SII-SWORD/CoKE huggingface dataset:
Jun-like transcription factor (JNK)
Type: Domain

The c-Jun NH(2)-terminal kinase (JNK) is a member of an evolutionarily conserved sub-family of mitogen-activated protein (MAP) kinases .
NolW-like (NolW-like)
Type: Domain

This is a group of NolW-like proteins, which are closely related to bacterial type II and III secretion system protein (

). NolW proteins have putative membrane-spanning regions .
Serine hydrolase domain (FSH-like_dom)
Type: Domain

This domain is found in a number of enzymes possessing esterase and hydrolase activity.

This domain can be found in budding yeast Fsh1/2/3, fission yeast Dfr1 and the human OVCA2 protein. Fsh1/2/3 are putative serine hydrolases . Dfr1 is a dihydrofolate reductase (DHFR) . OVCA2 is a putative serine-hydrolase that has been linked to cancers . Proteins containing this domain also includes Aspergillus terreus esterase LovG, which catalyzes the release of covalently bound dihydromonacolin L from LovB during lovastatin biosynthesis .
Flagellar assembly protein A (FapA)
Type: Family

Members of this family include FapA (flagellar assembly protein A),

, found in Vibrio vulnificus. The synthesis of flagella allows bacteria to respond to chemotaxis by facilitating motility. Studies examining the role of FapA show that the loss or delocalization of FapA results in a complete failure of the flagellar biosynthesis and motility in response to glucose mediated chemotaxis. The polar localization of FapA is required for flagellar synthesis, and dephosphorylated EIIAGlc (Glucose-permease IIA component) inhibited the polar localization of FapA through direct interaction .
Meiotic nuclear division protein 1 (Mnd1)
Type: Family

This entry includes budding yeast Mnd1 and fission yeast Mcp7. Mnd1 forms a complex with hop2 to promote homologous chromosome pairing and meiotic double-strand break repair . Mcp7 interacts with Meu13 and is required for meiotic recombination .
Flagellar hook capping protein (FlgD)
Type: Family

FlgD is known to be absolutely required for hook assembly, yet it has not been detected in the mature flagellum . It appears to act as a hook-capping protein to enable assembly of hook protein subunits .
Chorion 2 (Chorion_2)
Type: Family

The chorion genes of Drosophila are amplified in response to developmental signals in the follicle cells of the ovary .
BlaI transcriptional regulatory family (BlaI_family)
Type: Family

Proteins in this entry are transcriptional regulators found in a variety of bacteria and a small number of archaea. Many are BlaI/MecI proteins which regulate resistance to penicillins (beta-lactams), though at least one protein (

) appears to be involved in the regulation of copper homeostasis . BlaI regulators repress the expression of penicillin-degrading enzymes (penicillinases) until the cell encounters the antiobiotic, at which point repression ceases and penicillinase expression occurs, allowing cell growth . MecI regulators repress the expression of MecA, a cell-wall biosynthetic enzyme not inhibited by penicillins at clinically achievable concentrations, until the presence of the antibiotic is detected . At this point repression ends and MecA expression occurs which, together with the switching off of the penicillin-sensitive enzymes, allows the cell to grow despite the presence of antibiotic.
Trm112-like (Trm112-like)
Type: Family

Trm112 is required for tRNA methylation in Saccharomyces cerevisiae (Baker's yeast) and is found in complexes with 2 tRNA methylases (Trm9 and Trm11) also with putative methyltransferase Ydr140w . Trm112 from S. cerevisiae (Ynr046w) is plurifunctional and a component of the eRF1 methyltransferase . The crystal structure of Ynr046w has been determined to 1.7 A resolution. It comprises a zinc-binding domain built from both the N- and C-terminal sequences and an inserted domain, absent from bacterial and archaeal orthologs of the protein, composed of three α-helices .

Trm112 has also been described in archaea (UPF0434 protein from Haloferax volcanii). UPF0434 proteins are found both in bacteria and archaea, and the study of interacting partners from the H. volcanii member appears to indicate that Trm112 is a general partner for methyltransferases in all organisms .

This entry also includes mitochondrial protein preY, an uncharacterised protein from vertebrates.
Photosynthetic reaction centre, H subunit (Photo_RC_H)
Type: Family

This entry describes the photosynthetic reaction centre H subunit, which has a single transmembrane helix and a large cytoplasmic domain . The core of the cytoplasmic domain has a PRC-barrel structure.

The photosynthetic apparatus in non-oxygenic bacteria consists of light-harvesting (LH) protein-pigment complexes LH1 and LH2, which use carotenoid and bacteriochlorophyll as primary donors . LH1 acts as the energy collection hub, temporarily storing it before its transfer to the photosynthetic reaction centre (RC) . Electrons are transferred from the primary donor via an intermediate acceptor (bacteriopheophytin) to the primary acceptor (quinine Qa), and finally to the secondary acceptor (quinone Qb), resulting in the formation of ubiquinol QbH2. RC uses the excitation energy to shuffle electrons across the membrane, transferring them via ubiquinol to the cytochrome bc1 complex in order to establish a proton gradient across the membrane, which is used by ATP synthetase to form ATP .

The core complex is anchored in the cell membrane, consisting of one unit of RC surrounded by LH1; in some species there may be additional subunits . RC consists of three subunits: L (light), M (medium), and H (heavy). Subunits L and M provide the scaffolding for the chromophore, while subunit H contains a cytoplasmic domain . In Rhodopseudomonas viridis, there is also a non-membranous tetrahaem cytochrome (4Hcyt) subunit on the periplasmic surface.
Organic solvent tolerance-like, N-terminal (OstA-like_N)
Type: Domain

This domain is found in a number of bacterial proteins, including the LPS-assembly protein lptD, which is involved in organic solvent tolerance . It is also found in lipopolysaccharide export system protein LptH that is responsible for lipopolysaccharide and lipoproteins transport to the outer membrane respectively, and important for cell envelope stability .
ATPase, AFG1-like (ATPase_AFG1-like)
Type: Family

This P-loop motif-containing family of proteins includes AFG1, LACE1 and ZapE.

ATPase family gene 1 (AFG1) is a 377 amino acid yeast protein with an ATPase motif typical of the family .

AFG1-like ATPase (also known as lactation elevated 1 or LACE1), the mammalian homologue of AGF1, is a mitochondrial integral membrane protein that is essential for maintenance of fused mitochondrial reticulum and lamellar cristae morphology. It has also been demonstrated that LACE1 mediates degradation of nuclear-encoded complex IV subunits COX4 (cytochrome c oxidase 4), COX5A and COX6A, and is required for normal activity of complexes III and IV of the respiratory chain .

ZapE is a cell division protein found in Gram-negative bacteria. The bacterial cell division process relies on the assembly, positioning, and constriction of FtsZ ring (the so-called Z-ring), a ring-like network that marks the future site of the septum of bacterial cell division [

,

. ZapE is a Z-ring associated protein required for cell division under low-oxygen conditions suggesting that ZapE is a stress-regulated cell division protein . It is an ATPase that appears at the constricting Z-ring late in cell division. It reduces the stability of FtsZ polymers in the presence of ATP in vitro .
Herpesvirus UL37 (Herpes_UL37)
Type: Family

The herpes simplex virus 1 (HSV-1) UL37 protein functions in both retrograde and anterograde transport of virion capsids, and plays critical roles in cytoplasmic virion envelopment by interacting with glycoprotein K and UL20 . It also interacts with UL36, which is thought to be an important early step in tegumentation during virion morphogenesis in the cytoplasm .
MmgE/PrpD (MmgE_PrpD)
Type: Family

This entry represents proteins from the MmgE/PrpD family, which includes 2-methylcitrate dehydratase (PrpD;

). PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle . This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an α+β domain . Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus . Citrate/2-methylcitrate dehydratase from Bacillus subtilis is involved in the tricarboxylic acid (TCA) and methylcitric acid cycles as it has both 2-methylcitrate dehydratase and citrate dehydratase activities .
Triabin/Procalin (Triabi/Procalin)
Type: Family

This family contains saliva proteins from haematophagous insects that counteract vertebrate host haemostasis events such as coagulation,
vasoconstriction and platelet aggregation . These include:

Triabin, a serine-protease inhibitor with a calycin fold . It forms a non-covalent complex with thrombin at a molecular ratio of 1:1, and inhibits thrombin-induced platelet aggregation.

Procalin is the major allergen of Triatoma protracta saliva .

Triafestin 1-2 from Triatoma infestans, which suppresses activation of the host plasma kallikrein-kinin system, leading to inhibition of the intrinsic coagulation pathway .

Dimiconin, which inhibits the intrinsic blood coagulation pathway by blocking the activation of host coagulation factor XII (F12) but not the enzymatic activity of activated F12 .

Triplatin, an inhibitor of platelet agregation and vasoconstriction through binding to distinct eicosanoids involved in inflammation that has a role in inhibiting host innate immunity .

Pallidipin, likely to fuction by a mechanism similar to that of triplatin .

Members of this family belong to MEROPS proteinase inhibitor family I59, clan IZ.
Proteinase inhibitor I11, ecotin (Prot_inh_ecotin)
Type: Family

This entry represents proteinase inhibitors that belong to MEROPS inhibitor family I11, clan IN. Ecotins are dimeric periplasmic proteins from Escherichia coli and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1 (

) . Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, Yersinia pestis, and Pseudomonas aeruginosa, all species that encounter the mammalian immune system inhibit neutrophil elastase strongly while ecotin from the plant pathogen Pantoea citrea inhibits neutrophil elastase 1000-fold less than the others .

They all potently inhibit pancreatic digestive peptidases trypsin and chymotrypsin, while showing more variable inhibition of the blood peptidases Factor Xa, thrombin, and urokinase-type plasminogen activator.
Chemoreceptor glutamine deamidase CheD (Chemorcpt_Glu_NH3ase_CheD)
Type: Family

CheD deamidates glutamine residues to glutamate on methyl-accepting chemotaxis receptors (MCPs). CheD-mediated MCP deamidation is required for productive communication of the conformational signals of the chemoreceptors to the cheA kinase . CheC is a CheY-P phosphatase (CheY controls flagellar rotation and is activated by phosphorylation). The activity of CheC is enhanced by its interaction with CheD, forming a CheC-CheD heterodimer. It is suggested that CheC exerts its effect on MCP methylation in Bacillus subtilis by controlling the binding of CheD to the MCPs .
Na+-transporting methylmalonyl-CoA/oxaloacetate decarboxylase, beta subunit (OadB_MmdB)
Type: Family

Members of this family are integral membrane proteins and includes oxaloacetate decarboxylase beta chain and methylmalonyl-CoA decarboxylase subunit beta. The decarboxylation reactions they catalyse are coupled to the vectorial transport of Na across the cytoplasmic membrane, thereby creating a sodium ion motive force that is used for ATP synthesis . The oxaloacetate decarboxylase sodium pump (OAD) is composed of an alpha subunit which catalyses the carboxyl-transfer from oxaloacetate to biotin, a beta subunit (represented in this entry) which catalyses the subsequent carboxyl-biotin decarboxylation and the coupled sodium transport and a gamma subunit subunit which stabilizes the OAD complex by interacting with alpha and beta subunits .
GTPase Era-like (GTPase_Era-like)
Type: Family

Era is an essential G-protein in Escherichia coli identified originally as a homologue protein to Ras (E. coli Ras-like protein), which contains a N-terminal GTPase domain followed by an RNA-binding KH domain, that plays a role in ribosome biogenesis. It binds to GTP/GDP and has GTPase activity. It specifically bind to 16S rRNA and serves as a chaperone for processing and maturation of 16S rRNA. GTP binding is required for RNA recognition, which in turn, stimulates the GTP-hydrolyzing activity. ERA is also a checkpoint for assembly of the 30S ribosomal subunit . ERAL1, the homologue in humans, is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit. It binds the 12S mitochondrial rRNA to a 33 nucleotide section delineating the 3' terminal stem-loop region . Mutations in this protein leads to Perrault syndrome, a rare recessive disorder characterised by ovarian dysgenesis and sensorineural deafness .

This entry also includes Origin-associated GTP-binding protein OapA, also known as ArvA, encoded by oapA gene which is part of the three-gene cluster oapABC (origin-associated proteins), involved in generation of extracellular vesicles (arv, archaeal vesiculating GTAse). OapA/ArvA has been described as an archaeal vesiculating GTPase that regulates vesicle production .
Monovalent cation proton antiporter subunit A (MrpA/MnhA1/PhaAB)
Type: Family

This family of proteins consists of bacterial multicomponent K+:H+ and Na+:H+ antiporters. The best characterised systems are the MrpABCDEFG system of Bacillus subtilis which functions as a Na+:H+ antiporter , PhaABCDEFG system of Rhizobium meliloti which functions in pH adaptation and as a K+ efflux system and the MnhABCDEFG system of Staphylococcus aureus which functions as a Na+:H+ antiporter.
Protein-export membrane protein SecF, bacterial (SecF_bac)
Type: Family

This entry rerpesents the SecF protein found in bacteria.

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.
Sulphate ABC transporter permease protein 2 (Sulph_transpt2)
Type: Family

Bacterial binding protein-dependent transport systems are multicomponent systems typically composed of a periplasmic substrate-binding protein, one or two reciprocally homologous integral inner-membrane proteins and one or two peripheral membrane ATP-binding proteins that couple energy to the active transport system. The integral inner-membrane proteins translocate the substrate across the membrane. It has been shown that most of these proteins contain a conserved region located about 80 to 100 residues from their C-terminal extremity. This region seems to be located in a cytoplasmic loop between two transmembrane domains . Apart from the conserved region, the sequence of these proteins is quite divergent, and they have a variable number of transmembrane helices.

This entry describes a subfamily of both CysT and CysW, paralogous and generally tandemly encoded permease proteins of the sulphate ABC transporter .
2-isopropylmalate synthase (IPM_Synthase)
Type: Family

Alpha-isopropylmalate synthase (

) catalyses the first step in the biosynthesis of leucine, the condensation of acetyl-CoA and alpha-ketoisovalerate to form 2-isopropylmalate synthase.
Thiosulphate/Sulfate-binding protein (Thiosulph/SO4-bd)
Type: Family

This entry represents thiosulfate/sulfate binding proteins. Sulfate binding protein (SBP) specifically binds sulfate and thiosulfate-binding protein (TSBP or CysP) specifically binds thiosulfate. They are involved in the ABC transport of sulfate and thiosulfate in eubacteria .

This family are an example of type 2 periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap .
Phosphate import ATP-binding protein PstB-like (PstB-like)
Type: Family

This entry includes a group of phosphate transport system permease proteins such as Phosphate import ATP-binding protein PstB and similar sequences mainly found in prokaryotes. They are membrane transport proteins that use the hydrolysis of ATP to function. They contain ABC (ATP-binding cassette-type) transporter domains.

Phosphate uptake is of fundamental importance in the cell physiology of bacteria because phosphate is required as a nutrient. The Pst system of E. coli comprises four distinct subunits encoded by the pstS, pstA, pstB, and pstC genes. The PstS protein is a phosphate-binding protein located in the periplasmic space . PstA and PstC are hydrophobic and they form the transmembrane portion of the Pst system . PstB is the catalytic subunit, which couples the energy of ATP hydrolysis to the import of phosphate across cellular membranes through the Pst system, often referred as ABC-protein. PstB belongs to one of the largest superfamilies of proteins characterised by a highly conserved adenosine triphosphate (ATP) binding cassette (ABC), which is also a nucleotide binding domain (NBD) .
2-isopropylmalate synthase, bacterial-type (LeuA_bact_synth)
Type: Family

The branched-chain amino acids are synthesised by a common pathway that leads from pyruvate and alpha-ketobutyrate to valine and isoleucine, and a branch that leads from the immediate precursor of valine, alpha-ketoisovalerate, to leucine . This pathway operates in archaea, bacteria, fungi and plants, but not mammals, making the enzymes suitable targets for the development of novel antibiotics and herbicides.

Isopropylmalate synthase is the enzyme responsible for the the first committed step in the leucine branch of this biosynthetic pathway, the conversion of alpha-ketoisovalerate to alpha-isopropylmalate. It is either dimeric or tetrameric, depending on the organism, with a monomer molecular mass of 60-70kDa, a dependence on divalent metal ions for activity, and an alkaline pH optimum . Like many other biosynthetic enzymes it is subject to feedback inhibition by the end product of the pathway, leucine.
Phosphate transport system permease protein PstA (Phosphate_PstA)
Type: Family

This entry describes PtsA, one of a pair of permease proteins in the ABC (high affinity) phosphate transporter . In a number of species, this permease is fused with the PtsC protein (

). In Escherichia coli, this transport system is induced when the concentration of extrallular inorganic phosphate is low. A constitutive, lower affinity transporter operates otherwise.
Phosphate ABC transporter, substrate-binding protein PstS (ABC_phos-bd_PstS)
Type: Family

PstS is the substrate-binding component of the ABC-type transporter complex pstSACB, involved in phosphate import. This protein is accompanied, generally in the same operon, by an ATP binding protein (pstB) and two permease proteins (pstC and pstA). The accumulation of this protein is enhanced under phosphate starvation .

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .
CocE/Serine esterase (CocE/Ser_esterase)
Type: Family

This family includes the cocaine esterase CocE and several putative serine esterases. CocE from Rhodococcus hydrolyses cocaine to benzoate and ecgonine methyl ester, allowing this bacterium to use cocaine as the sole source of carbon and energy. The amino acid sequence of cocaine esterase has a region of similarity with the active serine consensus of X-prolyl dipeptidyl aminopeptidases, suggesting that the cocaine esterase is a serine esterase .
Citramalate synthase (Citramal_synthase)
Type: Family

(R)-citramalate synthase catalyses the condensation of pyruvate and acetyl-coenzyme A to form (R)-citramalate, the first dedicated step in the citramalate pathway. The citramalate pathway constitutes the main pathway for isoleucine biosynthesis in Geobacter sulfurreducens .
Aspartate-semialdehyde dehydrogenase, peptidoglycan lacking (Asp_semi-ald_DH_pep-lack)
Type: Family

This entry represents the subgroup of aspartate dehydrogenases found primarily in organisms lacking peptidoglycan. In addition to its role in aspartate metabolism, the enzyme from Sulfolobus solfataricus has been shown recently to exhibit RNase activity, suggesting that these enzymes may perform additional cellular functions .

This entry also matches malonyl-CoA reductases from archaeal Metallosphaera and Sulfolobus spp, which have sequence identity to aspartate-semialdehyde dehydrogenase, suggesting a common ancestor for both proteins .

Aspartate-semialdehyde dehydrogenase (

), the second enzyme in the aspartate pathway, converts aspartyl phosphate to aspartate-semialdehyde, the branch point intermediate between the lysine and threonine/methionine pathways. Based on sequence alignments, the aspartate-semialdehyde dehydrogenase family appears to have at least three distinct subfamilies. Most studies have been performed on enzymes isolated from Gram-negative bacteria . The N-terminal domain forms the active site and NADP-binding pocket, while C-terminal domain is primarily involved in hydrophobic intersubunit contacts. The catalytic mechanism involves the formation of a covalent thioester acyl-enzyme intermediate mediated through nucleophilic attack by an active site cysteine residue on the substrate aspartyl phosphate. Release of inorganic phosphate is followed by hydride transfer from NADPH to yield the product. The recently described archaeal structure suggests that the two subgroups of aspartate semi-aldehyde dehydrogenase share similar structures and have an identical catalytic mechanism, despite their relatively low sequence identity . Unlike the bacterial enzymes, the archaeal enzyme utilised both NAD and NADP as cofactor.
Fumarate hydratase, class II (Fum_hydII)
Type: Family

Fumarate hydratase class II (also known as Fumarase C) catalyses the stereospecific interconversion of fumarate to L-malate as part of the metabolic citric acid or Kreb's cycle. The recent three-dimensional structure of fumarase C from Escherichia coli has identified a binding site for anions which is generated by side chains from three of the four subunits within the tetramer. These same side chains are found in the three most highly conserved regions within the class II fumarate hydratase family. Putative fumarases from several species (Mycobacterium tuberculosis, Streptomyces coelicolor, Pseudomonas aeruginosa) branch deeply, although within the same branch of a phylogenetic tree rooted by aspartate ammonia-lyase sequences.