SII-SWORD/CoKE huggingface dataset:
Eukaryotic-type methylenetetrahydrofolate reductase (Fadh2_euk)
Type: Family

This entry represents a family that includes methylenetetrahydrofolate reductase.

The enzyme activities methylenetetrahydrofolate reductase (

) and 5,10-methylenetetrahydrofolate reductase (FADH) (

) differ in that the former (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while the latter (assigned in many bacteria) is flexible with respect to the acceptor. Both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as one or the other, this family describes the subset of proteins found in eukaryotes, and currently designated methylenetetrahydrofolate reductase(

). This protein is an FAD-containing flavoprotein.
DNA polymerase III, delta prime subunit (DNA_pol_HolB)
Type: Domain

DNA-directed DNA polymerase (

) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. DNA polymerase III is a complex, multi-chain enzyme responsible for most of the replicative synthesis in bacteria. The enzyme also has 3' to 5' exonuclease activity. It has a core composed of alpha, epsilon and theta chains, that associate with a tau subunit which allows the core dimerisation to form the PolIII' complex. PolIII' associates with the gamma complex (gamma, delta, delta', psi and chi chains) and with the beta chain. This domain is the N-terminal half of the delta' subunit of DNA polymerase III. Delta' is homologous to the gamma and tau subunits, which form an outgroup for phylogenetic comparison. The gamma/tau branch of the tree is much more tightly conserved than the delta' branch, and some members of that branch score more highly against this model than some proteins classified as delta'. The noise cut-off is set to detect weakly scoring delta' subunits rather than to exclude gamma/tau subunits.
Potassium-transporting ATPase A chain (KdpA)
Type: Family

Kdp is a high affinity ATP-driven K+ transport system in Escherichia coli. It is a membrane complex (KdpFABC) composed of four subunits, KdpA, KdpB, KdpC and KdpF, although KdpF is not present in some species . It maintains intracellular homeostasis, cell shape and turgor under potassium-limiting conditions. KdpA is the K+-transporting subunit of this complex, while KdpB is a P-type ATPase that provides the energy for K+ transport. Both subunits are joined by KdpC, a probable catalytic chaperone and KdpF, that may stabilize the complex. KdpC and KdpF have single transmembrane helices and no known homologues outside of Kdp .

This family represents the KdpA subunit of KdpFABC complex.
Protein YjdM (YjdM)
Type: Family

The function of YjdM is not clear. It is not involved in phosphonate metabolism .
Pyridoxine kinase (PyrdxlKinase)
Type: Family

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .

This entry represents pyridoxal kinase (

), which is required for the synthesis of pyridoxal-5-phosphate from vitamin B6, and catalyses the conversion of pyridoxal to pyridoxal 5'-phosphate in the presence of ATP. Escherichia coli has an enzyme PdxK that acts
in vitro
as a pyridoxine/pyridoxal/pyridoxamine kinase, but mutants lacking PdxK activity retain a specific pyridoxamine kinase, PdxY . PdxY acts in the salvage pathway of pyridoxal 5'-phosphate biosynthesis. Mammalian forms of pyridoxal kinase are more similar to PdxY than to PdxK.
RarD protein (RarD)
Type: Family

This uncharacterised protein is predicted to have many membrane-spanning domains.
L-threonine 3-dehydrogenase (L-Threonine_3-DHase)
Type: Family

L-threonine 3-dehydrogenase is a tetrameric, zinc-binding, NAD-dependent enzyme involved in threonine catabolism. It catalyses the conversion of L-threonine and NAD(+) to L-2-amino-3-oxobutanoate and NADH. In Escherichia coli His-90 modulates substrate specificity and is believed to be part of the active site. Closely related proteins include sorbitol dehydrogenase, xylitol dehydrogenase, and benzyl alcohol dehydrogenase. Eukaryotic examples of this enzyme have been demonstrated experimentally but are not detected by this entry.
Mannonate dehydratase (Man_deHydtase)
Type: Family

This Fe2+-requiring enzyme plays a role in D-glucuronate catabolism in Escherichia coli. Mannonate dehydratase converts D-mannonate to 2-dehydro-3-deoxy-D-gluconate. An apparent equivalog is found in a glucuronate utilization operon in Bacillus stearothermophilus T-6.
Glycosyl transferase WecG/TagA/CpsF (WecG_TagA_CpsF)
Type: Family

The WecG member of this family, believed to be UDP-N-acetyl-D-mannosaminuronic acid transferase, plays a role in enterobacterial common antigen (eca) synthesis in Escherichia coli. Another family member, the Bacillus subtilis TagA protein, is involved in the biosynthesis of the cell wall polymer poly(glycerol phosphate). The third family member, CpsF, CMP-N-acetylneuraminic acid synthetase has a role in the capsular polysaccharide biosynthesis pathway. Also included in this group is Xanthomonas campestris pv. campestris GumM, a glycosyltransferase participating in the biosynthesis of the exopolysaccharide xanthan .
UPF0324 inner membrane protein YeiH-like (UPF0324_YeiH-like)
Type: Family

This entry represents a family of uncharacterised multi-pass membrane proteins, which are found in both Gram-positive and Gram-negative species, such as YeiH from E. coli. Members of this family are found so far only in one archaeal species, Archaeoglobus fulgidus. These proteins have a molecular weight of approximately 35 to 38kDa and may be associated to sulfate export transporter function.
4-aminobutyrate aminotransferase, eukaryotic (4NH2But_aminotransferase_euk)
Type: Family

4-aminobutyrate aminotransferase eukaryotic (

) is a class III pyridoxal-phosphate-dependent aminotransferase. The enzyme catalyses the conversion of 4-aminobutanoate and 2-oxoglutarate into succinate semialdehyde and L-glutamate. The degree of sequence difference between this set and known bacterial examples is greater than the distance between either set the most similar enzyme with distinct function, and so the prokaryotic and eukaryotic sets have been placed into separate families. This family describes known eukaryotic examples of the enzyme. Alternate names include GABA transaminase, gamma-amino-N-butyrate transaminase, and beta-alanine--oxoglutarate aminotransferase.
4-aminobutyrate aminotransferase, bacterial (4NH2But_aminotransferase_bac)
Type: Family

Eukaryotic 4-aminobutyrate aminotransferase (

) is a class III pyridoxal-phosphate-dependent aminotransferase. The enzyme catalyses the conversion of 4-aminobutanoate and 2-oxoglutarate into succinate semialdehyde and L-glutamate. The degree of sequence difference between this set and known bacterial examples is greater than the distance between, in either set, the most similar enzyme with a distinct function, and so the prokaryotic and eukaryotic sets have been placed into separate families.
Na/Pi-cotransporter II-related/YqeW-like protein (NaPi_cotrn-rel/YqeW-like)
Type: Family

This family describes essentially the full length of an uncharacterised protein from Bacillus subtilis (YqeW) and corresponding lengths of longer proteins from Escherichia coli and Treponema pallidum. There is homology to one other group of proteins, type II sodium/phosphate (Na/Pi) cotransporters. A well-conserved repeated domain in this family, approximately 60 residues in length, is also repeated in the Na/Pi cotransporters, although with greater spacing between the repeats. The two families share additional homology in the region after the first repeat, share the property of having extensive hydrophobic regions, and may be similar in function.
Peptidase S49, protease IV (Pept_S49_pIV)
Type: Family

This group of serine peptidases belong to MEROPS peptidase family S49 (protease IV family, clan S-). The predicted active site serine for members of this family occurs in a transmembrane domain.

Signal peptides of secretory proteins seem to serve at least two important biological functions. First, they are required for protein targeting to and translocation across membranes, such as the eubacterial plasma membrane and the endoplasmic reticular membrane of eukaryotes. Second, in addition to their role as determinants for protein targeting and translocation, certain signal peptides have a signalling function.

During or shortly after pre-protein translocation, the signal peptide is removed by signal peptidases. The integral membrane protein, SppA (protease IV), of Escherichia coli was shown experimentally to degrade signal peptides . The member of this family from Bacillus subtilis has only been shown to be required for efficient processing of pre-proteins under conditions of hyper-secretion . These enzymes have a molecular mass around 67kDa and a duplication such that the N-terminal half shares extensive homology with the C-terminal half and was shown in E. coli to form homotetramers. E. coli SohB, which is most closely homologous to the C-terminal duplication of SppA, is predicted to perform a similar function of small peptide degradation, but in the periplasm. Many prokaryotes have a single SppA/SohB homologue that may perform the function of either or both.

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .
Peptidase S49, SppA (Pept_S49_SppA)
Type: Domain

This group of serine peptidases belong to MEROPS peptidase family S49 (protease IV family, clan S-). The predicted active site serine for members of this family occurs in a transmembrane domain. This group of sequences represent both long and short forms of the bacterial SppA and homologues found in the archaea and plants.

Signal peptides of secretory proteins seem to serve at least two important biological functions. First, they are required for protein targeting to and translocation across membranes, such as the eubacterial plasma membrane and the endoplasmic reticular membrane of eukaryotes. Second, in addition to their role as determinants for protein targeting and translocation, certain signal peptides have a signalling function.

During or shortly after pre-protein translocation, the signal peptide is removed by signal peptidases. The integral membrane protein, SppA (protease IV), of Escherichia coli was shown experimentally to degrade signal peptides. The member of this family from Bacillus subtilis has only been shown to be required for efficient processing of pre-proteins under conditions of hyper-secretion .

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .
Acetylornithine/Succinylornithine transaminase family (AcOrn/SuccOrn_fam)
Type: Family

This family of proteins, for which ornithine aminotransferases form an outgroup, consists mostly of proteins designated acetylornithine aminotransferase. However, the two very closely related members from Escherichia coli are assigned different enzymatic activities. One is acetylornithine aminotransferase (

), ArgD, an enzyme of arginine biosynthesis, while another is succinylornithine aminotransferase, an enzyme of the arginine succinyltransferase pathway, an ammonia-generating pathway of arginine catabolism . Members of this family may also act on ornithine, like ornithine aminotransferase (

) and on succinyldiaminopimelate, like N-succinyldiaminopmelate-aminotransferase (

, DapC, an enzyme of lysine biosynthesis) .
2,4-diaminobutyrate 4-transaminase (Dat)
Type: Family

This family consists of L-diaminobutyric acid transaminases. This general designation covers both

(diaminobutyrate-2-oxoglutarate transaminase, which uses glutamate as the amino donor in DABA biosynthesis), and

(diaminobutyrate--pyruvate transaminase, which uses alanine as the amino donor). Most members with known function are

, and at least some annotations as

in current databases at time of model revision are incorrect. A distinct branch of this family contains examples of

nearly all of which are involved in ectoine biosynthesis.

has also been characterised as part of an alternative polyamine biosynthetic pathway in Vibrio cholerae. A related enzyme is 4-aminobutyrate aminotransferase (EC

), also called GABA transaminase. These enzymes all are pyridoxal phosphate-containing class III aminotransferase.
Drug resistance transporter EmrB-like (EmrB-like)
Type: Family

This subfamily of drug efflux proteins, a part of the major facilitator family, is predicted to have 14 potential membrane-spanning regions. Members with known activities include EmrB (multiple drug resistance efflux pump) in Escherichia coli, FarB (antibacterial fatty acid resistance) in Neisseria gonorrhoeae , TcmA (tetracenomycin C resistance) in Streptomyces glaucescens, RibZ (riboflavin transporter) in Peptoclostridium difficile , etc. In most cases, the efflux pump is described as having a second component encoded in the same operon, such as EmrA of E. coli.
Tetrapyrrole biosynthesis, glutamate-1-semialdehyde aminotransferase (4pyrrol_synth_GluAld_NH2Trfase)
Type: Family

Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway . The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin .

The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (

), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase (

) to charge a tRNA with glutamate, glutamyl-tRNA reductase (

) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase (

) to catalyse a transamination reaction to produce ALA.

The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase,

) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase,

) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase (

) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.

Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (

). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase (

) .

This entry represents glutamate-1-semialdehyde (GSA) aminotransferase (

), which catalyse a transamination reaction to produce 5-aminoaevulinic acid during the first stage of tetrapyrrole biosynthesis by the C5 pathway . This enzyme has a high degree of similarity to amino acid transaminases, and is classed as a class III aminotransferase.
Co-chaperone Hsc20 (HscB)
Type: Family

The final step of iron-sulfur protein assembly involves transfer of an iron-sulfur cluster from a cluster-donor to a cluster-acceptor protein . This process is facilitated by a specialized chaperone system, which consists of a molecular chaperone from the Hsc70 family, HscA in E. coli, and a co-chaperone of the J-domain family, Hsc20/HscB (known as Jac1 in fungi) . The co-chaperone HscB recruits the scaffold protein for Fe-S cluster biogenesis Isu1/IscU, guiding it to the chaperone HscA , and enhances the intrinsic ATPase activity of the HscA .
Ribonuclease HIII (RNase_HIII)
Type: Family

This family describes bacterial RNase HIII.

Ribonuclease HIII

cleaves RNA from DNA-RNA hybrids. It catalyses endonucleolytic cleavage to 5'-phospho-monoesters. Two types of ribonuclease H in Bacillus subtilis, RNase HII (rnhB) and RNase HIII (rnhC), are both known experimentally and are quite similar to each other. The only RNase H homologue in the Mycoplasmas resembles rnhC. Archaeal forms resemble HII more closely than HIII .
Serine dehydratase, alpha subunit (Ser_deHydtase_asu)
Type: Family

L-serine dehydratase converts serine into pyruvate in the gluconeogenesis pathway from serine. This model describes the alpha chain of an iron-sulphur-dependent L-serine dehydratase, found in Bacillus subtilis. A fairly deep split in a UPGMA tree separates members of this family of alpha chains from the homologous region of single chain forms such as found in Escherichia coli. This family of enzymes is not homologous to the pyridoxal phosphate-dependent threonine deaminases and eukaryotic serine deaminases.
Iron-sulphur-dependent L-serine dehydratase beta subunit (Fe-S_L-Ser_bsu)
Type: Family

L-serine dehydratase, also called serine deaminase, catalyses the conversion of L-serine and water to pyruvate and ammonia during gluconeogenesis from serine. The enzyme forms a heterooctamer of four alpha chains and four beta chains.

This family describes the beta chain of an iron-sulphur-dependent L-serine dehydratase of the Firmicutes and Deinococcus radiodurans. A fairly deep split in a UPGMA tree separates members of this family of beta chains from the homologous region of single chain forms such as found in Escherichia coli. This family of enzymes is not homologous to the pyridoxal phosphate-dependent threonine deaminases and eukaryotic serine deaminases.
Iron-sulphur-dependent L-serine dehydratase single chain form (Fe-S_L-Ser_mono)
Type: Family

This enzyme is also called serine deaminase. L-serine dehydratase converts serine into pyruvate in the gluconeogenesis pathway from serine. This enzyme is comprised of a single chain in Escherichia coli, Mycobacterium tuberculosis, and several other species, but has separate alpha and beta chains in Bacillus subtilis and related species. The beta and alpha chains are homologous to the N-terminal and C-terminal regions, respectively, but are rather deeply branched in a UPGMA tree. This enzyme requires iron and dithiothreitol for activation
in vitro
, and is a predicted 4Fe-4S protein. Escherichia coli Pseudomonas aeruginosa have two copies of this protein [

,

, .
DNA-binding protein Tfx, archaea (Tfx_DNA-bd_arc)
Type: Family

This entry represents a family of Tfx DNA-binding proteins, which is restricted to the archaea. TfX has a 2-layer α/β topology. Homology among the members is strongest in the helix-turn-helix-containing N-terminal region. Tfx from Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum) is associated with the operon for molybdenum formyl-methanofuran dehydrogenase and binds a DNA sequence near its promoter.
Fe-S hydro-lyase, tartrate dehydratase alpha-type, catalytic domain (Fe-S_hydro-lyase_TtdA-typ_cat)
Type: Domain

This entry represents various Fe-S type hydro-lyases, including the alpha subunit from both L-tartrate dehydratase (TtdA;

) and class 1 fumarate hydratases (

), which includes both aerobic (FumA) and anaerobic (FumB) types . A number of Fe-S cluster-containing hydro-lyases share a conserved motif, including argininosuccinate lyase, adenylosuccinate lyase, aspartase, class I fumarate hydratase (fumarase), and tartrate dehydratase (see

). Proteins in this group represent a subset of closely related proteins or modules, including the Escherichia coli tartrate dehydratase alpha chain and the N-terminal region of the class I fumarase (where the C-terminal region is homologous to the tartrate dehydratase beta chain). The activity of archaeal proteins in this group is unknown.

Fumarate hydratase (also known as fumarase) is a component of the citric acid cycle. In facultative anaerobes such as E. coli, fumarase also engages in the reductive pathway from oxaloacetate to succinate during anaerobic growth. Three fumarases, FumA, FumB, and FumC, have been reported in E. coli. fumA and fumB genes are homologous and encode products of identical sizes which form thermolabile dimers of Mr 120,000. FumA and FumB are class I enzymes and are members of the iron-dependent hydrolases, which include aconitase and malate hydratase. The active FumA contains a 4Fe-4S centre, and it can be inactivated upon oxidation to give a 3Fe-4S centre .