SII-SWORD/CoKE huggingface dataset:
(2R)-phospho-3-sulpholactate synthase, ComA (ComA_synth)
Type: Family

Methanogenic archaea produce methane via the anaerobic reduction of acetate or single carbon compounds . Coenzyme M (CoM; 2-mercaptoethanesulphonic acid) serves as the terminal methyl carrier for this process. Previously thought to be unique to methanogenic archaea, CoM has also been found in methylotrophic bacteria.

Biosynthesis of CoM begins with the Michael addition of sulphite to phosphoenolpyruvate, forming 2-phospho-3-sulpholactate (PSL). This reaction is catalyzed by members of this family, PSL synthase (ComA) . Subsequently, PSL is dephosphorylated by phosphosulpholactate phosphatase (ComB) to form 3-sulpholactate , which is then converted to
3-sulphopyruvate by L-sulpholactate dehydrogenase (ComC;

) . Sulphopyruvate decarboxylase (ComDE;

) converts 3-sulphopyruvate to sulphoacetaldehyde . Reductive thiolation of sulphoacetaldehyde is the final step.

This entry also includes some proteins from plants and fungi, such as HEAT-STRESS-ASSOCIATED 32 from Arabidopsis .
Protein of unknown function DUF211 (DUF211)
Type: Family

This entry represents a group of prokaryotic proteins of unknown function that includes Uncharacterized protein MJ0319 from Methanocaldococcus jannaschii (

).
Protein of unknown function DUF212 (DUF212)
Type: Family

No protein in this family has been characterised. This family is believed to be related to the PAP2 family, which includes phosphatases such as type 2 phosphatidic acid phosphatase (PAP2) and haloperoxidases.
Carboxyltransferase domain, subdomain C and D (CT_C_D)
Type: Domain

Urea carboxylase (UC) catalyses a two-step, ATP- and biotin-dependent carboxylation reaction of urea. It is composed of biotin carboxylase (BC), carboxyltransferase (CT), and biotin carboxyl carrier protein (BCCP) domains. The CT domain of UC consists of four subdomains, named A, B, C and D. This domain covers the C and D subdomains of the CT domain. This domain covers the whole length of 5-oxoprolinase subunit B (PxpB, originally called KipI (kinase A inhibitor) from Bacillus subtilis [[see

,

,

]). It can also be found in S. cerevisiae urea amidolyase Dur1,2, which is a multifunctional biotin-dependent enzyme with domains for urea carboxylase and allophanate (urea carboxylate) hydrolase activity .

PxpB forms a complex with KipA, which is covered by the A and B subdomains of the CT. This complex shares protein structure and sequence similarity with the CT domain of urea amidolyase from K. lactis, but residues that are important for CT catalysis are not conserved in KipA and KipI. Therefore, the PxpB-KipI complex is unlikely to have CT activity .
Cytochrome C biogenesis protein, transmembrane domain (Cyt_c_assmbl_TM_dom)
Type: Domain

This entry represents the transmembrane domain of Cytochrome C biogenesis proteins also known as disulphide interchange proteins, such as DsbD from E. coli and DipZ from Mycobacterium. These proteins posses a protein disulphide isomerase like domain that is not found within the aligned region of this family.

DsbA and DsbC, periplasmic proteins of E. coli, are two key players involved in disulphide bond formation. DsbD generates a reducing source in the periplasm, which is required for maintaining proper redox conditions . DipZ is essential for maintaining cytochrome c apoproteins in the correct conformations for the covalent attachment of haem groups to the appropriate pairs of cysteine residues .
Glycosyl transferase, family 19 (Glyco_trans_19)
Type: Family

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'.

These enzymes belong to the glycosyltransferase family 19

. Lipid-A-disaccharide synthetase

is involved with acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase

and tetraacyldisaccharide 4'-kinase

in the biosynthesis of the phosphorylated glycolipid, lipid A, in the outer membrane of Escherichia coli and other bacteria. These enzymes catalyse the first disaccharide step in the synthesis of lipid-A-disaccharide.
Glucokinase (Glucokinase)
Type: Family

Glucokinases (

) are found in invertebrates and microorganisms and are highly specific for glucose. These enzymes phosphorylate glucose using ATP as a donor to give glucose-6-phosphate and ADP .
Glu-tRNAGln amidotransferase C subunit (GatC)
Type: Family

This entry includes the C subunit of the bacterial/archaeal aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferases (known as GatC) and eukaryotic Glu-tRNAGln amidotransferases.

Aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase ([ec:6.3.5.-]) allows the formation of correctly charged Asn-tRNA(Asn) or Gln-tRNA(Gln) through the transamidation of misacylated Asp-tRNA(Asn) or Glu-tRNA(Gln) in organisms which lack either or both of asparaginyl-tRNA or glutaminyl-tRNA synthetases. The reaction takes place in the presence of glutamine and ATP through an activated phospho-Asp-tRNA(Asn) or phospho-Glu-tRNA(Gln) . The enzyme is composed of three subunits: A (an amidase), B and C. It also exists in eukaryotes as a protein targeted to the mitochondria.

The heterotrimer GatABC is involved in converting Glu to Gln and/or Asp to Asn, when the amino acid is attached to the appropriate tRNA. In Lactobacillus, GatABC is responsible for producing tRNA(Gln). In Archaea, GatABC is responsible for producing tRNA(Asn), while GatDE is responsible for producing tRNA(Gln). In lineages that include Thermus, Chlamydia, or Acidithiobacillus, the GatABC complex catalyses both tRNA(Gln) and tRNA(Asn).
ABC3 transporter permease, C-terminal (ABC3_permease_C)
Type: Domain

This domain is found in members of the ABC type 3 transporter family . Proteins containing this domain include:

Cell division protein FtsX from Gram-negative and Gram-positive bacteria. It is a component of the septal ring . It may insert division proteins into the cytoplasmic membrane .

Permease protein MacB 1. It is part of the tripartite efflux system MacAB-TolC .

Lipoprotein-releasing system transmembrane protein LolC. It is part of an ATP-dependent transport system LolCDE responsible for the release of lipoproteins targeted to the outer membrane from the inner membrane .

Putative hemin transport system permease protein HrtB. It may be Part of the ABC transporter complex hrt involved in hemin import .

Bacitracin export permease protein BceB. It is art of the ABC transporter complex BceAB (TC 3.A.1.123.5) involved in bacitracin export .

ABC transporter permease YtrF. It is part of the ABC transporter complex YtrBCDEF that plays a role in acetoin utilization during stationary phase and sporulation .

ABC transporter permease protein YxdM. It is part of the ABC transporter complex YxdLM which could be involved in peptide resistance .
7TM GPCR, serpentine receptor class u (Sru) (7TM_GPCR_serpentine_rcpt_Sru)
Type: Family

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 .

The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to sense and respond to several hundred different chemicals because each neuron detects several stimuli . Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' . Chemoreception in C. elegans is mediated by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). More than 1300 potential chemoreceptor genes have been identified in C. elegans, which are generally prefixed sr for serpentine receptor. The receptor superfamilies include Sra (Sra, Srb, Srab, Sre), Str (Srh, Str, Sri, Srd, Srj, Srm, Srn) and Srg (Srx, Srt, Srg, Sru, Srv, Srxa), as well as the families Srw, Srz, Srbc, Srsx and Srr . Many of these proteins have homologues in Caenorhabditis briggsae.

This entry represents serpentine receptor class u (Sru) from the Srg superfamily .
DNA replication helicase domain (DNA_helicase_dom)
Type: Domain

This entry represents a domain found in viral DNA replication helicases, bacterial ATP-dependent DNA helicase Pif1 and eukaryotic ATP-dependent DNA helicase PIF7.
Sodium-dependent phosphate transport protein (Na/Pi_transpt)
Type: Family

This family consists of sodium-dependent phosphate transport proteins of the solute carrier family SLC34A . It includes mammalian type II renal Na+/Pi-cotransporters and other proteins from lower eukaryotes and bacteria, some of which are also Na+/Pi-cotransporters. In kidneys these proteins may be involved in actively transporting phosphate into cells via Na+ cotransport in the renal brush border membrane .
Vacuolating cytotoxin (Vacuolating_cytotoxin)
Type: Family

Helicobacter pylori is a micro-aerophilic bacterium with the extraordinary ability to establish infections in human stomachs that can last for years or decades, despite immune and inflammatory responses and normal turnover of the gastric epithelium and overlying mucin layer in which it resides. Most H. pylori strains secrete a toxin (VacA) that induces multiple structural and functional alterations in eukaryotic cells. The most prominent effect of VacA is its capacity to induce the formation of large cytoplasmic vacuoles in eukaryotic cells. In addition, VacA interferes with the process of antigen presentation, increases permeability of polarised epithelial cell monolayers, and forms anion-selective membrane channels. Formation of channels in endosomal membranes of cells may be an important feature of the mechanism by which VacA induces cell vacuolation. H. pylori vacA encodes a ~139kDa protoxin, which undergoes cleavage of a 33-residue N-terminal signal sequence and C-terminal proteolytic processing to yield a mature secreted toxin. Purified VacA degrades during prolonged storage into two fragments (of ~34 and 58kDa), which are derived from the N-and the C terminus of the toxin respectively. The mass of the experimentally intact toxin (~88.2kDa) corresponds closely to the sum of the masses of the two proteolytic fragments .

Secondary structure predictions suggest that a 35kDa portion of the VacA C-terminal domain is rich in amphipathic β-sheets, and this region exhibits low-level similarity to members of the family of autotransporter proteins. In addition, at the C terminus of VacA, there is a phenylalanine-containing motif that is commonly found in autotransporter proteins, as well as in numerous Gram-negative bacterial outer membrane proteins. An intact N-terminal portion of VacA is not required for proteolytic processing of the protoxin. However, the N-terminal 32 amino acids of the mature VacA are predicted to form the only contiguous hydrophobic region in the protein that is long enough to span the membrane. What is more, isogenic H. pylori mutant strains in which the C-terminal VacA domain is disrupted, fail to express or secrete any detectable VacA, which is probably attributable to the degradation of export-incompetent toxin precursors within the periplasm. It is speculated that the VacA protoxin may undergo proteolytic cleavage at multiple sites downstream from amino acid 854 of the protoxin, which would yield a 33kDa cell-associated domain, as well as a fragment of ~15kDa .
Uncharacterised protein family UPF0060 (UPF0060)
Type: Family

This entry describes a family of integral membrane proteins. Some members of this family have been proposed to function as a thallium-specific efflux pump .
Protein adenylyltransferase SelO (SelO)
Type: Family

SelO and its homologues are widespread among most eukaryotic taxa, and are also common in many major bacterial taxa. SelO is a conserved pseudokinase that transfers AMP from ATP to Ser, Thr, and Tyr residues on protein substrates (AMPylation). It contains a protein kinase fold with ATP flipped in the active site . In eukaryotes, it is a mitochondrial protein that may be involved in redox biology .
Putative antitoxin (Put_antitoxin)
Type: Family

Proteins in this family are possibly the antitoxin component of a toxin-antitoxin (TA) module. TA loci are though to be mobile cassettes that move frequently within and between chromosomes and may function as stress-response elements beneficial to free-living prokaryotes .
Domain of unknown function DUF218 (DUF218)
Type: Domain

This domain contains several highly conserved charged amino acids, suggesting this may be an enzymatic domain. It is found in Escherichia coli YdcF, which has been shown to bind S-adenosyl-L-methionine (AdoMet), but whose biochemical function has not been identified . It is also found in Escherichia coli SanA and Salmonella typhimurium SfiX (

), which are involved in vancomycin resistance . SfiX may also be involved in murein synthesis. This domain is also found in envelope biogenesis factor ElyC, which plays a critical role in the metabolism of the essential lipid carrier used for cell wall synthesis .
Preprotein translocase YajC (Preprotein_translocase_YajC)
Type: Family

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins . The translocase protein subunits are encoded on the bacterial chromosome.
Phosphoribosylformylglycinamidine synthase subunit PurS (PurS)
Type: Family

Phosphoribosylformylglycinamidine(FGAM) synthetase,

, catalyses the fourth step in the de novo purine biosynthetic pathway .

5-phosphoribosylformylglycinamide (FGAR) + glutamine + ATP = FGAM + glutamate + ADP + Pi

In eukaryotes and many bacterial systems (including Escherichia coli and Salmonella typhimurium), the FGAM synthetase is encoded by the large form of PurL (lgPurL), which contains an N-terminal ATPase domain and a C-terminal glutamine-binding domain. In archaeal and other bacterial systems, however, FGAM synthetase is encoded by separate genes, making it a multisubunit (rather than multidomain) enzyme. The protein is composed of the small form of PurL (smPurL), which is homologus to the ATPase domain of lgPurL, PurQ which is homologous to the glutamine-binding domain of of lgPurL, and PurS, whose function is not known.

This entry represents the PurS subunit (also known as YexA) of the multisubunit FGAM synthetase. Recent studies showed that disruption of the purS gene in Bacillus subtilis resulted in a purine auxotrophic phenotype, due to defective FGAM synthetase activity . Therefore, the PurS protein appears to be required for the function of the PurL and PurQ subunits of the FGAM synthetase, but the molecular mechanism for the functional role of PurS is currently not known.
Zinc finger, Dof-type (Znf_Dof)
Type: Domain

This entry consists of proteins containing a Dof domain, which is a zinc finger DNA-binding domain that shows resemblance to the Cys2 zinc finger, although it has a longer putative loop where an extra Cys residue is conserved . AOBP, a DNA-binding protein in pumpkin (Cucurbita maxima), contains a 52 amino acid Dof domain, which is highly conserved in several DNA-binding proteins of higher plants.

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.
Signal transduction histidine kinase, osmosensitive K+ channel sensor, N-terminal (Sig_transdc_His_kinase_KdpD_N)
Type: Domain

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

This entry represents the N-terminal domain found in KdpD sensor kinase proteins, which regulate the kdpFABC operon responsible for potassium transport . The N-terminal domain forms part of the cytoplasmic region of the protein, which functions as the sensor domain responsible for sensing turgor pressure . It recognises K+ and C-di_AMP (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
Gibberellin regulated protein (GASA)
Type: Family

This is the GASA gibberellin regulated cysteine rich protein (GRPs) family. The expression of these proteins is up-regulated by the plant hormone gibberellin, most of these proteins have a role in plant development and some of its members have antimicrobial activity . There are 12 cysteine residues conserved within the alignment giving the potential for these proteins to possess 6 disulphide bonds.

Included in this family are some GRPs found in fruits and pollens that have been identified as allergens, including peach Pru p 7, Japanese apricot Pru m 7, orange Cit s 7, pomegranate Pun g 7, and cypress pollen GRP .
Potassium transporter (K+_transporter)
Type: Family

This is a family of K+ potassium transporters that are conserved across phyla, having both bacterial (KUP) , yeast (HAK) , and plant (AtKT/POT) sequences as members. POT1 from Arabidopsis thaliana plays an essential role in telomere maintenance .
Polysaccharide chain length determinant, N-terminal domain (LPS_length_determ_N)
Type: Domain

A number of related proteins are involved in the synthesis of lipopolysaccharide, O-antigen polysaccharide, capsule polysaccharide and exopolysaccharides. Chain length determinant protein (or wzz protein) is involved in lipopolysaccharide (lps) biosynthesis, conferring a modal distribution of chain length on the O-antigen component of lps . It gives rise to a reduced number of short chain molecules and increases in numbers of longer molecules, with a modal value of 20. The MPA/MPA2 proteins function in CPS and EPS polymerisation and export .
Major outer sheath protein, N-terminal (MOSP_N)
Type: Domain

This entry represents the N-terminal region of major outer sheath proteins from spirochaetales. These proteins are present on the bacterial cell surface. In Treponema denticola the major outer sheath protein (Msp) binds immobilized laminin and fibronectin supporting the hypothesis that Msp mediates the extracellular matrix binding activity of T. denticola .
Beta-1,4-galactosyltransferase (Galactosyl_T)
Type: Family

Beta-1,4-galactosyltransferase is responsible for catalysing the transfer of galactose onto proteins or lipids . Studies on C.elegans have shown that the enzyme is required for susceptibility to pore-forming crystal toxins, together with glycosyltransferase genes bre-1, bre-2, bre-3 and bre-5 .

In mammals, the protein is found in long and short forms. The short form is preferentially located in the golgi complex , where it catalyses the production of lactose in the lactating mammary gland; it may also be responsible for the synthesis of complex-type N-linked oligosaccharides of various glycoproteins, as well as the carbohydrate moieties of glycolipids. The short form is preferentially targeted to the plasma membrane of many cell types , where it functions as a recognition molecule during various cell-cell and cell-matrix interactions, by binding to specific oligosaccharide ligands on opposing cells, or in the extracellular matrix.

This entry also includes other members of the glycosyltransferase 7 family, such as xylosylprotein 4-beta-galactosyltransferase and beta-N-acetyl-D-glucosaminide beta-1,4-N-acetylglucosaminyl-transferase.