SII-SWORD/CoKE huggingface dataset:
GPCR, rhodopsin-like, 7TM (GPCR_Rhodpsn_7TM)
Type: Domain

This entry spans the seven transmembrane regions of rhodopsin-like GPCRs. It also identifies some non rhodopsin-like GPCRs, including a number of taste receptors and vomeronasal receptors.

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .
Glycine cleavage system H-protein, subgroup (GCV_H_sub)
Type: Family

This is a family of glycine cleavage H-proteins, part of the glycine cleavage system (GCS) found in bacteria, archaea, and the mitochondria of eukaryotes. GCS is a multienzyme complex consisting of 4 different components (P-, H-, T- and L-proteins) which catalyzes the oxidative cleavage of glycine . The H-protein shuttles the methylamine group of glycine from the P-protein (glycine dehydrogenase) to the T-protein (aminomethyltransferase) via a lipoyl group, attached to a completely conserved lysine residue .

This entry represents the glycine cleavage system H protein. The genome of Aquifex aeolicus contains one protein belonging to this group, and four more related proteins not included here; it seems doubtful that all of these homologues are authentic H proteins. The Chlamydial homologue of the H protein is nearly as divergent as the Aquifex outgroup, is not accompanied by P and T proteins, and is not included in this entry.
Neuromodulin, C-terminal (Neuromodulin_C)
Type: Domain

This entry represents the C-teminal domain of neuromodulin. Although its function is uncertain, the N-terminal (

) region is well conserved and contains both a calmodulin binding domain, and sites for acylation, membrane attachment and protein kinase C phosphorylation. Structural predictions suggest that this domain may exist as an extended, negatively-charged rod with some similarity to the side arms of neurofilaments, indicating that the biological role of neuromodulin may depend on its ability to form a dynamic membrane-cytoplasm-calmodulin complex .

Neuromodulin (also known as growth-associated protein 43 or GAP-43) is a component of the motile growth cones. It is membrane protein whose expression is widely correlated with successful axon elongation . It is a crucial component of an effective regeneration response in the nervous system . Although its function is uncertain, the N-terminal region is well conserved and contains both a calmodulin binding domain, and sites for acylation, membrane attachment and protein kinase C phosphorylation. Structure predictions suggest that the C-terminal region may exist as an extended, negatively-charged rod with some similarity to the side arms of neurofilaments, indicating that the biological role of neuromodulin may depend on its ability to form a dynamic membrane-cytoplasm-calmodulin complex .
Zinc finger, FYVE-related (Znf_FYVE-rel)
Type: Domain

The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn
2+
ions . The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue.

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
CTP synthase, N-terminal (CTP_synthase_N)
Type: Domain

CTP synthase is involved in pyrimidine ribonucleotide/ribonucleoside metabolism, catalysing the synthesis of CTP from UTP by amination of the pyrimidine ring at the 4-position . The enzyme exists as a dimer which consists of an N-terminal synthetase domain and C-terminal glutaminase domain that aggregates as a tetramer. This gene has been found roughly 500 bp upstream of enolase in both beta (Nitrosomonas europaea) and gamma (Escherichia coli) subdivisions of Proteobacterium .

This entry represents the N-terminal synthetase domain of CTP synthase.
Glycosyl transferase family 3, N-terminal domain (Glycosyl_Trfase_fam3_N_dom)
Type: Domain

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

This N-terminal domain is found in various family 3 glycosyl transferases, including anthranilate phosphoribosyltransferase (TrpD,

) and thymidine phosphorylase (

). All these proteins can transfer a phosphorylated ribose substrate. Thymidine phosphorylase catalyses the reversible phosphorolysis of thymidine, deoxyuridine and their analogues to their respective bases and 2-deoxyribose 1-phosphate . This enzyme regulates the availability of thymidine and is therefore essential to nucleic acid metabolism. It promotes metastasis in Hepatocellular carcinoma (HCC) and may serve as a marker of poor prognosis in HCC, being a potential target for the treatment of HCC . Thymidine phosphorylase is also involved platelet activation and thrombosis leading to the development of cardiovascular diseases, thus, it has been suggested as a new target for cardiovascular disease treatment .
Conserved hypothetical domain CHP03000, planctomycetes (CHP03000_planctomycetes)
Type: Domain

This domain is found, so far, only in the Planctomycetes (Pirellula sp. strain 1 and Gemmata obscuriglobus), in up to six proteins per genome, and may be duplicated within a protein. The function is unknown.
Conserved hypothetical domain CHP03009, planctomycetes (CHP03009_planctomycetes)
Type: Domain

This domain is found, so far, only in the Planctomycetes (Pirellula sp. strain 1 and Gemmata obscuriglobus), in up to four proteins per genome, and may be duplicated within a protein. The function is unknown.
Sulphur relay, TusC/DsrF (Sulphur_relay_TusC/DsrF)
Type: Family

This entry includes TusC and DsrF proteins.

The three proteins TusB, TusC, and TusD form a heterohexamer responsible for a sulphur relay reaction. In large numbers of proteobacterial species, this complex acts on a Cys-derived persulphide moiety, delivered by the cysteine desulphurase IscS to TusA, then to TusBCD. The activated sulphur group is then transferred to TusE (DsrC), then by MnmA (TrmU) for modification of an anticodon nucleotide in tRNAs for Glu, Lys, and Gln .

The sulphur relay complex TusBCD is also found, under the designation DsrEFH, in phototrophic and chemotrophic sulphur bacteria, such as Chromatium vinosum or Chlorobium tepidum . In these organisms, it seems the primary purpose is related to sulphur flux, such as oxidation from sulphide to molecular sulphur to sulphate.
Sulphur relay, TusD/DsrE (Sulphur_relay_TusD/DsrE)
Type: Family

This entry includes TusD and DsrE proteins.

The three proteins TusB, TusC, and TusD form a heterohexamer responsible for a sulphur relay reaction. In large numbers of proteobacterial species, this complex acts on a Cys-derived persulphide moiety, delivered by the cysteine desulphurase IscS to TusA, then to TusBCD. The activated sulphur group is then transferred to TusE (DsrC), then by MnmA (TrmU) for modification of an anticodon nucleotide in tRNAs for Glu, Lys, and Gln .

The sulphur relay complex TusBCD is also found, under the designation DsrEFH, in phototrophic and chemotrophic sulphur bacteria, such as Chromatium vinosum or Chlorobium tepidum . In these organisms, it seems the primary purpose is related to sulphur flux, such as oxidation from sulphide to molecular sulphur to sulphate.
Sugar transferase, PEP-CTERM system associated (Sugar_tfrase_EpsB_2)
Type: Family

Members of this protein family belong to the family of bacterial sugar transferases (

). Nearly all are found in species that encode the PEP-CTERM/exosortase system XrtA predicted to act in protein sorting in a number of Gram-negative bacteria (notable exceptions appear to include Magnetococcus sp. (strain MC-1) and Myxococcus xanthus (strain DK 1622)). These genes are generally found near one or more of the PrsK, PrsR or PrsT genes that have been related to the PEP-CTERM system by phylogenetic profiling methods. The nature of the sugar transferase reaction catalysed by members of this clade is unknown and may conceivably be variable with respect to substrate by species. These proteins are homologues of the EpsB protein found in Methylobacillus sp. 12S , which is also associated with a PEP-CTERM system, but of a distinct type. A name which appears attached to a number of genes (by transitive annotation) in this family is "undecaprenyl-phosphate galactose phosphotransferase", which comes from relatively distant characterised enterobacterial homologues, and is considerably more specific than warranted from the currently available evidence.
Exopolysaccharide biosynthesis operon, EpsL, proteobacteria (EpsL_proteobac)
Type: Family

The epsL gene is described as a component of the methanolan exopolysaccharide biosynthesis operon in Methylobacillus sp. 12S , although no other information regarding its possible function is suggested. Homologues of this gene are found in several other exopolysaccharide operons in a small number of species. These operons contain a subset of the methanolan operon genes by homology and synteny, including the epsH gene which is proposed to act as an "exosortase" directing proteins with a C-terminal tag (PEP-CTERM) to the exopolysaccharide layer. Each of the genomes in which these genes and epsL are found also encode genes with these C-terminal tags.
XrtA-associated ATPase-like (XrtA-assoc_ATPase-like)
Type: Family

Members of this entry are probable ATPases in that they contain the nucleotide binding P-loop motif GXXGXGKTT, a motif DEAQ similar to the DEAD/H box of helicases, extensive homology to ATPases of MSHA-type pilus systems and to GspA proteins associated with type II protein secretion systems.
Conserved hypothetical protein CHP03016, PEP-CTERM (CHP03016_PEP-CTERM)
Type: Family

Members of this protein family are found predominantly in exopolysaccharide biosynthesis operons marked by the presence of the EpsH-family putative exosortase and presence in the genome of the PEP-CTERM protein sorting signal. Members of this family may be distantly related to the EpsL family (

).
Chain length determinant protein EpsF (Chain_len_reg_EpsF)
Type: Family

Sequences in this family of proteins are members of the chain length determinant family (

) which includes the wzc protein from Escherichia coli. This family of proteins are homologous to the EpsF protein of the methanolan biosynthesis operon of Methylobacillus sp. 12S . The distribution of this protein appears to be restricted to a subset of exopolysaccharide operons containing a syntenic grouping of genes including a variant of the EpsH exosortase protein. Exosortase has been proposed to be involved in the targeting and processing of proteins containing the PEP-CTERM domain to the exopolysaccharide layer.
PEP-CTERM system-associated, FemAB-related (PEP-CTERM_FemAB-rel)
Type: Family

Members of this entry are found always as part of extended exopolysaccharide biosynthesis loci in bacteria. In nearly every case, these loci contain determinants for the processing of the PEP-CTERM proposed C-terminal protein sorting signal. This family shows remote, local sequence similarity to the FemAB protein family (see

).
Transcription regulator EpsA (Tscrpt_reg_EpsA)
Type: Family

Proteins in this family include a C-terminal LuxR transcriptional regulator domain (

). These proteins are positioned proximal to either EpsH-containing exopolysaccharide biosynthesis operons of the Methylobacillus type , or the associated PEP-CTERM-containing genes.
Undecaprenyl-phosphate galactose phosphotransferase, WbaP (Undecaprenyl-P_galact_Ptfrase)
Type: Family

The WbaP (formerly RfbP) protein has been characterised as the first enzyme in O-antigen biosynthesis in Salmonella typhimurium. The enzyme transfers galactose from UDP-galactose to a polyprenyl carrier (utilizing the highly conserved C-terminal sugar transferase domain,

) a reaction that takes place at the cytoplasmic face of the inner membrane. The N-terminal hydrophobic domain is then believed to facilitate the "flippase" function of transferring the liposaccharide unit from the cytoplasmic face to the periplasmic face of the inner membrane. This model includes the enterobacterial enzymes, where the function is presumed to be identical to the S. typhimurium enzyme as well as a somewhat broader group which are likely to catalyse the same or highly similar reactions based on a phylogenetic tree-building analysis of the broader sugar transferase family. Most of these genes are found within large operons dedicated to the production of complex exopolysaccharides such as the enterobacterial O-antigen. The most likely heterogeneity would be in the precise nature of the sugar molecule transferred.
Undecaprenyl-phosphate glucose phosphotransferase, WcaJ (Undecaprenyl-P_gluc_Ptfrase)
Type: Family

This family of proteins encompasses the Escherichia coli WcaJ protein involved in colanic acid biosynthesis , the Methylobacillus EpsB protein involved in methanolan biosynthesis , as well as the GumD protein involved in the biosynthesis of xanthan . All of these are closely related to the well-characterised WbaP (formerly RfbP) protein which is the first enzyme in O-antigen biosynthesis in Salmonella typhimurium. The enzyme transfers galactose from UDP-galactose (NOTE: not glucose) to a polyprenyl carrier (utilising the highly conserved C-terminal sugar transferase domain,

) a reaction that takes place at the cytoplasmic face of the inner membrane. The N-terminal hydrophobic domain is then believed to facilitate the "flippase" function of transferring the liposaccharide unit from the cytoplasmic face to the periplasmic face of the inner membrane. Most of these genes are found within large operons dedicated to the production of complex exopolysaccharides such as the enterobacterial O-antigen. Colanic acid biosynthesis utilises a glucose-undecaprenyl carrier , knockout of EpsB abolishes incorporation of UDP-glucose into the lipid phase and the C-terminal portion of GumD has been shown to be responsible for the glucosyl-1-transferase activity .
PEF-CTERM protein sorting domain (PEF_CTERM_arc)
Type: Domain

This domain, distantly related to the PEP-Cterm domain described in entry

, is found in Methanosarcina mazei (Methanosarcina frisia) in four different proteins, as well as in other archaea such as Methanococcoides burtonii. Several proteins with this domain have their genes only a short distance from archaeosortase C, a proposed integral membrane transpeptidase .
Exopolysaccharide biosynthesis polyprenyl glycosylphosphotransferase (EPS_sugar_tfrase)
Type: Family

Members of this family are generally found near other genes involved in the biosynthesis of a variety of exopolysaccharides. These proteins consist of two fused domains, an N-terminal hydrophobic domain of generally low conservation and a highly conserved C-terminal sugar transferase domain (

). Characterised and partially characterised members of this subfamily include Salmonella WbaP (originally RfbP) , Escherichia coli WcaJ , Methylobacillus EpsB , Xanthomonas GumD , Vibrio CpsA , Erwinia AmsG , Group B Streptococcus CpsE (originally CpsD) , and Streptococcus suis Cps2E . Each of these is believed to act in transferring the sugar from, for instance, UDP-glucose or UDP-galactose, to a lipid carrier such as undecaprenyl phosphate as the first (priming) step in the synthesis of an oligosaccharide "block". This function is encoded in the C-terminal domain. The liposaccharide is believed to be subsequently transferred through a "flippase" function from the cytoplasmic to the periplasmic face of the inner membrane by the N-terminal domain. Certain closely related transferase enzymes such as Sinorhizobium ExoY and Lactococcus EpsD lack the N-terminal domain and are not identified by this entry.
UDP-glucose/GDP-mannose dehydrogenase (UDP-Glc/GDP-Man)
Type: Family

Enzymes in this family catalyse the NAD-dependent alcohol-to-acid oxidation of nucleotide-linked sugars. Examples include UDP-glucose 6-dehydrogenase (

) , GDP-mannose 6-dehydrogenase (

) , UDP-N-acetylglucosamine 6-dehydrogenase (

) , UDP-N-acetyl-D-galactosaminuronic acid dehydrogenase , UDP-N-acetyl-D-mannosaminuronic acid dehydrogenase and UDP-N-acetyl-D-mannosamine dehydrogenase . These enzymes are most often involved in the biosynthesis of polysaccharides and are often found in operons devoted to that purpose. All of these enzymes contain three domains,

,

, and

for the N-terminal, central, and C-terminal regions respectively.
PEP-CTERM, putative polysaccharide export protein (PEP-CTERM_polysacc_export)
Type: Family

This entry describes a set of polysaccharide biosynthesis/export proteins. Members are variable in either containing or lacking a 78-residue insert, but appear to fall within a single clade. The genomic context of these genes also include genes that encode components of the PEP-CTERM/EpsH (exosortase) protein sorting system.
Polysaccharide export EpsE (Polysacc_export_EpsE)
Type: Family

Sequences in this family of proteins belong to the polysaccharide export protein family, which includes the Wza from Escherichia coli. This family of proteins are homologous to the EpsE protein of the methanolan biosynthesis operon of Methylobacillus sp. 12S . The distribution of this protein appears to be restricted to a subset of exopolysaccharide operons containing a syntenic grouping of genes including a variant of the EpsH exosortase protein . Exosortase has been proposed to be involved in the targeting and processing of proteins containing the PEP-CTERM domain to the exopolysaccharide layer.
Tyrosine-protein kinase, chain length determinant protein EpsG (Tyr_kinase_chain_length_EpsG)
Type: Family

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups :

Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis . RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction .

Cytoplasmic/non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases .

The proteins in this family are homologues of the EpsG protein found in Methylobacillus sp. 12S and are generally found in operons with other Eps homologues. The protein is believed to function as the protein tyrosine kinase component of the chain length regulator (along with the transmembrane component EpsF).
Conserved hypothetical protein CHP03032 (CHP03032)
Type: Domain

This protein family is uncharacterised. A number of motifs are conserved perfectly among all member sequences. The function of the protein s in this entry are unknown.
Lambda-type exonuclease (Lambda-type_endonuclease)
Type: Domain

Members of this entry are found often in phage genomes and in prokaryotic genomes in uncharacterised regions that resemble integrated prophage regions .