SII-SWORD/CoKE huggingface dataset:
Disulphide bond formation protein DsbB/BdbC (DiS_bond_form_DsbB/BdbC)
Type: Family

Disulphide bonds contribute to folding, maturation, stability, and regulation of proteins, in particular those localized out of the cytosol. Oxidation of selected pairs of cysteines to disulphide in vivo requires cellular factors present in the bacterial periplasmic space or in the endoplasmic reticulum of eukaryotic cells .

The disulfide bond formation protein B (DsbB) is a component of the pathway that leads to disulphide bond formation in periplasmic proteins of Escherichia coli and other bacteria. The DsbB protein oxidises the periplasmic protein DsbA which in turn oxidises cysteines in other periplasmic proteins in order to make disulphide bonds . DsbB acts as a redox potential transducer across the cytoplasmic membrane. It is a membrane protein which spans the membrane four times with both the N- and C-termini of the protein are in the cytoplasm. Each of the periplasmic domains of the protein has two essential cysteines. The two cysteines in the first periplasmic domain are in a Cys-X-Y-Cys configuration that is characteristic of the active site of other proteins involved in disulphide bond formation, including DsbA and protein disulphide isomerase .

This entry also includes disulphide bond formation protein BdbC from Bacillus subtilis which functionally corresponds to the well-characterised E. coli DsbB .
Exonuclease VII, large subunit (Exonuc_VII_L)
Type: Family

Exonuclease VII (

) is composed of two nonidentical subunits; one large subunit and 4 small ones . Exonuclease VII catalyses exonucleolytic cleavage in either 5'-3' or 3'-5' direction to yield 5'-phosphomononucleotides. The large subunit also contains the OB-fold domains that bind to nucleic acids at the N terminus.
Tetrapyrrole biosynthesis, uroporphyrinogen III synthase (4pyrrol_synth_uPrphyn_synth)
Type: Domain

This entry represents uroporphyrinogen III synthase (

) which functions during the second stage of tetrapyrrole biosynthesis. This enzyme catalyses the inversion of the final pyrrole unit (ring D) of the linear tetrapyrrole molecule, linking it to the first pyrrole unit (ring A), thereby generating a large macrocyclic structure called uroporphyrinogen III . The enzyme folds into two α/β domains connected by a β-ladder, the active site being located between the two domains . Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase .

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 (

) .
HPr(Ser) kinase/phosphorylase (HPr(Ser)_kin/Pase)
Type: Family

This entry represents the bifunctional HPr serine kinase/phosphorylase (HprK/P). It catalyses the phosphorylation of a specific serine residue in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). It also catalyses thedephosphorylation of seryl-phosphorylated HPr (P-Ser-HPr). The two antagonistic activities of HprK/P are regulated by several intracellular metabolites, which change their concentration in response to the absence or presence of rapidly metabolisable carbon sources (glucose, fructose, etc.) in the growth medium. HprK/P is the sensor in a multicomponent phosphorelay system that controls catabolite repression, sugar transport and carbon metabolism in Gram-positive bacteria .
Photosystem I PsaL, reaction centre subunit XI (PSI_PsaL)
Type: Domain

The trimeric photosystem I of the cyanobacterium Synechococcus elongatus recomprises 11 protein subunits. Subunit XI, PsaL, from plants and bacteria is one of the smaller subunits with only two transmembrane α helices. PsaL interacts closely with PsaI .
Tetraacyldisaccharide 4'-kinase (LpxK)
Type: Family

Tetraacyldisaccharide 4'-kinase (LpxK) phosphorylates the 4'-position of a tetraacyldisaccharide 1-phosphate precursor (DS-1-P) of lipid . This enzyme is involved in the synthesis of lipid A portion of the bacterial lipopolysaccharide layer (LPS). It is organised into two α/β/α sandwich domains linked by a two-stranded β-sheet .
Cobalamin (vitamin B12)-binding module, cap domain (Cbl-bd_cap)
Type: Domain

Cobalamin-dependent methionine synthase (

) is a large modular protein that catalyses methyl transfer from methyltetrahydrofolate (CH3-H4folate) to homocysteine. During the catalytic cycle, it supports three distinct methyl transfer reactions, each involving the cobalamin (vitamin B12) cofactor and a substrate bound to its own functional unit . The cobalamin cofactor plays an essential role in this reaction, accepting the methyl group from CH3-H4folate to form methylcob(III)alamin, and in turn donating the methyl group to homocysteine to generate methionine and cob(I)alamin.

Methionine synthase is a large enzyme composed of four structurally and functionally distinct modules: the first two modules bind homocysteine and CH3-H4folate, the third module binds the cobalamin cofactor and the C-terminal module binds S-adenosylmethionine. The cobalamin-binding module is composed of two structurally distinct domains: a 4-helical bundle cap domain (residues 651-740 in the Escherichia coli enzyme) and an α/β B12-binding domain (residues 741-896) (

). The 4-helical bundle forms a cap over the α/β domain, which acts to shield the methyl ligand of cobalamin from solvent . Furthermore, in the conversion to the active conformation of this enzyme, the 4-helical cap rotates to allow the cobalamin cofactor to bind the activation domain (

). The α/β domain is a common cobalamin-binding motif, whereas the 4-helical bundle domain with its methyl cap is a distinctive feature of methionine synthases.

This entry represents the 4-helical bundle cap domain. This domain is also present in other shorter proteins that bind to B12, and is always found N terminus to the α/β B12-binding domain.
ABC transporter substrate-binding protein PnrA-like (PnrA-like)
Type: Domain

Proteins containing this domain were originally annotated as basic membrane lipoproteins . However, several proteins containing this domain were later predicted as ABC transporter substrate-binding proteins, such as PnrA (also known as TmpC or TP0319) and RfuA (also known as Tpn38 or TP0298) from Treponema pallidum. PnrA transports purine nucleosides , while RfuA transports riboflavin . Proteins containing this domain also include Med from Bacillus subtilis. Med was annotated as a transcriptional activator protein that regulates comK . This domain can also found at the N terminus of glutamate receptor-like proteins from Dictyostelium (slime mold) .
Exonuclease VII, small subunit (Exonuc_VII_S)
Type: Family

Exonuclease VII is composed of two non-identical subunits; one large subunit and 4 small ones . This enzyme catalyses exonucleolytic cleavage in either 5'-3' or 3'-5' direction to yield nucleoside 5'-phosphates.
L-arabinose isomerase (Lara_isomerase)
Type: Family

This entry includes L-arabinose isomerases, AraA, (

). These enzymes catalyse the reaction: L-arabinose => L-ribulose. This reaction is the first step in the pathway of L-arabinose utilisation as a carbon source after entering the cell L-arabinose is converted into L-ribulose by the L-arabinose isomerases enzyme .
CDP-diacylglycerol pyrophosphatase (CDP-diacylglyc_Pase)
Type: Family

The CDP-diacylglycerol pyrophosphatases

play a role in the regulation of phospholipid metabolism by inositol, as well as regulating the cellular levels of phosphatidylinositol .
N-acetylglucosamine-6-phosphate deacetylase (GlcNAc_6-P_deAcase)
Type: Family

Three enzymes are required for N-acetylglucosamine (NAG) utilization in Escherichia coli: enzyme IInag (gene nagE), N-acetylglucosamine-6-phosphate deacetylase (gene nagA), and glucosamine-6-phosphate isomerase (gene nagB) .
This entry represents the N-acetylglucosamine-6-phosphate deacetylases (NagA),

.

NagA catalyzes the hydrolysis of the N-acetyl group of N-acetyl-glucosamine-6-phosphate (GlcNAc-6-P) to glucosamine 6-phosphate and acetate. This is the first committed step in the biosynthetic pathway to amino-sugar-nucleotides, which is needed for cell wall peptidoglycan (murein) and teichoic acid biosynthesis. Deacetylation of N-acetylglucosamine is also important in lipopolysaccharide synthesis and cell wall recycling .
Nitrate reductase chaperone, NarJ (NO3_reductase_chaperone_NarJ)
Type: Family

The nitrate-reducing system, nitrate reductase (

), is stimulated by anaerobiosis, nitrate, and nitrite. The NarJ/delta subunit is not part of the nitrate reductase enzyme but is needed for assembly of the multisubunit enzyme complex. In the absence of the delta subunit the core alpha beta enzyme complex is unstable . The delta subunit is essential for enzyme activity
in vivo
and
in vitro
. Although NarJ is required for correct assembly of active enzyme, it dissociates and is not part of the active enzyme. The Escherichia coli (strain K12) NarJ, which is a chaperone required for proper molybdenum cofactor insertion and final assembly of the membrane-bound respiratory nitrate reductase 1. NarJ is required for the insertion of molybdenum into the apo-NarG subunit, maybe by keeping NarG in an appropriate competent-open conformation for the molybdenum cofactor insertion to occur. NarJ maintains the apoNarGH complex in a soluble state. Upon insertion of the molybdenum cofactor, NarJ seems to dissociate from the activated soluble NarGH complex, before its association with the NarI subunit on the membrane .
Uronate isomerase (Uronate_isomerase)
Type: Family

Uronate isomerase (also known as glucuronate isomerase) catalyses the reaction D-glucuronate to D-fructuronate and also converts D-galacturonate to D-tagaturonate .
Malate/L-lactate dehydrogenase-like (Malate/L-lactate_DH-like)
Type: Family

The malate dehydrogenase (MDH) of some extremophilies is more similar to the L-lactate dehydrogenases (L-LDH)

from various sources than to other MDHs .

This family consists of bacterial and archaeal malate/L-lactate dehydrogenases and related proteins. The archaebacterial malate dehydrogenase

,

deviates from the eubacterial and eukaryotic enzymes having a low selectivity for the coenzyme (NAD(H) or NADP(H)) and catalyzing the reduction of oxalacetate to malate more efficiently than the reverse reaction .
Segregation and condensation protein A (ScpA)
Type: Family

This family represents ScpA, which along with ScpB (

) interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation . The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli , where MukB (

) is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE (

) or MukF (

), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.
Adaptor protein ClpS, core (ClpS_core)
Type: Domain

In the bacterial cytosol, ATP-dependent protein degradation is performed by several different chaperone-protease pairs, including ClpAP. ClpS directly influences the ClpAP machine by binding to the N-terminal domain of the chaperone ClpA. The degradation of ClpAP substrates, both SsrA-tagged proteins and ClpA itself, is specifically inhibited by ClpS. ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins .

ClpS is a small alpha/beta protein that consists of three α-helices connected to three antiparallel β-strands . The protein has a globular shape, with a curved layer of three antiparallel α-helices over a twisted antiparallel β-sheet. Dimerization of ClpS may occur through its N-terminal domain. This short extended N-terminal region in ClpS is followed by the central seven-residue β-strand, which is flanked by two other β-strands in a small β-sheet.
Endolytic murein transglycosylase (MLTG-like)
Type: Family

Endolytic murein transglycosylase (also known as MltG, YrrL and YceG) functions as a peptidoglycan terminase that cleaves nascent peptidoglycan strands endolytically to terminate their elongation. The structure of E. coli MltG has been solved by X-ray crystallography (PDB: 2r1f). It has an extended N terminus topped by a globular head domain with an observable cleft where residues with the highest level of conservation are found .

Caution: This protein is often misannotated as aminodeoxychorismate lyase (PabC) due to the promiximty to PabC in numerous proteobacteria.
Large ribosomal RNA subunit accumulation protein YceD (YceD)
Type: Family

This family includes the large ribosomal RNA subunit accumulation protein YceD. Gene knockout in
Escherichia coli
leads to significant reduction of 23S rRNA. These proteins are nearly universally conserved in bacteria and plants. In
Nicotiana benthamiana
leaves the protein is localized in chloroplasts .
Menaquinone biosynthesis enzyme (Menaquinone_biosynth)
Type: Family

This family includes two enzymes which are involved in menaquinone (vitamin K2) biosynthesis. One which catalyses the conversion of cyclic de-hypoxanthine futalosine to 1,4-dihydroxy-6-naphthoate, and one which may be involved in the conversion of chorismate to futalosine . These enzymes comprise two domains with α/β structures, a large domain and a small domain. A pocket between the two domains may form the active site, a conserved histidine located within this pocket could be the catalytic base .
AlgH-like (AlgH-like)
Type: Family

This entry represents a group of bacterial proteins, including AlgH from Pseudomonas aeruginosa, VC_0467 from Vibrio cholerae and YqgE from Escherichia coli. AlgH is involved in the transcriptional regulation of alginate biosynthesis . VC_0467 has been described as a putative translation repressor (

). This family was previously known as UPF0301.
Flagellar assembly factor FliW (Flagellar_assembly_factor_FliW)
Type: Family

FliW binds to the C-terminal region of flagellin, which is implicated in polymerisation, and participates in the assembly of the flagellum . FliW is part of a three-part feedback loop: in Bacillus subtilis FliW inhibits CsrA (an RNA-binding protein) which inhibits FliC translation; hence FliW is required for FliC (flagellin) production .
YcaO-like domain (YcaO-like_dom)
Type: Domain

This domain comprises the whole of a protein in Methanocaldococcus jannaschii and Methanobacterium thermoautotrophicum, all but the N-terminal 60 residues from a protein of Mycobacterium tuberculosis, and all but the C-terminal 180 residues from a protein in Haemophilus influenzae and Escherichia coli, among proteins from published complete genomes. This domain contains a conserved ATP-binding pocket .

The domain can be found in Escherichia coli YcaO, which is known to be involved in beta-methylthiolation of ribosomal protein S12 . YcaO-like domains have been shown to be catalytically active, and to use ATP to activate amide backbones during peptide cyclodehydrations . It is likely to be involved in post-translational modification (PTM) of amino acid residues. In Methanopyrus kandleri and Methanocaldococcus jannaschii YcaO is involved in thioamidation .
XdhC- CoxI (XdhC_CoxI)
Type: Domain

This domain is often found in association with an NAD-binding region, related to TrkA-N (

). XdhC is believed to be involved in the attachment of molybdenum to Xanthine Dehydrogenase .
Carboxyltransferase domain, subdomain A and B (CT_A_B)
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 A and B subdomains of the CT domain. This domain covers the whole length of KipA (kinase A) from Bacillus subtilis . 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 .

KipA forms a complex with KipI, which is covered by the C and D subdomains of the CT. The KipI-KipA 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 KipA-KipI complex is unlikely to have CT activity .
Carboxymuconolactone decarboxylase-like (CMD-like)
Type: Domain

The catechol and protocatechuate branches of the 3-oxoadipate pathway, which are important for the bacterial degradation of aromatic compounds, converge at the common intermediate 3-oxoadipate enol-lactone. Carboxymuconolactone decarboxylase (CMD) is involved in protocatechuate catabolism. In some bacteria a gene fusion event leads to expression of CMD with a hydrolase involved in the same pathway .
COX15/CtaA family (COX15/CtaA_fam)
Type: Family

This is a family of integral membrane proteins. CtaA (also known as heme A synthase) is required for cytochrome aa3 oxidase assembly in Bacillus subtilis . COX15 is required for cytochrome c oxidase assembly , and is involved in the synthesis of heme A . COX15 forms highly stable complexes through hydrophobic interactions, and this multimerization is evolutionarily conserved, independent of heme levels and heme a synthase catalytic activity. There are four conserved histidine residues critical for eukaryotic heme a synthase activity . Mutations of COX15 are associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome, due to impaired stability (S344P) or catalytic function (R217W).

In some cases, heme A synthase is found fused to protoheme IX farnesyltransferase, an enzyme that converts protoheme IX to heme O.

In addition, heme A synthase can be found fused with mitochondrial ferredoxin as in etp1 .
CoA-binding (CoA-bd)
Type: Domain

This domain has a Rossmann fold and is found in a number of proteins including bacterial Redox-sensing transcriptional repressor Rex , succinyl CoA synthetases , malate and ATP-citrate ligases .
Copper chaperone SCO1/SenC (SCO1/SenC)
Type: Family

The SCO (an acronym for Synthesis of Cytochrome c Oxidase) family is involved in biogenesis of respiratory and photosynthetic systems. Members of this family are required for the proper assembly of cytochrome c oxidase (COX). They contain a metal binding motif, typically CXXXC, which is located in a flexible loop.
Regulatory protein RecX (Regulatory_RecX)
Type: Family

RecX is a putative bacterial regulatory protein . The gene encoding RecX is found downstream of recA, and it is suggested that the RecX protein might be regulator of RecA activity by interaction with the RecA protein or filament .
BioY protein (BioY)
Type: Family

BioMNY, a high-affinity biotin transporter, is a member of the ECF (energy-coupling factor) transporters. ECF transporters share a common architecture consisting of pairs of ABC (ATP-binding cassette)-containing ATPases, a conserved transmembrane protein and a transmembrane substrate-capture protein. In the case of the biotin transporter these are represented by BioM, BioN and BioY respectively .
Creatininase/formamide hydrolase (Creatininase/forma_Hydrolase)
Type: Family

This family includes the enzymes creatininase and 2-amino-5-formylamino-6-ribosylaminopyrimidin-4(3H)-one 5'-monophosphate deformylase, also known as formamide hydrolase.

Creatinase or creatinine amidohydrolase (

) catalyses the hydrolysis of creatinine to creatine, which can then be metabolised to urea and sarcosine by creatinase (

). Creatininase is a member of the urease-related amidohydrolase superfamily . Formamide hydrolase catalyses the hydrolysis of the formamide of 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-monophosphate (FAPy) to form 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (APy) (

) .

This family also includes 3-dehydro-scyllo-inosose hydrolase from the marine, hyperthermophilic bacterium
Thermotoga maritima
. The enzyme converts 3-dehydro-scyllo-inosose (diketo-inositol) to 5-dehydro-L-gluconate by catalysing ring-opening hydrolysis, and is a component of the myo-inositol degradation pathway.
T. maritima
is unable to grow on myo-inositol as a single carbon source .
Sulfur carrier protein FdhD (FdhD)
Type: Family

FdhD is a protein essential for the activity of formate dehydrogenases (FDHs) , but it is not a component of membrane-bound formate dehydrogenase . In Escherichia coli, it has been shown to function as a sulfurtransferase between IscS to the molybdenum cofactor prior to its insertion into formate dehydrogenase . Sulfur transfer between IscS and FDH is a indispensable step for FDH activity .
Sulphur relay, DsrE/F-like (Sulphur_relay_DsrE/F-like)
Type: Family

Four small, soluble proteins (DsrE, DsrF, DsrH and DsrC) are encoded in the dsr gene region of the phototrophic sulphur bacterium Chromatium vinosum D. The dsrAB genes encoding dissimilatory sulphite reductase are part of the gene cluster, dsrABEFHCMK. The remaining proteins that are encoded are a transmembrane protein (DsrM) with similarity to haem-b-binding polypeptides and a soluble protein (DsrK) resembling [4Fe-4S]-cluster-containing heterodisulphide reductase from methanogenic archaea. DsrE is a small soluble protein involved in intracellular sulphur reduction . In E. coli, the DsrEFH homologue TusBCD interacts with the DsrC homologue TusE in a sulfur relay system during 2-thiouridine biosynthesis .

This family includes DsrE/F and the homologues TusD/C.
Protein arginine methyltransferase NDUFAF7 (NDUFAF7)
Type: Family

NDUFAF7 (NADH:ubiquinone oxidoreductase complex assembly factor 7), also known as MidA or mitochondrial protein midA homologue, plays a role in mitochondrial complex I activity .
Aspartyl/glutamyl-tRNA amidotransferase subunit B-like (Asn/Gln_tRNA_amidoTrase-B-like)
Type: Homologous_superfamily

This domain superfamily is found in GatB and proteins related to bacterial Yqey. The domain is about 140 amino acid residues long. This domain is found at the C terminus of GatB which transamidates Glu-tRNA to Gln-tRNA. The function of this domain is uncertain. It does however suggest that Yqey and its relatives have a role in tRNA metabolism.
Glycosyl hydrolase-like 10 (GHL10)
Type: Domain

This TIM barrel domain is found in a group of bacterial glycosyl-hydrolase-like proteins falling into the family GHL10 .
Protein of unknown function UPF0178 (UPF0178)
Type: Family

This entry describes proteins of unknown function.