like V-type domain is necessary for homophilic and heterophilic intercellular adhesion
Binds and activates the Arp2/3 complex via the C-terminal domain. Interacts with actin via the WH2 domain
The N-terminal C2 domain mediates the association with lipid membranes upon calcium binding. An additional second C2 domain may stand in between the C2 domain and the PLA2c domain
The LYR motif mediates interaction with NDUFAB1 and is required for the function in mitochondrial fission
The FAD-binding PCMH-type domain does not bind FAD covalently
The N-terminal TPR repeat region contains an acidic patch that is important for interaction with histones (PubMed:24946827, PubMed:27618665). A C-terminal, highly polar region mediates interaction with dimeric histone H2A and H2B, but is not involved in interaction with heterotetrameric histone H3 and H4 (PubMed:27618665)
The HDAg-like domain is essential for transcriptional repression, and mediates the interaction with the RNA polymerase II complex
The propeptide region and the N- and C-terminal thirds of the mature protein are necessary for neural induction activity. Although cleavage doesn't appear essential for activity, residues surrounding the cleavage site are necessary for activity (By similarity). The propeptide region is both necessary and sufficient for bmp-inhibitory activity
The two activities reside in distinct domains (N-terminal amidase and C-terminal synthetase). The two domains expressed independently are folded and functional (By similarity)
Consists of an N-terminal FAD-binding domain with a Rossman fold, a substrate-binding domain and a C-terminal helix that bridges the 2 domains close to the antibiotic-binding site. This last helix is flexible and may contribute to their different substrate specificities
The C-terminal domain (551-712) is responsible for the Golgi localization
The cysteine motif may be involved in metal binding
The C2 domain is required for RapGAP activity
The N-terminus (1-40) is necessary for interaction with CNS5B
The C-terminal 58 amino acids (residues 228-285) are required for RCD1-binding and attenuation of light and defense signaling
The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex
The oligomeric secretin consists of an outer membrane ring connected via a thin cylindrical wall to a conical, periplasmic region that exposes N-terminal petals connected by flexible linkers. These petals harbor the binding site of YscD/SctD, a component of the inner membrane ring
The kinase domain is not sufficient by themself for proper function and that the non-conserved N-terminal and C-terminal domains are critical for the biological activity. The C-terminus promotes interaction of ELM1 and TOS3 kinases with SNF1
Both protease activity and an intact zinc finger are required for H2A monodeubiquitination
The last 95 residues are required for correct localization (PubMed:22753055). The C-terminus determines the oligomerization state of the protein; there are many small foci for FloA. Swapping with the C-terminus of FloT leads to fewer large foci (PubMed:25909364). N-terminally tagged, purified protein lacking the first 10 residues oligomerizes, with 12mer to about 50mer complexes found (PubMed:27362352)
The inhibitor sequence (IS) is a substrate recognition motif that docks to the active site cleft of the catalytic subunit rendering the holoenzyme inactive
Binding of cAMP to the 2 tandem cyclic-nucleotide binding domains (CNB-A and CNB-B) induces a conformational change in BCY1, causing the interaction surface with the catalytic subunit to be destroyed and eventually the dissociation of the R dimer from the C subunits
The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with smc2 forming a V-shaped heterodimer
Exists in an 'open' form that permits binding of the long chain acyl-coenzyme A substrate and release of the corresponding 3-ketoacyl ACP product. Catalysis and intermediate steps in the process are proposed to occur in a 'closed' form of the enzyme
LysM domains are involved in Nod factors perception, especially in chitooligosaccharide-binding
The C-terminal transmembrane and cytoplasmic domains are required for the trafficking of the protein to the inner membrane complex
A Gly-cisPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of L-amino acids (PubMed:24302572, PubMed:27224426)
The FYVE-type zinc-finger is necessary for early endosome localization. Recruitment to endosomal membranes via this domain requires the presence of phosphatidylinositol 3-phosphate or other phosphatidylinositides
The PH domain is necessary for localization to the ruffle membrane. Recruitment to ruffle membrane occurs through binding of phosphoinositides by the PH domain. This domain also contributes to the lipid-binding properties of the protein
The PID14 protease inhibitor domain is sufficient for inhibition of host cysteine proteases
The WW 1 domain mediates interaction with TP53, TP73, TFAP2C, LITAF and WBP1
The loop (92-105) connecting the two anti-parallel beta-strands (85-91 and 106-112) confers the function to the peptide
The His/Pro-rich (HRR) region contains approximately 12 tandem internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR binds heparan sulfate and possesses antiangiogenic, antibacterial and antifungal properties through binding Candida cells, and preferentially lysing the ergosterol-containing liposomes at low pH. The tandem repeats also bind divalent metal ions and heme
SUMO interaction motif 1 (SIM) mediates the binding to polysumoylated substrates
Full-length S1 protein and the C-terminal domain (residues 285-481) bind tmRNA; the interaction is disrupted in a concentration-dependent manner by POA. 2 POA molecules bind to the C-terminal domain (residues 285-481) and S1 motif 4 (residues 285-368)
Contains an amphipathic helix (''ruler helix'') that has a dual role of facilitating membrane attachment and glycan counting. The ruler helix contains three positively charged side chains (Lys-67, Arg-71 and Lys-74) that can bind the pyrophosphate group of the LLO substrate and thus limit the addition of GalNAc units to three
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (363-393) inactivates kinase activity under calcium-free conditions (By similarity)
Contains a masked and non-functional KDEL endoplasmic reticulum retrieval motif
Corresponds to the N-terminal half of the enzymatic domain
Nucleotide binding is coupled to a conformational shift at the periplasmic gate. This shift is akin to unlocking a swinging door: allowing just enough space for molybdate to slip into the cell. The lower cytoplasmic gate, identified as gate I, remains open throughout the MolBC-A mechanism, and cytoplasmic gate II closes in the presence of nucleotide
The F-BAR domain mediates membrane-binding and membrane tubulation
Rho-GAP domain is required to promote GRIA1 exocytosis from recycling endosomes. Rho-GAP and BAR domains are necessary for the control of long-term potentiation in hippocampal neurons (By similarity). In dendrites, BAR domain mediates the recruitment to patches where plasma membrane is deformed by acto-myosin mediated contractile forces (PubMed:25498153)
The ubiquitin-like region is necessary for its localization to stress granules (SGs) in a VCP-independent manner (PubMed:29804830). The AN1-type 1 and 2 zinc finger domains are necessary for the recruitment of the 26S proteasome to SGs (PubMed:29804830). Both the AN1-type 1 and 2 zinc finger domains and the ubiquitin-like region are necessary for efficient SGs clearance upon specific arsenite-induced responses (PubMed:29804830)
The LIM zinc-binding domains mediate interaction with LPAR2
Consists of two domains which are linked by a long alpha-helix. The N-terminal domain is essential for dimerization and the C-terminal domain has the class I MTase fold
The helical collagen-like domains from three protein chains assemble into a coiled coil and mediate trimerization
The cholesterol recognition/amino acid consensus (CRAC) region directly binds cholesterol, as well as campesterol and 27-hydroxycholesterol (PubMed:29149604). Has much lower affinity for epicholesterol (PubMed:29149604)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; a methyltransferase (CMeT) domain responsible for methylations; and 2 acyl-carrier protein (ACP) domains that serve as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
Contains an N-terminal DNA-binding domain and a C-terminal dimerization domain (PubMed:12847518, PubMed:16533030, PubMed:23298157). Contains two metal binding sites per subunit, site A (corresponding to metal ion 2) and site C (corresponding to metal ion 1), which both contribute to the metal selectivity of MntR. A large metal cation is needed at the A site to correctly orient and position the C site ligands. Smaller, non-cognate metal cations bind at the A site, but disrupt the C site, blocking the full activation of MntR. Binding at the C site also favors Mn(2+) and Cd(2+) over other metals (PubMed:16533030, PubMed:23298157)
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (PubMed:25216349)
Contains two pairs of conservatively spaced Cys (Cys pair 1 and 2) possibly involved in forming some heterodimers
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (PubMed:18978088, PubMed:20479000)
Each subunit has two RNA-binding sites, one at the surface of the hexameric ring, and one at the center of the open ring structure, where RNA helicase activity is thought to take place
The cysteine framework is I (CC-C-C). Alpha5/8 pattern
Contains an N-terminal DNA-binding domain and a C-terminal ligand-binding domain, which can accommodate a variety of structurally unrelated antimicrobial agents. The C-terminal domain is also involved in dimerization
The HAMP domains are critical for the sensitivity to fungicides such as fludioxonil, as well as for activation of HOG1
The second, third and fourth zinc finger domains are necessary for repressing gene transcription
The signal peptide guides the autotransporter protein to the periplasm where it is lipid-anchored (presumably) in the outer membrane. Insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, where subsequent cleavage by NalP or a host protease liberates C2
Contains 1 metal-binding domain: 6 to 8 copper ions are chelated within a single copper-thiolate cluster and are coordinated via cysteinyl thiolate bridges to 10 cysteine ligands. 6 copper ions are trigonally coordinated, whereas the other 2 are only digonally coordinated
Exhibits patches of positively charged residues, which form binding sites for acidic Glu-rich peptides
The FF ER export motif at the C-terminus is not sufficient to support endoplasmic reticulum exit, and needs assistance of Gln-501 for proper recognition of COPII coat components
Has an acidic N-terminus (AA 1-52) followed by a Ser-, Thr-, Pro-rich domain (AA 125-233) and a basic C-terminus (AA 461-555)
Contains two ACAD domains separated by a short linker. The two domains interact to form a single active site
The C-terminal domain is required for transcriptional activation
In the 3D-structure the McsB dimer adopts a flat 'domino tile' shape, with the two active sites opening on the same side. Individual subunits are composed of the N-terminal catalytic, ATP:guanido phosphotransferase domain (PD, residues 1-263) and the C-terminal dimerization domain (DD, residues 264-355), which are linearly organized in a PD-DD-DD*-PD* manner (asterisk denotes the partner protomer). The PhK-like catalytic phosphotransferase domain is structurally adapted to target protein substrates. The C-terminal DD of McsB contains a pArg-binding pocket that allows pArg-carrying proteins to allosterically enhance McsB kinase activity
The second PDZ domain (PDZ2) mediates homodimerization and heterodimerization with Tjp2 and Tjp3 (By similarity). PDZ2 domain also mediates interaction with Gja1 (PubMed:9707407)
The Ala/Pro-rich domain may contain discrete activation and repression subdomains and also can mediate protein-protein interactions
The nonribosomal peptide synthase is composed of three domains. The adenylation (A) domain is responsible for the adenylation and activation of beta-alanine using ATP (Probable). The thiolation (T) or peptidyl carrier protein domain (PCP) contains the prosthetic group 4'-phosphopantetheine; activated beta-alanyl-AMP is transferred to the prosthetic group via thiolation (PubMed:35385687). The condensation (C) domain performs the selection of the amine substrate, tryptamine, and the condensation of this amine with beta-alanine via an amide bond (Probable)
Contains 1 atypical KH domain, which is still capable of binding RNA
Consists of three domains. The N-terminal dimerization domain has the same fold as the IIA domain of the mannose transporter of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS). The middle domain is similar to HPr and the C-terminus is similar to the N-terminal domain of enzyme I (EI) of the PTS. The IIA domain of DhaM (via phospho-His-9), instead of ATP, is the phosphoryl donor to dihydroxyacetone (Dha). The phosphoryl flow likely involves HPr ('His-15') -> DhaM (His-435 -> His-170 -> His-9) -> DhaL-ADP -> Dha. The HPr-like domain of DhaM cannot efficiently substitute for the general carrier protein HPr
The NTF2 domain heterodimerizes with NXT1 and NXT2
The entire ARM repeats region mediates binding to CDH1/E-cadherin. The N-terminus and first three ARM repeats are sufficient for binding to DSG1. The N-terminus and first ARM repeat are sufficient for association with CTNNA1. DSC1 association requires both ends of the ARM repeat region
The EEXXXDDL motif is required for the interaction with ATR/mei-41
The DIM domain (143-214) is necessary but not sufficient for heterodimerization
Contiguous repeats of the 11-mer LEA motif is characteristic of group 3 LEA proteins and form an amphipathic helical structure under water-deficient conditions (PubMed:25675104)
The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling
The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators (such as CRP) and with upstream promoter elements
The IMD domain consisting of an antiparallel dimer of three-helix bundles, featuring on one side a positively charged. The N-terminal alpha-helix inserts into the lipid bilayer. Also forms homodimers and homooligomers. The residue Trp-141 is essential for oligomer formation
The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels (PubMed:24560927). It is unclear which EF-hand binds calcium as none of the 4 EF-hand domains seem to contain a canonical calcium-binding site
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 75-107, leaving each N-terminal inhibitory region (residues 27-56) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 27-56) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity (By similarity)
The protein kinase domain is predicted to be catalytically inactive. The DWD box is required for interaction with DDB1A (By similarity)
The PRONE (plant-specific Rop nucleotide exchanger) domain is responsible for the GEF activity. The intrinsic dissociation of ROP4-GDP is stimulated 15-fold by the PRONE domain (PubMed:15980860), whereas that of ROP1-GDP is increased 350-fold (PubMed:16415208)
The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are probably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (PubMed:29899445). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (By similarity)
The N-terminal divalent cation-dependent polymerase/primase domain (Pol) functions as an independent domain (PubMed:17174332). Deletion of the Pol domain (residues 1-288) yields a protein severely impaired in NHEJ on blunt or 5'-overhangs (PubMed:18281464)
The central 3'-phosphoesterase domain (PE) (PubMed:17174332). Mutations in the PE domain argue against this domain being involved in residue deletion during NHEJ (PubMed:18281464)
The C-terminal ATP-dependent ligase domain (Lig) functions as an independent domain (PubMed:17174332). Loss of the Lig domain (residues 449 to 762) forces NHEJ to rely on another ligase, which decreases fidelity for blunt and 5'-overhang DSB (PubMed:18281464)
The WxxxF motif is involved in the interaction with the PTS1-receptor docking protein PEX14
The TPR repeats are involved in the interaction with the C-terminal peroxisomal targeting signal PTS1 of MLS1 and MLS2
Composed of 3 domains: an N-terminal RNA-binding domain that prevents transcriptional termination, and two PTS regulation domains, PRD 1 and PRD 2. PRD 1 is the target of negative control exerted by EII-Glc and PRD 2 is the target of HPr
The BH3 domain is required for interaction with SEPTIN4 isoform ARTS and thereby for XIAP-mediated ubiquitination and subsequent induction of apoptosis
Gln-246 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
C2H2-type zinc-finger domains 5 and 6 are important for the interaction with SOX9
The first 30 amino acids of the cytoplasmic domain contain a major binding site to alpha-actinin-2. This interaction is necessary to promote muscle cell fusion
The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinoma cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading (By similarity)
The arginine-rich motif (ARM, residues 55-73) plays a role in regulation of at least 1 endogenous gene (FTN_1103)
Has a recognition domain (REC, residues 83-858) and a nuclease domain (NUC, residues 1-51 and 859-1629). The crRNA-target DNA twist through the domains in a different manner than in the S.pyogenes and S.aureus orthologs (PubMed:26875867). The NUC lobe has 2 endonuclease domains. The discontinuous RuvC-like domain in NUC cleaves the target DNA noncomplementary to crRNA while the HNH nuclease domain cleaves the target DNA complementary to crRNA (Probable)
The protein is evolutionarily related to retrotransposon Gag proteins: it contains the capsid (CA) and nucleocapsid (NC) subdomains of gag
In addition to the capsid (CA) and nucleocapsid (NC) subdomains of gag proteins, this isoform contains subdomains of pol, namely a protease (PRO) domain and a predicted reverse transcriptase (RT)-like domain
The ring finger is important for its antiapoptotic effect
The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31. Does not interact with other PUB domain-containing proteins. Phosphorylation at Tyr-56 prevents interaction with RNF31
The N-terminus may contain the DNA-binding domain. Last 40 residues of the C-terminus are required for chromosome segregation
The cytoplasmic domain is a rigid structure with 4 domains (residues 480 to 599 form an unnamed domain) plus the 3 FtsK (ATPase) domains which are connected by short linkers (PubMed:25865481)
The transmembrane domain and its C-terminal lysine-rich flanking region (LFR) (26-61) are both necessary and sufficient for targeting to the outer envelope membrane
The N-terminal TOPLESS domain (TPD) (1-210) binds directly to a 12-amino acid LxLxL EAR motif peptide
Activated by phosphorylation at the first response regulatory domain, which induces dimerization mediated by the two response regulatory domains and allows the two substrate-binding sites to approach each other and the condensation reaction to occur (Probable). The diguanylate cyclase activity is harbored by the GGDEF domain (By similarity)
Alpha-helical parts of the C-terminal intracellular region may mediate heterodimeric interaction with gbb-1
Does not incorporate into the lipid membrane
Heparin-binding motifs (HBMs) are characterized by an XBBXBX or XBBBXXBX sequence, where X is any neutral amino acid and B is a positively charged basic amino acid, and are defined as the consensus sequence necessary for protein-heparin interactions
The minimum ATG1-binding domain (residues 441 to 500) comprises two alpha-helices and a linker connecting them (PubMed:24793651)
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-118 is required to stabilize the incoming nucleotide at the 3'-site
Contains an intracytoplasmic twice repeated motif referred as immunoreceptor tyrosine-based activator motif (ITAM). These motifs are involved in triggering cell activation upon receptors aggregation
The CKK domain binds microtubules and specifically recognizes the minus-end of microtubules (PubMed:24486153)
The poly-Lys disordered region (350-354) mediates the formation of liquid-liquid phase separation (LLPS), an essential step for nucleation and formation of the NLRP6 inflammasome complex
The Death domain mediates the interaction with PIDD1 and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn probably recruit 7 CASP2 to form the PIDDosome. The Death domain mediates a direct interaction with the Death domain of RIPK1
Contains a I helix thought to serve as the substrate-binding pocket
The structure is characterized by a pore region with a massive beta-barrel organization which is embedded in the outer membrane and shows some protrusions into the S-layer, a stalk region consisting of a trimeric coiled coil, and a collar region at the base of the stalk (PubMed:35577074). More precisely, SlpA exhibits a tripartite organization, with its C-terminal part forming a homotrimeric 30-stranded OM beta-barrel (OMBB), its central part forming a long trimeric coiled coil that can traverse the large periplasmic space, and the extreme N-terminal part forming an SLH domain trimer that can interact with the PG layer (PubMed:35943982)
The PDZ 1 domain mediates interaction with ANKS4B, DOCK4, USHBP1, USH1G, SLC4A7
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface (By similarity). The surface exposed region contains four YadA-like head domains and extended stalk regions, multiply segmented by FGG, HANS, DALL and neck motifs (PubMed:23213248)
The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8) (PubMed:28117447). The motif locates to a long loop in the arm domain called the bowtie tail (PubMed:28117447). Integrin-binding stabilizes an alternative conformation of the bowtie tail (PubMed:28117447). Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1 (PubMed:28117447)
the 9aaTAD motif (residues 237 to 245) is a transactivation domain present in a large number of yeast and animal transcription factors
The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of akt1 and directly interferes with akt1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing akt1 association to membrane lipids and subsequent activation of akt1 signaling (By similarity)
In contrast to other poly(A) RNA polymerases, lacks any RNA-binding domain
A beta-sheet wrapped around a long alpha-helix. Structurally similar to tubular lipid-binding (TULIP) superfamily proteins (PubMed:36403098). The structure of OrfX1-OrfX3 is very similar to OrfX2 from C.botulinum type A2 (AC C1FUH4, PDB:6EKV) (PubMed:36403098)
The YEATS domain specifically recognizes and binds acylated histones, with a marked preference for histones that are crotonylated. Also binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity. Binds crotonylated lysine through a non-canonical pi-pi-pi stacking mechanism. The YEATS domain also binds DNA
In IrtA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused (PubMed:16385031). In addition, IrtA contains an N-terminal siderophore interaction domain (SID) that binds FAD (PubMed:19948799)
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity (By similarity)
The N-terminal leucine-rich repeat (LRR) domain is necessary for localization to vimentin filaments. The C-terminus is necessary for localization to the cell membrane
Upon heterologous expression, a small proportion of the isolated Pyrin domain forms homodimers and higher oligomers
The PPIase cyclophilin-type domain has high structural similarity with PPIA, but has extremely low and barely detectable proline isomerase activity (in vitro) (By similarity). Only about half of the residues that surround the PPIA active site cleft are conserved
Each subunit forms a right-handed beta-helix with 8 complete coils that stack upon each other
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute (PubMed:29476152). KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full-length protein. The 4 KH domains are important to suppress HIV-1 infectivity
The coiled coil domain is essential for dimerization
The EQMIL and WNIIE motifs are required for dendritic localization
Binding to inorganic phosphate induces dimerization and stabilization of the ligand binding domain
The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes (By similarity). Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions (PubMed:23761074, PubMed:26686642)
Recruited to clathrin-coated pits via SH3 domain 2
The two SH3 domains cooperate to maintain the protein in an autoinhibited conformation that prevents promiscuous membrane binding
The 2 HIN-200 domains are able to interact with RUNX2
In isoform 1, the N-terminal region preceding the ANK repeats interacts with the 6 ANK repeats in an intramolecular manner, thereby restricting access to ligands, such as SHARPIN and SPTAN1
The tyrosine-based internalization signal is proposed to function in clathrin-mediated endocytosis and recycling
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 81 and 105
The PDZ-binding motif interacts with PDZ-domain of scaffolding protein DLG4 in heterologous cells
The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity
The cysteine framework is III (CC-C-C-CC). Classified in the M-4 branch, since 5 residues stand between the fourth and the fifth cysteine residues
In contrast to other GTP-binding proteins, it is characterized by a circular permutation of the GTPase motifs described by a G4-G3-G1 pattern
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) or reductase domain (R) that releases the newly synthesized peptide from the enzyme (By similarity). LpsB is composed of only one module which is required for the activation of D-lysergic acid activation and its incorporation in the final ergot alkaloid (By similarity)
The N-terminus (1-13) is important for the regulation of the oxygen-dependent activation of the transcription factor activity, an internal region (123-177) is required for the interactions with ACPB1 and ACPB2, while the C-terminus (343-358) is required for positive regulation of gene transcription
Has a similar fold to the mitochondrial iron chaperone frataxin
There are 2 calcium binding sites with high and low affinity, respectively
The FERM domain is organized in a clover-shaped structure that comprises three subdomains identified as F1 (residues 2-82), F2 (residues 96-198), and F3 (residues 204-296). In the active form, the subdomain F3 adopts two mutually exclusive conformational isomers where a row of four phenylalanine side chains (Phe250, Phe255, Phe267 and Phe269) must point in the same direction. In the autoinhibited form, the F3 subdomain interacts with the C-terminal domain (residues 516-581) and stabilizes the structure, selecting only one possible arrangement of phenylalanine side chains. The FERM domain mediates binding to membrane lipids and signaling molecules
In the CSD domain, Trp-43 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring
(Microbial infection) N- and C-terminal domains are required for AAV transduction
The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Transplantation of the transmembrane segment S4 into HVCN1, generates a functional voltage-activated proton channel
The galectin-like domain has been demonstrated not to bind lactose, glucose, maltose, mannose, heparin, fucose, L-arabinose, N-acetyl-D-galactosamine, or N-acetyl-D-glucosamine. It interacts directly with the second and the third EGF-like domain of MIC6, and with part of the acidic domain
The MAR (micronemal adhesive repeat) domain was at first proposed to be TSR1-like (thrombospondin type 1-like repeat) by PubMed:9027753, but PubMed:17491595 found that this domain represents a previously unknown protein fold. This domain is jointly responsible for interacting with MIC4 and for host-cell adhesion
The two internal repeats IR1 and IR2, in the C-terminus, are required for the interaction with host ADA2
All four putative helical domains of PspA are critical for the formation of the 36-mer. In contrast, not all four helical domains are required for the formation of the inhibitory PspA-PspF complex
The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding (By similarity). The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides (PubMed:25256292)
The C-terminal segment (CTS) binds to RNA with high affinity in the nanomolar range but without apparent sequence specificity
The size and flexibility of the betaB6-betaB5 hairpin loop at residues 191-205 are crucial for activity. Variation of the loop sequence results in an altered DNA nicking profile including novel sites
The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum. Isoform PACE4D lacks the propeptide domain
The sterol-sensing domain (SSD) is required for sterol pathway signals to stimulate hmg2 ER-associated degradation and detects both geranylgeranyl pyrophosphate and a secondary oxysterol signal
The mature protein has 4 domains; a metalloprotease domain (S1, approximately residues 87-761), S2 (762-860, equivalent to PKD), and 2 collagen-binding domains S3a (865-979) and S3b (992-1104) (PubMed:9922257). The metalloprotease S1 domain is composed of 3 subdomains which together resemble a saddle; an activator domain (residues 93-367), the catalytic peptidase subdomain (377-646) and a helper subdomain (654-767) (By similarity)
Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers (PubMed:1740423, PubMed:8336701, PubMed:2028256, PubMed:8939742). The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif (PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine (By similarity)
Has short and long regions consisting of (E/V/I)S dipeptide repeats. These Ser-rich regions have 28 and 1000 repeats respectively
The SAP domain is necessary for specific binding to nuclear scaffold/matrix attachment region (S/MAR) elements in DNA. The RNA-binding RGG-box region is necessary for its association with inactive X chromosome (Xi) regions and to chromatin-associated RNAs (caRNAs) (By similarity). Both the DNA-binding domain SAP and the RNA-binding RGG-box region are necessary for the localization of Xist RNA on the Xi (PubMed:20833368). The ATPase and RNA-binding RGG-box regions are necessary for oligomerization (By similarity)
The uncleaved pseudo signal peptide prevents receptor's oligomerization and coupling to G(i) subunits. It is also responsible for the rather low receptor localization at the plasma membrane (PubMed:22689579)
The C-terminal part is sufficient to function as an AP endonuclease
The lid loop assumes one of 2 conformations allowing opening and closing of the active site; in the 3D structure one dimer is open while the other is closed (PubMed:24470304). Another structure with FMN (3X0Y) proposes a different lid loop that may interact with the loop predicted here (By similarity)
Has a C-terminal deletion compared to that of other Brucella species
The N-terminal domain likely catalyzes substrate activation by formation of an initial acyl-AMP intermediate, the central region contains the phosphopantetheine attachment site, and the C-terminal domain catalyzes the reduction by NADPH of the intermediate thioester formed from the attack of the phosphopantetheine thiol at the carbonyl carbon of acyl-AMP (PubMed:17102130). Large-scale domain motions occur between the adenylation and thiolation states. Phosphopantetheine binding alters the orientation of a key Asp, resulting in a productive orientation of the bound nicotinamide. This ensures that further reduction of the aldehyde product does not occur (PubMed:28719588)
The CXXC zinc finger mediates binding to CpG-DNA (PubMed:29276034). It mediates binding to DNA sequences containing unmethylated cytosine or 5-carboxylcytosine in 5'-CCG-3' DNA sequence motifs (By similarity)
The N-terminal region is intrinsically disordered
The N-terminal PH domain allows ITK to be recruited to the plasma membrane by an activated PI3 kinase. This domain contains also a proline-rich region (PRR). The adjoining domain is a SH3 domain, which binds to PRR (from itself or from other proteins). Next, a SH2 domain is required for binding tyrosine-phosphorylated substrates. In the C-terminal region, the kinase domain is required for tyrosine phosphorylation
U-box 1 is critical to the ubiquitin ligase activity, and U-box 2 mediates interaction with host target
The first 150 amino acids are capable of cleaving the signal sequence of LagA, the lactococcin G alpha precursor
The C-terminal region exerts intrasteric control that autoregulates kinase activity
In contrast to the related Lilrb4a protein, does not contain any copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). PhqB has the following architecture: A1-T1-C1-A2-T2-R. PhqB finishes with a reductase-like domain (R) for peptide release, which is consistent with the monooxopiperazine moiety of paraherquamide (Probable)
C-terminal domain, rather than the kinase activity, is required for the full function of the enzyme. This region may be a protein interaction domain that regulates kinase localization, activation and transcriptional activity. When C-terminally truncated, the enzyme shows a reduction in the Thr-Glu-Tyr (TEY) phosphorylation level, in the in vitro kinase activity, in its nuclear localization and in its inhibitory effect on cell growth
A conserved histidine residue in the third TMD (His-107) may play an essential role in the pH sensitivity of SLCO1A5/OATP1A5-mediated substrate transport
The N-terminal half of RapA contains the necessary structural determinants for substrate binding and enzymatic activity, and the C-terminal half contains the binding site for PhrA peptide (PubMed:22267516). The central TPR3 to TPR5 repeats provide the binding specificity toward the Phr peptide inhibitor (PubMed:22267516)
The pro-region is necessary but not sufficient for wnt-inhibitory activity. The central region is required for muscle induction activity (By similarity)
The unliganded VWA domain has an inactive 'locked' conformation whereby the scissile Arg-256|Lys-257 bond is protected from proteolytic activation
The PA14 dyad binds strongly to pectin as well as to polygalacturonic acid and alfalfa cell walls, but to a lesser extent
The lumenal domain contains two regions of approximately 650 AA that exhibit 20% identity. The cytoplasmic domain serves as a Golgi retention/recycling signal
Consists of a catalytic N-terminal domain linked to a reiterated non-catalytic C-terminal domain
Has 3 domains, the helical N-terminus (residues 18-124), a beta-barrel central domain (125-233) and a helical C-terminus (234-417). The lid loop (residues 131-142) change conformation when FMN is bound and close the FMN-binding site. Other regions that probably contribute to FMN binding are residues 178-184 and 281-291
The N-terminal domain (1-98) determines the lipid droplet size
Amino acid residues involved in both uptake and excretion, or solely in excretion, are located in the cytoplasmic loops and the cytoplasmic side of transmembrane segments, whereas residues involved in uptake are located in the periplasmic loops and the transmembrane segments. The SH-group of Cys-370 seems to be important for both uptake and excretion and may be necessary for recognition of the NH(2)-group of cadaverine
The arginine, glycine rich domain, which contains a number of RGG motifs, is necessary to regulate nucleocytoplasmic localization
Contains a N-terminus DWNN domain, a zinc-finger domain and a C4C4 zinc-binding RING finger domain (By similarity). The ring finger may indeed be a U-box domain (By similarity)
The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins
The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding
The DOCKER domain probably mediates the GEF activity
The RING-type zinc finger domain is essential for ubiquitin ligase activity (By similarity). It coordinates an additional third zinc ion (PubMed:22118460)
Arg-722 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The C-terminal coiled-coil domain is involved in oligomerization and the interaction with PKD1 (PubMed:18694932, PubMed:19556541). The isolated coiled-coil domain forms a homotrimer in vitro; the homotrimer interacts with a single PKD1 chain (PubMed:19556541). The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro) (PubMed:18694932)
The N-terminal domain is sufficient to bind to viral RNAs and promote their degradation. The second and fourth zinc fingers are involved in binding to specific viral RNAs (PubMed:20451500). Contains a divergent PARP homology ADP-ribosyltransferase domain which lacks the structural requirements for NAD[+] binding (PubMed:25635049). It is therefore inactive (PubMed:25043379, PubMed:25635049)
The C-terminal residues 567 to 606 are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12; and the C-terminal 17 residues are required for the ATG8 lipidation (By similarity)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (398-428) inactivates kinase activity under calcium-free conditions (By similarity)
The EGF-like domains mediate interaction with CNTN1. The fibronectin type-III domains 3-5 mediate interaction with BCAN. The fibronectin type-III domains 1-2 and 7-9 mediate interaction with SCN2B
In the disassembly complex (PDB:6P8V) Cap6 (also called Trip13) crystallizes as a right-handed spiral; the top 4 subunits bind ATP while the bottom 2 do not. A CdnC monomer lies along the surface of the hexamer at the interface of subunits 5 and 6, with Cap7 (this protein) at its tip, over the central hexamer pore. The N-terminus of Cap7 extends into the pore, contacting 5/6 Cap6 subunits
The Clp repeat (R) domain is important for membrane association and is essential for the in vivo functions, but not for the ATPase activity
Binds to ife-3 using a bipartite interface in the C-terminal domain which comprises a canonical helix which engages the ife-3 dorsal surface and a non-canonical helix which engages the ife-3 lateral surface
Lys-116 may be involved in the precise positioning of the nucleophilic Lys-115
The SMB domain mediates interaction with SERPINE1/PAI1. The heparin-binding domain mediates interaction with insulin
The Asp/Glu-rich (acidic) region mediates binding to calcium
The pyrin domain mediates homotypic interactions with pyrin domain of other proteins
The extracellular domain assumes a distinct boomerang shape when not bound to IZUMO1R/JUNO (PubMed:27309818). Interaction with IZUMO1R/JUNO triggers a conformation change, so that the IZUMO1 extracellular domain assumes an upright conformation (PubMed:27309818)
The small repeats A-A-P-[AVI] are also present in many proteins constituting the protective envelope of other species
Circular dichroism measurements suggest that the protein is largely unstructured in the absence of interaction with PAP1
The PDZ domain mediates interactions with FZD5, FZD8, ASIC3, GRID2, CFTR, CLCN3 and ADRB1
The coiled-coil region probably mediates association to membranes, targeting to the Golgi, and interactions with GOLGA3, RHOQ, and STX6
The N-terminal 15 residues are required for interaction with both FtsZ and MreB, while the C-terminal 63 residues are required for interaction with MreB
The WW 1 domain mediates interaction with TP73, TFAP2C, LITAF, WBP1 and probably TP53
The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1 (By similarity)
The ligand binding region binds directly to 17 L-amino acids
Has a penicillin insensitive transglycosylase domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase domain (cross-linking of the peptide subunits)
The FAT domain forms three discontinuous subdomains of alpha-helical TPR repeats plus a single subdomain of HEAT repeats. The four domains pack sequentially to form a C-shaped a-solenoid that clamps onto the kinase domain (PubMed:23636326)
The arm domain (residues 95-139) is inserted in the first ABC transporter domain. Its deletion abrogates the growth arrest and translation inhibition effect of the double Q-188/Q-470 mutation. When deleted impairs fitness in long-term (up to 6 days) growth in stationary phase (PubMed:24389466). Probably contacts ribosomal protein L1 (PubMed:24389465)
The P-site tRNA interaction motif (PtIM domain, residues 242-322) probably interacts with the P-site tRNA(fMet) as well as the 23S rRNA
The kinase domain and the juxtamembrane region constitute the catalytic core of PknA. Interaction between core and C-terminal domains is crucial for activity
The N-terminal domain binds DNA non-specifically and the C-terminal GAF-like domain is crucial to its correct folding and function. The non-specific DNA-binding activity of the N-terminal domain is modulated by the C-terminal domain, which perhaps in combination with another unknown factor, confers activity and specificity
The THAP-type zinc finger mediates DNA-binding but is not required for repression of gene expression
The EF-hand domain probably mediates calcium-binding. It is not required for channel activation (PubMed:11959145)
Interaction of the cytoplasmic N- and C-terminal domains is important for channel activity
The N-terminal region is responsible for interaction with TLR2 (PubMed:19880448). It is also important in mediating tyrosine phosphorylation of SOCS-3 (PubMed:21451109)
Consists of a soluble N-terminal domain and C-terminal probable beta-barrel in the outer membrane with 14 predicted beta-strands (Probable). Expression of just the C-terminal domain restores about 30% levels of TbpB lipoprotein and nearly 100% levels of fHbp lipoprotein on the cell surface in strains B16B6 and MC58, and confers surface expression of lipoproteins TbpB, LbpB and fHbp, but not HpuA in E.coli (PubMed:27572441)
The Zinc finger domains 1 and 5 bind single-stranded and double-stranded RNAs (PubMed:21471153). The Zinc finger domain 1 binds DNA in vitro (PubMed:21471153)
Does not contain ARM repeats, but instead Ser charged repeats. May have specificity for cargos distinct from that of other importin alpha subunits
Consists of an N-terminal cap, a leucine-rich repeat domain (LRR), and an Ig-like interrepeat domain
The phorbol ester binding activity is zinc and calcium-dependent
Divided into an N-terminal domain (TMD0) comprising four transmembrane helices and the following core domain (coreABCB9) (PubMed:18952056). TMD0 is required for lysosomal localization and LAMP1, LAMP2 and YIF1B interaction (PubMed:15577206, PubMed:18175933, PubMed:20377823, PubMed:22641697, PubMed:30877195). The core domain is required for homodimerization and peptide transport activity (PubMed:18952056, PubMed:20377823)
The RRM 2 domain is required for the binding to target RNA, and the RRM 1 and RRM 3 domains seem to contribute to the affinity of the interaction with RNA
The RRM2 domain and the C-terminal residues 290-339 contribute to nuclear localization
The RRM3 domain mediates nuclear export and cytoplasmic localization in a manner dependent on RNA- binding
The PH domain is not a critical determinant of the membrane localization. The PH domain of isoform 4 is necessary and sufficient to inhibit enzyme activity of other PLC-delta enzymes
The C2 domain binds anionic phospholipids promiscuously in the presence of calcium while the N-terminal region (1-174) show a specific affinity for phosphatidylinositol 3-monophosohate
The ATP binding site comprises residues located in alpha-1 and alpha-2 helices and beta-2 and beta-3 strands, which are involved in van der Waal's interactions, and Glu-1072 which forms an hydrogen bond with the adenine ring
Contains three di-leucine motifs in the C-terminus which are required for recycling from the plasma membrane to the TGN. The di-leucine 1478-Leu-Leu-1479 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1458-Leu-Leu-1459 motif is a sorting signal for retrograde trafficking to TGN via early endosomes
The di-leucine motif is required for sorting to clathrin-coated endosomes upon ca(2+)-dependent PRKCA activation
The APO motifs may provide ligands for 4Fe-4S centers
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of tin-9.2/tim-10b from the cytoplasm into the mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across the mitochondrial outer membrane (By similarity)
The N-terminal part (1-88) has an inhibitory function on the enzymatic activity
Lacks the Zn(2+) binding motif and the C-terminal dimerization appendix that are found in MetRSs from several organisms including E.coli MetRS
The amino acid composition of the SD repeat region is different from that of other SD repeats, containing a very high percentage of alanine residues
The ligand binding A region is specifically involved in collagen binding
The KaiA C-terminal domain mediates homodimerization and formation of a stable complex with KaiB and KaiC. The N-terminal pseudoreceiver domain (PsR, residues 1-146 in these experiments) is not necessary for most KaiA functions, while the linker region (residues 147-179) between the 2 domains is probably required at least for KaiA:KaiB interaction (PubMed:24112939, PubMed:28302851). Undergoes large conformational changes in the KaiABC complex which inactivates the second KaiA monomer, preventing it from activating the KaiC CII domain (PubMed:28302851). The PsR domain binds oxidized quinones (By similarity)
Contains a winged helix-turn-helix domain connected to an alpha-helical dimerization domain
Has 2 domains; discontinuous domain I (residues 1-149 and 291-331) forms a nucleotide-binding domain while domain II (residues 150-290) binds substrate
The PH domain binds relatively non-specifically to several phosphoinositides, including PI(5)P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities
The second H-T-H motif is necessary for transcriptional activation
Binds to vesicles enriched in neutral phospholipids via its C2 domain. The interaction is favored by Mg(2+) rather than Ca(2+)
The PGF motif may be involved in the interaction with HBS1 and is required for silencing of germline transposons
The C-terminal domain is required for localization to the cilium basal body and role in ciliogenesis
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif also mediates interaction with ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs)
Contains two aspartate-rich motifs, designated as FARM (the first aspartate-rich motif) and SARM (the second aspartate-rich motif). Rv0989c contains arginine in place of the second Asp in its FARM and first Asp in its SARM. The primary role of the FARM and SARM is the chelation of the divalent magnesium ion cofactors that assist substrate binding and catalysis, but it may also play a role in determining product chain length
The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (PubMed:19345194)
The N-terminal domain binds peptidoglycans through LysM motif. In addition, this motif is required for PilQ stability and multimerization (PubMed:21097635). The cytoplasmic domain contains three discontinuous tetratricopeptide repeat (TPR) motifs involved in protein-protein interactions (PubMed:27297880)
Folds into a unique two-domain structure. The structure consists of two domains, domains 1 and 2, which are connected via a long linker. The interior of the C-terminal domain is not optimally packed, leaving a cavity lined by hydrophobic residues unoccupied. This cavity may sequester a hydrophobic ligand
Isoform B, displayed in this entry, is the only one of the isoforms to contain both a transmembrane region and 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. The 2 ITIM motifs of isoform B are required for the inhibition of CLEC1B and GP6:FCER1G signaling and platelet activation
The UBR-type zinc finger domain is necessary for interaction with Diap1 and anti-apoptotic activity (PubMed:25146930). Domain is also sufficient for interaction with cos (PubMed:27195754)
The RING-type zinc finger domain is not necessary for interaction with Diap1 and anti-apoptotic activity
The NIDO domain (also known as globular region 1 or G1) contributes to the localization to the basal membrane probably by binding to vkg
The EGF-like 1 and nidogen G2 beta-barrel domain (also known as globular region 2 or G2) contribute to the localization to the basal membrane probably by binding to vkg
The EGF-like 2-8 domains (also known as the ROD domain) is necessary but not sufficient for localization to the basal membrane
The LDL-receptor class B 1-4 domains (also known as globular region 3 or G3) is necessary for cell-extracellular matrix (ECM) interactions. Also, contributes to the localization to the basal membrane probably by binding to laminins
Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate. The PH domain is necessary and sufficient for plasma membrane relocalization
The C-terminal domain contains an export signal that is recognized by the ABC transporter complex PaxBD
The N-terminal part seems to be a myosin/calmodulin-binding domain, and the C-terminal a tropomyosin/actin/calmodulin-binding domain. These two domains are separated by a central helical region in the muscle forms
The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by FAM109A and FAM109B as endosomes mature, all three interactions rely on F&H motifs, an approximately 12-13 amino-acid sequence centered around Phe and His residues essential for binding (By similarity)
The UBP-type zinc finger domain is required for the interaction with the SAGA complex
Amino acid residues between 299-311 are important for both protein expression and enzymatic activity. The minimal catalytic domain is located between positions 299-651. Single amino acid substitutions in the stem domain from MEB patients abolished the activity of the membrane-bound form but not the soluble form. This suggests that the stem domain of the soluble form is unnecessary for activity, but that some amino acids play a crucial role in the membrane-bound form
The JAZ-interaction domain (JID) (99-150) is sufficient for interaction with MYB proteins and most of the TIFY/JAZ proteins
Contains 2 important clusters of amino acid residues in the C terminus (C-terminal sequence 1 or CS1, residues 624 to 628; and CS2, residues 639 to 662). CS1 specifically participates in transcriptional silencing and/or repression in a context-dependent manner, whereas CS2 is universally required for all functions of ABF1
The protein is composed of 2 domains; the N-terminal domain contains the phospholipase C active site (PLC), in a cleft which is also occupied by the 3 zinc ions. The C-terminal domain is a putative phospholipid-recognition domain, which shows structural homology with phospholipid-binding C2-like domains from a range of eukaryotic proteins. The ability to bind membrane phospholipids in a Ca(2+) dependent manner is conferred by this C-terminal domain (By similarity)
The first PHD domain is essential for its E3 ubiquitin ligase activity
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins (PubMed:23201271, PubMed:24192928). The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities (PubMed:23201271)
The C2H2-type zinc fingers mediate binding to the telomeric double-stranded 5'-TTAGGG-3' repeats. The last C2H2-type zinc finger is required for telomeric-binding
The N-terminal ATPase-like domain seems to have lost ATPase activity, but may still bind nucleotides (Probable). The C-terminal Toprim (topoisomerase/primase) domain probably has the endonuclease activity, but when expressed alone (residues 348-578) has not activity, showing it requires the N-terminal ATPase-like domain for function (PubMed:33885789)
Homeobox domain 2 confers nuclear targeting
The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity. The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3. The J domain is required to reduce PRKN cytoplasmic aggregation
The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome. The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation. The UIM domains are not required to reduce PRKN cytoplasmic aggregation
The Kinase-inducible domain (KID, 177-204) is required for interaction with HDA19
Contains a conserved PPE N-terminal domain and a variable C-terminal domain (PubMed:31375544). The C-terminal region includes a SH3-like region, a leucine zipper DNA-binding motif and a functional nuclear localization signal (NLS) (PubMed:28071726, PubMed:31375544)
Has the structural arrangement of two alpha-helices stabilized by disulfide bonds (CSalpha/alpha 3(S-S))
Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and Olf signaling pathways. C2H2-type zinc fingers 14-19 mediate the interaction with SMAD1 and SMAD4, while zinc fingers 28-30 mediate the interaction with EBF1. zinc fingers 2-8 bind the 5'-CCGCCC-3' DNA sequence in concert with EBF1, while zinc fingers 9-13 bind BMP target gene promoters in concert with SMADs (By similarity)
Consists of 2 domains; the N-terminus (residues 1-593) has the N-acyltransferase activity while the C-terminus (residues 594-874) has polyprenol monophosphomannose (PPM) synthase activity
The APEAR motif (ATG8-PE association region) plays a key role in ATG4 recruitment to autophagosomal membranes and ATG8 deconjugation (PubMed:28330855). The LIR (LC3-interacting region act cooperatively) and APEAR motifs for the interaction with ATG8 (PubMed:28287329, PubMed:28330855)
The HA-8 region can be cleaved and exposed at the cell surface where it plays a role as a minor histocompatibility HLA-A*0201-restricted antigen
The D-box motifs play a key role in RNF157 stabilization
Most of the protein is composed of disordered regions (PubMed:21316364). Zinc-binding induces structural rearrangement by promoting molten globule state formation (PubMed:21995432)
The SUN domain probably plays a role in the nuclear anchoring and/or migration. Required for the localization of unc-83 and anc-1 at the nuclear membrane
The N-terminus is required for deacetylase activity. The C-terminus contains a signal sequence necessary for FtsH-dependent degradation
The calponin homology (CH) domain binds to actin filaments and is required for their recruitment to the bud neck
The Ras-GAP domain is required for contraction of the actomyosin ring. It probably does not stimulate GTPase activity (By similarity)
The D-box motifs play a key role in RNF157 stabilization (By similarity)
The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins PubMed:16239146. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (By similarity). Stalk region is sufficient for interaction with TSPAN15 (By similarity)
Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains
The MBT repeats specifically recognize and bind histone H3 di- and tri-methylated at 'Lys-9' (H3K9me2/3)
The C-terminal domain (451-488) is necessary and sufficient for peroxisomal targeting
Contains an N-terminal substrate-binding domain (CBM18) and a GH19 catalytic domain (PubMed:29756783). The CBM18 domain is involved in binding of the insoluble substrate chitin nanofiber (PubMed:29459179). The CBM18 domain is not required for catalytic activity, but possesses antifungal activity (PubMed:29756783)
The conserved DDXXXXD and NSE/DTE motifs are important for the catalytic activity, presumably through binding to Mg(2+)
Contains a N-terminal TRAM-like domain, an iron-sulfur cluster in the central region and a C-terminal catalytic domain. The tRNA-binding site is probably formed at the interface of the three regions
The C-terminal tubulin-binding domain mediates direct binding to microtubules, independently of dynein-dynactin complex, and induces their bundling and stabilization. The 4.1-binding domain is necessary for its cortical stability and spindle orientation
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). FgAQP3 has NPA/NPV motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
Predicted to have 4 domains. The N-terminus (about residues 1-103) binds ssDNA and is required to bind the small subunit; it probably has an OB-fold. The predicted catalytic domain is residues 104-266. Three alpha-helices are predicted in the C-terminal region (residues 267-301, 307-349 and 353-393), their removal singly or in pairs reduces small subunit-binding; none of the deletions have exonuclease activity. The extreme C-terminus (394-456) is required for exonuclease activity (PubMed:22718974). The N-terminus (residues 1-257) at low levels does not confer processing of msDNA and at higher levels is lethal. Lethality of this fragment is not counteracted by the small subunit (PubMed:26626352)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). MalG has the following bimodular architecture: A1-T1-C1-A2-T2-R. MalG finishes with a reductase-like domain (R) for peptide release, which is consistent with the monooxopiperazine moiety of malbrancheamide (PubMed:31548667)
The PDZ-binding motif specifically binds the PDZ domain of SNX27: the specificity for SNX27 is provided by the 2 residues located upstream (Glu-388 and Ser-389) of the PDZ-binding motif
The L13 loop movement regulates the transition between active and inactive conformations by repositioning Lys-386, which, in turn, mediates the rearrangement of the binuclear metal center
Consists of an N-terminal domain (NTD) and two tandem RNA recognition motifs, RRM1 and RRM2, followed by a C-terminal glycine-rich region
Contains a nuclear localization sequence and is mostly nuclear; however, its nuclear export sequence permits it to transport mRNAs to the cytoplasm and even to synapses as part of neuronal granules
The C2 1 domain mediates localization to the cell membrane
The N-terminus (1-57) is involved in the formation of the multimer. The C-terminus (471-502) binds calmodulin in a calcium-dependent fashion and contains probably an autoinhibitory domain
The Gln/Pro-rich N-terminus and the Arg/Asp/Glu/Lys-rich charged domain are critical in protecting glutamatergic ASH sensory neurons from degeneration. ASH neurons expressing isoforms lacking these domains show progressive degeneration
Modular protein that contains an aryl carrier protein (ArCP) domain which bears a phosphopantetheinyl arm to attach the activated salicylic acid, a condensation/cyclization domain involved in the cyclization of the cysteine, an adenylation domain which activates the cysteine residue into an aminoacyl-AMP ester and a peptidyl carrier protein (PCP1) domain which bears a phosphopantetheinyl arm to attach the activated cysteine
(Microbial infection) N- and C-terminal domains are essential for mediating AAV transduction
PDZ protein interaction domains may not be essential for function in vulval induction
Contains two DNA recognition domains (TRD), each specifying recognition of one of the two defined components of the target sequence
Has a helix-hinge-helix sructural motif
The Zn-binding N-terminal domain (residues 1-65) binds to the MqsR mRNA interferase toxin and makes contact with the DNA phosphate backbone, while the C-terminus (residues 70-131) binds the promoter in a sequence-specific manner. They are linked by a short flexible domain (PubMed:22789559)
The extracellular regions of the homodimer interact in a side-by-side fashion while facing opposite directions (PubMed:27434672, PubMed:27386547). Each extracellular region consists of three domains, LB1 (ligand-binding 1), LB2 and CR (cysteine-rich) (PubMed:17360426). The two lobe-shaped domains LB1 and LB2 form a venus flytrap module (PubMed:27434672, PubMed:27386547). In the inactive configuration, the venus flytrap modules of both protomers are in the open conformation associated with the resting state (open-open) and the interdomain cleft is empty (PubMed:27434672). In addition, each protomer contains three anions, which reinforce the inactive conformation, and one calcium ion (PubMed:27434672). In the active configuration, both protomers of extracellular regions have the closed conformation associated with agonist-binding (closed-closed) (PubMed:27434672, PubMed:27386547). The ligand-binding cleft of each protomer is solely occupied by an aromatic amino-acid (PubMed:27434672, PubMed:27386547). Calcium is bound at four novel sites, including one at the homodimer interface (PubMed:27434672, PubMed:27386547). Agonist-binding induces large conformational changes within the extracellular region homodimer: first, the venus flytrap module of each protomer undergoes domain closure (PubMed:27434672, PubMed:27386547). Second, the LB2 regions of the two protomers approach each other, resulting in an expansion of the homodimer interactions involving LB2 domains (PubMed:27434672, PubMed:27386547). Third, the CR regions of the two subunits interact to form a large homodimer interface that is unique to the active state (PubMed:27434672, PubMed:27386547). The CR regions are brought into close contact by the motion involving LB2 since the two domains are rigidly associated within each subunit (PubMed:27434672, PubMed:27386547)
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of timm13-B from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (329-359) inactivates kinase activity under calcium-free conditions (By similarity)
Zinc fingers 3 and 4 mediate recognition of the target element, ZF3 interacting with the 5' half (TGC) and ZF4 interacting with the 3' half (CGC)
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (CMeT) domain responsible for the incorporation of methyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (Probable). The DH and CMeT domains are inactive due to mutations of their catalytic residues, as consistent with the required reactions to synthesize 6-hydroxymellein (Probable). The ER domain could be active, but it should not affect the PKS chemistry due to the inactive DH domain (Probable)
Consists of two domains, a catalytic domain (formed by residues 1-166 and 286-365 from the N and C termini, respectively) and a dimerization domain (residues 167-285)
The C-terminus is required for recruitment to the Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment
The APEAR motif (ATG8-PE association region) plays a key role in ATG4 recruitment to autophagosomal membranes and ATG8 deconjugation. The LIR (LC3-interacting region act cooperatively) and APEAR motifs for the interaction with ATG8
Contains three distinc domains: N-terminal helical motifs involved in dimerization, followed by a heme-oxygenase-like (HO-like) central domain and a C-terminal monoiron cupin domain (PubMed:30728519, PubMed:33468680). The central domain catalyzes the two sequential N-hydroxylations of L-NMA and the cupin domain enables oxidative rearrangement and N-N bond formation to yield the N-nitrosourea product (PubMed:30728519). The central HO-like domain can bind Fe(2+) and use it to capture O(2), forming a peroxo-Fe2(III/III) intermediate, which is an intermediate in both hydroxylation steps (PubMed:32511919). Structural changes accompany diiron cofactor assembly in the HO-like domain (PubMed:33468680)
The leucine zipper region is part of a larger coiled coil
The PY-motif is required for the interaction with RSP5 ubiquitin-ligase and the HSE-mediated gene expression
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase. ApmA has the following architecture: A-T-C-A-T-R with a C-terminal reductase (R)-domain that acts in the reductive release of the shunt product N-benzoylphenylalaninol in the two-modular NRPS apmA
The BRCA2 repeat-like region is required for rad-51 binding
The C-terminal domain (268-393) is organized into 2 subdomains that bear structural similarities to SH3-like domains. Both subdomains adopt a similar 5-stranded beta-barrel-like fold and are connected to each other by a short linker of 5 residues. The 5 beta-sheets are packed at approximately right angles against each other. A highly conserved groove formed at the interface between the 2 subdomains, comprised of Lys residues 302 and 391 and other positively charged residues, may possibly be the site of RNA-binding
The C-terminal residues 653 to 691 are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12; and the C-terminal 17 residues are required for the ATG8 lipidation (By similarity)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase (By similarity). NRPS10 has the foolowing architecture: A-T-C-A-T-C (PubMed:15387811)
The S1 motif domain is important for trimerization and RNA-binding
Contains an N-terminal SANT domain that mediates histone/DNA binding, a central SWIRM domain to mediate interaction with chromatin associated proteins, and a C-terminal MPN domain that contains the metalloprotease activity
The BAR domain mediates interaction with the exocyst components EXOC4 and EXOC8 and is required for the function in cell migration. It also mediates the interaction with PLXND1
Fibronectin type-III 6 motif is essential for the role of unc-40 in a TGF-beta-like signaling pathway
The hinge domain, which separates the large intramolecular coiled coil regions, allows the homodimerization, forming a V-shaped homodimer. The N- and C-terminus together form the head domain
The C-terminal domain (558-707) is necessary and sufficient for Golgi targeting
The PB1 domain mediates homodimerization
The UBA domain is required for ubiquitin binding
The LIR motif is required for the interaction with ATG8 proteins and for vacuolar import (PubMed:21606687). The LIR motif is required for NBR1 function as receptor for autophagosomal degradation of ubiquitinated proteins under stress conditions (PubMed:23341779)
The C-terminal region (474-908) is responsible for the repressor activity
Contains an N-terminal deubiquitinase domain (DUB) (PubMed:26598703). The DUB domain does not interfere with the ubiquitin conjugation activity catalyzed by the central domain of SdeA, which causes toxicity (PubMed:27049943)
The J-like region, although related to the J domain does not stimulate ATPase activity of mtHSP70. It nevertheless mediates the heterodimerization with the J domain of PAM18 and is therefore essential for PAM complex function
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The NPXY site is also involved in clathrin-mediated endocytosis
The LIM zinc-binding domains mediate glucocorticoid receptor coactivation and mediates interaction with tcf3 and tcf7l2. The LIM zinc-binding 2 and LIM zinc-binding 3 domains mediate targeting to focal adhesions and actin stress fibers. The LIM zinc-binding 4 domain mediates targeting to the nuclear matrix (By similarity)
The LD (leucine and aspartate-rich) motif 3 functions as a nuclear export signal
The LisH mediates head to tail dimerization
Region A does not confer susceptibility to infection by Gibbon Ape Leukemia Virus (GaLV) and Feline leukemia virus subgroup B (FeLV-B). Substitution of Human SLC20A1 region A by region A of murine SLC20A1 prevents viral infection
Has an N-terminal TIR domain and an C-terminal antiparallel beta-sheet
The N-terminal region interacts with DNA, and the C-terminal region is involved in oligomerization and binding of cobalamin
Consists of two subdomains separated by an active site cleft containing the catalytic zinc ion
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (Probable)
The N-terminal domain (residues 1-502, also called GA57BK) forms a dimer; when reconstituted with intact GyrB or the C-terminus of GyrB (residues 448-675) can catalyze quinolone-mediated DNA breaks (PubMed:20805881). The C-terminal domain (CTD, residues 514-838) contains 6 tandemly repeated subdomains known as blades, each of which is composed of a 4-stranded antiparallel beta-sheet (PubMed:22457352, PubMed:23869946). The blades form a circular-shaped beta-pinwheel fold arranged in a spiral around a screw axis, which binds DNA (PubMed:22457352, PubMed:23869946). Unlike in E.coli, isolated CTD both binds and wraps DNA and is able to introduce writhe into DNA, but the holoenzyme in M.tuberculosis is missing the GyrA acidic tail found in E.coli and thus does not couple DNA wrapping and ATP binding as well as E.coli (PubMed:22457352). There are 2 GyrA-boxes in the CTD; mutations in GyrA-box (residues 537-543, the canonical box) affect supercoiling but not decatenation, those in GyrA-box-1 (residues 743-749, conserved in some Actinobacteria) affect both, suggesting there is a novel DNA-binding pathway in M.tuberculosis compared to E.coli (PubMed:23869946)
Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL1 SH2 domains. The HLH motif is absolutely required for the induction of pseudohyphal growth in yeast and mediates heterodimerization with NEDD9 (By similarity)
The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK11
Cca1 contains two alpha-helices (His-81 to Thr-86 and Glu-479 to Asp-484) and a beta-sheet (His-120 to Lys-131) that are not seen in cca2, suggesting that cca1 has lost A-adding activity because this beta-sheet reduces the flexibility of the loop (Asp-122 to Glu-139) as compared to CCA- and A-adding enzymes
The ERhxxExxxhh motif (residues 231-241) has been suggested to serve to distinguish between A-adding and CC-adding proteins as A-adding enzymes have a small amino acid in the first position while CC-adding enzymes have an E in the first position
The calponin-homology (CH) domains are essential for its function during attachment assembly and the interaction with pat-4
The TID (telomerase inhibiting domain) domain is sufficient to bind TERT and inhibit its activity
The NEAT domain is responsible for binding Fe(3+) and Fe(2+) heme and fibrinogen. The NEAT domain is an inhibitor of apolactoferrin activity, while the C-domain confers resistance to bovine lactoferricin
Probably exists in a closed and an open conformation due to interaction of the C-terminal coiled-coil domain with an N-terminal region including the calponin-homology (CH) and the LIM zinc-binding domain. The conformational change is regulated by RAB13
The C-terminal histone fold domain is sufficient to direct CENH3 to centromeres
The N-terminal domain interacts with the C-terminal domain of LAYN. An interdomain interaction between its N-terminal and C-terminal domains inhibits its ability to bind LAYN. In the presence of acidic phospholipids, the interdomain interaction is inhibited and this enhances binding to LAYN
Composed of two domains: the N-terminal highly flexible intrinsically disordered domain (IDD) and the C-terminal rigid kinase core domain (KCD) (PubMed:29494752, PubMed:29884774, PubMed:32157138). IDD is unstructured and highly dynamic, allowing transient interactions with the rigid KCD. This interaction modulates the accessibility of the KCD active site (PubMed:29884774). In closed state, IDD masks the autophosphorylation site, thereby decreasing the activity of PtkA. In open state conformation, IDD is away from the autophosphorylation site, making it accessible for phosphorylation and activation of PtkA (PubMed:29884774). Phosphorylation of PtkA by serine/threonine kinase induces conformational changes of IDD, which promotes the open state (PubMed:29884774). IDD had a greater inhibitory effect on the catalytic activity of KCD in the presence of the drugs esculin and inosine pranobex (PubMed:32157138)
The C-terminal region is necessary for nucleus and cytoplasmic localization (PubMed:19523114). The N-terminal region is necessary for nucleus and nuclear bodies localization (PubMed:19523114). Regions containing Arg-Gly-Gly repeats (RGG/RXR-box) may be preferentially methylated by PRMT1 (PubMed:16879614)
The second BPTI/Kunitz inhibitor domain is able to inhibit trypsin. It has however no activity toward chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator (By similarity)
The transmembrane domain 1 and 2 function as a signal-anchor and stop-transfer sequence, respectively, generating a double-spanning integral membrane protein with a N- and C-terminal cytoplasmic orientation (PubMed:24223779). Transmembrane domain 1 and 2 are probably sufficient to mediate membrane translocation and topology formation in a N-myristoylation-independent manner (PubMed:24223779). Transmembrane domain 2 is sufficient to block the protein secretion pathway (PubMed:24223779). The two coiled-coil domains are necessary for its endoplasmic reticulum (ER) three-way tubular junction localization (PubMed:27619977). The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation (PubMed:24223779, PubMed:27619977)
The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by FAM109A and FAM109B as endosomes mature
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS6 has the following architecture: A-T-C
The middle region has homology to RecA with ATPase motifs including the RadA KNRFG motif, while the C-terminus is homologous to Lon protease (By similarity). Unlike most bacteria many S.pneumoniae do not have the N-terminal putative zinc-finger
The C-terminal region (79-168) is involved in BOLA recognition in GRXS-BOLA apo-heterodimer
In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659)
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines (PubMed:25636800)
The mature peptide (63-87) probably forms alpha-helices which disrupt target cell membranes
The LIM zinc-binding 3 (LIM 3) domain provides the structural basis for recognition of tyrosine-containing tight turn structures (By similarity). This domain is necessary and sufficient for interaction with TBX5
The LIR motif interacts with ATG8 family proteins and is necessary to target the ER fragments to autophagosomes for subsequent lysosomal degradation
The reticulon homology domain provides capacity to bend the membrane and promotes ER scission (PubMed:26040720, PubMed:31930741). It is required for homooligomerization (PubMed:31930741). This domain does not show relevant similarities with reticulon domains, preventing any domain predictions within the protein sequence
The N-terminal guanylate cyclase domains are required for enzyme activity. Fragments or isoforms containing the first 470 amino acid residues are fully active
Coiled-Coils at the N-terminal half are essential for autophagy (By similarity)
Divided into 4 Cys-rich domains by 3 spacer sequences termed B1-B3 (PubMed:23498952). Each cystein-rich domain contains the conserved copper-binding motif Cys-X-Cys-X6-Cys-X-Cys-X4-Cys-X-Cys-X2-Cys (PubMed:23498952). The copper-binding domains together are able to chelate up to 16 copper ions (PubMed:23498952)
The complementarity-determining region CDR1 confers specificity to the peptide antigen. Assumes a loop structure that recognizes the peptide-HLA-A*02-B2M complex
The complementarity-determining region CDR3 confers specificity to the peptide antigen. Assumes a loop structure that recognizes the peptide-HLA-A*02-B2M complex. Recognizes M/matrix protein 1-derived peptide mainly via its xRSx motif
The PIP-box mediates the interaction with PCNA (PubMed:21628590, PubMed:23000965)
The initiation motif is required for efficient chain initiation by the APC/C complex E2 ligase UBE2C. It determines the rate of substrate's degradation without affecting its affinity for the APC/C, a mechanism used by the APC/C to control the timing of substrate proteolysis during the cell cycle (PubMed:21700221)
The cytosolic domain interacts with sigma factor SigM
Lacks a cytoplasmic PDZ-binding domain, which has been implicated in function of related LRFN proteins
Contains an N-terminal flavodoxin-type domain and a C-terminal ketoreductase domain (PubMed:21081168). The C-terminal residues participate in intercatalytic domain interaction and play a pivotal role in stabilization of loop I, which is responsible for interaction with phosphopentethine moiety-linked fatty acyl substrates of CoA or ACP (PubMed:23163771)
Harbors two domains: an N-terminal domain, that exhibits DNase activity, and a C-terminal domain, comprising a duplicate DNA binding helix-hairpin-helix motif. The C-terminal domain is responsible for the enzyme's resistance to high ionic strength, it acts as a facilitator for DNA binding at high salt concentrations
Gln-307 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The TIR domain mediates NAD(+) hydrolase (NADase) activity (PubMed:29395922). The TIR domain crystallizes as a homodimer (PubMed:24076024, PubMed:24265315, PubMed:24275656). The TIR domain is a structural mimic of the TIR domain of host TIRAP (PubMed:24275656). Whole protein and the TIR domain (residues 120-250) abolish the interaction of host proteins TIRAP and TLR4 (PubMed:24265315). The N-terminal region is required for localization to the host cell membrane while the TIR domain is required for tubule formation (PubMed:19196716)
The FHA domain is necessary for the interaction with NDD1
The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity
The TSP type-1 repeats in the extracellular domain mediate binding to phosphatidylserine (PubMed:17960134). They are also required for bacterial recognition and binding to bacterial outer membrane lipopolysaccharide (PubMed:21245295)
Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains, a number of features are positioned to inhibit the kinase activity: (1) an atypical AAAS motif in an alanine-rich (A-rich) loop that replaces the canonical glycine-rich (G-rich) nucleotide-binding loop and limits ATP binding by establishing an unusual selectivity for ADP and (2) an N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket (PubMed:25498144). Nucleotide-binding opens the substrate binding pocket and flips the active site from inside the hydrophobic core into a catalytically competent, solvent-exposed posture (PubMed:27499294)
The DIX domain mediates interaction with AXIN1 and inhibition of AXIN1-mediated JNK activation through MAP3K1. Mediates interaction with DVL2; this interaction is required for activation of Wnt signaling (By similarity)
The N-terminal extension wraps intimately around the catalytic domain where, tethered by a disulfide bond, it forms additional interactions with a unique extended loop that protrudes from the catalytic core. It might contribute to the conformational stability of the active site cleft and surrounding regions
The C-terminal WH domain is essential for its stimulating effect on the MCM-loading activity
A linker region between the coiled-coil and PDZ region holds the protein in an inactive state
Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 (By similarity)
The SAP domain is necessary for specific binding to nuclear scaffold/matrix attachment region (S/MAR) elements in DNA (PubMed:9405365, PubMed:11003645). The RNA-binding RGG-box region is necessary for its association with inactive X chromosome (Xi) regions and to chromatin-associated RNAs (caRNAs) (PubMed:14608463, PubMed:28622508). Both the DNA-binding domain SAP and the RNA-binding RGG-box region are necessary for the localization of Xist RNA on the Xi (By similarity). The ATPase and RNA-binding RGG-box regions are necessary for oligomerization (PubMed:28622508)
The sequence organization of E3BP is highly similar to E2, having an N-terminal lipoyl-binding domain (LD), a central peripheral subunit binding domain (PSBD), and the C-terminal core region connected by disordered linkers
E3BP is bound in a tripod-like manner and the interaction to the E2 core is primarily mediated by a loop region of E3BP (residues Pro-317 to Leu-336)
The GLEBS region mediates interaction with BUB3
The microtubule-binding region is required for efficient loading of BUB3 onto kinetochores and proper mitosis
The protein is evolutionarily related to retrotransposon Gag proteins. It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells. Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons
Contains an extra N-terminal domain, a S1-like RNA-binding domain and a conserved P-loop NTPase domain
The N-terminal region seems to be important for proper quaternary structure. The C-terminal region contains the substrate-binding site
Contains an N-terminal receiver domain and a C-terminal output domain that are both required for binding to RpoS. IraP and IraD interact with the N-terminal domain. IraM interacts with the C-terminal domain and, more weakly, the N-terminal domain
Unique C-terminus confers high proteasome-dependent instability to isoform 2
The LPQG motifs are catalytically important and conserved among many retroviruses
HERV-K Gag polyprotein contains regions homologous to the matrix (MA), capsid (CA) and nucleocapsid (NC) proteins from infectious retroviruses. Evidence suggests that HERV-K(HML-2) Gag polyprotein can be cleaved into mature MA, CA and NC under certain circumstances. However, the exact boundaries as well as the size of processed Gag proteins have not been precisely determined yet
Possesses an immunoglobulin V-like domxain, a mucin domain, a single transmembrane region, and a cytoplasmic tail containing a tyrosine phosphorylation motif
Contains 7 zinc fingers of the C2HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence
In the heterotetrameric form, EsxS adopts a long helical conformation that pairs with a second EsxS monomer in an antiparallel manner that allows the N- and C-termini of two EsxS subunits to interact with an EsxR subunit at each end of the EsxS dimer thus creating a molecule with four-helix bundles at its extremities
The PGAP2-like region interacts with the PGAP2IP-like region
The N-terminal region (1-100) is important for both SKP2A binding and ubiquitin-mediated degradation
Consists of three sections from the N- to the C-terminus: [4Fe-4S] cluster-binding domain, beta-sheet and C-terminal tail. The beta-sheet and the C-terminal tail interact with AprA to stabilize the AprA/AprB heterodimer
The N-terminal part (residues 1 to 249) is essential for function and confers locus specificity
The C-terminus (residues 126 to 135) is required for the interaction with host NRL1 and the ability to enhance the association of NRL1 with SWAP70
The C-terminal coiled-coil domain is essential for cortical membrane localization and oligomerization
The PDZ-binding domain interacts with all three PDZ domains of DGL4
The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA (PubMed:24990967). The interdomain linker (411-429) acts as a hinge to fix the relative orientation of the 2 RRMs (PubMed:24990967). The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs (PubMed:23500490, PubMed:24990967). A continuous hydrophobic interface is formed between the 2 RRMs (PubMed:24990967)
The N-terminal (1-560) region seems to be regulated by upstream components of the ET signal transduction pathway, and may in turn regulate the C-terminal region. The C-terminal (454-1294) region regulates downstream events of ET and jasmonate signaling pathways, and can confer constitutive responses to ET. The C-terminal (1047-1294) region is necessary and sufficient for interactions with ETP1 and ETP2 (PubMed:19196655). The nuclear localization signal (1262-1269) is required for interaction with ETR1 (PubMed:25843012)
The POLO box domains are involved in the asymmetric cytoplasmic localization
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (347-377) inactivates kinase activity under calcium-free conditions
Is composed of a ring composed by 8 residues, and a tail of 10 or 12 residues (Probable). The peptide is threaded when the C-terminal tail is inserted throught the isopeptide-bonded ring (Probable)
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface (PubMed:21397187). PUM2 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine
Contains two Ra/cadherin-like domains composed mostly of beta-sheets joined by a linker region. Proper folding and stability are dependent on the binding of one calcium ion per protein molecule
The extracellular region of the ACE2 enzyme is composed of two domains. The first is a zinc metallopeptidase domain (residues 19-611). The second domain is located at the C-terminus (residues 612-740) and is 48% identical to human collectrin
The RRM domain is required to promote mitochondrial RNA processing
BRCT domain 1 is required to prevent abnormal chromosome condensation. It binds directly to the SWI-SNF chromatin remodeling complex (PubMed:19925808)
BRCT domains 2 and 3 recognize phosphoserine/phosphothreonine marks on proteins with high selectivity, and mediate interaction with phosphorylated CDC27. They also mediate the dual recognition of phosphoserine and phosphotyrosine in the C-terminal tail of histone H2AX (PubMed:22139841, PubMed:22908299, PubMed:22908299)
Arg-340 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
In contrast to M.tuberculosis, the propeptide is required for correct proteasome folding and assembly. The propeptide is positioned strategically at the region where it can act as an assembly-promoting factor by linking its own beta-subunit to two adjacent alpha-subunits at the same time
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent cleavage (PubMed:15615856)
The WH2 domain acts as the DAD (diaphanous autoregulatory) domain and binds to actin monomers
Regulated by autoinhibition due to intramolecular GBD-DAD binding
The severing activity is dependent on covalent attachment of the FH2 domain to the C-terminus
The C-terminal domain (689-914) is necessary and sufficient for Golgi targeting
The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated (By similarity). It is essential for its ability to repress the transcriptional activator activity of CLOCK-BMAL1 heterodimer (By similarity)
The phosphothreonine-binding FHA domain is required for the interaction with MPH1 and controlling recombination donor preference during mating-type switching
The acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules (By similarity)
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of TICAM1 recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines (PubMed:25636800)
PDZ domains are required for localization at the adherens junctions. SH3 domain is necessary for let-413 dependent lateral distribution. L27 domain is responsible for homooligomerization and interaction with ajm-1
The acidic serine aspartate-rich MEPE-associated (ASARM) motif is sufficient when phosphorylated to inhibit bone mineralization by osteoblasts and cartilage mineralization by chondrocytes by binding hydroxyapatite crystals during the mineralization stage (PubMed:15843468, PubMed:22766095, PubMed:26051469). It can also inhibit dentin mineralization (By similarity)
The dentonin region is sufficient to promote dental pulp stem cell proliferation. It can also stimulate bone formation, osteoblast differentiation, and activate integrin signaling pathways
The 11 zinc fingers are highly conserved among vertebrates, exhibiting almost identical amino acid sequences. Different subsets or combination of individual zinc fingers gives the ability to CTCF to recognize multiple DNA target sites
The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (By similarity)
Contains a well-conserved 23 amino acid extended signal peptide region (ESPR) preceding a typical N-terminal signal sequence. ESPR region may be involved in regulating the translocation of the autotransporter across the inner membrane into the periplasm
The PDZ domain is required for apical location
Glu-127 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-210 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group
All four putative extracellular loops are crucial for invasion of mammalian cells
The C-terminal domain (CTD, residues 494-769) contains 6 tandemly repeated subdomains known as blades, each of which is composed of a 4-stranded antiparallel beta-sheet. The blades form a flat, toroidal beta-pinwheel fold, to which DNA probably binds. Unlike most CTDs, this organism is missing the canonical GyrA-box. The isolated CTD does not impart writhe, DNA wrapping necessary for supercoil introduction. The ability to supercoil DNA is recovered if the CTD is swapped with the CTD of T.maritima (residues 482-804)
Composed of three structural domains: an N-terminal zinc-peptidase domain, a central helix-turn-helix motif, and a C-terminal GAF-type domain
The N-terminal inhibitory domain contains conserved sequence elements important for cytoplasmic retention (Region I) and proteolytic processing (Region II) of the protein (By similarity). Region I is also required for ASI1/2/3-mediated negative regulation of transcription
Tne C-terminal domain is important for its transactivation activity
The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of smc-5, forming a V-shaped heterodimer
Shows an alpha-helical coiled coil structure (35 repeating heptads) related to the alpha-type fibrous proteins (K-M-E-F class)
Consists of four domains: the N-terminal editing domain, the N-terminal catalytic domain, the anticodon-binding domain and the C-terminal extension (Probable). The first domain (about residues 1-163) is required for editing of incorrectly charged tRNA (PubMed:14663147). When it is deleted the enzyme shows pronounced misacylation of tRNA(Pro) with alanine (PubMed:14663147)
The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane
The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (By similarity). It also mediates homodimerization and regulates kinase activity (By similarity)
The Roc domain mediates homodimerization and regulates kinase activity
The HPR motif (90-97) is required for intracellular targeting at membranes
The KEN box is required for the association with the APC/C-Cdh1 complex, ubiquitination and degradation
Contains two DNA recognition domains, each specifying recognition of one of the two defined components of the target sequence (PubMed:3025838, PubMed:2838725). The recognition domains can be exchanged between different S proteins, generating enzymes that have new sequence specificities (PubMed:2838725)
The N-terminal inhibitory domain contains conserved sequence elements important for cytoplasmic retention (Region I) and proteolytic processing (Region II) of the protein. Region I is also required for ASI1/2/3-mediated negative regulation of transcription
The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity. It lacks the O helices present in high-fidelity DNA polymerases in the fingers domain
The N-terminal destruction box (D-box) motifs 1 and 2 act as a recognition signal for degradation via the ubiquitin-proteasome pathway
The coiled coil domain mediates interaction with NONO, and can also mediate formation of long, linear homooligomers (in vitro). The coiled coil domain is required for optimal DNA binding, and optimal transcription activation
May consist of two protein domains: the one in the N-terminal side cleaves the alpha-1,4-glucosidic bond in starch, and the other in the C-terminal side catalyzes other activities, including the reconstitution of an alpha-1,4-glucosidic linkage for cyclizing the maltooligosaccharide produced
The lysosomal targeting motif, together with the second PQ-loop mediate targeting to the lysosome
The helix-loop-helix domain is necessary and sufficient for the interaction with DRG1
The MPN (JAB/Mov34) domain mediates interaction with TSSC4 and SNRNP200. Has structural similarity with deubiquitinating enzymes, but lacks the residues that would bind the catalytic metal ion
Contains three distinct domains: an N-terminal catalytic domain that contains a binuclear Zn(2+) cluster, a central dimerization domain and a C-terminal sterol carrier protein type 2 (SCP-2)-like fold domain
The HMG box is critical for TOX-dependent CD4-positive T cell lineage commitment
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif bind the SH2 domain of PTPN6
Adopts a canonical dual specific tyrosine phosphatase (DUSP) fold, similar to eukaryotic DUSPs (PubMed:23524133). In the absence of ligand, the protein phosphatase loop is disordered and the general acid loop adopts an open conformation, placing the catalytic aspartate, Asp-105, more than 11 angstroms away from the active site (PubMed:23524133). Ligand binding reduces the conformational dynamics that occur on multiple timescales in the loops at the active site (PubMed:23524133)
Deletion of the C-terminus (from residues 122 on) results in constitutive repression of modA (PubMed:8931336). Contains two major domains: the N-terminal domain I forms a winged helix-turn-helix motif and interacts with DNA (Probable). The C-terminal domain II is the olybdate-binding component and contains a tandem repeat of the Mop domain, each of which forms a beta-barrel (Probable) (PubMed:12581638). The N-terminal domain plays a major role in the dimerization of the protein whereas the C-terminal domain contributes to the stability of the complex (Probable)
Deletion of the N- or the C-terminal 10 amino acids abolishes activity, while a region that includes amino acids 56 to 80 is dispensable for activity. Contains a predicted HTH motif, which may bind DNA
A possible nuclear localization signal exists in all isoforms where Asp-626--631-Arg are deleted
Has 3 domains that are structurally very similar to those in PMP1; light chain (nLC, equivalent to the light chain), N-heavy chain (nHN) and C-heavy chain (nHC)
Contains three transmembrane helices and a N-terminal amphiphilic helix located on the cytoplasmic surface (PubMed:23676677, PubMed:26673816). Residues from different subunits participate in forming the active site (PubMed:10220339, PubMed:23676677). Contains three catalytic and substrate-binding sites centred about the membrane/cytosol interface (PubMed:26673816). The gamma-phosphate of the ATP is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane (PubMed:26673816)
The presence of Trp residues has a clear effect on thermal stability. Of the mutants containing a single Trp residue, only that containing Trp-113 was found to give active protein
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (355-385) inactivates kinase activity under calcium-free conditions (By similarity)
Contains a regulatory C-terminal extension (C2) with a ferredoxin-like fold. The C2 domains from each MetN subunit in a transporter dimerize to form an eight-stranded beta sheet
Contains 3 domains: the flavin adenine dinucleotide (FAD)-binding domain, the cap domain and the membrane-binding domain
The N-terminal domain (region 81-193 aa) interacts with PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) and PI(4)P (phosphatidylinositol 4-phosphate), and it is the responsible for the recruitment of phg2 to the plasma membrane
Can alternate between open and closed states for binding TMAO
The RGS domain is involved in translocation to the plasma membrane
Has 3 domains; an N-terminal OB-like domain (about residues 1-100), a central, circularly permutated GTPase module (residues 104-270) and the C-terminal zinc-finger domain (residues 280 to 350) (PubMed:25904134). The C-terminal domain has 2 regions; the zinc-binding domain (residues 287-319) is required for binding to 30S ribosomes while the extreme C-terminus (residues 320-350) helps remove RbfA from the mature 30S subunit
The C-terminus is required for assembly of the restriction enzyme complex. The individual domains assume different positions in the enzyme, allowing the holoenzyme to regulate the methylase, endonuclease and translocation states
The WD40 repeats are involved in the binding of PTS2-containing proteins
The subunit comprises two main parts, an N-terminal [FeFe]-hydrogenase-like domain (residues 1 to 240) that coordinates clusters 1, 2 and 3, and a domain similar to molybdopterin-containing enzymes (residues 241 to 767) whose first subdomain coordinates cluster 4
The FYVE-type zinc finger domain is necessary and sufficient for endosome targeting and localization to the plasma membrane
The N-terminal catalytic domain forms an (alpha/beta)8 TIM barrel and binds Mn(2+) (PubMed:22352945). The C-terminus (residues 366 to 517), is important for increased thermostability (PubMed:20117081) and for condensation of the 2 substrates (PubMed:22352945, PubMed:20117081). The regulatory domain binds L-Leu (the pathway end product) in the dimer interface (By similarity)
The N-terminal part of the mature protein (59-100) forms an alpha-helix which acts as a membrane-active peptide. It is necessary and sufficient for the toxin's antimicrobial, insecticidal, cytolytic and cytotoxic activity
Contains a unique N-terminal appendage positioned within the active site and in contact with catalytically essential histidine residue (PubMed:20489200). This appendage modulates substrate access to the enzyme. It may increase the efficiency of protein display by reducing the unproductive hydrolytic cleavage of enzyme-protein covalent intermediates that form during the cell wall anchoring reaction (PubMed:26324714)
The N-terminal domain seems to play a role in the reaction cycle of thr catalytic subunit such as ATP8A2
The N-terminus is necessary for nuclear localization. The C-terminus is necessary for transcriptional activity
The regions 203-253, 256-333 and 335-377 are thought to contain either alpha helical or beta pleated sheet motifs
The C-terminus (residues 252-747) interacts with EsxB, the whole protein is required for interaction with EccCa1 (PubMed:14557536)
Cluster B is an all-cysteinyl-liganded 4Fe-4S cluster; cluster C is a mixed Ni-Fe-S cluster is to be the active site of CO oxidation. Cluster D is also an all-cysteinyl-liganded 4Fe-4S cluster that bridges the two subunits of the CODH dimer
2 residues (Tyr-52 and Arg-55) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
AC 1 and AC 2 (clusters of acidic amino acids) contain sorting information. AC 1 directs TGN localization and interacts with the TGN sorting protein PACS-1
The second and third WW domains are responsible for interaction with the PY-motif of R-SMAD (SMAD1, SMAD2 and SMAD3)
The CCHC FOG-type zinc fingers 1, 2, 3 and 5 bind directly to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is essential for the interaction with GATA-type zinc fingers
Contains a hydrophobic cavity in the center of the structure and ligand-binding clefts between two subunits
The D-box (destruction box) acts as a recognition signal for association with the APC/C complex, ubiquitination and degradation (PubMed:23328397)
The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs (PubMed:21237665). The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias) (PubMed:24757166)
2 residues (Tyr-49 and Arg-52) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
The CORNR box motifs in the C-terminal region may be necessary and sufficient for binding to unligated nuclear hormone receptors. Sequences flanking these motifs may determine the precise nuclear hormone receptor specificity (By similarity)
The amphipathic helix in the C-terminal region binds to membranes and facilitates atg18 binding to PtdIns3P to target the atg2-atg18 complex to the PAS
The N-terminus is dedicated to mating-type repression
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable. Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity (By similarity)
Shows a strong structural resemblance to the argonaute/Ago subfamily. The domains (N, PAZ, MID and PIWI) and linkers (L0, L1, and L2) assemble into a typical bi-lobed (N-PAZ lobe and MID-PIWI lobe) architecture, in which the 5' and 3' ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. However, the relative orientation of these two lobes differs significantly between Siwi and the Ago-clade proteins: the N-PAZ lobe in Siwi rotates significantly downward. Additional hinge motions between N and PAZ domains exist, due to a distinct set of contacts at the interface. Three out of the four residues in the DEDH catalytic tetrad are well-preserved. The fourth, Glu-708, is located in a disordered loop and likely joins the active site upon the guide-target RNA duplex formation. This 'unplugged' active site scheme is found in Agos of some bacteria
4Fe-4S iron-sulfur-binding is required for protein stability and helicase activity
The C-terminal transmembrane domain is cleaved in response to ER stress and the N-terminal fragment containing the bZIP domain is sufficient for transcription activation
The C-terminal and HLH domains are essential for transcriptional repression
Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain (By similarity). The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA (By similarity)
The C-terminal domain is required for interaction with TLR4 but not with PE9
The first Pro-rich domain interacts with the SH3 domain of CAS family members, such as BCAR1 and NEDD9
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains
(Microbial infection) The basic-rich region is essential for yopT recognition and cleavage
Contains an N-terminal LytE region, which consists of three consecutive LysM domains, and a C-terminal esterase domain. LytM domains are essential for anchoring protein to the cell wall
The GLEBS region mediates interaction with BUB3 (PubMed:24462186, PubMed:24462187)
The protein kinase domain may be catalytically impaired due to the lack of the conserved Asp active site at position 486, which is replaced by a Asn residue
The N-terminal cysteine-rich ferredoxin-like domain is not required for activity
Has an additional transmembrane segment in the N-terminus compared to many other ZIP family members. This extra helix is important for activity in vivo
The two metal binding sites M1 and M2 that are halfway through the membrane form a binuclear metal center. The multiple conserved zinc-binding sites (M1,M5, M6 and M3) appear to constitute a route of zinc release to the cytoplasm (PubMed:28875161). M1 is the primary transport site essential for activity, whereas M2 plays an auxiliary role presumably by serving as an additional transport site and modulating the properties of the primary transport site (PubMed:31914589). Cd(2+) at M1 can readily be replaced by externally added Zn(2+), whereas Cd(2+) at M2 cannot (PubMed:28875161, PubMed:31914589). ZIP proteins seem to operate via a two-domain elevator-type mechanism for zinc transport (Probable)
The caspase domain lacks the active site residues involved in catalysis
The TonB box in the Oar plug domain is important for PopC secretion
The alpha-1 domain is a structural part of the peptide-binding cleft
The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:21543847, PubMed:21943705, PubMed:19177349, PubMed:26758806, PubMed:24395804, PubMed:7694806, PubMed:8906788, PubMed:2784196, PubMed:28250417, PubMed:22245737, PubMed:19542454, PubMed:20619457, PubMed:20844028). Mediates the interaction with TAP1-TAP2 complex (PubMed:8805302)
Forms a right-handed beta-helix that is stabilized by disulfide bonds. The building blocks of this beta-helix correspond to tandem repeats with the consensus sequence T-C-T-X-S-X-X-C-X-X-A-X
The basic N-terminal Arg/Pro-rich region binds heparin and heparan sulfate. Binds collagens type I and type II through its leucine-rich repeat domain
The HIN-200 domains mediates dsDNA binding via electrostatic interactions
Contains FG repeats. The FG repeat region is required for acting as a cofactor of HIV-1 Rev
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box (By similarity)
Intrinsically disordered protein (Probable)
The C-terminal ATP-binding domain is required for both kinase and phosphatase activities and contains the GlnB binding site
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl groups; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
The acidic serine aspartate-rich MEPE-associated (ASARM) motif is sufficient when phosphorylated to inhibit bone mineralization by osteoblasts and cartilage mineralization by chondrocytes by binding hydroxyapatite crystals during the mineralization stage. It can also inhibit dentin mineralization
Contains an ion transport-like region is related to the membrane segments of voltage-gated ion channels
The SH3 domain plays a major role in substrate interactions. The SH2 domain of PTK6 plays a role in protein-protein interactions, but is likely more important for the regulation of catalytic activity (By similarity)
Each of the immunoglobulin-binding region repeats can bind the Fc region of an immunoglobulin (PubMed:2938951). Cell wall anchoring is confered by the LPXTG motif and following sequences (residues 482-516) which are necessary and sufficient to target other proteins to the cell wall (PubMed:1638631). The YSIRK-G/S motif in the signal sequence plays a role in the secretion efficiency for SpA, it may have a specialized recognition mode (Probable)
The central domain (GIL, residues 153-492) is sufficient for c-di-GMP binding
In the disassembly complex (PDB:6P8V) Cap6 (also called Trip13) crystallizes as a right-handed spiral; the top 4 subunits bind ATP while the bottom 2 do not. A CdnC monomer lies along the surface of the hexamer at the interface of subunits 5 and 6, with Cap7 (also called HORMA) at its tip, over the central hexamer pore. The N-terminus of Cap7 extends into the pore, contacting 5/6 Cap6 subunits
The RCK N-terminal domain binds NAD and possibly other effectors. This is expected to cause a conformation change that regulates potassium transport
Gln-310 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. For SLAMF1 a 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). SH2D1A binding is mediated by either three 'prongs' (for high affinity binding involving ITSM 1) or a combination of any two also including non-phosphorylated Tyr-281 of ITSM 1 thus providing a positive feedback loop implicating SH2D1A-dependent recruitment of activating FYN. ITSM 2 needs to be phosphorylated on Tyr-327 for SH2D1A binding
The propeptide domain acts as an intramolecular chaperone for the folding of the catalytic domain (PubMed:16322767). Also acts as an inhibitor of the catalytic domain thereby regulating SUB2 activity during secretion (PubMed:16322767)
The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1 (By similarity). Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface
The central and C-terminal regions are required for dimerization
The CoCUN region mediates binding to ubiquitin. Does not interact with NEDD8
The two glycerophosphodiester phosphodiesterase domains are predicted to be extracellular and the kinase domain cytoplasmic
The C-terminal domain has toxic activity, which can be exchanged between N-terminal sections from different toxin molecules
The formation of methylphloracetophenone leading to dibenzufurans such as usnic acid requires a 1,6-Claisen-style condensation performed by a terminal CLC domain that simultaneously aromatizes the tetraketide and releases it from the PKS (PubMed:26895859)
The SAM domain is required to retain SMAD8 in the endoplasmic reticulum. membrane protein (By similarity)
The cysteine framework is XVII (C-C-CC-C-CC-C)
The C-terminal repeats are critical for activity
The 5-phosphatase domain (residues 568 to 856) selectively removes the phosphate group at the 5' position of inositol of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
The C-terminal proline-rich domain is required for the function and associates with clathrin heavy chain CHC1
The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for interaction with CD160 and BTLA
The C-terminal 14 residues mediate binding to the N-terminus of PduP, which encapsulates PduP into BMCs
The 2 circularly premutated PDZ domains act to negatively regulate protease action on intact RseA; mutations in PDZ 1 (PDZ-N) have a more deleterious effect than similar mutations in PDZ 2 (PDZ-C). A 31 residue insertion in PDZ-C (between Val-261 and Met-262) domain inhibits protease activity, whereas deletion of residues 203-279 alleviates the PDZ-inhibition, allowing cleavage of intact RseA
Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers (PubMed:25258363, PubMed:25999311). The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine (PubMed:25258363)
The C-terminal coiled coil region mediates homodimerization
The ubiquitin-like domain mediates interaction with the E3 ubiquitin-protein ligase RNF126 which is responsible for the BAG6-dependent ubiquitination of client proteins (PubMed:21743475, PubMed:24981174, PubMed:28104892, PubMed:27193484). SGTA also binds this domain and competes with RNF126 to antagonize client protein ubiquitination and degradation (PubMed:28104892). The ubiquitin-like domain also mediates the interaction with USP13 (PubMed:24424410)
The SAM domains mediate the localization to postsynaptic regions of neurons
The C-terminal domain (CTD, residues 499-810) contains 6 tandemly repeated subdomains known as blades, each of which is composed of a 4-stranded antiparallel beta-sheet. The blades form a flat, toroidal beta-pinwheel fold, to which DNA probably binds, inducing mild positive superhelicity (about 0.3 links/protein) (PubMed:15897198, PubMed:15123801)
The C-terminus contains two copies of a helix-hairpin-helix (HhH) motif that are dispensable for activity and thermal stability
B box-type zinc binding domain is required for targeting this protein to lampbrush chromosome loops and for normal functioning of this protein in the oocyte
The cytoplasmic domain controls FRC elongation but is dispensable for contraction (PubMed:25347465). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (By similarity)
The myosin motor domain binds to actin
The coiled-coiled domain is necessary for dimerization
The tail domain is a globular cargo-binding domain involved in vectorial vesicle transport
The LEM domain is required for inner nuclear membrane (INM) localization and contains a BANF1 conserved binding motif which allows localization to chromatin (PubMed:16339967, PubMed:32494070). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disk, both the LEM domain and the disordered regions are necessary for localization to the NE core (PubMed:32494070)
The disordered regions, also named low complexity domain, confer the ability to phase separate (PubMed:32494070). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disk, both the LEM domain and the disordered regions are necessary for localization to the NE core (PubMed:32494070). During NE reformation, the proline-arginine-rich sequence within the disordered region binds microtubules, targeting LEM2 condensation to spindle microtubules traversing the nascent NE (PubMed:32494070)
The winged-helix (WH) region (residues 395-503) activates the ESCRT-II/ESCRT-III hybrid protein CHMP7 to form co-oligomeric rings around spindle microtubules to facilitate early nuclear sealing
The guanylate cyclase domain is required for Sema-1a-mediated axon repulsion
The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation (By similarity). Removal of the C-terminal regulatory domain increases activity
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis. The LID domain is a solvent-exposed domain that is much shorter in Mycobacterium than in many other bacteria like E.coli
Members of the RBR family are atypical E3 ligases. They interact with an E2 conjugating enzyme and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate
Monalysin structure belongs to the Aerolysin-like PFTs fold family but is devoid of obvious receptor-binding domain
The ring domain is sufficient for the interaction with ANAC
Presence of both a nuclear localization sequence (NLS) and a nuclear export sequence (NES)
In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif
The cysteine framework is C-C-C-CC-C
The large coiled coil domain is required for homodimerization
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 90 and 114
The C-terminal extension is not essential for ribosome assembly, but is important for the formation or the stability of the complex
The coiled coil domain is necessary and sufficient for interaction with sas-5
The BTB domain mediates the interaction with the androgen receptor/AR and HDAC1. Also mediates the interaction with SP1
The CHHC region interacts with the 5' splice site of the U12-type Intron
In addition to ubiquitin-binding at the Cys-91 active site, a proximal ubiquitin-binding site is also present at Cys-23 Occupancy of the active site is needed to enable tight binding to the second site. Distinct binding sites for the ubiquitins may allow to discriminate among different isopeptide linkages (i.e. 'Lys-48'-, 'Lys-63'-linked polyubiquitin) in polyubiquitin substrates and achieve linkage-specific deubiquitination
The C3H1-type 1 domain is required for degradation in somatic blastomeres
The C3H1-type 2 domain targets the protein to P granules, is involved in germ cell positioning in embryos and is required for default nos-2 expression
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface (PubMed:19540345). PUM2 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine (By similarity)
The DCB (dimerization and cyclophiln-binding) and HUS (homology upstream of Sec7) domains are necessary for dimerization. The DCB domain is proposed to support constitutive homodimerization; the HUS domain interacts with the DCB domain which may occur intramolecular or intermolecular (By similarity)
The N-terminus (residues 1-108) interacts with KaiC, while the C-terminus (109-380) autophosphorylates and is probably responsible for self-association. The N-terminal domain stimulates the C-terminus to autophosphorylate; KaiC does not stimulate autophosphorylation of the C-terminal domain
Consists of 4 functional domains: (1) the N-terminal GT44 domain (glycosyltransferase, also named GTD), which mediates glucosylation of host small GTPases, (2) an autoprocessing region that catalyzes autoprocessing to release the N-terminal GT44 domain in the host cytosol, (3) the translocation region that forms a pore to promote translocation of the GT44 and peptidase C80 domains across the endosomal membrane and (4) the receptor-binding (CROPS) region that mediates binding to host cells and contribute to entry into cells
The four-helical bundle region mediates binding to phospholipids, such as phosphatidylserine and phosphatidic acid (By similarity). This promotes localization to the inner face of the cell membrane close to small GTPases (By similarity)
The N-terminal sequence motif LXXXLL is necessary for localization to the vacuole membrane (tonoplast)
The 2 G (guanine nucleotide-binding) domains are essential for activity and function cooperatively. The KH-like domain is required for ribosome recognition
Possible isomerization of Pro-358 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA
Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro) (PubMed:28981703). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro) (PubMed:28981703)
Modular protein that contains a condensation domain, an adenylation domain which activates the alanine residue into an aminoacyl-AMP ester and a peptidyl carrier protein domain which bears a phosphopantetheinyl arm to attach the activated amino acid
Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes (By similarity). The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with NHERF1 and for targeting NHERF1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation
The PDZ 1 domain participates in the interaction with the PID domain of NUMB, and participates in the isoform-specific ubiquitination of NUMB. The PDZ 2 domain of isoform 2 participates in the interaction with IGSF5/JAM4, other isoforms containing this domain may also interact with IGSF5/JAM4 (By similarity)
Composed of two BON domains that form an interconnected opposing pair (PubMed:33315009). The N-terminal BON domain interacts with BamA (PubMed:33847565). The C-terminal BON domain binds anionic phospholipids through an extensive membrane:protein interface (PubMed:33315009)
The presence of both Myb domains is required for high affinity telomeric DNA-binding
The N-terminal acidic region is intrinsically disordered (By similarity). This region contributes to LPL binding (PubMed:20620994). It stabilizes LPL and protects LPL against loss of activity (By similarity)
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins. Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain. Interacts with HIP1 (via coiled coil domain) (By similarity)
The C-terminus (residues 99-159) is sufficient to bind and neutralize toxin when expressed in E.coli
The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain. It targets the protein to insoluble protein aggregates
The PDZ domain probably binds peptides ending with C-terminal Tyr-X-Phe sequences, which activates proteolysis. In the absence of OMP peptides the PDZ domain inhibits peptidase activity
The LIR motif (LC3-interacting region) is required for its interaction with lgg-1
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (By similarity). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (PubMed:23791178)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (290-320) inactivates kinase activity under calcium-free conditions (By similarity)
The C-terminal region contains two separate nuclear receptor-interacting domains (ID1 and ID2), each of which contains a conserved sequence referred to as the CORNR box. This motif is necessary and sufficient for binding to unligated nuclear hormone receptors, while sequences flanking the CORNR box determine the precise nuclear hormone receptor specificity
Crystallizes with 5 domains; the first 4 form a ring through which ssDNA may pass (seen in A. fulgidus crystals). The C-terminal domain (654-715) lies perpendicular to the ring and is able to bind ssDNA, which may cause it to may act as a molecular brake, inhibiting helicase activity (PubMed:18056710)
The PY-motifs are required for the interaction with RSP5 ubiquitin-ligase
Contains G-L-F-G repeats. The FG repeat domains in Nup98 have a direct role in the transport
The carboxy-terminal segment (CTS) binds to RNA with high affinity in the nanomolar range but without apparent sequence specificity
The size and flexibility of the betaB6-betaB5 hairpin loop at residues 198-212 are crucial for activity. Variation of the loop sequence results in an altered DNA nicking profile including novel sites
The entire WD repeat region is required for the interaction with ORC, CDT1 and GMNN, as well as for association with chromatin and for binding to histone H3 and H4 trimethylation marks H3K9me3 and H4K20me3 (By similarity). Centrosomal localization requires additional conformation
The protomer folds into three distinct domains: an N-terminal nucleotide binding domain, a central helical domain involved in dimerization and a C-terminal substrate binding domain
The Pru (pleckstrin-like receptor for ubiquitin) domain mediates interactions with rpn2 and ubiquitin
The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33. Stalk region is sufficient for interaction with TSPAN15
Has two domains of the BPTI family. The N-terminal domain bind to the active site of thrombin, the C-terminal domain binds at the fibrinogen recognition exosite
Death domain is responsible for interaction with RANBP9. It also mediates interaction with ARHGDIA and RIPK2 (By similarity)
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala/Ser/Val (NPA)
The polypeptide has an alpha-hairpin structure. Two subunits dimerize to form a four-helix, rod-like structure. Each subunit is composed of a cap structure and of tandem 11 residue repeats with the sequence [TI]-X-X-X-A-X-X-X-A-X-X. Each repeat forms three helical turns with an average of 3.7 residues per turn, as opposed to 3.6 residues per turn for a classical alpha helix. Contrary to other proteins, where the protein core is stabilized by hydrophobic interactions and contains little water, this protein contains in its interior over 400 ordered water molecules with a semi-clathrate structure. Most likely, the interaction with the surface of ice crystals is mediated by bound water molecules that protrude between the helices
The C-terminal region is required for binding to CDKN3-CDK2 complexes and the modulation of CDKN3 activity
The zinc-finger domain mediates direct interaction with DNA and phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate) (PubMed:26609676). In vitro oxydation causes reversible disulfide bond formation between Cys residues in the zinc-finger domain and reversible loss of zinc ion binding (PubMed:26609676)
Ectopic expression of the histone fold domain acts as a dominant-negative mutant resulting in differentiation inhibition
This molecule consists of two distinct domains, a small domain and a large domain. The structure of the large domain repeats a motif observed in the dimeric IDH. Such a fusional structure by domain duplication enables a single polypeptide chain to form a structure at the catalytic site that is homologous to the dimeric IDH, the catalytic site of which is located at the interface of two identical subunits
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable MCD1 protein, forming a ring structure
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Lys and Val residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins
The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP (By similarity). They are essential to limit the length of ubiquitin chains (By similarity)
The LIM zinc-binding 2 (LIM 2) domain interacts with TBX4
The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. Pum is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine
The NT5 region (73-100) is required for actin-binding activity
Polybasic regions located between residues 266 and 557 are involved in binding PKC
The PDZ domain binds to the last three or four amino acids of DGKZ. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane
Contains an N-terminal catalytic domain and a C-terminal auxiliary domain (PubMed:33684445). A putative active site is located in a cleft within the interface of two subdomains (PubMed:33684445)
Contains an N-terminal PPIase domain, an IF (Insert in the Flap) domain and a C-terminal domain (CTD). Aggregation suppressing activity against chemically unfolded protein is exerted mainly by the CTD while N- and C-terminal domains contribute to thermal protein aggregation suppression. The CTD probably contributes to hexamerization
The N-terminal domain (AA 2-20) is essential for its effect on cell growth and survival
The GxxxG glycophorin motif in the transmembrane domain is required for CEK1 activation and subsequent invasive filamentation on agar medium
The cytoplasmic C-terminal calmodulin-binding motif (residues 301 to 317) is important for CEK1 activation and subsequent invasive filamentation on agar medium
The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice. TOG 1 and TOG 2 are critical for microtubule polymerase activity
The PHD domains recognize both active and repressive histone methylation marks at the intronic repeat elements in genes
The LRR (leucine-rich repeat) domain mediates interaction with host PKN1 and inhibition of NF-kappa-B-dependent gene expression
2 residues (Tyr-41 and Arg-44) present in a large hydrophobic pocket are probably involved in substrate specificity. They are important for desuccinylation activity, but dispensable for deacetylation activity
S100A16 proteins, but not other S100 proteins, have only one functional Ca(2+) binding site per monomer. Upon Ca(2+) binding, undergoes conformational changes leading to the exposure of hydrophobic patches which could be implicated in the Ca(2+)-dependent nuclear export. Binds Zn(2+). Ca(2+) and Zn(2+) do not bind to the same site. Does not bind Cu(2+)
The toxic domain is at the C-terminus (residues 1264-1427); expression of this domain in E.coli reduces viability nearly 1000-fold
Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function (By similarity)
Consists of three domains. The N-terminal dimerization domain has the same fold as the IIA domain of the mannose transporter of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS). The middle domain is similar to HPr and the C-terminus is similar to the N-terminal domain of enzyme I (EI) of the PTS. The IIA domain of DhaM (via phospho-His-9), instead of ATP, is the phosphoryl donor to dihydroxyacetone (Dha). The phosphoryl flow likely involves HPr ('His-15') -> DhaM (His-432 -> His-169 -> His-9) -> DhaL-ADP -> Dha. The HPr-like domain of DhaM cannot efficiently substitute for the general carrier protein HPr
The YXXXXLphi motif mediates interaction with eIF4E1
The C-terminal C-Ala domain (residues 756 to 968) is not required for catalytic activity and can bind DNA (in vitro) (PubMed:27911835). The C-terminal C-Ala domain (residues 756 to 968), along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs. The human domain can be used in vitro to replace the corresponding domain in E.coli (PubMed:19661429)
High-affinity binding to heparin/glycosaminoclycan (GAG) is mediated by a large, highly positively charged surface at the interface of dimer's subunits involving approximately residues 25-40, 386-393, and 419-425
The N-terminal CRISPR-associated Rossman fold (CARF) probably binds the cA4 effector. ssRNase activity resides in the C-terminal HEPN domain
In addition to the iron-sulfur cluster, contains two additional oxygen-labile iron ions
May be secreted as a 4 coiled-coil complex with EsxA (PubMed:16048998). The C-terminal domain is required for interaction with both EsxA and EccCb1; the last 7 amino acids are necessary and sufficient for EccCb1 binding and secretion (PubMed:16973880)
Binds 3 calcium ions via the second, third and fourth EF-hand. EF-2 and EF-3 bind both magnesium and calcium, while EF-4 binds only calcium. At the resting state, magnesium is bound to EF-2 and EF-3 and upon activation, both sites bind calcium simultaneously while EF-4 is the last one to be occupied
Three specific residues, Phe-158, Leu-161 and Asn-177 are conserved between non-primate mammals whereas the respective residues are serine, phenylalanine and threonine in primates (PubMed:19056333). The two residues at positions 158 and 161 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil (PubMed:19056333). The presence of an asparagine at position 177 is important for the maintenance of the quaternary structure resulting in stability at cold temperature and improved catalytic activity toward retinal (PubMed:19056333)
The membrane anchor N-terminal domain is required for activity. The iron-binding domain is required for protein stability and function
An internal domain (143-652) is sufficient for assembly into supercomplex with Toc complex
Residues 235-420 contain a binding site for preprotein transit peptides
Consists of two tandem domains of about 15% identity and similar three-dimensional topology that interact to form a pseudo-dimeric structure. The N-terminal domain (residues 1-258) plays an important regulatory role in facilitating the catalytic function of the C-terminal domain (residues 259-460). The N-terminal domain alone does not show any activity. The C-terminal domain alone is much less active comparing to the full-length protein. The full-length protein is 13 times more active than the C-terminal domain alone
BH4 domain mediates interaction with ITPR1
Contains a N-terminal NAI2 domain (192-490)
Substrate binds in a cavity formed at the dimer interface
The N-terminal PH domain allows ITK to be recruited to the plasma membrane by an activated PI3 kinase. This domain contains also a proline-rich region (PRR). The adjoining domain is a SH3 domain, which binds to PRR (from itself or from other proteins). Next, a SH2 domain is required for binding tyrosine-phosphorylated substrates. In the C-terminal region, the kinase domain is required for tyrosine phosphorylation (By similarity)
The TPR repeats mediate protein-protein interactions and are essential for its function. Expression of such repeats in plants accelerate flowering
The coiled-coil domain mediates the specific interaction with dys-1
The RING-type 1 zinc finger domain is required for ubiquitination activity
Members of the RBR family are atypical E3 ligases (PubMed:17456438, PubMed:23770917). They interact with E2 conjugating enzymes and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain (PubMed:17456438, PubMed:23770917)
The target ssRNase active sites are probably within the 2 HEPN-like folds, and the 2 folds interact in vivo (PubMed:26593719)
The four-helical bundle region mediates binding to phospholipids, such as phosphatidylserine and phosphatidic acid (PubMed:25882477). This promotes localization to the inner face of the cell membrane close to small GTPases (By similarity)
Cleavage causes major structural rearrangement of more than half the 13-domain structure from a native to a compact induced form
Consists of an N-terminal FAD-binding domain with a Rossman fold, a substrate-binding domain and a C-terminal helix that bridges the 2 domains close to the antibiotic-binding site. This last helix is flexible, is not found in TetX of Bacteroides species, and may contribute to their different substrate specificities (PubMed:28481346). Binds chlortetracycline in a different orientation (180 degrees rotated on its long axis) compared to tetracycline substrate binding to TetX; binding of chlortetracycline alters conformation FAD and the last helix (PubMed:28481346)
Gln-173 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Residues 1178-1195 comprise a putative nuclear localization signal; nuclear localization is required for the regulation of period length of the circadian clock
The DNA-binding domain (residues 813-951) binds to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and has high affinity for DNA sequences rich in guanine that form G-quadruplex (G4) structures
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (343-373) inactivates kinase activity under calcium-free conditions (By similarity)
Consists of two domains: an N-terminal CheW-like coupling domain and a C-terminal two-component receiver domain
The Cx14C/Cx13C motifs are involved in the recognition by the mitochondrial MIA40-ERV1 disulfide relay system and the subsequent transfer of disulfide bonds by dithiol/disulfide exchange reactions to the newly imported protein
The C-terminal domain (496-565) is responsible for the localization to the trans-Golgi network/early endosome
The first serine protease domain is catalytically active, whereas the second domain lacks the essential His residue of the catalytic triad at position 363, and the third domain lacks the essential Asp residue of the catalytic triad at position 679. The second and third domains are therefore predicted to be inactive (By similarity)
The third dsRNA-binding domain (DRBM 3) contains an additional N-terminal alpha-helix that is part of a bi-partite nuclear localization signal, together with the sequence immediately C-terminal to DRBM 3. The presence of DRBM 3 is important to bring together the N-terminal and the C-terminal part of the bi-partite nuclear localization signal for import mediated by TNPO1 (PubMed:24753571). RNA binding interferes with nuclear import (PubMed:19124606, PubMed:24753571)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (365-395) inactivates kinase activity under calcium-free conditions
The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24859340). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (By similarity). The activating sterol is likely to be cholesterol (PubMed:35658032). The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH (PubMed:35658032)
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). AQP9 has NPA/NLA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium
The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+)
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensors regions required for activation of the channel
A tripeptide motif (TDE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
Domain I (which is divided into 2 non-contiguous regions Ia and Ib) is required for binding to cells, but not for ADPRT activity (Probable) (PubMed:2170123). A subtilisin-digested fragment starting about residue 417 and extending to the C-terminus has full ADPRT activity (PubMed:2170123)
Amino acids 31-34, 96-99 and 241-244 are necessary for interaction with the Importin alpha/Importin beta receptor. The first 18 amino acids, amino acids 69-76 and 179-182 are necessary for interaction with TNPO3. Amino acids 31-34, 96-99 and 241-244 are necessary for nuclear localization
The C-terminal domain has a high percentage of Ser, Pro and Thr residues
The BTB domain mediates homodimerization. Its dimer interface mediates peptide binding such as to corepressors BCOR and NCOR2 (PubMed:18212045). Interaction with corepressors through the BTB domain is needed to facilitate the rapid proliferation and survival of GC B-cells but is not involved in the T(FH) formation and BCL6-mediated suppression of T(H)2 and T(H)17 differentiationrequired for GC formation (By similarity)
The globular domain is dispensable for prion formation and incompatibility function. However, the het-S globular domain, but not the het-s globular domain, is essential for programmed cell death
The prion domain (PrD) is unstructured in its native, soluble form, and forms a form a beta solenoid with a hydrophobic core in its amyloid form. It is both necessary and sufficient for amyloid formation and prion propagation
Lacks the N-terminal domain required for the association of regulatory subunits into dimers in other eukaryotes
The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity (By similarity). The coiled coil domain is important for higher order multimerization by promoting the initial dimerization (PubMed:21680743)
The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs
The N-terminal extension, may be the regulatory domain
The cytoplasmic region is involved in recruitment of the downstream cell division protein FtsW. The transmembrane segment and the membrane-proximal periplasmic region form a coiled-coil structure and are required for septal localization and interaction with FtsB. The C-terminal region is required for interaction with FtsQ. Contains a leucine zipper-like (LZ) motif, which is required for optimal interaction with FtsB
The TPR repeats mediate protein-protein interactions. Expression of such repeats in plants generate a dominant-negative mutant
PsoF is a unique bifunctional enzyme catalyzing two different types of reactions at completely separate steps of the pseurotin biosynthetic pathway and comprised an unusual combination of two domains, one homologous to a methyltransferase (MT) and another to an FAD-containing monooxygenase (FMO) (PubMed:24939566)
The UEV domain is required for the interaction of the complex with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs of HIV-1 P6 protein and human spumaretrovirus Gag protein
The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity
The angiostatin binding domain (850-1047) allows the binding to angiostatin
The KEN and D (destructive) boxes are required for the cell cycle-controlled ALK2 degradation by the anaphase promoting complex (APC) pathway
The DCB domain is required for both homodimerization and interaction with CYP protein. Heterotypic interaction of DCB domain with the N-terminal part of the SEC7 domain is required for membrane association and catalytic activity of the protein
The tandem Agenet domains (AGDs) mediate the specific recognition of the histone 3 lysine 9 dimethylation (H3K9me2) mark
Modular protein that contains an adenylation domain which activates the alanine residue into an aminoacyl-AMP ester, a peptidyl carrier protein domain which bears a phosphopantetheinyl arm to attach the activated alanine and a condensation domain involved in the condensation of this amino acid with a second amino acid bound at the carrier protein domain of another module
The N-terminal domain contains a vast hydrophobic cavity that is buried by the C-terminal domain. This cavity may bind the RNAP and become unmasked only upon binding to the nontemplate DNA strand
Contains a canonical alpha/beta-hydrolase fold with an atypical catalytic dyad
The N0, N1, N2 and N3 domains are periplasmic, while the secretin and S domains form a channel that is partially inserted in the outer membrane. The N1, N2 and N3 domains each form a periplasmic ring. The secretin domain forms a double beta-barrel structure; the outer barrel has a diameter of about 110 Angstroms while the inner barrel forms the central gate with a small pore in the closed state (By similarity). The S domain interacts with pilotin OutS (PubMed:23897461)
The EF-hand domain probably mediates calcium-binding. It is not required for channel activation
The BC, DE and FG loops form a tripartite wedge that blocks the substrate-binding site of target cysteine proteases (PubMed:20951777). The BC loop interacts with the catalytically active cysteine and histidine residues of the protease catalytic center (PubMed:20951777) (Probable)
A C-terminal fragment containing the RING domain interacts with UBC35 while the full-length protein does not
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (358-388) inactivates kinase activity under calcium-free conditions (By similarity)
The CLIR and LIR-like motifs are required for interaction with AT8 family proteins
The GGEEF domain is required for function
Residues 610-690 form a beta-strand plug which closes one end of the shell; the other end of the shell is closed by the 5-bladed beta-propeller domain in YenB
Contains an aspartic proteinase-like domain in the C-terminal region. However, the enzyme is inactive. A comparison of the structure with pepsins showed significant differences in the critical substrate binding residues and in the flap tyrosine conformation that could contribute to the lack of proteolytic activity of PE_PGRS16
Consists of 4 domains; domains 1-3 have a similar toplological core while domain 4 folds over and closes the active site from a hinge region. Mutants in the hinge region (residues 262 and 368-369) generally increase KM for glucose 1-phosphate 2-fold while reducing kcat about 10-fold (PubMed:18690721)
The linker region between repeat III and IV probably plays a role in the inactivation of the channel. The C-terminal part may be implicated in the anchoring of the protein to the membrane by interfering with or restricting its lateral diffusion
The conserved PP2C phosphatase domain (250-651) is interrupted by an insertion of approximately 100 amino acids
The LIM domains are sufficient for the role in PLM synaptogenesis
The tight homohexamer forms a pore with an opening of about 5.0 Angstroms in diameter which is positively charged. Sulfate ions are bound in one crystal form in both the pore and between hexamers which may represent metabolite flux. The C-terminal flexible tail, which is the most variable part of CcmK proteins, seems to be involved in packing of hexamers in layers
The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization
The Tudor domain specifically recognizes and binds symmetrically methylated Siwi and Ago3
The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes (By similarity). Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions (PubMed:23761074, PubMed:26567222)
The CCHC FOG-type zinc fingers 1, 4 and 5 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is essential for the interaction with GATA-type zinc fingers
The 4 N-terminal Arg residues do not affect the overall fold, but are important for the antimicrobial potency
The C-terminal cytoplasmic domain is important for channel ion selectivity
The SH2 domain mediates interaction with tyrosine-phosphorylated proteins (PubMed:18722344). However, not involved in the binding to phosphorylated BCAR1 (PubMed:18722344). Required for cell cycle progression in response to INS/insulin (PubMed:24216110). Required for regulation of EFR-induced DNA synthesis (PubMed:18722344)
Each monomer can bind two substrate molecules, yet there is only one active site for the whole trimeric enzyme, which is located at the interface between two neighboring chains and formed by the N-terminal barrel from chain A and the C-terminal barrel from chain B
The propeptide domain acts as an intramolecular chaperone for the folding of the catalytic domain (By similarity). Also acts as an inhibitor of the catalytic domain thereby regulating SUB2 activity during secretion (PubMed:16879884, PubMed:19214190)
The coiled-coil domain and the B30.2 domain are both necessary for interaction with HN and PAX6 (By similarity). They are also involved in MED15-binding (PubMed:16904669)
WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain. The SP domain is involved in EFNB1-binding
Undergoes helix-strand structural transitions upon substrate-binding: the 130's region interconverts between an inactive helical state and the canonically active strand state (PubMed:28154009). Other caspases rest constitutively in the strand conformation before and after substrate-binding (PubMed:28154009)
The helical domain (460-611) is required for self-activation
The pyrin domain mediates homotypic interaction with PYCARD/ASC (PubMed:19158676, PubMed:19158675)
The 9 residue linker permits DLP1 (tethered to DLP2) considerable flexibility; it is long enough to allow the GTPase domains (dynamin-type G) of DLP1 and DLP2 to heterodimerize. Two regions within the tip of the trunk are required for homodimerization; deletion of residues 348-401 and 509-542 prevents DLP2 dimerization, but not formation of a DLP1-DLP2 dimer
Neither C2 domains mediates Ca(2+)-dependent or Ca(2+)-independent phospholipid binding
The N-terminal CRISPR-associated Rossman fold (CARF) probably binds the cOA effector. ssRNase activity resides in the C-terminal HEPN domain
Specifically interacts with PI3P, PI4P, PI5P, and PI(3,5)P2
Contains three domains, the FAD binding domain, the NADPH binding domain, and the dimerization domain (PubMed:12390015). The binding of the substrate induces a conformational change that results in the sequestration of the substrate at the dimer interface (PubMed:12390015, PubMed:16388586)
The ZIP domain (80-130) is necessary and sufficient for the interaction with ZPR3 (PubMed:18408069)
The transcriptional activation domain (TAD) (149-188) overlaps with the destruction element (DE) (154-165)
The JAZ-interaction domain (JID) (93-160) is sufficient for interaction with MYB proteins and most of the TIFY/JAZ proteins (PubMed:21335373, PubMed:23943862)
The C-terminal half contains an active nuclear localization signal (NLS)
A conserved histidine residue in the third transmembrane domain (His-136) might play an essential role in the pH sensitivity of SLCO2B1/OATP2B1-mediated substrate transport (PubMed:19129463). Transmembrane domain 1 (TM1) may be localized within the substrate binding pocket (PubMed:29871943)
The N-terminal fragment (residues 1-88) binds hox promoter DNA
DNA binding and bending properties of the HMG domains of mouse and human SRY differ form each other. Mouse SRY shows less extensive minor groove contacts with DNA and a higher specificity of sequence recognition than human SRY
Each subunit creates a channel spanning the outer leaflet of the inner membrane and up to the periplasmic space
The C-terminal domain (residues 230-320) is required to recognize and bind RNA; recognition of cognate RNA also requires a region closer to the N-terminus
The basic domain binds to the canonical E-box (5'-CANNTG-3'), with a particular preference for TA relative to AT or CG in the variable central nucleotide positions
Perforin consists of three domains: (1) the MACPF domain, which includes the central machinery of pore formation, (2) the EGF-like domain, which forms a 'shelf-like' assembly connecting the MACPF and C2 domains, and (3) the C2 domain, which mediates calcium-dependent binding to lipid membranes (PubMed:21037563, PubMed:35148176). The C2 domain is critical for initial calcium-dependent interaction with lipid membranes of the target cell: calcium-binding causes a significant structural rearrangement, leading to oligomerization and deployment of the two transmembrane beta-strands (named CH1/TMH1 and CH2/TMH2) that enter the membrane as amphipathic beta-hairpins (PubMed:21037563, PubMed:26306037, PubMed:35148176). The third calcium-binding site (Ca(2+) 3), which constitutes the weakest affinity site, triggers structural rearrangements in the C2 domain that facilitate its interaction with lipid membranes (PubMed:26306037)
Contains an incomplete active site due to the presence of a Gly residue in position 72 instead of a Gln, probably explaining the inability to hydrolyze GTP
A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-151
Two distinct periplasmic domains, one located in the proximity of the transmembrane domain and the other located towards the C-terminal part of the protein are both involved in the interaction with XcpY
Side chains of Lys-111, Lys-144 and Lys-174 capture Ser that is misactivated by AARS/AlaRS
The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for full GAP activity
The extracellular domain (26-234) is required for dimerization
The N-terminal part (1-200) directs accumulation in prespore vesicles
The C-terminal part (333-532) binds cellulose and cotE simultaneously and specifies incorporation into the coat
The N-terminal half of KdtA, especially the first 30 amino acid residues, is responsible for determining the number of Kdo residues that are transferred to lipid IVA
The YEATS domain specifically recognizes and binds acylated histones, with a marked preference for histones that are crotonylated (PubMed:27105114, PubMed:27545619). Also binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity (PubMed:25417107, PubMed:27105114). Binds crotonylated lysine through a non-canonical pi-pi-pi stacking mechanism (PubMed:30374167, PubMed:30385749). The YEATS domain also binds DNA (PubMed:30385749)
Homodimerizes by swapping the N-terminal TIR and C-terminal nucleotide-binding domains. Ligand binding induces lid closure and repositions the TIR domain (PubMed:32877915). The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity (By similarity)
Has a discontinuous central core of beta sheets stabilized by a disulfide bond that is flanked by 2 structural domain repeats on each side; the protein forms an elongated 'S'-shaped structure (PubMed:26922638)
Arranged into two tetraheme clusters and the extra heme 4 is located asymmetrically between the two regions
The PHD domain is involved in the binding to H3K4me3
The second C2 domain/C2B is required for the inhibitory role in both clathrin-mediated and bulk endocytosis (PubMed:26589353, PubMed:29311685). The transmembrane domain and the first C2 domain/C2A are critical for the inhibitory role in clathrin-mediated endocytosis or bulk endocytosis, respectively (PubMed:26589353)
The zinc-finger motif is essential for transcription activation
The N-terminal BAR domain is required for the interaction with FREE1
Has three domains with a flexible linker between the domains II and III, and assumes an 'L' shape (Probable). In the assembled complex, domain III contacts 2 of the RuvB subunits (PubMed:36002576)
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 645, which is replaced by a Glu residue
The Asp-Pro-Phe (DPF) motifs, which are found in many presynatic proteins, are thought to mediate an interaction with Alpha-adaptin
Contains a PilZ-like fold that binds two molecules of c-di-GMP via two well-conserved c-di-GMP-binding motifs, RXXXR and D/NXSXXG
The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2 (PubMed:21238436). The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2 (By similarity)
PTB domain recognizes multiple ligands by engaging different amounts of surface area dictated by tertiary contacts rather than primary sequence. This may allow interactions with a diverse set of proteins during asymmetric division and specification of cell fate
The target ssRNase active sites are within the 2 HEPN-like folds which interact in vivo (PubMed:26593719, PubMed:27256883, PubMed:28086085). The X-ray structure in complex with crRNA shows a crRNA-recognition lobe (REC, residues 1-498) which makes most of the contacts with crRNA and is essential for pre-crRNA cleavage, and a nuclease lobe (NUC, residues 499-1389) which also makes a few contacts with the crRNA repeat and is responsible for target ssRNA cleavage (PubMed:28086085). Binding of crRNA induces conformational changes that probably stabilize crRNA-binding and facilitate target ssRNA recognition (PubMed:28086085). Mutagenesis of the crRNA and this protein show the stem loop and 3'-direct repeat of the crRNA are essential for target ssRNase while the 5'-end of the crRNA and its bulge-containing stem are essential for pre-crRNA cleavage (PubMed:28086085)
DH (RhoGEF) domain interacts with Rac1-related GTPases
The large coiled coil domain may mediate homodimerization
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture (PubMed:28723891, PubMed:32228865). The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping (PubMed:32228865). Forms a central ion-conduction pore lined by the side chains of the pore-lining helices (PubMed:32228865). Conserved isoleucine residues (Ile-46 in the first module and Ile-271 in the second module) in the center of the pore serve as the gate in the closed conformation (PubMed:32228865). In the widened channel in the open conformation, Ser-45 and Ile-46 in the first module (and Thr-274 and Ile-271 in the second module), establish a constriction essential for potassium selectivity (PubMed:32228865)
The N-terminus Ig-like V-type domain is necessary for heterophilic intercellular adhesion
The EAL domain contains a functional active site loop (loop 6), which plays crucial roles in stabilizing the overall protein structure and participating in catalysis, and also controls c-di-GMP and Mg(2+) ion binding
Contains an N-terminal DNA binding region and a C-terminal effector-binding cavity (PubMed:33224125, PubMed:33068046). The C-terminal region also contains a metal binding site (PubMed:33224125). The divalent metal ion is not directly involved in the interaction with DNA, but it plays an important role in interaction with D-galactonate (PubMed:33224125)
The C-terminal region is required for nuclear mRNA export
The C-terminal domain of this protein is probably involved in association of subunits consequent on ribitol binding
The N-terminal region is involved in phosphatidylethanolamine-binding and is required for apg-6/atg8-PE conjugation
The flexible region (FR) is required for apg-5/atg7-binding
The handle region (HR) contains the apg-6/atg8 interaction motif (AIM) and mediates binding to apg-6/atg8. It is crucial for the cytoplasm-to-vacuole targeting pathway (By similarity)
Consists of two domains: an N-terminal heme-based oxygen-sensor domain, and a C-terminal catalytic domain that exhibits histidine kinase activity (PubMed:21852234). The coordination and oxidation state of the sensor domain heme iron profoundly affect the enzyme's catalytic activity (PubMed:26212354)
Corresponds to the C-terminal half of the enzymatic domain
One side of the hexamer is concave which is lined by hydrophobic residues, the other side has a slightly protruding, 6-stranded beta-barrel which is occluded in PDB:3CGI by side chains
The N-terminal globular head (Vh) comprises of subdomains D1-D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. In isoform 2 (metavinculin) a 68 residue insertion in the tail domain promotes actin severing instead of bundling. An intramolecular interaction between Vh and Vt masks the F-actin-binding domain located in Vt. The binding of talin and alpha-actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin-binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly
The C-terminal region negatively affects catalytic efficiency for correct nucleotide insertion, thus decreasing the fidelity of the enzyme
PH domain confers substrate specificity and recognition. Able to discriminate between RAC1, RHOA, and CDC42
DH domain alone was unable to confer substrate specificity and recognition
The PID domain, truncated by 11 amino acids, as observed in isoform 2, but not full-length, mediates the interaction with RAB6A
The basic N-terminal Arg/Pro-rich region binds heparin and heparan sulfate (By similarity). Binds collagens type I and type II through its leucine-rich repeat domain (PubMed:11847210)
Lacks C-terminal domain that mediates direct interactions with nucleoporins
Contains a novel CRM1-dependent nuclear export signal that compensates in cis for the loss of the nuclear pore targeting domain
The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation (By similarity). The zinc fingers and the N-terminus are independently important for establishing the L/R axis
PDZ 5 mediates the C-terminal binding of GRIA2 and GRIA3. PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1. PDZ 7 mediates interaction with CSPG4 (By similarity)
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that may mediate interaction with nuclear receptors
The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1 (By similarity)
Extracellular region (481-515) contains a binding side for alpha-L/beta-2 and alpha-M/beta-2 integrin
The C-terminal region is required for cogwheel and tubule formation
The amphipathic helix 1 (AH1) is required for extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex
LIM zinc-binding domains 1-4 are sufficient for the localization to dense bodies, adhesion plaques and M lines in body wall muscles
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 78-109, leaving each N-terminal inhibitory region (residues 27-56) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 27-56) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity (By similarity)
The BAH domain is required for localization to specific sites on polytene chromosomes
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol (By similarity). It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (PubMed:15718238, PubMed:16709157)
The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions (PubMed:22464331). The second domain also recognizes and binds histones that are butyrylated and crotonylated (PubMed:26365797)
The F-BAR domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod (By similarity)
Interacts with AmtB almost exclusively via a long surface loop containing Tyr-51 (T-loop), the tip of which inserts deeply into the cytoplasmic pore exit, blocking ammonia conduction (PubMed:17220269, PubMed:17190799). Uridylylation probably sterically blocks the T-loop region from interacting with AmtB (PubMed:17190799)
PDR1 contains several specific functional domains including an N-terminal DNA-binding domain (DBD) containing the Zn(2)-C6 fungal-type zinc finger; an inhibitory domain (ID) that may be involved in the negative regulation of the activity of the protein; a middle homology region (MHR) that probably assists the C6 zinc cluster in DNA target discrimination; and a C-terminal activation domain (AD) that binds to the KIX domain of GAL11A for recruitment to target promoters
The 9aaTAD motif (residues 1091 to 1099) is a transactivation domain present in a large number of yeast and animal transcription factors
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). NPS2 has the following architecture: A-T-C-T-C-T-C (PubMed:28842536)
The mature peptides (45-79 and 84-116) probably form alpha-helices which disrupt target cell membranes
The protein is composed of 20 tandem core repeats (the BuD domain) with 1 base-specifying residue (BSR, residue 13), which recognizes 1 base pair in the target DNA
The C-terminal hexapeptide motif is required for homooligomerization and for its activation
The C-terminal domain is important for localization to synapses and axons
The PH domain is required for kif1-mediated transport probably through its binding and docking onto membrane of cargo vesicles
Consists of two domains: a catalytic domain homologous to metallophosphoesterases (MPEs) and a helical insertion domain (HI domain) inserted in the middle of the catalytic domain
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains (PubMed:22733822, PubMed:22492721). The UMI motif also mediates interaction with ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs) (PubMed:22742833)
The PWWP domain probably mediates the binding to H3K36me3
The chromodomain serves to recognize and bind to H3K9me
The extracellular domain mediates homodimerization. One or more cysteines in the extracellular domain is essential for the formation of dimers probably by forming a disulfide bond
The cytoplasmic domain mediates the interaction with LCK
The central DNA-binding region is composed of 23.5 tandem core repeats with 1 base-specifying residue (BSR residue 13, also called the repeat variable diresidue, RVD, residues 12 and 13) each of which recognizes 1 base in the target DNA. The BSR is the only residue which contacts DNA in a sequence-specific manner
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-57 and Arg-60) that bind to malonylated and succinylated substrates and define the specificity
The ligand binding domain (LBD) is monomeric in solution. Ligand binding does not cause major conformational changes or alterations in the oligomeric state of the LBD
The PPxY motif 2 mediates interaction with WWOX (By similarity). Both PPxY motifs mediate interaction with NEDD4
The poly-Pro region is essential for plasma membrane localization upon stimulation
The LIM domain 3 is critical for focal adhesion targeting and the suppression of paxillin (PXN) tyrosine phosphorylation. The LIM domain 3 alone or both LIM domains 3 and 4 can mediate interaction with AR (By similarity)
The C-terminal domain could be responsible for the substrate recognition
The C-terminal domain binds DNA and the N-terminal domain is involved in dimerization. Both domains are essential for normal function
Based on a mutagenesis study of the catalytic fragment (residues 1-394), the (p)ppGpp phosphohydrolase domain seems to encompass approximately the first 203 residues, while the (p)ppGpp synthase domain seems to be found between residues 87 and 394
The RING finger domain, in addition to its role in ubiquitination, functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite nuclear localization signal (NLS) (By similarity)
The WD40 domain (386-731) is necessary and sufficient for TRIB1 binding (PubMed:27041596)
The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates the interaction with the AP-2 complex subunit apb-1
The C-terminus (aa 369-435) is required for the recovery of chemotaxis from odorant-induced adaptation but is dispensable for behavioral adaptation to chemoattractant isoamyl alcohol
The EF3-like region is necessary and sufficient for interaction with GCN20
The nuclear localization may reside in the C-terminus (between 259 and 339 AA)
The light chain (LC) has protease activity. HC has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD). The N-terminus of the TD wraps an extended belt around the perimeter of the light chain, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol. The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane
The C-terminal 18 residues mediate the interaction with the wH-like region of CdvB
Protein interactions mediated by the Arg-rich domain are not essential for viability, but do contribute to an essential U1 snRNP function
The N-terminal domain binds peptidoglycans through LysM motif. In addition, this motif is required for PilQ stability and multimerization. The cytoplasmic domain contains three discontinuous tetratricopeptide repeat (TPR) motifs involved in protein-protein interactions
Made of tandem repeats of a 38 amino acid segment
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIM8 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (Probable)
The N-terminal domain (1-440) mediates the interaction with Delta receptors
The ANK repeats are involved in Delta receptor internalization
The RING fingers mediate the E3 ligase activity. The third RING finger probably plays a central role in this process. The role of the other RING fingers remains unclear
Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands (PubMed:18832158, PubMed:18755977). The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity (PubMed:18832158, PubMed:18755977)
Contains an N-terminal aldehyde dehydrogenase (ALDH) domain and a C-terminal iron-dependent alcohol dehydrogenase (ADH) domain, interconnected by a short linker
All three domains (PPIase domain and the flanking N- and C-terminal domains) are essential for activity
The RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling
The bromodomain binds histones
The AT-hook region (1568-1919) contains at least 3 DNA-binding sites with different characteristics
Changes in the ATP-binding site of the helicase domain can affect the activity of the nuclease domain
The lid loop assumes one of 2 conformations allowing opening and closing of the active site
The C-terminus contains a key domain which is responsible for the RNA digestion activity (PubMed:28322335)
The C-terminal domain mediates copper(1+) binding and is involved in the copper(1+)-dependent-ATOX1 interaction. The C-terminal domain appears to act to limit transport through the pore by regulating the rate of exit of copper ions at the intracellular side. The N-terminal domain can collect copper(2+) from copper(2+) carriers in blood. The N-terminal domain, in the trimeric arrangement, tunes its reactivity with copper, promoting copper(2+) reduction and copper(1+) stabilization thanks to the presence of histidine (His) and methionine (Met) motifs. The bis-His motif directly coordinate to copper(2+), whereas the Mets motif is involved in copper(1+) binding. The ligand switching between the bis-His motif and the Mets motif is regulated by pH
Isoform 1 transmembrane signal-anchor domain is necessary for its own mRNA to be recruited to the endoplasmic reticulum (ER) which will undergo unconventional ERN1-dependent splicing in response to ER stress. Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively. Isoform 2 N-terminus and C-terminus regions are necessary for DNA-binding and strong transcriptional activity upon ER stress, respectively. Isoform 2 C-terminus region contains a nuclear exclusion signal (NES) at positions 182 through 204. Isoform 2 C-terminus region contains a degradation domain at positions 204 through 256 (By similarity). Isoform 1 and isoform 2 N-terminus domains are necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation (PubMed:16332684)
Contains two potential transactivation domains A and B
Maintains pseudo twofold symmetry even though it contains an uneven number of transmembrane domains
The C3H1-type zinc finger domains are necessary for ARE-binding activity (PubMed:10330172)
An elongated protein with a middle beta-sheet wrapped around a long alpha-helix. Structurally similar to tubular lipid-binding (TULIP) superfamily proteins. The N-terminal domain (residues 35-175) folds very similarly to OrfX2 (residues 6-168), another protein of the same locus (PubMed:29067689). This structure is very similar to OrfX3 in the OrfX1-OrfX3 complex from P.bifermentans (AC A0A5P3XKL3, PDB:8BGM)
The cysteine framework is XVIII (C-C-CC-CC)
Intrinsically unstructured in the absence of binding partners. Folds upon binding to DNA or RNF2
Binds and activates the Arp2/3 complex via the C-terminal domain. Interacts with actin via the WH2 domain (By similarity)
The cysteine framework is XXXII (C-CC-C-C-C)
Contains an N-terminal helix-turn-helix DNA-binding domain, connected via a linker to the central catalytic domain and the C-terminal domain, which plays roles in dimerization, catalytic function and DNA binding. The N-terminal domain is required for both ligase and repressor activities. It may orient the active site and thereby play an important role in enzymatic activity
The WD domains are required for nucleolar localization and U3 small nucleolar RNAs binding
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for l- to d- amino acid conversion) are present within the NRP synthetase. NRPS4 has the following architecture: A-T-C-A-C
The molecule is in a coiled coil structure that is formed by 4 polypeptide chains. The N-terminal and C-terminal regions exhibit a prominent seven-residues periodicity
The signal peptide, cleaved at the inner membrane, guides the polyprotein to the periplasmic space. Then, insertion of the C-terminal translocator domain (or beta-domain) in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface, with subsequent autocatalytic cleavage. Finally, the mature AIDA protein remains in contact with the cell surface via non-covalent interactions with the translocator pore
Consists of two discrete domains, an N-terminal cytochrome b domain from residues 81 to 179 and a C-terminal flavin-binding domain from residues 180 to 566. In addition there is an extended C-terminal tail (PubMed:2329585, PubMed:11914072). The cytochrome b domain is required for efficient cytochrome c reduction (PubMed:11914072)
Fragments of the mature protein (residues 61-80, 101-120 and 121-140) prevent uptake of M.tuberculosis by a human macrophage-like cell line (PubMed:25041568)
Has 5 domains; domain I (residues 1-202, also called the G domain), II (203-305, also called the beta barrel domain), III (306-386) V (387-479) and the C-terminal domain (CTD 480-607) which is BipA-specific. Domains I-V are homologous to domains in EF-G and LepA; although the domains are similar, their relative arrangement among these proteins is different. Domains I and II are not required for ribosome binding, although in their absence no 30S binding under stress is seen, whereas domains III, V and the CTD are required to bind both 70S and 30S ribosomes. The data suggests interdomain communication modulates GTPase and ribosome binding
The NRPS-like carboxylic acid reductase (CAR) has an unusual domain architecture (A-T-R), with the adenylation domain A activating and thioesterifying the carboxylic acid which is then channeled through the phosphopantetheine arm of the T domain, the thioester reductase domain R reducing the carboxylic acid to the corresponding aldehyde
Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-603 has an important role in the selective binding of succinyl-CoA over acetyl-CoA
AOL adopts the six-bladed beta-propeller fold and contains 6 binding sites per monomer, each located between two adjacent blades (PubMed:27318092, PubMed:28041800). The 6 binding sites that are non-equivalent, and owing to minor differences in amino-acid composition they exhibit a marked difference in specific ligand recognition (PubMed:27318092, PubMed:28041800)
Contains two aspartate-rich DDxxD motifs, designated as FARM (the first aspartate-rich motif) and SARM (the second aspartate-rich motif)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (318-348) inactivates kinase activity under calcium-free conditions
Contains a DsbA-like thioredoxin domain connected via a linker to a C-terminal domain reminiscent of the winged helix-turn-helix fold
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. TpzA has the following architecture: A1-T1-C1-A2-T2-C2-T3
The protein kinase domain is predicted to be catalytically inactive and seems to have very low intrinsic kinase activity. This low kinase activity can be increased by interaction with BRAF
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA) (Probable). AQFP2 has NPA/NAA motifs which is in accordance with the fungal aquaporins (NPx and NxA) (Probable)
Consists of a large A domain and a smaller P domain connected by a linker. The thermally induced motion of the flexible linker-loop region leads to the uncovering of a high-affinity substrate-binding site that is essential to capture nonnative proteins at high temperatures
The N-terminus transmembrane region forms low conductance pores (50-80 pS); larger conductance pores (260-320 pS) are formed by the whole protein. Refolding of the periplasmic domain may be required to make the large conductance pores (PubMed:10636850). The structure of the whole protein is controversial; the periplasmic domain may or may not be inserted into the cell outer membrane to form a larger pore. The protein with a narrow 8 sheet beta-barrel and a periplasmic domain may be an intermediate in formation of the larger pore (Probable). The disulfide bond is necessary for formation of the larger pore; disulfide-bonded protein inserts into the membrane without reduction (PubMed:2211627, PubMed:21069910). The isolated C-terminal periplasmic domain binds peptidoglycan (PubMed:25135663, PubMed:27866852). A region in the isolated periplasmic domain bulges from the rest of the protein (resides 302-328) and is stabilized by the disulfide bond (PubMed:25135663)
The WY domain contains 3 alpha-helices and is required for the interaction with the host MAPKKK epsilon
The ankyrin repeats are required for targeting the protein to the NV junction by interacting with NVJ1
The PH domain strongly binds to phosphoinositides and is required for targeting the protein to the late Golgi membranes
The FFAT (two phenylalanines in an acidic tract) motif is required for interaction with SCS2 and is required for targeting the protein to the ER
The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions. The FYVE domain is required for its function in regulating TLR3 signaling (PubMed:25736436)
Its C-terminal part of the heavy chain interacts with ESR1 (By similarity). The N-terminus of the heavy chain associates with the C-terminus of the light chain to form the heterodimer complex
Has bilobed structure, with the REC lobe (residues 25-591) connected to the NUC lobe (662-1300) by a discontinuous wedge domain (PubMed:28431230, PubMed:28562584). The REC lobe binds the (pre-)crRNA and the crRNA-target DNA heteroduplex (PubMed:28431230, PubMed:28562584). The heteroduplex as well as part of the DNA downstream of the heteroduplex is protected in the central cavity formed by the NUC and REC lobes, which also positions target and non-target DNA for cleavage after domain rearrangement (PubMed:28431230, PubMed:28562584). The LKL region (residues 662 to 679) inserts into target dsDNA initiating its disruption to allow crRNA hybridization, is also involved in determining the non-target strand cleavage site (PubMed:28562584). A 'septum' formed by residues 197-204 and 1061-1070 separates the 2 DNA strands, preventing their reannealing, this region also influences the non-target cleavage site (PubMed:28562584)
Amino acids 178-210 are essential for repression activity
Domain B contains 35 x 9 AA tandem repeats, and 2 x 17 AA repeats
The tify domain is required for dimerization
The jas domain (168-193) is required for interaction with COI1
Binds to MYC2 via a cryptic CMID domain (16-58) instead of the absent jas domain
Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain (Probable). The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA (Probable)
The methyl-CpG-binding domain (MBD) functions both in binding to methylated DNA and in protein interactions (By similarity). The number of MBD domains may affect binding affinity, mobility within the nucleus, and subnuclear localization (By similarity). The C-terminal domain (232-306) has a very strong chromatin binding affinity and thus is coined 'sticky-C' (StkC) (PubMed:19647732). StkC confers intranuclear immobility, but has no effect on subnuclear localization (PubMed:19647732). It is necessary for the interaction with IDM2 and IDM3, and for the anti-silencing function (PubMed:25684209)
The C2H2-type domain 1 is essential for binding to and repressing lin, while the C2H2-type domain 2 contributes to lin binding
PH domain confers substrate specificity and recognition. Able to discriminate between RAC1, RHOA, and CDC42 (By similarity)
A region including the PH domain and partially overlapping with the Rho-GAP domain mediates interaction with phosphoinositides
The homeobox contain essential residues (Ile-54, Lys-57, Ala-61) for binding to the 5'-TAATCC-3' motif of the targe gene promoters
The homeobox is incomplete and cannot bind to the 36 bp motif found in the promoters of the target genes
The 9aaTAD motif is a conserved putative nine amino acid transactivation motifs in C-terminus of the LEUTX region
The head domain possess two actin-binding sites, a classic ATP-dependent one and a secondary salt-dependent one (located inside the GPR domain)
The cyclic nucleotide binds in the C-terminal bacterial STING region (PubMed:32877915). Comparison of structures from 2 different bacteria suggests that cyclic nucleotide binding causes domain rotation, which forms a lid and seals the nucleotide-binding pocket (Probable)
In EgtU the transmembrane domain (TMD) and the solute-binding domain (SBD) are fused
The Bromo domain recognizes and binds acetylated histones. Also recognizes and binds histones that are butyrylated
The loop (82-95) connecting the two anti-parallel beta-strands (76-81 and 96-101) confers the function to the peptide
Contains a collagen like domain, which probably promotes oligomerization
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Timm8ab from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity)
The two fingers are functionally distinct and cooperate to achieve specific, stable DNA binding. The first finger is necessary only for full specificity and stability of binding, whereas the second one is required for binding
Exists in a closed inactive form by an intramolecular interaction between the N- and the C-terminal domains. The proline-rich motif is critical both for PI3K-AKT activity inhibition and MAP3K5 activation. The PH and C2 domains are necessary for the binding to phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its tumor-suppressive function. The C2 and Ras-GAP domains constitutively bind to MAP3K5 and facilitate the release of 14-3-3 proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY motif, are crucial for its cell membrane localization and neuronal migration function. The PH domain is necessary but not sufficient to activate the JNK signaling pathway through ERN1 (By similarity)
The DNA-binding domain seems to be involved in the suppression of pseudohyphae formation under nitrogen-rich conditions and in haploids. This region is also involved in the regulation of budding pattern of haploids
The NEE-box motif is required for the association to RPD3
The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase
The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase
The PPIase FKBP-type domain contributes to the chaperone activity (PubMed:15664653). Required for the inhibition of calcineurin phosphatase activity (PubMed:15850699)
The TPR repeats are important for the chaperone activity (PubMed:15664653). In another study, these repeats appear to be dispensable for chaperone activity (PubMed:15850699). Dispensable for PPIase activity (PubMed:15850699). Dispensable for the inhibition of calcineurin phosphatase activity (PubMed:15850699)
The N-terminal disordered part (1-146) binds unspecifically dsDNA and expand the binding and moving range of CGAS on dsDNA (PubMed:28214358, PubMed:28314590, PubMed:28363908). The disordered and positively charged residues enhance CGAS-DNA phase separation by increasing the valencies of DNA-binding (By similarity). The N-terminus is required to sense chromatin and its phosphorylation blocks its activation by chromatin DNA (By similarity). When the N-terminal part (1-146) is missing the protein bound to dsDNA homodimerizes (PubMed:28214358)
Rhamnose is bound near the active site, but there are also additional rhamnose-binding sites far away from the active site, which possibly function as a carbohydrate-binding region
The reticulon homology domain provides capacity to bend the membrane and promotes ER scission (PubMed:26040720). It is required for homooligomerization (By similarity). This domain does not show relevant similarities with reticulon domains, preventing any domain predictions within the protein sequence
The structure of Zmp1 is similar to anthrax lethal factor (LF) metalloprotease domain IV. The S-loop of Zmp1 undergoes large motions upon substrate binding and seems to exhibit a function analogous to that of LF domain III, thus contributing to sequence specificity and substrate binding. An aliphatic-aromatic network and the diverting loop contribute to Pro-Pro specificity
The open, reduced form of PAPS reductase is able to bind PAPS, whereas the closed oxidized form cannot. A movement between the two monomers of the dimer may allow this switch in conformation to occur
The C2 domain is essential for membrane ingression during cytokinesis, but not for recruitment to the actomyosin ring
The SH3 domain interacts with the C-terminal region of PTK2/FAK1
The C-terminal domain (1001-2236 aa) is required for mitotic DNA replication in the eye but not for DNA endoreplication in salivary glands
Binds DNA via its HMG boxes. When bound to the mitochondrial light strand promoter, bends DNA into a U-turn shape, each HMG box bending the DNA by 90 degrees
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner. AF-1 seems to provide the major transactivation function in differentiated cells
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D-amino acid conversion) are present within the NRP synthetase. ChyA has the following architecture: A-T-C-A-T-C
The last loop motif confers selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) as acyl donor
Seems to consist of two repeat of a full-length coronin
The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation
The FIDO domain mediates the phosphocholine transferase activity
The Ras-GAP domain is required for contraction of the actomyosin ring and is needed for the interaction with TEM1. It probably does not stimulate GTPase activity
May change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as ion channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity)
The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice. TOG 1-2 show strong and TOG 3-4 weak tubulin binding; TOG 1-5 are required for full ability to promote MT polymerization
The N-terminal domain is necessary and sufficient for dimer formation. The C-terminal domain is responsible for the transcription activation function
The finger loop 2 blocks access to the orthosteric site of the muscarinic acetylcholine M1 receptor. Comparison of MT7 alone and MT7 in complex with CHRM1 shows that finger loops 1 and 3 undergo large structural rearrangements upon binding to CHRM1, facilitating extensive interactions with the receptor, while finger loop 2 is mostly unchanged
Repression domain 1 (RD1) is involved in transcriptional repression. RD1 is necessary for its interaction with PML
AAA-cassette D1 is required for interaction with PEX1. ATP-binding in AAA-cassette D1 is required for attachment to PEX15. ATP-binding and hydrolysis in AAA-cassette D2 is required for release from PEX15 and proper function in PEX5 dislocation
Both zinc fingers are required for DNA binding in vitro
The periplasmic loop between the two transmembrane domains modulates channel kinetics, and in particular the length of time the channel remains in the open conformation
The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3)
The Myb-extension domain (509-540) is necessary and sufficient for telomere binding
The cytoplasmic N-terminal region is not required for endolytic transglycosylase activity under normal culture conditions
Divided into 5 Cys-rich domains by 4 spacer sequences termed B1-B4 (PubMed:23498952). Each cystein-rich domain contains the conserved copper-binding motif Cys-X-Cys-X6-Cys-X-Cys-X4-Cys-X-Cys-X2-Cys (PubMed:23498952). The copper-binding domains together are able to chelate up to 24 copper ions (PubMed:23498952)
The UBA domain is not required for correct subcellular location, gene silencing or interaction with pAbp
The RRM domain lacks RNA-binding properties and does not bind RNA in vitro. It is not required for P-body localization or for interaction with AGO1 or miRNAs but is required for silencing. May play a role in protein-protein interactions
The very flexible region (621-646) acts as a substrate channel lid, having two main open/closed conformations
The protein kinase domain is predicted to be catalytically inactive. Lacks the conserved Asp active site at position 854, which is replaced by an Asn residue
The N-terminal leucine-rich repeat (LRR) domain is necessary for localization to vimentin filaments (PubMed:26466680). The C-terminus is necessary for localization to the cell membrane (PubMed:26578515)
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. Isoform Alpha-deltaE6 lacks the hinge region that connects the modulating domain and the DNA binding domain
The C-terminal domain regulates nucleolar localization (PubMed:25825154)
Contains 7 domains: 2 C (condensation) domains, 2 A (adenylation) domains, 2 T (thiolation) domains, and one R (reduction) domain at its C-terminus. The first T domain likely acts as a lyine-specific peptidyl-carrier protein, and carries a lyine residue that is transferred to it by the first A domain. The C domain catalyzes the condensation of two isonitrile-containing moieties to both amino groups of the lysine bound to the T domain, a rare activity in nonribosomal peptide biosynthesis. Finally, the R domain catalyzes a four-electron thioester reduction, releasing the product from the NRPS and forming a terminal alcohol product
Residues 146 to 150 play a role in odorant (2-heptanone) activation
The signal peptide, cleaved at the inner membrane, guides the autotransporter protein to the periplasmic space. Then, insertion of the C-terminal translocator domain in the outer membrane forms a hydrophilic pore for the translocation of the passenger domain to the bacterial cell surface (PubMed:12813066). The crystallized section of the passenger domain is an entwined trimer, and forms a bent coiled coil 8 nm long and 2.2 nm in diameter. It includes a transition from a right-handed to left-handed coiled coil which occurs over 14 residues (PubMed:20178846)
Contains the RXG motif, which is important for substrate binding and prenyltransferase activity. The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs
Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. PTPN6 seems to bind predominantly to the first ITIM motif (By similarity)
The jas domain (139-163) is required for interaction with COI1 and Pseudomonas syringae HopZ1a
The MIF2 homology domain II targets centromeres and binds the alpha satellite DNA in vivo
The LisH domain mediates tetramerization and interaction with SNT1
EGF-like domains 2 and 5 which have an odd number of cysteines might enable the formation of intermolecular disulfide bonds
Cytoplasmic proline-rich regions could serve as docking domains for intracellular SH3-containing proteins
The positive regulatory (PR) domain is required for egl-43 protein stability but is dispensable for anchor cell (AC) invasion and preventing AC proliferation
The C2H2-type zinc-finger domains 1, 2 and 3 are dispensable for anchor cell (AC) invasion and preventing AC proliferation
The C2H2-type zinc-finger domains 4 and 5 may be required for anchor cell (AC) invasion and preventing AC proliferation
The DWD boxes are required for interaction with ddb1
The doublecortin domains are involved in the binding to microtubules
Has a modular structure: a carbohydrate-binding module (CBM) at the N-terminus, a linker rich in serines, threonines, and prolines, and a C-terminal carbohydrate esterase catalytic module. The genes for catalytic modules and CBMs seem to have evolved separately and have been linked by gene fusion
Both the N-terminus (residues 1-76) and the C-terminus (residues 90-134) have RNA chaperone activity for splicing of td, a bacteriophage T4 pre-mRNA (PubMed:17267410)
Comprised of a NH2-terminal actin-binding domain, 24 immunoglobulin-like internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. Filamin repeat 20 interacts with filamin repeat 21 masking the ligand binding site on filamin repeat 21, resulting in an autoinhibited conformation. The autoinhibition can be relieved by ligands like ITGB7 or FBLIM1. Filamin repeats 19 and 21 can simultaneously engage ligands
The transmembrane domain and residues 288-424 are essential for its interaction with DHX58/LGP2
Contains 126 imperfect repeats of a consensus octapeptide A-G-Y-G-S-T-X-T; further on a 16-residue and a regional 48-residue periodicity is superimposed
The N-terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments
The JAMM motif may mediate the protease activity
The BH3 motif is required for interaction with Bcl-2 proteins and cytotoxicity
In unstressed cells, spontaneous homotrimerization is inhibited. Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation. In heat stressed cells, HSF1 homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity. The D domain is necessary for translocation to the nucleus. 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors
The normal, monomeric form, PRPN(C), has a mainly alpha-helical structure. Misfolding of this form produces a disease-associated, protease-resistant form, PRPN (Sc), accompanied by a large increase of the beta-sheet content and formation of amyloid fibrils. These fibrils consist of a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization. In addition, the heparan-sulfate proteoglycan, GPC1, promotes the association of PRPN (C) to lipid rafts and appears to facilitate the conversion to PRPN (Sc)
Contains 3 very unusual FN3 domains in the extracellular domain. The second FN3 domain is involved in the binding to PTTH dimer
Antiviral activity requires delivery of the thyroglobulin domain to the endosomal membrane
Tudor domain specifically binds peptides with symmetrically dimethylated arginines (sDMA) and may facilitate protein-protein interactions (PubMed:32338603). The Tudor domain contains the conserved arginine and aspartic acid residues, which play a structural role, but lacks two of the four conserved aromatic residues, so it is unclear whether it is functional to recognize a methylated substrate (PubMed:32338603)
The fibronectin type-III, SPRY and coil-coil domains are necessary for C4da axon patterning
Each molecule contains 12 transmembrane helices, forming the N bundle (TM1-6) and the C bundle (TM7-12) (PubMed:25959928). These N and C bundles are connected with a linker loop between TM6 and TM7 (PubMed:25959928). The substrate-binding pocket is located at the interface between the N and C bundles (PubMed:23665960, PubMed:25959928). Substrate recognition is coupled to the transport cycle by the concomitant movement of the transmembrane helices and the key tyrosine and arginine residues in the substrate-binding site (PubMed:25959928)
PDZ 1 domain is responsible for cytoplasmic clustering of isoform 1
When compared to homologous enzymes known to reduce CoA disulfide, this enzyme shows a narrower access channel for CoA substrates, which suggests that this restriction might be responsible for the enzyme's poor activity toward the bulky CoA disulfide substrate (PubMed:23530771). The substrate channel was widened by making four mutations along the channel wall (Y65A, Y66A, P67G, and H367G), leading to a fourfold increase in kcat for the NAD(P)H-dependent reduction of CoA disulfide and enhanced activity toward the substrate at lower temperatures (PubMed:29988575). It suggests that substrate channel morphology is an important determinant of substrate specificity for this family of pyridine nucleotide disulfide oxidoreductase (PNDOR) enzymes (PubMed:29988575)
The cysteine framework is I (CC-C-C). Alpha3/6 pattern
Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer (PubMed:33106658). Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of atg9-containing vesicles, thereby enabling growth into autophagosomes (PubMed:33106658)
The BACON domain was initially thought to act as a carbohydrate-binding domain. However, it does not bind carbohydrates and may rather be required to distance the catalytic module from the cell surface and confer additional mobility to the catalytic domain for attack of the polysaccharide (PubMed:24463512)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (332-362) inactivates kinase activity under calcium-free conditions
Contiguous repeats of the 11-mer LEA motif is characteristic of group 3 LEA proteins and form an amphipathic helical structure under water-deficient conditions
Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that capture N-terminally myristoylated target peptides. Phe residues within the hydrophobic beta sandwich are required for myristate binding (PubMed:22085962)
The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating (PubMed:27325704). Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure
The intact transmembrane domain is required for Pig production, its replacement with 2 TMs from an E.coli membrane protein (MalF) does not allow Pig synthesis; although the chimeric protein is found in the membrane it does not self-associate
EAR motifs are involved in transcriptional repressor activity
The N-terminal 453 amino acids are dispensable, while the C-terminal 630 amino acids are required for function
The C-terminal domain mediates homodimerization (PubMed:16399794). By mediating SBF2/MTMR13 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 homotetramerization (PubMed:16399794)
The PH domain binds preferentially phosphatidylinositol 3,4,5-trisphosphate (PubMed:16399794). Appears to be dispensable for localization to membranes (PubMed:23297362)
The histidyl-tRNA synthetase-like region and protein kinase domains are necessary for eIF-2-alpha kinase activity and eIF-2-alpha-mediated translational control (PubMed:10655230). The histidyl-tRNA synthetase-like domain is necessary for binding to uncharged tRNAs (PubMed:16601681). Kinase domain 1 is a degenerate kinase domain (PubMed:10504407)
Atypical member of the structural maintenance of chromosomes (SMC) protein family (PubMed:26733688, PubMed:27059856). Like other members of the SMC family, has ATPase activity, which is probably necessary for its engagement with chromatin, and a SMC hinge domain (PubMed:26733688, PubMed:27059856). However, the SMC hinge domain adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. This suggests that protein may assemble as a head-to-head parallel dimer without adopting a hairpin shape at the hinge domain, unlike the dimeric arrangement conventionally found in other members of the SMC protein family (PubMed:26733688). The SMC hinge domain binds DNA and RNA (PubMed:26091879)
The C-terminal domain (831-955) is involved in cold-tolerance
The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain. The FERM domain contains the subdomains F1, F2 and F3. It is preceded by a F0 domain with a ubiquitin-like fold. The F0 domain is required for integrin activation and for localization at focal adhesions
The transmembrane segment and the membrane-proximal periplasmic region, which forms a coiled-coil structure, are required for interaction with FtsL and recruitment of downstream division proteins. The C-terminal region is required for interaction with FtsQ, but is not required for recruitment of the downstream division protein FtsI. Contains a leucine zipper-like (LZ) motif, which is required for optimal interaction with FtsL
In the homohexamer the 2 domains (called CI and CII, joined by a linker) self-associate to each form a 'donut' layer; the compactness and local conformation of the domains varies over the cell cycle and impacts function (PubMed:15304218, PubMed:15347809, PubMed:16628225, PubMed:29892030, PubMed:35427168). CII has the autokinase and autophosphatase activities, both CI and CII have (weak) ATPase activity; CI has the clock pacemaker role (PubMed:17901204, PubMed:26113637, PubMed:22304631). The CI ring undergoes structural changes driven by ATP hydrolysis that together with the KaiC phosphorylation state regulate KaiB binding (PubMed:29892030). The C-terminus of CII (residues 488-519) is disordered, extending from the top of the structure near the central pore (PubMed:15304218, PubMed:15347809, PubMed:16628225). The A-loop (residues 488-497) switches between a buried and exposed state, determining the levels of autokinase and autophosphatase activities. When the A-loop is exposed it interacts with KaiA, activating the autokinase activity (PubMed:18728181). Binding to KaiA occurs via the extreme C-terminus which assumes a coiled-coil structure upon binding (PubMed:26200123). KaiB interacts with the CI domain which has bound ADP (PubMed:28302852). Communication between CI and CII occurs via the Glu-214-Arg-217-Gln-394 triad (PubMed:35427168)
The runt domain is responsible for the DNA-binding properties of the alpha subunit and also mediates interaction with subunit beta. The transactivation domain is located downstream of the runt domain
The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated further by FLT3LG binding (By similarity)
The 3 tudor-like domains (also named Spin/Ssty repeats) specifically recognize and bind methylated histones (PubMed:23077255, PubMed:24589551). H3K4me3 and H3R8me2a are recognized by tudor-like domains 2 and 1, respectively (PubMed:24589551)
The C-terminus is important for mediating interaction with e(y)2
The ACB (acyl-CoA-binding) domain is truncated and may be non-functional
The N-terminal hydrophilic pocket is crucial for flipping activity. The central cavity of LtaA shows a unique amphiphilic architecture
The N-terminal domain mediates haploid invasive growth and yeast cell-cell adhesion
The regions containing tandem repeats are required to project the N-terminal region into the extracellular environment and to mediate adhesion to polystyrene and to host cells. In allele CaO19.8979, the N-terminal tandem repeat region is expended and contains up to 90 repeats and the C-terminal tandem repeat region has one more repeat
The cysteine framework is C-C-C-CC-C-C
This toxin is amphipathic in nature with a hydrophobic face on one side of the molecule (composed of residues 51-Phe-Met-52 and 73-His--Phe-80) and a hydrophilic (mostly cationic) face on the opposite side (composed of residues 56-Ile--Lys-61 and 64-Arg--Pro-65)
Modular protein that contains a first peptidyl carrier protein domain which bears a phosphopantetheinyl arm to attach the activated amino acid, a condensation domain, an adenylation domain which activates the alanine residue into an aminoacyl-AMP ester and a second peptidyl carrier protein domain
The protein has two highly different native conformations, an inactive open conformation that cannot bind cdc20 and that predominates in cytosolic monomers, and an active closed conformation
The structure indicates that the N-terminal domain may bind to the 23S rRNA, while the C-terminal domain may bind to the mRNA, which could then be implicated in transcriptional and translational control of the S10 operon. However, it is not known if the S10 operon is controlled in this fashion in this organism
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site (PubMed:22139424). There are however other Ca(2+) sensor regions required for activation of the channel (PubMed:22139424)
The thyroglobulin type-1 domain mediates interaction with HN
The jas domain (115-140) is required for interaction with COI1
Lacks the domain involved in allosteric regulation present in CarB CPSases
Domain B contains 32 X 9 AA tandem repeats, and 1 X 17 AA repeats
Contains three polyglutamine repeats which could correspond to the transactivation domain. The length of the repeats is polymorphic. In the arrhythmic mutant JRK, deletion of this region leads to the loss of circadian rhythmicity and altered light response
The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization
Consists of a ring of transmembrane domains, which shield a highly conserved extracellular structural funnel extending into the middle of the lipid bilayer (PubMed:30283133). The conserved catalytic His residue is located at the bottom of this funnel and is connected to the intracellular DltC through a narrow tunnel (PubMed:30283133)
Composed of a globular head region and a rod-like C-terminal coiled coil domain. The rodlike tail sequence is highly repetitive, composed of a heptapeptide repeat pattern characteristic of alpha-helical coiled coils. May form filamentous structures in the cell
The EF-hand domain 2 appears to lack a functional calcium binding site
The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels
The basic N-terminal Arg/Pro-rich region binds heparin and heparan sulfate (PubMed:11007795). Binds collagens type I and type II through its leucine-rich repeat domain (By similarity)
Has an N-terminal DNA-binding domain that inserts into the DNA major groove, a central flap domain and C-terminal hood domain. The hood domain binds the PatS6 peptide. Upon PatS6 binding the flap domain probably moves considerably
The WD40 domain (1-533) is interacting with KIN10
The P.falciparum Export Element (PEXEL) motif, also known as the vacuolar transport signal (VTS), is a pentameric sequence (RxLxE/Q/D) required for the translocation of proteins across the parasitophorous vacuole membrane (Probable). In the endoplasmic reticulum, the motif is cleaved after the leucine residue and the N-terminus is N-acetylated (PubMed:20332084)
The N-terminal sequence (1-125) is sufficient to address heterologous proteins to chloroplasts
The N-terminal acidic region is intrinsically disordered (PubMed:26725083). This region contributes to LPL binding, stabilizes LPL and protects LPL against loss of activity (PubMed:26725083, PubMed:27929370)
Truncation of either the N- or C-terminal of C-Myb leads to increased transformation and transactivation potential
The N-terminus (1-56) contributes to the transfer of UFM1 from UBA5 to UFC1
Contains 3 zinc-binding sites. Site 1 has a structural role and site 2 is the Zn(2+) sensing site. Site 3 residues do not bind metal ions with a physiologically relevant affinity, but contribute to dimer stability
The CFEM domain is involved in heme-binding and contains 8 cysteines and is found in proteins from several pathogenic fungi, including both human and plant pathogens (PubMed:27617569). The CFEM domain adopts a novel helical-basket fold that consists of six alpha-helices, and is uniquely stabilized by four disulfide bonds formed by its 8 signature cysteines (PubMed:27617569)
Consists of two pseudosymmetrical 6-helix bundles lining an internal hydrophilic cavity, which faces the cytoplasmic side of the membrane and probably contains the binding sites for both cosubstrates (PubMed:12110569, PubMed:19706416). The cytoplasmic loop connecting the membrane-spanning segments 4 and 5 is close to the sugar binding site and may participate directly in cosubstrate translocation by MelB (PubMed:12421811). The charged residue Arg-141 is probably involved in the reaction of cosubstrate translocation or substrate release in the inner compartment (PubMed:12421811)
Gln-345 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
MORN domains promote interaction with ARC6 and CDP1/PARC6 but prevent binding to FTSZ1, FTSZ2, MIND and MINE proteins
The coiled-coil motif is required for homodimerization
The PH domain mediates interactions with PSMD1 and ubiquitin. Preferential binding to the proximal subunit of K48-linked diubiquitin allows UCHL5 access to the distal subunit (By similarity)
The ball and chain domain mediates the inactivation of KCNMA1. It occludes the conduction pathway of KCNMA1 channels, and comprises the pore-blocking ball domain (residues 1-17) and the chain domain (residues 20-45) linking it to the transmembrane segment. The ball domain is made up of a flexible N-terminus anchored at a well ordered loop-helix motif. The chain domain consists of a 4-turn helix with an unfolded linker at its C-terminus
The N-terminal region is required for binding to CCL8
An autoinhibitory domain is present in the N-terminal region of the protein
Contains an N-terminal HAS-barrel domain, which mediates interaction with NurA, followed by a central RecA-like catalytic core and a C-terminal four-helix bundle
The LRRG motif is required for recruitment to phosphatidylinositols including phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)
Adopts a novel structural fold that may be an intermediate scaffold between disulfide-directed hairpin (DDH) and the inhibitor cystine knot motif (ICK)
The SUN domain is involved in the binding to MPS2 and is important for modulating chromosome motion events that act in meiotic chromosome juxtaposition and by extension, promoting proper morphogenesis of the synaptonemal complex
Contains a C-terminal HD-GYP (modified HD) domain, which is involved in degradation of cyclic di-GMP. The GYP motif is required for interaction with GGDEF domain-containing proteins
The protein kinase domain is catalytically inactive, but nevertheless important for SUB function
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (298-328) inactivates kinase activity under calcium-free conditions (By similarity)
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 84 and 106
Several domains are necessary for interacting with OS9. The region in the cytoplasmic tail that is necessary for interaction with OS9, is also required for its transport
The N-terminus (residues 1-209) has carbonic anhydrase (CA) activity (PubMed:24907906). The C-terminus has 3 repeats that are similar to the small subunit of RuBisCO (rbcS), called SSUL. The SSUL are connected by flexible linkers. The N-terminal domain probably forms a scaffold on which CcmN and maybe other carboxysomal proteins assemble, while the C-terminus binds and coalesces RuBisCO (By similarity)
The C-terminal domain mediates copper(1+) binding and is involved in the copper(1+)-dependent-ATOX1 interaction. The C-terminal domain appears to act to limit transport through the pore by regulating the rate of exit of copper ions at the intracellular side. The N-terminal domain can collect copper(2+) from copper(2+) carriers in blood. The N-terminal domain, in the trimeric arrangement, tunes its reactivity with copper, promoting copper(2+) reduction and copper(1+) stabilization. The Mets motif is involved in copper(1+) binding
Arg-360 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
The C-terminus is required for the regulation of synapse and axon development
Contains at least 2 actin-binding domains, one on each side of the LIM domain. Both domains bind actin monomers and filaments. The C-terminal domain binds filaments more efficiently than the N-terminus
Contains two DNA recognition domains, each specifying recognition of one of the two defined components of the target sequence (PubMed:3025838). The recognition domains can be exchanged between different S proteins, generating enzymes that have new sequence specificities (PubMed:2838725)
Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-709) has a proapoptotic effect
The periplasmic domain interacts with MzrA (PubMed:20889743) (Probable). The periplasmic domain assumes a PDC sensor fold (PubMed:28423182). The HAMP domain by itself is intrinsically disordered (PubMed:17635923). The cytoplasmic dimerization domain (CDD, residues 223-289) forms an osmosensitive core; increasing osmolarity stabilizes this segment, enhancing its autophosphorylation rate and consequently, downstream phosphotransfer to OmpR and signaling (PubMed:17635923, PubMed:28256224). The autophosphorylation activity of the CDD is inhibited by the angucycline antibiotic waldiomycin which probably binds to it (PubMed:27999439). The soluble EnvZ C-terminal fragment (residues 180-450) is capable of conferring osmolarity-sensitive expression of OmpC in the absence of the membrane anchor (PubMed:17635923)
The peptidase M12B domain does not require a conserved Zn-metalloprotease consensus motif to contribute to regulation of lrp-1 protein levels
Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to a putative PH domain present in its tail domain
Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-707) has a proapoptotic effect
The nucleotide-binding domain consists of a twisted six-stranded antiparallel beta-sheet flanked by two pairs of alpha-helices, forming an hydrophobic pocket that interacts with the adenine ring of ATP. The ATP binding site comprises residues located in alpha-1 and alpha-2 helices and beta-2 and beta-3 strands, which are involved in van der Waal's interactions, and Glu-1081 which forms an hydrogen bond with the adenine ring
Contains three di-leucine motifs in the C-terminus which are required for recycling from the plasma membrane to the TGN. The di-leucine 1487-Leu-Leu-1488 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1467-Leu-Leu-1468 motif is a sorting signal for retrograde trafficking to TGN via early endosomes
Consists of a large Rossmann fold domain and a small domain, which are connected by a flexible linker
The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-53 and Tyr-99/Tyr-100
The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated (PubMed:20417597). It is essential for its ability to repress the transcriptional activator activity of CLOCK-BMAL1 heterodimer (PubMed:26037310)
The INbox mediates interaction with aurkb/aurora-B
An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes (By similarity). The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface
N-terminal part (1-266) has GTPase activity. Required for proper cellular localization. Mutation of this region is a severely defective loss of function. Mutants have defective morphogenesis of neural retinal tissue, agenesis of the corpus callosum due to defectuous midline fusion of the cerebral hemispheres (PubMed:11044403). Mutants show defects in axon guidance and fasciculation (PubMed:11283609)
The extracellular domain is necessary for the uptake of dsRNA
The C-terminal extension may have a role in proper incorporation of the BChl c binding protein during chlorosome assembly
The N-terminal half could sense signals such as pH or a change in membrane potential and regulates the catalytic activity of the C-terminal half
The two conserved Cys that bind zinc constitute the zinc-hook, which separates the large intramolecular coiled coil regions. The 2 Cys residues coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another Rad50 molecule, thereby forming a V-shaped homodimer (By similarity)
The N-terminal region is required for targeting to late endosomes/lysosomes. It does not traverse the membrane but contains a membrane-embedded intramembrane domain and interacts with the lipids phosphatidic acid (PA) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PA and PI(3,5)P2 are required for the protective effect against mitochondrial stress
The FIIND (domain with function to find) region may be involved in homomerization, but not in CASP1-binding. Contrary to allele 1, allele 3 does not undergo autocatalytic cleavage in this region
Has an N-terminal GT8 domain and a C-terminal GT-D domain. The GT8 has very little glucose transferase activity in the third glycosylation step, but is able to transfer galactose from UDP-galactose to PsrP-GlcNAc-Glc-Gal or PsrP-GlcNAc-Glc-Glc in the fourth step. The C-terminal GT-D domain catalyzes transfer of galactose and glucose to the acceptor protein (PsrP-GlcNAc-Glc) in both the third and fourth glycosylation steps
The N-terminal domain (1-384) is necessary and sufficient for interaction with SAG101
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains (PubMed:19500350). The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin (PubMed:21041483). The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs) (PubMed:22742833)
The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized TWHHN (By similarity). The N-terminal palmitoylated peptide is cleaved at the Heparan sulfate-binding Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (By similarity)
The PDZ domain functions as a gatekeeper to the protease tunnel and defines resting and active conformations of the protease
The FYVE domain appears to be dispensable for membrane targeting and activity but may be important to increase avidity to membrane
The polybasic region (PBR) is responsive to the binding to phosphoinositides (PtdInsPs)
The interaction with ATN1 is mediated by the coiled coil domain
The extracellular domain is sufficent for conferring apical characteristics on the salivary gland membrane
Contains a cytoplasmic DNA-binding N-terminal domain, a transmembrane domain and a periplasmic C-terminal domain (PubMed:7830562, PubMed:24946151). A cluster of aromatic amino acids within the transmembrane domain is important for lysine-dependent regulation of CadC (PubMed:18086202). The transmembrane domain of CadC is important for the interaction with LysP, but the periplasmic domain of CadC is also important in facilitating correct positioning of the two proteins (PubMed:24056175). A cluster of negatively charged amino acids (Asp-198, Asp-200, Glu-461, Glu-468 and Asp-471) forms a negatively charged patch on the surface of the periplasmic domain and is crucial for pH detection (PubMed:21216950). Dimerization requires the periplasmic domain, but not the transmembrane domain (PubMed:24946151). Conformational changes at the dimer interface may functionally influence the transcriptional activity (PubMed:21308846)
The CCHC FOG-type zinc fingers 1, 2, 3 and 5 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is probably essential for the interaction with GATA-type zinc fingers
The presence of a 'disulfide through disulfide knottin' structurally defines this protein as a knottin
The protein contains a weakly acidic N-terminal transactivation domain (TAD) followed by a second TAD rich in proline, serine and threonine. Each of these domains may be required for transcriptional activation of a subset of target genes
The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils. Four skip residues (Skip1: Thr-1188, Skip2: Glu-1385, Skip3: Glu-1582 and Skip4: Gly-1807) introduce discontinuities in the coiled-coil heptad repeats. The first three skip residues are structurally comparable and induce a unique local relaxation of the coiled-coil superhelical pitch and the fourth skip residue lies within a highly flexible molecular hinge that is necessary for myosin incorporation in the bare zone of sarcomeres (PubMed:26150528)
The YXXXXLphi motif mediates interaction with eIF4E1 (PubMed:11389445). Compared to other members of the family this YXXXXLphi is atypical and interaction with eIF4E1 is weaker (PubMed:11389445)
MHC class I alpha-1 like and MHC class I alpha- like regions down-regulate the cell surface expression of KLRK1
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF-1
Displays a non-canonical transmembrane assembly, which is termed the NhaA fold. A unique assembly of two pairs of short helices connected by crossed, extended chains creates a balanced electrostatic environment for the binding of the substrate ions (PubMed:15988517). Is organized into two functional regions: the pH sensor region, a cluster of amino-acyl side chains involved in pH regulation, and a catalytic region containing the ion-binding site located approximately 9 Angstroms apart from the pH sensor region (PubMed:33129932)
Shows two different conformational changes in response to pH and substrate ions (PubMed:19396973, PubMed:22694117). The first change is induced by a rise in pH from 6 to 7 and marks the transition to the pH-activated state (PubMed:19396973). The second conformational change is induced by the substrate ions Na(+) and Li(+) at pH above 7 (PubMed:19396973). This movement would cause a charge imbalance at the ion-binding site that may trigger the release of the substrate ion and open a periplasmic exit channel (PubMed:19396973). The transport mechanism may involve Asp-163 switching between forming a salt bridge with Lys-300 and interacting with the proton and/or sodium ion (PubMed:25422503, PubMed:27708266, PubMed:28330875). The salt bridge may stabilize the conformation (PubMed:28330875)
Contains an N-terminal catalytic kinase domain and a C-terminal PQQ binding domain
The six transmembrane regions are tightly packed within each subunit without undergoing domain swapping (PubMed:32267231). Transmembranes TM1-TM3 are positioned on the inner circle of the channel tetramer and participate in inter-subunit interactions that are central to the assembly of the ion conduction pore (PubMed:32267231). The RxxxFSD motif within transmembrane TM1 coordinates a network of specific inter- and intra-subunit interactions with other conserved residues on TM2 and TM3 and plays a key role in the tetrameric assembly of the channel (PubMed:32267231). Transmembrane TM4-TM6 are positioned on the periphery of the channel and do not contribute to contacts with neighboring subunits (By similarity). Transmembrane TM1 forms the pore-lining inner helix at the center of the channel, creating an hourglass-shaped ion permeation pathway in the channel tetramer (By similarity). Hydrophobic residues (Leu-35, Leu-39 and Leu-42) on the C-terminal half of the TM1 helix form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel (PubMed:32267231). Thr-38 is required for potassium ion selectivity (PubMed:32267231)
The extracellular region contains three distinct subdomains: a membrane proximal alpha domain, a central beta domain and an unstructured C-terminal gamma domain. The C-terminal region of the beta domain is critical for interaction with PBP-2B. Contains multiple septal localization epitopes that are located within the transmembrane region and within the extracellular region. These epitopes may represent sites of interaction with other divisomal proteins
The CBS domains bind adenosine derivatives (AMP, ATP, NADP and SAM) (PubMed:20959390). The CBS domains can also bind calf-thymus DNA and E-boxes recognized by transcription factors (PubMed:20934423). Binding of the nucleotides induces protein conformational changes (PubMed:20934423, PubMed:20959390)
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydrogenase (DH) domain that reduces hydroxyl groups to enoyl groups, a beta-ketoreductase domain (KR) that reduces beta-ketone groups to hydroxyl groups; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm
Three calcium ions are usually bound at the interface of each cadherin domain
The cytoplasmic PPxY motifs mediate interaction with the WW domains of ITCH
The serine protease 1 and 2 domains are catalytically active, whereas the serine protease 3 domain lacks the essential Ser residue of the catalytic triad at position 1011 and is predicted to be inactive
The N-terminus is required for efficient association with MHC class I molecule and for a stable interaction between MHC I and calreticulin. Binding to TAP is mediated by the C-terminal region
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase. AsqK has the following architecture:A-T-C-A-M-T-C
Consists of three domains, an N-terminal domain, a central functional domain, and a unique C-terminal domain containing a zinc knuckle-like motif containing 4 cysteines
The LRR (leucine-rich repeat) domain is involved in autoinhibition of the enzyme activity by interacting with the catalytic domain
NapA contains a C-terminal cysteine rich domain (c-CRD), but lacks the N-terminal CRD (n-CRD) found in the yeast homolog YAP1. It probably also contains embedded in the c-CRD a nuclear export signal, with which the nuclear export protein CRM1 may interact in the absence of inter- or intramolecular disulfide bonds (or otherwise oxidized/modified cysteines) within the c-CRD
Has mobile N-loop (residues 59-96) that changes position in a redox-dependent manner being folded against the protein in the closed reduced state, protecting its [2Fe-2S] cluster, or away from the protein in the open oxidized state. The open form complexes with the MoFe and Fe subunits of nitrogenase protecting them from O(2) (PubMed:26654855)
C2 domains are necessary for calcium-dependent cell membrane association. C2 domains are necessary for neuronal progenitor cell differentiation in a calcium-independent manner (PubMed:25450385)
The protein structure shows 2 N-terminal domains, the central catalytic and C-terminal anticodon recognition domain. Comparison with the E.coli structure shows the N-terminal domains (editing region) are quite flexible with respect to the catalytic domain. The C-terminal domain recognizes the anticodon region of the tRNA while the acceptor arm is sandwiched between the N-terminal domains and the catalytic domain (PubMed:12875846)
The promoter-specific activation domain interacts with the transcriptional coactivator EP300
The highly charged acidic domain may serve a structural role to interact with lipids or proteins on the cytoplasmic surface of the Golgi apparatus
The Grh/CP2 DB domain is required for direct DNA-binding (By similarity). The Grh/CP2 DB domain is essential to maintain the undifferentiated state of embryonic stem cells (PubMed:28982712)
Keap1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins
The SH3 domain mediates binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) (By similarity). It is also required to ensure podocyte integrity while the phosphatase domain is dispensible for podocyte maintenance (PubMed:27246398, PubMed:31723089, PubMed:32390516)
The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure. The antagonist CP-376395 binds at an allosteric site, far from the presumed binding site for the physiological peptide ligand
Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions. Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) (PubMed:19794495). The bromo domains also recognize and bind a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (PubMed:27105113)
The SAM domain is required to retain SMAD8 in the endoplasmic reticulum
The C-terminal domain is essential for the homodimerization and the interaction with CBL. While the interaction with CBL is apparently mediated via the hydrophobic region of this domain, the highly charged region is apparently required for the homodimerization
Multidomain protein; including an N-terminal starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a acyl carrier protein (ACP) domain, a methyltransferase domain (CMeT) and a reductive NADPH-binding domain that is required for NADPH-dependent product release (Ref.1). The CMet adds methyl groups as check-point tags, which are recognized by KS, such that a lack of methylation causes release of immature products at the triketide stage
Adopts the canonical beta-jellyroll structure present in E.coli Lpt proteins
The N-terminal 21 amino acids are necessary and sufficient for translocation into the host cell (By similarity). The C-terminal region, composed of several highly conserved proline-rich repeats, interacts with the SH3 domain of BAIAP2 and BAIAP2L1, and the GTPase binding domain (GBD) of WASL/N-WASP and WAS/WASP. The N-terminal translocation signal and two proline-rich repeats are sufficient for triggering actin polymerization, but each additional repeat gives higher activity
The structure is characterized by a full length helix-turn-helix conformation between residues Ile-2-Leu-21, Leu-22-Leu-25 and Lys-26-Thr-30, respectively
The zinc-finger is necessary for DNA binding
The GXXXG motif may mediate oligomerization (PubMed:26322679). The C-terminus is necessary for its localization at ER-plasma membrane (ER-PM) junctions as well as for the store-dependent rearrangement of ER-PM junctions (PubMed:26644574)
The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP (By similarity). The C-terminal tail is necessary for lysosomal transport (PubMed:21896273)
The proline-knot motif (118-127) may be involved in targeting to lipid bodies
The kinase domain is required for import of dsRNA into cells
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP binding. Assembling and disassembling the active center during each catalytic cycle provides an effective means to prevent GTP hydrolysis
The F-BAR domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod
The tandem repeat region, which may form a leucine zipper structure, is essential for dimerization as well as for enzyme stability
Activation domains C-terminal of (and distinct from) the forkhead domains are necessary for transcriptional activation
Adopts a distorted helix spanning from residues Gly-7 to Pro-11 and a regular alpha-helix from Val-12 to Arg-20 in membrane mimetic environment, and a random structure in water
The N-terminus (residues 17-34) interact with ClpA and ClpX
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensors region required for activation of the channel
The WW domains mediate interaction with PPxY motif-containing proteins (PubMed:21191027). The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2 (By similarity)
Second messenger binding causes a series of shifts that enclose the cAAA molecule
PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1 and EPHB2 and with the C-terminus of PPFIA1 and PPFIA4. PDZ 4 and PDZ 5 mediate interaction with the C-terminus of GRIA2 and GRIA3. PDZ 4, PDZ 5 and PDZ 6 mediate homomultimers. PDZ 7 mediates interaction with PDZ domain of GRASP1. PDZ 6 mediates interaction with the C-terminal of liprins-alpha. PDZ 1, PDZ 2 and PDZ 3 mediate interaction with the PDZ-binding motif of FRAS1. PDZ 4 and PDZ 5 mediate interaction with PRLHR (By similarity). PDZ 7 domain binds CSPG4
There is a putative zinc finger domain which may bind to iron
The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival
EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium-binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity (PubMed:11525164). A one-residue insertion in the EF5-binding loop prevents the glutamyl residue at the C-terminal end of the loop from serving as the canonical bidentate calcium ligand (PubMed:11525164). EF5 acts as a high-affinity magnesium-binding domain instead (PubMed:27541325). Magnesium, may affect dimerization (PubMed:27541325). EF5 may bind either calcium or magnesium depending on the context
The C2 domain 1 is not necessary for calcium-mediated translocation and association to the plasma membrane. The C2 domain 2 is necessary for calcium-mediated translocation and association to the plasma membrane
The C-terminus (pos. 119-205) exhibits guanine nucleotide exchange activity
The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions (PubMed:22464331). Also recognizes and binds histones that are butyrylated (PubMed:26365797)
The PEST region is essential for the interaction with ITPR1, and, when phosphorylated, is also the RRM1-binding region. The PDZ-binding region is required for maximal interaction with ITPR1 and is also responsible for the IP3-insensitive interaction with ITPR1
The PIP-box K+4 motif mediates both the interaction with pcna and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with pcna, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination (PubMed:19595719)
The conserved PP2C phosphatase domain (240-639) is interrupted by an insertion of approximately 100 amino acids
The cytosolic domain interacts with sigma factor SigD
Binding of tRNA to MiaE induces a protein conformational change that influences the electronic structure of the diiron site
The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation
The length of the coiled coil are required to adjust the space between outer plaque and the central plaque
Both the spacer region (also known as the recognition (R) domain) and C-terminal domain are required for stable binding to the DNA repair bubble (PubMed:16246722). However, both domains are dispensable for incision of DNA bubble structures (PubMed:16246722, PubMed:32821917, PubMed:32522879)
The FCP1 homology domain does not contain the canonical D-x-D-x-[TV] active site, suggesting that it probably does not display phosphatase activity in vivo
The N-terminal domain (62-541)and the C-terminal domain (583-705) are both required for functional gamete fusion. A positive charge, and not a conserved primary amino acid sequence, is required for a functional C-terminal domain. The N-terminal domain may be involved in interactions with another membrane-bound protein on female gametes, while positively charged C-terminus may function through electrostatic interactions with the sperm plasma membrane
NFRKB seems to be mostly disordered. The wing-helix like domain doesn't bind DNA (By similarity)
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains responsible for L- to D-amino acid conversion are present within the NRP synthetase. IvoA has the following mono-modular architecture: A-T-E-C
The repetitive domain of pro-SPAI serves as a substrate for transglutaminase
The serine protease 1 and 2 domains are catalytically active, whereas the serine protease 3 domain lacks the essential Ser residue of the catalytic triad at position 1009 and is predicted to be inactive
The thiamine monophosphate phosphatase activity resides in the HAD domain (297-571), while the TenA domain (85-292) has thiamine salvage hydrolase activity (PubMed:27677881)
A 7-bladed beta-propeller torus, about 54 by 46 Angstroms, with a depth of about 25 Angstroms and a central pore
Contains imperfect repeats of a consensus octapeptide A-G-Y-G-S-T-X-T; further on a 16-residue and a regional 48-residue periodicity is superimposed
Contains a methionine-rich region, which includes a helix that covers the entrance to the type 1 (T1) copper site and blocks access to the T1 site in the absence of excess copper (PubMed:11867755, PubMed:21903583). This methionine-rich insert is involved in the binding and oxidation of Cu(+) (PubMed:21903583). It also binds additional copper ions, which are important for the copper-associated regulation of activity (PubMed:11867755, PubMed:12794077, PubMed:21903583). The methionine-rich region provides at least three additional Cu(+) binding sites: Cu5 (sCu), Cu6 and Cu7, which play related but distinct roles in CueO oxidase activities (PubMed:25679350). The internal Cu5 site functions as an electron-transfer mediator connecting surface-exposed sites Cu6 and Cu7 to site T1. Both Cu6 and Cu7 are probable substrate oxidation sites on the protein surface (PubMed:25679350)
XynA is a modular enzyme. The number of CBM6 (carbohydrate binding type-6) domains varies between strains. The polymeric substrate can interact with several of these CBM6 domains (By similarity)
Binds three molecules of c-di-AMP, each in a pocket located between two subunits. c-di-AMP binding is accompanied by conformational changes of both the fold and the position of the B-loop
The Asp-Asp-Xaa-Xaa-Asp/Glu(DDXXD/E) motifs is important for the catalytic activity, presumably through binding to Mg(2+)
The EIIB domain is phosphorylated by phospho-EIIA on a cysteinyl or histidyl residue, depending on the transported sugar. Then, it transfers the phosphoryl group to the sugar substrate concomitantly with the sugar uptake processed by the EIIC domain. The EIIB domain is also able to transfer its phosphoryl group to a specific histidine residue in ManR, which leads to its inactivation
The N-terminal region contains the catalytic domain and the C-terminal region contains regulatory elements
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (By similarity). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane
The coiled-coil and the proline-rich region are responsible to the binding to talA
The conserved Arg-467 in the Arf-GAP domain probably becomes part of the active site of bound small GTPases and is necessary for GTP hydrolysis
The WW domain binds to the phosphorylated tandem 7 residues repeats of RPB1
The cytoplasmic domain is involved in the binding of DAB1 and in the recruitment of JNK-interacting proteins. Isoforms, which lack part of the cytoplasmic domain, are unable to recruit members of the family of JNK interacting proteins (JIP) to the cytoplasmic tail (By similarity)
The N-terminal input region plays an essential role in DSF perception. DSF binds with high affinity to a 22-amino acid sensor region at the N-terminus (PubMed:28369120). The response regulatory domain, but not the HPt domain, is required for repression of DSF biosynthesis (PubMed:16940295)
The N-terminus is the reverse transcriptase, the C-terminus (downstream of residue 430) is also required for msDNA synthesis (PubMed:2466332). The C-terminus was originally suggested to have RNase H activity, but may have another nuclease activity instead (Probable)
The lumenal magnetite interacting component (MIC, residues 37-57) probably binds magnetite
The PH domain mediates binding to membranes. It is required for efficient GEF activity
The coiled coil domain is required for the interaction with CDC3 and BEM4, but not for interaction with CDC12 or with itself
The basic motif is essential for the association with PI(4)P and PI(5)P
The cytosolic nudix box binds ADP-ribose and is required for channel activation by ADP-ribose (PubMed:15561722, PubMed:16601673, PubMed:30467180)
Contains two well-defined domains connected by a flexible linker. The C-terminal domain may serve as an important protein-binding surface for interaction with other Bam components or substrates. In addition, contains a long unstructured N-terminal region, which is required to stabilize the BamCD complex. Only the N-terminus of this protein is observed in the Bam complex in X-ray or EM structures, most of the protein must be highly mobile (PubMed:26900875, PubMed:26901871, PubMed:27686148, PubMed:26744406)
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme (By similarity). The transmembrane domain is essential for translocation to the mitochondria upon induction of apoptosis
The ANK repeat domain consists of a convex stem structure followed by a crescent-shaped structure that surrounds the protein core
The 9aaTAD motif (residues 75 to 83) is a transactivation domain present in a large number of yeast and animal transcription factors
Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with NHERF1 and for targeting NHERF1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation (By similarity). The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes
Extreme C-terminal region (AA 487-492) is required for its proper localization into a spherical shell around the developing forespore. N-terminus (AA 1-64) is functionally important although largely dispensable for proper localization
The cyclic nucleotide binds in the C-terminal bacterial STING region
The C-terminal part appears to promote nuclear export
Contains a large N-terminal domain that would serve as the catalytic core subunit, and a smaller C-terminal domain that would act to modulate this enzymatic activity
The helical domain (492-627) is required for self-activation
The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3). The tudor-like regions simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first tudor-like subdomain and unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains (PubMed:21489993). The linker region plays a role in the formation of a histone H3-binding hole between the reader modules formed by the tudor-like regions and the PHD-type zinc finger by making extended contacts with the tandem tudor-like regions
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA) (PubMed:17994007). The YDG domain contains a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. 2 specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other 3 bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand (PubMed:18772888). The YDG domain also recognizes and binds 5-hydroxymethylcytosine (5hmC)
Contains 8 types of repeats which are distributed in 3 regions
Seems to have at least five separate non-overlapping active inhibitory domains; two for trypsin, two for chymotrypsin and one for elastase. They can be bound to the domains simultaneously
The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding
Crystal structures of Rv1692 reveal a unique architecture, a fusion of a predicted haloacid dehalogenase fold with a previously unidentified GCN5-related N-acetyltransferase (GNAT) region. Although not directly involved in acetyl transfer, or regulation of enzymatic activity in vitro, the GNAT region is critical for the solubility of the phosphatase
Regulated by intramolecular binding to a C-terminal auto-inhibitory domain. Effector binding abolishes this interaction and activates the protein (By similarity)
Contains two constriction sites and may exist in a closed pore state
The tyrosine-protein phosphatase 2 domain (D2) mediates dimerization. The extreme N- and C- termini of the D2 domain act to inhibit dimerization and removal of these sequences increases dimerization and inhibits enzyme activity (By similarity)
The CARD domain mediates interaction with CASP1 and NLRC4 (PubMed:14634131, PubMed:11967258)
The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3). The tudor-like regions simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first tudor-like subdomain and unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains (PubMed:21489993, PubMed:21777816, PubMed:22100450). The linker region plays a role in the formation of a histone H3-binding hole between the reader modules formed by the tudor-like regions and the PHD-type zinc finger by making extended contacts with the tandem tudor-like regions (PubMed:22837395)
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA) (PubMed:17673620). It contains a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. 2 specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other 3 bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand (PubMed:18772889). The YDG domain also recognizes and binds 5-hydroxymethylcytosine (5hmC) (PubMed:21731699)
There are 3 contiguous domains conserved in the CDPK subfamily: a kinase domain, an autoinhibitory (junction) domain and a calmodulin-like domain. The autoinhibitory domain (330-360) inactivates kinase activity under calcium-free conditions (By similarity)
The CUE domains specifically bind RPS7/eS7 polyubiquitinated by MOT2/NOT4 and HEL2
Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to a putative PH domain present in its tail domain (By similarity)
The SAP domain is required for nuclear targeting
The SP-RING-type zinc finger mediates interaction with UBC9 and CDC3 and is required for E3 activity
The cysteine framework is C-CC-C-C-C-C-C-C-C
The holoenzyme may undergo conformational shifts upon DNA binding: the nuclease domain of RecB may swing away from the DNA exit tunnel in RecC. When Chi DNA binds to the RecC tunnel, the nuclease domain may then swing back to its original position (that seen in crystal structures), allowing it to nick the DNA 3' of the Chi site and then rotate to load RecA. At high Mg(2+) the nuclease domain may swing back more frequently, explaining differences seen in assays performed at high Mg(2+) (PubMed:25073102). As ssDNA is unwound and fed to the RecD subunit the latter transmits conformational changes through each subunit to activate the RecB nuclease (PubMed:27644322)
The C-terminal part contains a large repetitive region which contains an unusually high percentage of glutamine, glycine and above all glutamic acid residues
The YDG domain recognizes and binds 5-hydroxymethylcytosine (5hmC)
Displays a compact beta-sandwich fold with interdependent beta-sheets. Possesses a large patch of basic residues that could play a role in membrane recognition
Sushi 1-3 domain represents the minimal unit capable of cofactor activity (PubMed:18252712). The property to discriminate self surfaces from non-self surfaces depends on the C-terminal region made of Sushis 19-20 (PubMed:21285368)
The PHD-type zinc finger is not required for 3'-end snRNA processing
The last two LRR (561-597) are necessary for elf18 binding and functionality
The cysteine framework is XXI (CC-C-C-C-CC-C-C-C)
The crystal structure reveals a seahorse-shaped subunit consisting of four domains: head, neck, body, and tail. The head domain contains the nucleotidyltransferase activity. The neck domain provides a specific template for the incoming ATP or CTP, whereas the body and tail domains may be involved in tRNA binding
A conserved histidine residue in the third TMD (His-107) may play an essential role in the pH sensitivity of SLCO1A2/OATP1A2-mediated substrate transport
The RRM domain mediates RNA binding; the RNA must have four nucleotides for efficient binding (PubMed:25852104). Mediates the interaction of NEXT complex with promoter upstream transcripts (PROMPTs) and potentially aberrant forms of other non coding RNAs, such as snRNAs (PubMed:25852104). The RRM domain exhibits specificity for polyuridine sequences (PubMed:25852104)
Each of the subunit of the dimer contains a smaller N-domain that associates tightly with a larger catalytic C-domain
Has an N-terminal beta-trefoil domain and a C-terminal pore-forming domain. The trefoil domain has barrel and cap subdomains; the cap has 3 possible carbohydrate-binding modules while the barrel is involved in host cell receptor binding
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residue at position 82
NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module (By similarity). Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product (By similarity). Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme (By similarity). Occasionally, methyltransferase domains (responsible for amino acid methylation) are present within the NRP synthetase (By similarity). NPS1 has the following architecture: A-T-C-T-C
Atypical member of the structural maintenance of chromosomes (SMC) protein family. Like other members of the SMC family, has ATPase activity, which is probably necessary for its engagement with chromatin, and a SMC hinge domain. However, the SMC hinge domain adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. This suggests that protein may assemble as a head-to-head parallel dimer without adopting a hairpin shape at the hinge domain, unlike the dimeric arrangement conventionally found in other members of the SMC protein family. The SMC hinge domain binds DNA and RNA
The N-terminal region mediates dimerization and homooligomerization (PubMed:28228481). Both the helicase ATP-binding domain and the helicase C-terminal domain form intramolecular interactions with the HRDC domain in a ATP-dependent manner (By similarity). The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding (By similarity)
The WXXF motif mediates binding with the GAE domain of proteins
The jas domains (101-120) and (197-222) are required for interaction with COI1
This protein contains a central IF rod domain characteristic of IF proteins but displays divergent head and tail domains
The cysteine framework is C-C-C-C-C
Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure
The internal domain (235-279) containing two internal membrane helices and the intervening residues that include the basic cluster VRS is sufficient for targeting recombinant proteins to endoplasmic reticulum and then to peroxisomes
The highly variable C-terminus domain and is involved in the specificity for the recognition by RPP13-Nd. 'Thr-152' and 'Arg-181' are critical for recognition by A.thaliana RPP13-Nd
The B chain is composed of two domains with each domain consisting of 3 homologous subdomains (alpha, beta, gamma)
The C-terminal region of the protein is not crucial for activity
The Thr/Pro-rich region (also termed 'hinge') may be a potential site for proteolysis
Contains an N-terminal winged-helix-turn-helix (wHTH) DNA-binding domain and a C-terminal alpha helix, which is mainly involved in dimerization (PubMed:30266832). Binding of cadmium causes subtle conformational changes in all key metal-binding residues and conserved DNA-binding residues (PubMed:30266832)
The N-terminal half may have an activating activity
The PDZ domain 6 mediates interaction with the C-terminus of TJP3 and is crucial for localization to the tight junctions (PubMed:12021270). The PDZ domain 8 interacts with CLDN1 but is not required for proper localization (PubMed:12021270)
The KH domain consists of approximately 70 amino acids and includes a conserved hydrophobic core, an invariant Gly-X-X-Gly motif, and an additional variable segment (PubMed:10811881). The third KH domain (KH3) binds a hairpin RNA loop containing the 5'-UCAY-3' motif on targeted molecules (PubMed:10811881). RNA binding by KH3 requires residues C-terminal to the KH domain (PubMed:10811881)
Contains an additional unique helical region at the C-terminus. This C-terminal region blocks a putative substrate-binding cleft, suggesting that a conformational change involving repositioning of this region is necessary to allow binding of the pyrrolyl-S-PltL substrate for its dichlorination by PltA
Contains a central ion-conduction pore surrounded by four voltage sensors which form the voltage-sensor paddles that move in response to membrane voltage changes through the fluid membrane interior, each voltage-sensor carrying their four positive charges across the membrane. It is thought that the S4 arginine residues move through the membrane's electric field to open the pore
Dimerizes via its N-terminal region
Binding to MYC is dependent on a Myc domain essential for oncogenic activity
The C-terminal coiled-coil domain is involved in oligomerization and the interaction with PKD1. The isolated coiled-coil domain forms a homotrimer in vitro; the homotrimer interacts with a single PKD1 chain. The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro)
The PDZ-binding motif is required for cell surface expression, neurite outgrowth promotion and interaction with DLG4
Contains a eukaryotic-like ubiquitin-associated (UBA) domain that mediates interaction with host ubiquitin
The N-terminal domain is essential for export and the C-terminal domain possess the FliA binding site
The N-terminal part (1-216), which is not required for deneddylating activity and CSN complex formation, is nevertheless essential for other aspects of CSN complex function, such as repression of c-fos/FOS expression
Appears to contain two domains of approximately equal size which are separated by a loop-like sequence
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute to transcript binding. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (By similarity). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for translocation to the cell membrane in response to increased cytosolic calcium levels (PubMed:24183667, PubMed:23791178)
The SMP-LTD domain is a barrel-like domain that can bind various types of glycerophospholipids in its interior (By similarity)
The PWWP domain specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and adopts a five-bladed beta-barrel fold with an extended C-terminal alpha-helix, with a conserved H3.3K36me3-binding aromatic cage formed by Phe-291 and Trp-294 of the beta1-beta2 loop and Phe-310 of the beta3-beta4 loop. Specific recognition of H3.3 histone is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains (PubMed:24590075)
The domain architecture includes a starter unit:ACP transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a malonyl-CoA:ACP transacylase (MAT) domain, a product template (PT) domain, 2 acyl-carrier (ACP) domains, and a thioesterase/Claisen cyclase (TE/CLC) domain (By similarity). The SAT domain receives a C6-fatty acid starter unit and transfers it onto the ACP for chain elongation. The KS accepts the hexanoyl-ACP unit and subsequent malonate extender units are loaded onto the ACP from the MAT domain for chain extension to generate the linear poly-beta-keto ACP-bound intermediate. The linear intermediate is then cyclized and aromatized in the PT domain. The resulting bicyclic intermediate is ultimately transferred from the ACP to the TE/CLC domain and undergoes Claisen-type C-C bond cyclization to release the product norsolorinic acid anthrone (noranthrone), which spontaneously oxidizes in vitro to norsolorinic acid (By similarity)
The Lys-Ser-Asn motif at positions 272 to 274 is important for the cofactor specificity for NADPH over NADH
The signal sequence and the kringle domain are highly similar to the apolipoprotein(a) precursor protein. This protein is however much shorter and does not contain any peptidase region
The PID domain binds to predominantly non-phosphorylated NPXY internalization motifs present in members of the LDLR and APP family; it also mediates simultaneous binding to phosphatidylinositol 4,5-bisphosphate (PubMed:11247302, PubMed:12234931)
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 37 and 61
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (PubMed:16030012). It can refold after extension suggesting an in vivo force-dependent function (By similarity). An anti-parallel coiled coil is located C-terminal to the SAH domain and mediates dimerization (By similarity)
The protein is evolutionarily related to retrotransposon Gag proteins (PubMed:29328915, PubMed:29328916). It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells (PubMed:29328915, PubMed:29328916). Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons (PubMed:29328916)
The PB1 domain mediates the association with NCF2/p67-PHOX
The PX domain mediates interaction with membranes enriched in phosphatidylnositol 3-phosphate
Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12
Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs 1 and 2 are essential for the association with nuclear receptors, and constitute the RID domain (Receptor-interacting domain) (By similarity)
The CRAL-TRIO domain is involved in interaction with inositol phospholipids
The DH domain is essential for transforming activity and directly catalyzes GDP-GTP exchange activity. It may interact with CCPG1
Cholesterol bound to SSD domain of SCAP or oxysterol bound to INSIG (insig1 or insig2) leads to masking of an ER export signal (also named MELADL motif) on scap possibly by moving the signal further away from the ER membrane
Members of the RBR family are atypical E3 ligases (By similarity). They interact with E2 conjugating enzymes and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain (By similarity)
The N-terminal domain (1-65) of the cytoplasmic isoform is a functional tRNA-binding domain, is required for nuclear localization, is involved in the interaction with DARS, but has a repulsive role in the binding to EEF1A1. A central domain (208-259) is involved in homodimerization and is required for interaction with HIV-1 GAG and incorporation into virions. The C-terminal domain (452-597) is not required for interaction with AIMP2
The mature polypeptide has three domains: The catalytic domain, an interposed protease-associated (PA) domain required for homodimerization and a C-terminal seven-stranded jelly-roll fibronectin (Fn) III-like domain
The propeptide is required as an intramolecular chaperone for zymogen maturation and secretion
The C2H2-type zinc finger 10 mediates interaction with EHMT1 and EHMT2
The SAT domain at the N-terminus facilitates crosstalk between the two PKSs hmp3 and hmp8 encoded by the cluster (PubMed:20222707)
The SMAD binding domain (SBD) interacts with the MH2 domains of SMAD2 or SMAD3
The N-terminal domain is required for efficient Ca(2+) uptake and for interaction with MCUR1. It is not required for targeting to the mitochondria, oligomerization, interaction with MICU1 and MICU2, or assembly of the uniplex complex
The cysteine-rich C-terminus is involved in its granular distribution in the cytoplasm (By similarity). The cysteine-rich C-terminus mediates protein-protein interactions, including interaction with HIV-1 Tat, transcription factors, AXIN1, CCNT1 (By similarity)
The N0, N1, N2 and N3 domains are periplasmic, while the secretin and S domains form a channel that is partially inserted in the outer membrane. The N1, N2 and N3 domains each form a periplasmic ring; the N0 domain was present but not resolved by electron microscopy. The secretin domain forms a double beta-barrel structure; the outer barrel has a diameter of about 110 Angstroms while the inner barrel forms the central gate with a small pore in the closed state
The N-terminus interacts with CcmM, while the 18 C-terminal residues (encapsulation peptide) are required for interaction with the hexameric shell proteins (CcmK2) and are predicted to form a helix. The 2 regions are separated by a linker
The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (PubMed:24687852). It also mediates homodimerization and regulates kinase activity (PubMed:30635421)
The coiled coil domains differentially mediate trimerization required for binding to nesprins and are proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation. The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton
Contains an N-terminal proline-rich region (PRR), which probably plays an important role in the regulation of function of RcsF and activation of the Rcs signaling system
The C-terminal loop (258-324) is required for ferredoxin binding
The Asn-rich domain is dispensable for deubiquitinating and deneddylating activities
The N-terminal domain (NTD) (63-170) has an intrinsic Mg(2+)-dependent endonuclease activity in vitro (PubMed:23690600). The glutaredoxin (GRX) domain (194-293) alone is able to complement yeast grx5 cells in vitro, but not the full-length GRXS16 protein
RRM4, together with the C- and N-terminal regions, is sufficient for RNA-binding. RRM 1 has no RNA-binding activity itself, but improves discrimination between poly(A) and poly(U) in combination with the other repeats (By similarity)
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site and may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol. The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane
The beta-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the alpha-1 domain of HLA-DRA. Forms hydrogen bonds with the peptide main chain via conserved amino acid in most HLA-DRB molecules. The polymorphic residues accomodate the side chains of the peptide conferring peptide specificity to distinct HLA-DRB1 alleles (PubMed:8145819, PubMed:28467828, PubMed:9782128, PubMed:9354468). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of TCR (PubMed:19303388)
Consists of two domains: a nucleotide-binding N-terminus that hydrolyzes GTP and a C-terminus domain necessary for polymerization. The domains are bridged by a long, central helix. The C-terminus is required for GTP hydrolysis in solution but not in crystals; it plays a role in filament assembly and in binding to TubR (PubMed:22847006). Interactions between the C-terminus and the following monomer drive polymerization (By similarity)
The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (By similarity)
Consist of two tandemly linked globin-like sequences which probably each bind a heme group and a C-terminal extension which may act as a cement between the eight subunits
The Val/Gly/Ala/Pro stretch may have a functional role in the conductance or permeation properties
Contains two distinct structural domains: an almost globular alpha/beta fold domain and an inserted cap domain which interacts with the alpha/beta fold domain
(Microbial infection) The WW domains mediate binding with matrix protein VP40
Each monomer is divided into three domains, each of which contains a six-stranded parallel beta sheet surrounded by alpha helices
Contains 1 EAR motif required for the interaction with TPL and TPRs (PubMed:25378179)
Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity (By similarity)
The C-terminal domain (75-142) is essential for nucleolar localization
The N-terminus (65-92) is required for heme inhibition, but not for activity
The N-terminal domain is important for secretion and protein stability
The LRR domain (34-508) binds more efficiently in vitro to human intestinal mucin-2 (MUC2) than does a nearly whole protein (26-792) suggesting the MucBP domains do not function in mucin-binding in Listeria
The N-terminal region (1-400) has DNA-dependent ATPase activity but no helicase activity
Consists of distinct N- and C-terminal domains (NPfA and CPfA, respectively), connected by a linker. NPfA acts as specific internal chaperone by mediating folding of its own C-domain (CPfA), but also functions as a non-specific molecular chaperone by preventing aggregation of unrelated proteins (PubMed:23551356, PubMed:25862541). The linker is dispensable since domains of this enzyme can assemble without the linker into a conjoined tetrameric form that exhibits higher activity than the parent enzyme, while each domain is inactive independently. The structural integrity of the conjoined enzyme is maintained through domain-domain interactions rather than the covalent linker (PubMed:25478837)
The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand
The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-terminal WH2 domain in the autoinhibited state of the protein. Binding of Rho-type GTPases to the CRIB induces a conformation change and leads to activation
The NTF2 domain heterodimerizes with NXT1 and NXT2. The formation of NXF1/NXT1 heterodimers is required for NXF2-mediated nuclear mRNA export
The C-terminal fragment, containing the TAP domain (also called UBA-like domain) and part of the NTF2-like domain, named the NPC-binding domain, mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF2 to the nuclear rim
Composed of a rhodanese domain and a P-loop domain, which probably binds geranyl diphosphate. The two activities are mechanistically different, but the rhodanese domain is important for both
The activation loop within the kinase domain is the target of phosphorylation/activation by upstream protein kinases (By similarity). The N-terminal region containing the kinase domain is responsible for the autophosphorylation
The histidine box domains may contain the active site and/or be involved in metal ion binding (Probable). The C-terminal sequence (-YNNKL) is necessary and sufficient for maintaining localization in the endoplasmic reticulum (PubMed:14690501)
Consists of two domains, an FAD-binding domain and a substrate-binding domain (PubMed:20006620). The inactive D-stereoisomer binds in mirror symmetry with respect to the catalytic axis, revealing absolute stereospecificity of hydrogen transfer to the flavin (PubMed:21383134)
Conserved residues in regions X1 (position 26), X2 (positions 39 to 44), X3 (positions 77 and 78), and X5 (positions 146 to 150) are all required for full binding activity of XLP1 to host soybean GIP1
Contrary to predictions, contains nine transmembrane helices, with an extracellular N-terminus and a cytoplasmic C-terminus. Besides, contains one long helix that dips into the membrane and then runs more or less parallel to the membrane surface
The C-terminal residues 650 to 689 are required for homodimerization, as well as the interactions with ATG3, ATG8 and ATG12; and the C-terminal 17 residues are required for the ATG8 lipidation (By similarity)
The UBAX-like region mediates the interaction with VCP. According to PubMed:19818707, it corresponds to a UBX domain, which is a hallmark for VCP-associated proteins. However, no canonical UBX is detected by prediction tools such as Pfam or PROSITE
The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys-11'-linked ubiquitin chains (PubMed:23827681)
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (PubMed:26656854). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer (By similarity)
Consists of a single catalytic domain, but remoldels its active-site architecture via a large structural change to exhibit dual activities
The first 19 residues target foreign proteins (tested with eGFP, mCherry and lacZ) to the BMC both in situ and in E.coli. The cargo is only detected by Western blot in broken shells, strongly suggesting this protein is normally found inside the BMC and not on its exterior
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation (By similarity). Autoinhibition of these functions is mediated by an interaction between the SH3 and F-BAR domains (By similarity). The F-Bar domain also mediates the binding to the cell actin cytoskeleton through the interaction with CAV-1 (By similarity)
Although it shares weak sequence similarity with SUA7/TFIIB, displays a similar subdomain organization as SUA7/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds
There are two distinct domains in this protein; the catalytic N-terminal, and the C-terminal which is involved in substrate specificity and in binding TIMP (tissue inhibitor of metalloproteinases)
Is composed of two domains, the N-terminal domain displays RNase activity and the C-terminal domain has both acid phosphatase and CobC activity, together with a role in enhancing the RNase H and dsRNase activities of the N-terminal domain
The Hydrophobic-Tyrosine-X (HbYX) motif is involved in proteasome activation
The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells
The N-terminal part (1-293) is a carbohydrate recognition domain (CRD) having three ricin B-type lectin domains with two carbohydrate-binding domains (PubMed:14561725). The CRD domain comprises of residues 11-159 and 160-293 and each of them has a beta-trefoil fold (PubMed:15194688, PubMed:17977832). Total of five carbohydrate molecules are bound by the CRD domain (PubMed:17977832). The CRD domain is sufficient for N-acetylgalactosamine (GalNAc)-binding (PubMed:14561725, PubMed:17977832). The CRD domain has weak hemagglutinating activity towards rabbit erythrocytes in the presence or absence of Ca(2+), but it is abolished in the presence of 10 mM EDTA or by lactose (PubMed:14561725)
The C-terminal part (291-442) is essential for oligomerization (PubMed:11471734, PubMed:14561725, PubMed:17965430). Oligomerization of the C-terminal part is induced upon binding of lactose. This C-terminal part is able to cause hemagglutination of rabbit erythrocytes probably due to hydrophobic interaction of the oligomer with the membrane leading to formation of ion-permeable pores in the membrane. Hemagglutinating activity of it is not inhibited by lactose, it is enhanced by Ca(2+) and completetely abolished in the presence of 10 mM EDTA (PubMed:14561725)
C-terminal part (342-361) has antibacterial activity especially toward Gram-positive bacteria S.aureus IFO 12732, and to a lesser extent toward Gram-positive bacteria B.subtilis IFO 3134 (PubMed:14999010, PubMed:17965430). Weak antibacterial activity toward Gram-negative bacteria P.aeruginosa ATCC 27853, and even weaker toward Gram-negative bacteria E.coli ATCC 43827. This C-terminal part disrupts the bacterial membrane leading to enhanced permeabilization of the bacterial membrane. It has membrane-permeabilizing activity also in artificial lipid vesicles (PubMed:14999010)
A tripeptide motif (QDE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding
The conserved lumenal (CL) domain (83-161) is present only in some FtsH homologs from organisms performing oxygenic photosynthesis
Residues 212-224 are capable of binding the PID domain of num-1 isoform a and isoform c
The C-terminal domain (308-483) is involved in UDP-Gal binding while the N-terminal domains (131-307) is involved in dyacylglycerol binding
The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:28649982, PubMed:10850706, PubMed:24990997). Mediates the interaction with TAP1-TAP2 complex
Contains the RXG motif, which is important for substrate binding and prenyltransferase activity. The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs
The N-terminal 41 amino acids are required for activity
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins (PubMed:28287329). Required for proteolytic activation and delipidation of ATG8 proteins (PubMed:32732290)
Removal of the N-terminus decreases solubility and/or structural integrity of the protein
Contains two domains separated by the central HhH motif. The C-terminal domain undergoes a conformational change upon DNA binding
Binds phosphatidylinositol 4,5-bisphosphate (PIP2) via its two PDZ domains. These domains target SDCBP2 to the plasma membranes and nucleoli, two PIP2-rich regions
The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes. Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions
The extracellular loop between the two transmembrane domains modulates channel kinetics, and in particular the length of time the channel remains in the open conformation
The cysteine framework is C-CC-CC-C-C-C-C-C-C-C
The TPR repeats mediate protein-protein interactions with substrate proteins, but also autoinhibit PPT1 phosphatase activity
Residues 1172-1189 comprise a putative nuclear localization signal; nuclear localization is required for the regulation of period length of the circadian clock
The DNA-binding domain (residues 810-949) binds to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and has high affinity for DNA sequences rich in guanine that form G-quadruplex (G4) structures
The DMAP1-binding domain mediates substrate recognition. It specifically recognizes a conformation-dependent protein determinant present in acid hydrolases (PubMed:23733939)
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is requirered for the induction of transport activity
The C-terminal domain (583-705) can replace the homologous domain in the Arabidopsis protein, while the N-terminal domain cannot
Both domains are absolutely required for activity. In the absence of the ACT domain, the enzyme not only loses its regulatory activity, but also its catalytic activity
Gln-252 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation
Based on a random mutagenesis study of the catalytic fragment (residues 1-385), the (p)ppGpp phosphohydrolase domain seems to encompass approximately the first 225 residues, while the (p)ppGpp synthase domain seems to be found between residues 226 and 385
The protein has two highly different native conformations, an inactive open conformation that cannot bind CDC20 and that predominates in cytosolic monomers, and an active closed conformation. The protein in the closed conformation preferentially dimerizes with another molecule in the open conformation, but can also form a dimer with a molecule in the closed conformation. Formation of a heterotetrameric core complex containing two molecules of MAD1L1 and of MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation and the conversion of the open to the closed form, and thereby promotes interaction with CDC20 (By similarity)
The N-terminus contains a number of repeats which contribute additively to bub-1 recruitment to unattached kinetochores. The repeats are not required for localization to kinetochores (By similarity)
The SET domain is not required for localization to nuclear foci
Has 2 lobes, each of which has an 8-strand beta barrel flanked on their N-terminus by a 4-strand handle domain. TbpB stabilizes the TF holo C-terminal lobe's conformation
The Asp-Pro-Phe (DPF) motifs, which are found in many presynatic proteins, are thought to mediate an interaction with AP-2alpha
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm (PubMed:26209694)
The extracellular N-terminal domain and transmembrane domains 1 and 2 mediate homooligomerization (PubMed:12194975). The highly conserved sequence IXXGXXXGA (residues 53-61) is a glycine zipper motif in which shallow grooves in the alpha-helices interact with one another (PubMed:14506226, PubMed:16709573, PubMed:33268889)
The transmembrane domain 1 (TMD1) and TMD2 mediate oligomerization by providing a homophilic interaction surface that stabilizes dimers/oligomers
The third intracellular loop (residues 231-243) is essential for signal transduction
The DAKSS motif (residues 335-339) is required for internalization of STE2 in response to alpha-factor-binding
The region from residue 251 to 294 which encompasses transmembrane domain 6 (TMD6), the extracellular loop between TMD6 and TMD7, and TMD7, is involved in the binding of alpha-factor (PubMed:11994008). Polar residues in TMD6 such as Gln-253 or Ser-254 influence receptor structure by forming intramolecular contacts between TMD6 and the neighbor TMDs (PubMed:9819407)
The C-terminal cytoplasmic domain is highly phosphorylated and involved in regulation of the pheromone response via promoting the formation of receptor-G-protein preactivation complexes (PubMed:2842059, PubMed:1653030, PubMed:8524302, PubMed:10866688, PubMed:11287148). This domain is in particular involved in the interaction with the G-alpha subunit GPA1 (PubMed:28958779)
STE2 has an extensive orthosteric binding pocket that involves residues throughout the extracellular half of the receptor
The RTR1-type zinc finger mediates interactions with RNA polymerase II complex subunits
Both the RRM domain and the arginine, glycine (RGG) rich domain are necessary for binding to the TXN 3'-untranslated region (By similarity). Both the RRM domain and the arginine, glycine (RGG) rich domain (RGG repeats) are necessary for optimal recruitment into SGs upon cellular stress. The C-terminal domain containing RGG repeats is necessary for translational repression
The SAWADEE domain (154-257) binds to mono-, di-, or trimethylated H3K9 histone peptides, but this interaction is blocked if H3K4 methylation is present
In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (PubMed:30842659). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (By similarity). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain (PubMed:30842659). This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (PubMed:30842659). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (By similarity)
The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding (PubMed:23878260). The fourth and fifth Ig-like C2-type domains are sufficient for homodimerization (PubMed:23878260). The fifth and seventh Ig-like C2-type domains are required for autophosphorylation and further activation (PubMed:23878260)
Upon tRNA-binding, the alphaC region transforms into a helix, which together with the alpha6 helix secures both ends of the tRNA variable loop (PubMed:36599985). The N-terminal disordered region is part of the catalytic pocket and essential for methyltransferase activity: upon S-adenosyl-L-methionine- and tRNA-binding, the N-terminal disordered region becomes ordered, sandwiched between the bound cofactor and the tRNA, and the WDR4 C-terminus attaches to the METTL1 N-terminus to stabilize the bound tRNA together (PubMed:36599982, PubMed:36599985). Together with WDR4, which also binds tRNAs, tRNAs undergo bending to facilitate G46 flipping into the catalytic pocket to be modified (PubMed:36599982, PubMed:36599985)
The C2H2-type zinc fingers determine the hotspot localization through its binding to specific DNA sequences (PubMed:22028627, PubMed:29478809). Variations in their sequence affect affinity towards DNA-binding motif (PubMed:22028627, PubMed:29478809)
The RxLR-dEER motif is required for the delivery of the effector to the host cell cytoplasm but does not bind phosphatidylinositol monophosphates (PubMed:17914356, PubMed:22977236, PubMed:21821794). The motif is cleaved after the RxLR sequence (PubMed:28522546). The RxLR motif (residues 44 to 47) plays a crucial role in the intracellular processing before secretion (PubMed:28522546). The Glu-rich part localized just after the cleavage site (residues 48 to 59) is required for homodimerization (PubMed:28522546)
The coiled coil domain (488-546) is required to inhibit endocytosis
PUB (PUG) domain is required for the interaction with CDC48A (Ref.8). PUB domain may serve as a protein-protein interaction domain implicated in the ubiquitin-proteasome pathway (PubMed:11587532)
Contains 2 BMC domains, trimerizes to give a hexamer. Each trimer forms a pore with an opening of about 13 Angstroms in diameter; depending on the conformation of conserved residues Glu-69 and Arg-70 the pore is open or closed. Dimerization of the trimers forms a small barrel-like compartment, accessible via the pore
Intrinsically disordered protein that undergoes folding upon phosphorylation (PubMed:25533957). Hypophosphorylated form interacts strongly with EIF4E using (1) the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and (2) the secondary EIF4E binding sites (residues 78-82) (PubMed:24207126, PubMed:25533957). Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957)