SII-SWORD/CoKE huggingface dataset:
TarS, C-terminal domain 1 (TarS_C1)
Type: Domain

This entry represents the C-terminal domain 1 (C1) of TarS from Staphylococcus aureus.

Beta-glycosyltransferase TarS is an enzyme responsible for the glycosylation of wall teichoic acid polymers of the S. aureus cell wall, a process that has been shown to be specifically responsible for methicillin resistance in MRSA. It contains a trimerisation domain composed of tandem carbohydrate binding motifs.The two C-terminally localised regions composed of a series of β-sheets participate in an extensive trimerisation interface and they assume an immunoglobulin-like fold. It is suggested that both carbohydrate binding domains may be involved in polyRboP binding, however unlike pullulanase, the CBMs of TarS are involved in the formation of an extensive trimerisation interface .
Yos9, dimerzation domain (Yos9_DD)
Type: Domain

This is the dimerization domain (DD) found in Yos9 from yeasts. Structural analysis revealed that this domain contributes to self association of Yos9. The overall fold of the domain can be classified as an α-β-roll architecture, comprising two α-helices and seven β-strands .
3-hydroxybutyryl-CoA dehydrogenase reduced Rossmann-fold domain (3HCDH_RFF)
Type: Domain

This domain is found in 3-hydroxybutyryl-CoA dehydrogenase present in E. coli. 3-hydroxybutyryl-CoA dehydrogenase catalyzes the second step in the biosynthesis of n-butanol from acetyl-CoA, in which acetoacetyl-CoA is reduced to 3-hydroxybutyryl-CoA. This domain is a reduced Rossmann-fold domain and, unlike the first Rossmann-fold domain, it is missing the catalytic residues and an NAD(H) binding cleft .
Protein of unknown function DUF5539 (DUF5539)
Type: Family

This is a family of unknown function found in primates.
Hakai, C2H2 zinc finger domain (Znf_Hakai)
Type: Domain

This is the C2H2 zinc finger domain found in E3 ubiquitin ligase Hakai. Hakai targets tyrosine-phosphorylated E-cadherin . It carries a Tyr(P)-binding domain, coined the HYB domain for Hakai phosphotyrosine (Tyr(P)) binding. HYB domain structure illustrates that it forms a zinc-coordinated homodimer in an antiparallel, intertwined configuration, utilizing residues from the Tyr(P)-binding region of two Hakai monomers. The C-terminal region of the HYB domain, which harbors the atypical zinc-coordination motif and key residues involved in the Tyr(P) interaction, plays an important role in the dimerization observed in the HYB domain .
Domain of unknown function DUF5622 (DUF5622)
Type: Domain

This is a domain of unknown function found in archaea-specific ribosomal proteins such as L46a which is suggested to directly bind to rRNA in the ribosome .
Nuclear polyadenylated RNA-binding 2 protein, CCCH zinc finger 1 (Nab2p_Zf1)
Type: Domain

This domain is found in nuclear polyadenylated RNA-binding 2 protein (Nab2p) present in Saccharomyces cerevisiae. Nab2p is a major family of Poly A-binding proteins whose interactions are thought to be crucial for the control of poly(A) tail length. This domain is the first of seven CCCH zinc fingers which are responsible for polyadenosine RNA binding. When combined with the next three zinc fingers (Zf1-4), these four zinc fingers together may bind RNA in the 3' to 5' direction .
Large polyvalent protein associated domain 25 (LPD25)
Type: Domain

This is an α and β fold domain found in polyvalent proteins of conjugative elements .
JAK, FERM F2 lobe domain (FERM_F2)
Type: Domain

This is an F2 lobe domain consisting of an acyl-CoA binding protein fold found in FERM region of Jak-family tyrosine kinases . Multidomain JAK molecules interact with receptors through their FERM and SH2-like domains, triggering a series of phosphorylation events, resulting in the activation of their kinase domains . Overall, the FERM region maintains the typical three-lobed architecture, with an F1 lobe consisting of a ubiquitin-like fold, an F2 lobe consisting of an acyl-CoA binding protein fold, and an F3 lobe consisting of a pleckstrin-homology (PH) fold. JAK1 FERM-F2 domain has been shown to act as the interaction site for the IFNLR1 box1 motif (PxxLxF) of class II cytokine receptors which is essential for kinase activation .
Large polyvalent protein-associated domain 1 (LPD1)
Type: Domain

This is an α helical domain with a conserved ExxARxxE motif that is found in polyvalent proteins of both conjugative elements and phages and prophages .
RuvB-like, AAA-lid domain (RuvB-like_C)
Type: Domain

This entry consists of the C-terminal region of several eukaryotic and archaeal RuvB-like 1 (Pontin or TIP49a) and RuvB-like 2 (Reptin or TIP49b) proteins. In zebrafish, the liebeskummer (lik) mutation, causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. Beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. The Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway . TBP-interacting protein 49 (TIP49) was originally identified as a TBP-binding protein, and two related proteins are encoded by individual genes, tip49a and b. Although the function of this gene family has not been elucidated, they are supposed to play a critical role in nuclear events because they interact with various kinds of nuclear factors and have DNA helicase activities. TIP49a has been suggested to act as an autoantigen in some patients with autoimmune diseases .
Domain of unknown function DUF5615 (DUF5615)
Type: Domain

This is a domain of unknown function found in potential toxin-antitoxin system component .
Pilin A4 (PilA4)
Type: Domain

This domain is found in the major pilin protein PilA. PilA4 binds to PilMNO forming a complex with a well-defined platform linking the cytoplasmic PilM protein to pilus subunits in the periplasm. It is comprised of one α-helix and 4 β-sheets .
Proprotein convertase subtilisin/kexin type 9, C-terminal domain 3 (PCSK9_C3)
Type: Domain

This entry represents the third subdomain found in the C-terminal cysteine/histidine-rich domain (CRD) of PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) . PCSK9 has been shown to regulate circulating LDL-R levels by controlling LDL-R degradation. Furthermore, numerous mutations in the PCSK9 gene have been identified and associated with hypercholesterolemia (gain of function) or hypocholesterolemia (loss of function) . The fully folded CRD, shows structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. The C-terminal domain from PCSK9 consists of three, three-stranded β-subdomains arranged in a pseudo threefold, and each of the subdomains in the CRD of PCSK9 consists of three structurally conserved disulfide bonds .
Proprotein convertase subtilisin/kexin type 9, C-terminal domain 2 (PCSK9_C2)
Type: Domain

This entry represents the second subdomain found in the C-terminal cysteine/histidine-rich domain (CRD) of PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) . PCSK9 has been shown to regulate circulating LDL-R levels by controlling LDL-R degradation. Furthermore, numerous mutations in the PCSK9 gene have been identified and associated with hypercholesterolemia (gain of function) or hypocholesterolemia (loss of function) . The fully folded CRD, shows structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. The C-terminal domain from PCSK9 consists of three, three-stranded β-subdomains arranged in a pseudo threefold, and each of the subdomains in the CRD of PCSK9 consists of three structurally conserved disulfide bonds .
Replicase polyprotein 1ab (Rep_1B)
Type: Domain

This entry relates to a regulatory domain found in replicase polyprotein 1ab found in Arterivirus. Structural studies of arterivirus helicase (nsp10), indicate that this domain undergoes conformational changes on substrate binding. Besides the large conformational change, it is suggested that the regions at the surface of domain 1B not directly involved in DNA binding may become flexible. For example, domain 1B residues Arg95, Gly125 and Ala131 become disordered after DNA binding. Together with domains 1A and 2A it forms a nucleic acid-binding channel where the single-stranded part of the DNA substrate is bound to .
Exosome complex exonuclease Rrp40, N-terminal domain, eukaryotes (Rrp40_N_euk)
Type: Domain

This is the N-terminal domain of Rrp40, an non-catalytic component of the RNA exosome complex from budding yeasts. The RNA exosome complex is responsible for degrading RNA molecules in the 3' to 5' direction. Rrp40 is a 'cap' protein and binds the RNase PH barrel on the opposite side from the S1/KH ring. The N-terminal domain of Rrp44 forms a long β-hairpin that is wedged in between Rrp41-Rrp42 and approaches the N terminus of the cap protein Rrp4 .
Serine/Threonine/Tyrosine Kinase found in polyvalent protein (Kinase-PolyVal)
Type: Family

This is a family of protein kinases found in polyvalent proteins of phages and prophages that although preserving their active site residues for ATP-binding and phosphotransfer appear to have lost the C-terminal subdomain characteristic of this superfamily .
Protein of unknown function DUF5585 (DUF5585)
Type: Family

This is a family of unknown function found in chordata.
ZHX, C2H2 finger domain (ZHX_Znf_C2H2)
Type: Domain

This is a C2H2 zinc-finger domain found in ZHX proteins such as ZHX1. ZHXs are multidomain proteins comprising two C2H2 zinc finger motifs and five homeodomains. Both homeodomains and zinc fingers are short protein modules involved in protein-DNA and/or protein-protein interactions; they are frequently associated with roles in transcriptional regulation. All members of the ZHX family are reported to be able to form both homo- and heterodimers via the region containing homeodomain 1 . ZHX1 is a transcriptional repressor which is ubiquitously expressed. It interacts with nuclear factor Y subunit A (NFYA) and DNA methyl transferase 3B (DNMT3B) for its repression activity. Changes in expression profiles of rat ZHX1 ortholog have been associated with glomerular disease. In addition to the five homeodomains, ZHX1, which also contains of two N-terminal C2H2 zincfingers forms homodimers via homeodomain and can also form heterodimers with ZHX3 .
Alpha-(1,3)-fucosyltransferase FucT, N-terminal (FucT_N)
Type: Domain

This is the N-terminal domain of the alpha chain found in Helicobacter pylori Fucosyltransferase protein which is involved in the production of Lewis x trisaccharide, a major component of lipopolysaccharide. The N-terminal domain contains the catalyst base, Glu-95 which is equivalent to the Asp-100 of other members of the glycosyltransferases-B family. The domain contains the pocket where LacNAc binds. The domain is composed of 2-10 heptad repeats and a conserved N-terminal α-β-α motif which has little sequence similarity to the conserved N-terminal motif in other glycosyltransferases .
Protein of of unknown function DUF5558 (DUF5558)
Type: Family

This is a family of unknown function found only in primates.
RNA editing 3' terminal uridylyl transferase 2 middle domain (Ret2_MD)
Type: Domain

Post-transcriptional RNA editing in Trypanosomatids (pathogenic protozoa) is catalyzed by a large multiprotein complex, the editosome. A key editosome enzyme, RNA editing terminal uridylyl transferase 2 (TUTase 2; RET2) catalyzes the uridylate addition reaction. RET2 structure consists of three domains: the N-terminal domain (NTD), the middle domain (MD) and the C-terminal domain (CTD). This MD domain is mainly composed of six helices and a four-stranded antiparallel β-sheet. structural comparison reveals that the fold of this MD is topologically similar to the binding domains of several RNA-binding proteins such as the RNA-binding domain of the U1A spliceosomal protein, the RRM domain of the human La protein and the CTD of an archaeal CCA-adding enzyme. The CTD of the archaeal CCA-adding enzyme has been shown to bind double-stranded tRNA stem substrate through the α-helices regions. Hence it is suggested that this domain might be an RNA-binding domain .
Dictyosteliid AID/APOBEC-like deaminase (DAAD)
Type: Family

This is a family of secreted AID/APOBEC-like deaminases found in dictyostellids that often shows lineage-specific expansions .
Csm1, subunit domain B (Csm1_B)
Type: Domain

This domain is found in the Csm1 subunit of the Csm complex found in Thermococcus onnurineus. Csm is a type III-A CRISPR-Cas system, which is an RNA-guided immune defense mechanism that detects and destroys foreign DNA or RNA. This domain is known as domain A and is positioned side by side with domain C. Both domain A and domain C adopt the BABBA topology. Domain A interacts primarily with domain B .
Glycoside Hydrolase 20C, C-terminal (Glyco_H_20C_C)
Type: Domain

This is the C-terminal domain of Glycoside hydrolase 20 C (GH20C) present in S. pneumoniae. GH20C possesses the ability to hydrolyse the beta-linkages joining either N-acetylglucosamine or N-acetylgalactosamine to a wide variety of aglycon residues. The C-terminal domain is commonly known as Domain III is important in dimerization as it forms the primary interface of the dimer. However, there is presently no evidence supporting dimerization as being necessary for catalysis. Domain III is unusual among structurally characterised GH20 enzymes but in GH20 enzymes possessing domain III, dimerization seems to be a conserved feature .
Trehalose-6-phosphate phosphatase, helical bundle domain (T6PP_helical)
Type: Domain

This is the N-terminal domain found in trehalose-6-phosphate phosphatase (T6PP,

) from parasitic nematodes such as Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. The N-terminal domain composed of a three-helix bundle is similar in topology to the Microtubule Interacting and Transport (MIT) domains of the Vps4-like ATPases from Sulfolobus acidocaldarius. MIT domains are protein-interacting domains typically associated with multivesicular body formation, cytokinetic abscission, or viral budding. Mutational analysis indicate that deletion or mutation of the MIT-like domain is highly destabilizing to the enzyme .

This helical bundle domain is also found towards the C terminus in TPS-1 and TPS-2 (trehalose phosphate synthase) from C. elegans, which otherwise show little similarity to T6PP in their N-terminal halves, corresponding to the catalytic domains .
GCN5-related N-acetyltransferase-like domain (GNAT-like)
Type: Domain

This is a domain with a GCN5-related N-acetyltransferase (GNAT) fold which can be found in Rv1692 phophatases. Crystal structure of Rv1692 indicates that this C-terminal extension, which is absent in other characterised HADSF members, resembles a small GCN5-related N-acetyltransferase (GNAT) fold. Furthermore, it is fused to the HADSF catalytic domain. Functional studies indicate that this GNAT region is not likely to be involved in acetyl group transfer using AcCoA and SucCoA, it could nonetheless be a regulatory domain. Furthermore, it is suggested that this GNAT domain is required for the solubility of the HADSF fold of Rv1692 and is potentially needed for the structural integrity of this enzyme .
C19orf38, Ig domain (C19orf38_Ig)
Type: Domain

This entry represents an Ig domain found in the uncharacterised human protein C19orf38, which is found across mammals. Family members have one predicted transmembrane region which is not included in this entry. The C19orf38 protein is also known as HIDE1 after Highly expressed in Immature DEndritic cell transcript 1 protein.
Vanadium chloroperoxidase, N-terminal (VCPO_N)
Type: Domain

This is the N-terminal domain found in Vanadium chloroperoxidase proteins from fungi .
Methyltransferase, fungal type, helix-turn-helix domain (HTH_51)
Type: Domain

This is helix-turn-helix domain found in polyketide synthases (PKSs) in fungi. They are multidomain enzymes that biosynthesise a wide range of natural products. Proteins containing this domain include citrinin polyketide synthases which contain a C-methyltransferase (CMeT) domain that adds one or more S-adenosylmethionine (SAM)-derived methyl groups to the carbon framework .
FeoB, cytosolic helical domain (FeoB_Cyto)
Type: Domain

FeoB is a G-protein coupled membrane protein essential for Fe(II) uptake in prokaryotes. In the structures, a canonical G-protein domain (G domain) is followed by a helical bundle domain (S-domain) which is represented by this entry .
Jumonji, helical domain (JHD)
Type: Domain

This 4-helix bundle domain is associated with the Jumonji domain
(

) .
DAHP synthase ferredoxin-like domain (DAHP_snth_FXD)
Type: Domain

This domain is found in 3-Deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAHPS) present in Thermotoga maritime. DAHPS catalyzes the first reaction of the aromatic biosynthetic pathway in bacteria, fungi, and plants, the condensation of PEP and E4P with the formation of DAHP. The domain is ferredoxin-like and is thought to play a critical role in feedback regulation of the enzyme .
Fumarylacetoacetase N-terminal domain (FAA_hydro_N)
Type: Domain

This is domain is found in the N-terminal region of fumarylacetoacetate (FAA) hydrolase (

). It is found, among others, in Pseudogulbenkiania ferrooxidans and Cupriavidus gilardii.
MobL relaxases (MobL)
Type: Family

This family includes members of relaxase enzymes. These enzymes initiate bacterial conjugation contributing to the spread of antibiotic resistance. These MobL relaxases are found mainly in Firmicutes. It is suggested that MobL type relaxases play a prominent role in horizontal gene transfer in Firmicutes bacteria. Family members carry a stretch of relaxase motif III 'HUH' sequence that is characteristic of the HUH endonuclease superfamily essential for enzymatic activity .
Endo-beta-N-acetylglucosaminidase LytB, LytB SH3 domain (LytB_SH3)
Type: Domain

This domain has can be found in endo-beta-N-acetylglucosaminidase LytB (

) of S. pneumoniae and other Gram-positive bacteria. It adopts a SH3-like fold .
NOD1/2, winged helix domain (NOD1/2_WH)
Type: Domain

This winged helix domain is found in the NOD1, NOD2 and related proteins that play a role in immune response . In NLRP3, this domain is important for ATB binding .
Domain of unknown function DUF5614 (DUF5614)
Type: Domain

This is an N-terminal domain found in C7orf25 protein UPF0415. It is distantly related to the PD-(D/E)XK nucleases .
MALT1 immunoglobulin-like domain (MALT1_Ig)
Type: Domain

This is an immunoglobulin-like domain which can be found in the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase. Malt1 is a key component of the Carma1/Bcl10/MALT1 signalosome and is critical for NF-kB signaling in multiple contexts. The MALT1 C-terminal Ig domain is suggested to recruit key factors to promote NF-kB activation. It is also proposed to undergo Lys63-linked ubiquitylation via TRAF6 in potentially nine different lysines to recruit the IKK complex .
Plavaka transposase (Plavaka)
Type: Family

This entry includes a transposase with an RNaseH catalytic domain that often has a histone binding BAM/BAH domain at the C terminus and is sometimes associated with TET/JBP family of dioxygenases in fungi .
Neuraminidase-like domain (Neuraminidase-like)
Type: Domain

This is a neuraminidase-like domain, which is structurally homologous to neuraminidases. It can be found in TcA subunit in tripartite Tc toxin complexes of bacterial pathogens. Functional analysis suggest that the neuraminidase-like domain acts as an electrostatic lock that opens at high or low pH values .
YcaO cyclodehydratase, C-terminal (YcaO_C)
Type: Domain

This is the proline-rich C-terminal domain found in ribosomal protein S12 methylthiotransferase accessory factor YcaO. It has been shown to be involved in both C protein recognition and cyclodehydration. The C-terminal domain resembles a tetratricopeptide repeat that mediates dimerization .
Domain of unknown function DUF5629 (DUF5629)
Type: Domain

This is a domain of unknown function found in hypothetical proteins from Pseudomonas species . Some members contain two copies of this domain.
Suv3, C-terminal domain 1 (Suv3_C_1)
Type: Domain

This domain is found in Suv3 present in Homo sapiens. Suv3 is an NTP-dependent RNA/DNA helicase that is necessary for the degradation of mature mtRNAs. Suv3 has been found to interact in vitro with polynucleotide phosphorylase. This domain makes up part of the C-terminal domain .
AAA lid domain (AAA_lid_10)
Type: Domain

This entry represents the α-helical AAA+ lid domain that is found to the C terminus of AAA domains.
Nicastrin, small lobe (Ncstrn_small)
Type: Domain

This domain is part of the protein Nicastrin, a component of gamma secretase present in Homo sapiens. Gamma-secretase is thought to contribute to Alzheimer's disease development by generating beta-amyloid peptides. This domain is the known as the small lobe which forms the 'lid'. The lid is an extended surface loop that covers the hydrophilic pocket that is thought to be responsible for substrate recruitment. On substrate binding, the large lobe is thought to rotate relative to the small lobe .
tRNA selenocysteine 1-associated protein 1, C-terminal (TSAP1_C)
Type: Domain

This entry represents the C-terminal region of selenocysteine tRNA 1 associated proteins (also known as TRNAU1AP), which is involved in the early steps of selenocysteine biosynthesis and tRNA(Sec) charging to the later steps resulting in the cotranslational incorporation of selenocysteine into selenoproteins. Selenium deficiency results in a variety of diseases, including cardiac disease . TRNAU1AP contains RNA recognition motifs (RRM) and a Tyr-rich region found in the C-terminal. The Tyr-rich region (amino acids 185-225) is conserved among several mammals, including human, chimp, dog, cattle, mouse and rat. Furthermore, constitutive deletion of exons corresponding to the Tyr-rich region in mouse resulted in embryonic lethality .
YAP binding domain (YBD)
Type: Domain

TEA domain transcription factors contain an N-terminal TEA domain (

) and a C-terminal YAP binding domain (YBD). This entry corresponds to the YBD that binds to the oncoproteins YAP and TAZ. The structure of the YBD shows that it has an Ig-like β sandwich fold .
TANK binding kinase 1, ubiquitin-like domain (TBK1_ULD)
Type: Domain

This is the ubiquitin-like domain (ULD) found in TANK-binding kinase 1 (TBK1). TBK1 is a serine/threonine kinase and a noncanonical member of the IKK family implicated in diverse cellular functions, including innate immune response as well as tumorigenesis and development . It has been reported that the ULD of TBK1 regulates kinase activity, playing an important role in signaling and mediating interactions with other molecules in the IFN pathway. Deletion of ULD indicates that it is required for the kinase domain to form an enzymatically active conformation. TBK1 ULD has a ubiquitin-like structure and an Ile44 hydrophobic patch, which is conserved among ULDs and IKK and IKK-related proteins. This hydrophobic patch is involved in ULD-SDD interactions in TBK1 and other IKK and IKK-related proteins .
Ribbon-helix-helix transcriptional regulator (RHH_8)
Type: Family

This family of proteins are likely to be transcriptional regulators that have an N-terminal ribbon-helix-helix domain. Although some members of the family are annotated as CopG, this family does not include that protein.
SUB1 protease prodomain ProdP9 (SUB1_ProdP9)
Type: Domain

This domain is the bound prodomain fragment ProdP9 of the SUB1 protein present in Plasmodium falciparum. SUB1 is a serine protease that processes a subset of parasite proteins that play indispensable roles in egress and invasion. The C-terminal stalk of ProdP9 binds in the active site groove in a substrate-like manner and is truncated at the N terminus as a result of the chymotrypsin digestion step used during purification. ProdP9 is structural similar to MIC5 from Toxoplasma gondii, despite low sequence identity .