SII-SWORD/CoKE huggingface dataset:
Zinc finger, UBR-type (Znf_UBR)
Type: Domain

It has been observed that the identity of N-terminal residues of a protein is related to the half life of the protein. This observation yields a rule, called the N-end rule . Similar but distinct versions of the N-end rule operate in all organisms examined, from mammals to fungi and bacteria. In eukaryotes, the N-end rule pathway is a part of the ubiquitin degradation system. Some proteins that have a very short half life contain a specific motif at their N terminus, the N-degron. It consists of a destabilising N-terminal residue and an internal Lys, which is the site of poly-Ub chain .

The UBR1 protein was shown to bind specifically to proteins bearing N-terminal residues that are destabilising according to the N-end rule, but not to otherwise identical proteins bearing stabilising N-terminal residues . UBR1 contains an N-terminal conserved region (the UBR-type zinc finger) which is also found in various proteins implicated in N-degron recognition. The UBR-type zinc finger defines a unique E3 class, most likely N-degron specific .
SoHo domain (SoHo_dom)
Type: Domain

Sorbin is an active peptide present in the digestive tract, where it has pro-absorptive and anti-secretory effects in different parts of the intestine, including the ability to decrease VIP (vasoactive intestinal peptide) and cholera toxin-induced secretion. It is expressed in some intestinal and pancreatic endocrine tumours in humans .

Sorbin-homology (SoHo) domains are found in adaptor proteins such as vinexin, CAP/ponsin and argBP2, which regulate various cellular functions, including cell adhesion, cytoskeletal organisation, and growth factor signalling . In addition to the sorbin domain, these proteins contain three SH3 (src homology 3) domains. The sorbin homology domain mediates the interaction of vinexin and CAP with flotillin, which is crucial for the localisation of SH3-binding proteins to the lipid raft, a region of the plasma membrane rich in cholesterol and sphingolipids that acts to concentrate certain signalling molecules. The sorbin homology domain of adaptor proteins may mediate interactions with the lipid raft that are crucial to intracellular communication .

Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus .
Villin headpiece (Villin_headpiece)
Type: Domain

Villin is an F-actin bundling protein involved in the maintenance of the microvilli of the absorptive epithelia. The villin-type "headpiece" domain is a modular motif found at the extreme C terminus of larger "core" domains in over 25 cytoskeletal proteins in plants and animals, often in assocation with the Gelsolin repeat. Although the headpiece is classified as an F-actin-binding domain, it has been shown that not all headpiece domains are intrinsically F-actin-binding motifs, surface charge distribution may be an important element for F-actin recognition . An autonomously folding, 35 residue, thermostable subdomain (HP36) of the full-length 76 amino acid residue villin headpiece, is the smallest known example of a cooperatively folded domain of a naturally occurring protein. The structure of HP36, as determined by NMR spectroscopy, consists of three short helices surrounding a tightly packed hydrophobic core .
Dynamin GTPase effector (GED)
Type: Domain

This entry represents the dynamin GTPase effector domain (GED) found in proteins related to dynamin. Its C-terminal region constitutes one of the helices of the bundle signalling element (BSE) or neck together with the N- and C-terminal regions from the GTPase domain, being in close proximity and functionally linked to it. The N-terminal region of GED is part of the stalk domain .

Dynamin is a GTP-hydrolysing protein that is an essential participant in clathrin-mediated endocytosis by cells. It self-assembles into 'collars' in vivo at the necks of invaginated coated pits; the self-assembly of dynamin being coordinated by the GTPase domain. Mutation studies indicate that dynamin functions as a molecular regulator of receptor-mediated endocytosis .
Potassium channel tetramerisation-type BTB domain (T1-type_BTB)
Type: Domain

This domain can be found at the N-terminal of voltage-gated potassium channel protein. It represents a cytoplasmic tetramerisation domain (T1) involved in assembly of alpha-subunits into functional tetrameric channels . This domain can also be found in proteins that are not potassium channels, like KCTD1 (potassium channel tetramerisation domain-containing protein 1). KCTD1 is thought to be a nuclear protein that functions as a transcriptional repressor. In KCTD1, the T1-type BTB domain mediates homomeric protein-protein interactions .
Protein A, Ig-binding domain (Protein_A_Ig-bd)
Type: Domain

This entry represents the immunoglobulin-binding domain found in the Staphylococcus aureus virulence factor protein A (SpA). Protein A contains five highly homologous Ig-binding domains in tandem (designated domains E, D, A, B and C), which share a common structure consisting of three helices in a closed left-handed twist. Protein A can exist in both secreted and membrane-bound forms, and has two distinct Ig-binding activities: each domain can bind Fc-gamma (the constant region of IgG involved in effector functions) and Fab (the Ig fragment responsible for antigen recognition) .
T antigen, Ori-binding (T_Ag_DNA-bd)
Type: Domain

The group of polyomaviruses is formed by the homonymous murine virus (Py) as well as other representative members such as the simian virus 40 (SV40) and the human BK and JC viruses . Their large T antigen (T-ag) protein binds to and activates DNA replication from the origin of DNA replication (ori). Insofar as is known, the T-ag binds to the origin first as a monomer to its pentanucleotide recognition element. The monomers are then thought to assemble into hexamers and double hexamers, which constitute the form that is active in initiation of DNA replication. When bound to the ori, T-ag double hexamers encircle DNA . T-ag is a multidomain protein that contains an N-terminal J domain, which mediates protein interactions (see

,

), a central origin-binding domain (OBD), and a C-terminal superfamily 3 helicase domain (see

,

) .

This entry represents the central origin-binding domain (OBD). The overall fold of the ~130-residue T-ag OBD can be described as a central five-stranded antiparallel β-sheet flanked by two α-helices on one side and one α-helix and one 3(10)-helix on the other. Both faces of the central β-sheet are largely hydrophobic and are protected from solvent by the helices, thus forming two hydrophobic cores . The T-ag OBD molecules are arranged as a spiral with a left-handed twist having six T-ag OBD's per turn. The spiral surrounds a central channel, the inner wall of which consists of α helices .
Hs1/Cortactin (Hs1_Cortactin)
Type: Repeat

The cortactin or HS1 repeat is a tandem repeat of 37-amino acid actin-binding domains. The repeat is named after human cortactin and HS1, proteins involved in cytoskeletal rearrangements implicated in cell migration and apoptosis, respectively. Cortactin contains 6.5 tandem copies of the repeat and is conserved among metazoans, although e.g. insect cortactin and splice variants contain fewer copies. Hematopoietic lineage cell specific protein 1 (HS1) contains 3.5 tandem copies of the cortactin repeat and is mainly expressed in hematopoietic cells. Both cortactin and HS1 contain a C-terminal SH3 domain (

). The cortactin repeat domain binds filamentous actin (F-actin) in proteins that modulate the assembly of the actin cytoskeleton. Secondary structure predictions indicate that the cortactin repeat could exhibit a helix-turn-helix structure .
ATP-grasp fold, ATP-dependent carboxylate-amine ligase-type (ATP-grasp_carboxylate-amine)
Type: Domain

The ATP-grasp domain has an unusual nucleotide-binding fold, also referred to as palmate, and is found in a superfamily of enzymes including D-alanine-D-alanine ligase, glutathione synthetase, biotin carboxylase, and carbamoyl phosphate synthetase, the ribosomal protein S6 modification enzyme (RimK), urea amidolyase, tubulin-tyrosine ligase, and three enzymes of purine biosynthesis. This family does not contain all known ATP-grasp domain members. All the enzymes of this family possess ATP-dependent carboxylate-amine ligase activity, and their catalytic mechanisms are likely to include acylphosphate intermediates.
Cytidylate kinase (Cytidylate_kin)
Type: Family

Cytidylate kinase (

) catalyses the phosphorylation of cytidine 5-monophosphate (dCMP) to cytidine 5 -diphosphate (dCDP) in the presence of ATP or GTP. UMP and dCMP can also act as acceptors .
PA domain (PA_domain)
Type: Domain

The PA (Protease associated) domain is found as an insert domain in diverse proteases, which include the MEROPS peptidase families A22B, M28, and S8A . The PA domain is also found in a plant vacuolar sorting receptor

and members of the RZF family, e.g.

. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors .
Picornavirus coat protein VP4 (Pico_P1A)
Type: Family

Picornaviruses are single-stranded RNA viruses. Processing of the viral polyprotein by picornains 3C and 2A generates capsid proteins VP0, VP1 and VP3, but VP0 undergoes an autolytic cleavage during virion assembly to generate capsid proteins VP2 and VP4 . The autolytic cleavage was originally thought to be the action of a serine-type peptidase, but from analogy with the similar autoproteolytic cleavages that are known for capsid proteins from nodaviruses (MEROPS peptidase family N1), tetraviruses (MEROPS peptidase family N2), picobirnaviruses (MEROPS peptidase family N5) and reoviruses (MEROPS peptidase family N7), it is more likely that VP0 is an asparagine-type peptidase; autocatalytic cleavage being promoted by cyclization of a conserved asparagine.
Delta-retroviral matrix protein (D_retro_matrix)
Type: Domain

Retroviral matrix proteins (or major core proteins) are components of envelope-associated capsids, which line the inner surface of virus envelopes and are associated with viral membranes . Matrix proteins are produced as part of Gag precursor polyproteins. During viral maturation, the Gag polyprotein is cleaved into major structural proteins by the viral protease, yielding the matrix (MA), capsid (CA), nucleocapsid (NC), and some smaller peptides. Gag-derived proteins govern the entire assembly and release of the virus particles, with matrix proteins playing key roles in Gag stability, capsid assembly, transport and budding. Although matrix proteins from different retroviruses appear to perform similar functions and can have similar structural folds which predominantly consist of four closely packed α-helices that are interconnected through loops, their primary sequences can be very different .

This entry represents matrix proteins from delta-retroviruses such as Human T-lymphotropic virus 1 and Human T-cell leukemia virus 2 (HTLV-2), both members of the human oncovirus subclass of retroviruses .
Phospholipase/carboxylesterase/thioesterase (PLipase/COase/thioEstase)
Type: Domain

This entry represents the α/β hydrolase domain found in phospholipases , carboxylesterases and thioesterases.
Polymerase/histidinol phosphatase, N-terminal (Pol/His_phosphatase_N)
Type: Domain

This domain is associated with the N terminus of members of the PHP superfamily, this includes:

subunit of bacterial DNA polymerase III,

eukaryotic DNA polymerase,

X-family of DNA polymerases,

histidinol phosphatases,

and a number of uncharacterised protein families.

In common for all PHP proteins is the presence of four conserved sequence motifs that contain invariant histidine and aspartate residues implicated in metal ion coordination. As part of DNA polymerases, the PHP domain was suggested to hydrolyse pyrophosphate and thereby shift the reaction equilibrium toward nucleotide polymerisation. However, it cannot be ruled out that the PHP domain possesses a nuclease activity, particularly in the repair polymerases of the X-family. No functional information is available for standalone proteins that belong to the PHP superfamily.

The crystal structure of the YcdX protein from Escherichia coli has been determined to 1.6-A resolution. YcdX has an unusual topology of a α7-β7 barrel compared with the more common α8-β8 (TIM) barrel. The C-terminal helix caps the barrel on the N-terminal side. The deep cleft at the C-terminal side of the barrel contains the three zinc binding residues. These residues are invariant in the YcdX family confirming their functional importance.

Only four proteins with known structures have a similar trinuclear zinc catalytic site. All four (nuclease P1, endonuclease IV, alkaline phosphatase, and phospholipase C) hydrolyse the phosphoester bond. This finding suggests a similar activity for YcdX. YcdX is among the genes significantly induced in response to the DNA damage, therefore indicating that members of the YcdX family may be involved in DNA repair .
Biotin protein ligase, C-terminal (BPL_C)
Type: Domain

This C-terminal domain has an SH3-like barrel fold, the function of which is unknown. It is found associated with prokaryotic bifunctional transcriptional repressors and eukaryotic enzymes involved in biotin utilization .
Cytochrome cd1-nitrite reductase, C-terminal domain superfamily (Cyt_cd1_C_sf)
Type: Homologous_superfamily

Cytochrome cd1 (cyt cd1) nitrite reductase is a dimeric enzyme of the bacterial periplasm that plays a key role in denitrification, the respiratory reduction of nitrite to nitric oxide in the nitrogen cycle. Each subunit of the cyt cd1 dimer contains one cytochrome c and one d1 haem group . The active site contains a specialised d1 haem, where the nitrite substrate is bound and reduced. This d1 haem is bound in an 8-bladed β-propeller . This superfamily represents the C-terminal region of the d1 domain.
Carboxypeptidase, activation peptide (M14A_act_pep)
Type: Domain

The peptidases are synthesised as inactive molecules, zymogens, with propeptides that must be removed by proteolytic cleavage to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts .

This entry represents a propeptide associated with peptidases belonging to MEROPS peptidase family M14A. It is found in the carboxypeptidases A and B .
Protein L, Ig light chain-binding (B1_Ig_chn-bd)
Type: Repeat

Protein L is a bacterial protein with immunoglobulin (Ig) light chain-binding properties. It contains a number of homologous b1 repeats towards the N terminus. These repeats have been found to be responsible for the interaction of protein L with Ig light chains .
Regulator of K+ conductance, N-terminal lobe (RCK_N)
Type: Domain

This entry represents the N-terminal lobe of the RCK domain.

The regulator of K+ conductance (RCK) domain is found in many ligand-gated K+ channels, most often attached to the intracellular carboxy terminus. The domain is prevalent among prokaryotic K+ channels, and also found in eukaryotic, high-conductance Ca2+-activated K+ channels (BK channels) . Largely involved in redox-linked regulation of potassium channels, the N-terminal part of the RCK domain is predicted to be an active dehydrogenase at least in some cases . Some have a conserved sequence motif (G-x-G-x-x-G-x(n)-[DE]) for NAD+ binding , but others do not, reflecting the diversity of ligands for RCK domains. The C-terminal part is less conserved, being absent in some channels, such as the kefC antiporter from Escherichia coli. It is predicted to bind unidentified ligands and to regulate sulphate, sodium and other transporters.

The X-ray structure of several RCK domains has been solved . It reveals an α-β fold similar to dehydrogenase enzymes. The domain forms a homodimer, producing a cleft between two lobes. It has a composite structure, with an N-terminal (RCK-N), and a C-terminal (RCK-C) subdomain. The RCK-N subdomain forms a Rossmann fold with two α helices on one side of a six stranded parallel β sheet and three α helices on the other side. The RCK-C subdomain is an all-β-strand fold. It forms an extension of the dimer interface and further stabilises the RCK homodimer . Ca2+ is a ligand that opens the channel in a concentration-dependent manner. Two Ca2+ ions are located at the base of a cleft between two RCK domains, coordinated by the carboxylate groups of two glutamate residues, and by an aspartate residue .

RCK domains occur in at least five different contexts:

As a single domain on the C terminus of some K+ channels (for example, many prokaryotic K+ channels).

As two tandem RCK domains on the C terminus of some transporters that form gating rings (for example, eukaryotic BK channels). The gating ring has an arrangement of eight identical RCK domains, one from each of the four pore-forming subunits and four from the intracellular solution.

As two domains, one at the N terminus and another at the C terminus of transporter (for example, the prokaryotic trk system potassium uptake protein A) .

As a soluble protein (not part of a K+ channel) consisting of two tandem RCK domains.

As a soluble protein consisting of a single RCK domain.
Iron hydrogenase, small subunit (Fe_hydrogenase_ssu)
Type: Domain

This family represents the small subunit of the Fe-only hydrogenases (

). The subunit is comprised of alternating random coil and α-helical structures that encompasses the large subunit in a novel protein fold .
DNA-binding RFX-type winged-helix domain (DNA-bd_RFX)
Type: Domain

The RFX family of transcription factors is characterised by a unique approximately 75-residue DNA-binding domain. RFX genes have been isolated in yeasts, nematode and vertebrates. The characteristic RFX-type HTH DNA binding domain has been recruited into otherwise very divergent regulatory factors functioning in a diverse spectrum of unrelated systems, including regulation of the mitotic cell cycle in fission yeast, the control of the immune response in mammals and infection by human hepatitis B virus .
PIK-related kinase, FAT (PIK-rel_kinase_FAT)
Type: Domain

The FAT domain is a domain present in the PIK-related kinases. Members of the family of PIK-related kinases may act as intracellular sensors that govern radial and horizontal pathways . This domain shows an α-helical structure .
FATC domain (FATC_dom)
Type: Domain

This entry represents the FATC domain in Serine/threonine-protein kinases and related proteins, including pseudo-kinases such as members of the SAGA and NuA4 complexes. The TOR1 FATC domain, in its oxidised form, consists of an α-helix and a well-structured COOH-terminal disulphide-bonded loop. Reduction of the disulphide bond dramatically increases the flexibility within the COOH-terminal loop region. The reduction may alter the binding behaviour of FATC to its partners . It has been proposed that the FAT domain could be of importance as a structural scaffold or as a protein-binding domain, or both .

Phosphatidylinositol kinase (PIK)-related kinases participate in meiotic and V(D)J recombination, chromosome maintenance and repair, cell cycle progression, and cell cycle checkpoints, and their dysfunction can result in a range of diseases, including immunodeficiency, neurological disorders and cancer. The catalytic kinase domain is highly homologous to that of phosphatidylinositol 3- and 4-kinases. Nevertheless, members of the PIK-related family appear functionally distinct, as none of them has been shown to phosphorylate lipids, such as phosphatidylinositol; instead, many have Ser/Thr protein kinase activity. The PI-kinase domain of members of the PIK-related family is wedged between the ~550-amino acid-long FAT (FRAP, ATM, TRRAP) domain and the ~35-residue C-terminal FATC domain .
Adaptor protein Cbl, N-terminal helical (Adaptor_Cbl_N_hlx)
Type: Domain

This entry represents the N-terminal four-helical bundle domain.

Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface.

The N-terminal region of Cbl contains a Cbl-type phosphotyrosine-binding (Cbl-PTB) domain, which is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle (4H) domain, an EF hand-like calcium-binding domain, and a divergent SH2-like domain. The calcium-bound EF-hand wedges between the 4H and SH2 domains, and roughly determines their relative orientation. The Cbl-PTB domain has also been named Cbl N-terminal (Cbl-N) or tyrosine kinase binding (TKB) domain .

The N-terminal 4H domain contains four long α-helices. The C and D helices in this domain pack against the adjacent EF-hand-like domain, and a highly conserved loop connecting the A and B helices contacts the SH2-like domain. The EF-hand motif is similar to classical EF-hand proteins. The SH2-like domain retains the general helix-sheet-helix architecture of the SH2 fold, but lacks the secondary β-sheet, comprising β-strands D', E and F, and also a prominent BG loop .
S1/P1 nuclease (S1/P1nuclease)
Type: Family

This family summarizes both S1 and P1 nucleases (

) which cleave RNA and single stranded DNA with no base specificity . S1 nuclease is more active on DNA than RNA. Its reaction products are oligonucleotides or single nucleotides with 5' phosphoryl groups . Although its primary substrate is single-stranded, it may also introduce single-stranded breaks in double-stranded DNA or RNA, or DNA-RNA hybrids. It is used as a reagent in nuclease protection assays and in removing single stranded tails from DNA molecules to create blunt ended molecules and opening hairpin loops generated during synthesis of double stranded cDNA. P1 nuclease cleaves its substrate at every position yielding nucleoside 5' monophosphates, and it does not recognize or act on double-stranded DNA . It is useful at removing single stranded strands hanging off the end of double stranded DNA and at completely cleaving melted DNA for simple DNA composition analysis.
DHHA1 domain (DHHA1_dom)
Type: Domain

This domain is often found adjacent to the DHH domain (

), and is called DHHA1 for DHH associated domain. DHHA1 is diagnostic of DHH subfamily 1 members . This domain is also found in alanyl tRNA synthetase (e.g.,

), suggesting that it may have an RNA binding function. The domain is about 60 residues long and contains a conserved GG motif.
Acyl transferase, LuxD (LuxD)
Type: Family

LuxD proteins are bacterial acyl transferases. Together with an acyl-protein synthetase (LuxE) and reductase (LuxC), they form a multienzyme complex. This complex channels activated fatty acids into the aldehyde substrate for the luciferase-catalyzed bacterial bioluminescence reaction .