SII-SWORD/CoKE huggingface dataset:
CO dehydrogenase/acetyl-CoA synthase complex beta subunit (CO_DH/Ac-CoA_synth_bsu)
Type: Family

The carbon monoxide dehydrogenase alpha subunit (

) catalyses the interconversion of CO and CO2 and the synthesis of acteyl-coA from the methylated corrinoid/iron sulphur protein, CO and CoA. Nomenclature follows the description for Methanosarcina thermophila. The complex is also found in Archaeoglobus fulgidus, not considered a methanogen, but is otherwise generally associated with methanogenesis.
Desulfoferrodoxin, N-terminal domain (Desulfoferrodoxin_N)
Type: Domain

The desulforedoxin domain is a small non-haem iron domain present in the desulforedoxin (Dx) and desulfoferrodoxin (Superoxide reductase or Dfx) proteins of some archeael and bacterial methanogens and sulfate/sulfur reducers. It constitutes essentially the full length of desulforedoxin, and the N-terminal domain of Desulfoferrodoxin.

Desulforedoxin is a small, single-domain homodimeric protein. Each subunit (of 36 amino acid residues) contains an iron atom bound to four cysteinyl sulfur atoms, Fe(S-Cys)4, in a distorted tetrahedral coordination. Its metal centre is similar to that found in rubredoxin type proteins .
UDP-3-O-acyl N-acetylglucosamine deacetylase (UDP-acyl_GlcNac_deAcase)
Type: Family

This entry represents the UDP-3-O-N-acetylglucosamine deacetylase family of proteins.

UDP-3-O-N-acetylglucosamine deacetylases are zinc-dependent metalloamidases that catalyse the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram-negative bacteria. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds . The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer α/β structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid . This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents .
Fructose-1,6-bisphosphatase class 2/Sedoheputulose-1,7-bisphosphatase (FBPase_class-2/SBPase)
Type: Family

Gluconeogenesis is an important metabolic pathway, which produces glucose from noncarbohydrate precursors such as organic acids, fatty acids, amino acids, or glycerol. Fructose-1,6-bisphosphatase, a key enzyme of gluconeogenesis, is found in all organisms, and five different classes of these enzymes have been identified.

This entry represents the class 2 fructose-1,6-bisphosphatases, which include GlpX and YggF of Escherichia coli (strain K12), which show different catalytic properties. The crystal structure of GlpX has been determined in a free state and in the complex with a substrate (fructose 1,6-bisphosphate) or inhibitor (phosphate). The crystal structure of the ligand-free GlpX revealed a compact, globular shape with two α/β-sandwich domains. The core fold of GlpX is structurally similar to that of Li+-sensitive phosphatases suggesting that they have a common evolutionary origin and catalytic mechanism. The structure of the GlpX complex with fructose 1,6-bisphosphate revealed that the active site is located between two domains and accommodates several conserved residues coordinating two metal ions and the substrate. A third metal ion is bound to phosphate 6 of the substrate. Inorganic phosphate strongly inhibited activity of both GlpX and YggF, and the crystal structure of the GlpX complex with phosphate demonstrated that the inhibitor molecule binds to the active site. Alanine replacement mutagenesis of GlpX identifies 12 conserved residues important for activity and suggested that Thr(90) is the primary catalytic residue .

A number of the proteins in this entry, particularly those from algae are bi functional and can catalyzes the hydrolysis of fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate to fructose 6-phosphate and sedoheptulose 7-phosphate, respectively.
Ribonucleotide reductase Class Ib, NrdI (RNR_NrdI)
Type: Family

Ribonucleotide reductases (RNRs) are enzymes that catalyse the conversion of ribonucleotides to the corresponding deoxyribonucleotides to provide the precursors of DNA synthesis. There are three classes (I-III) of RNRs and four known subclasses within class I RNRs (Ia-Id) , which differ by their metal cofactor, their stable organic radical and sequence . Class I consists of two homodimeric subunits: alpha2, which catalyses the reversible one-electron oxidation of a conserved cysteine residue to a thiyl radical, which is initiated by a dinuclear metallocofactor and tyrosyl radical positioned in the beta2 subunit. Class Ib RNR is encoded in four different genes: nrdH, nrdI, nrdE (alpha subunit) and nrdF (beta subunit) and has Mn2 in the dimetal cluster to oxidize a nearby tyrosine residue to a stable radical.

This family represents NrdI, a flavoprotein activase which provides superoxide that binds to the beta subunit and forms a hydrophilic channel connecting their active sites .
Ribonuclease M5 (RNase_M5)
Type: Family

Ribonuclease M5 is required for correct processing of both the 5' and 3' ends of 5S rRNA precursor. It cleaves both sides of a double-stranded region yielding mature 5S rRNA in one step .
Orotate phosphoribosyl transferase domain (Or_phspho_trans_dom)
Type: Domain

Orotate phosphoribosyltransferase (OPRTase) is involved in the biosynthesis of pyrimidine nucleotides. This entry represents the orotate phosphoribosyl transferase domain.
CTP synthase (CTP_synthase)
Type: Family

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

Phosphoserine phosphatase (

), also known as O-phosphoserine phosphohydrolase, is involved in both serine and glycine biosynthesis. It catalyzes the reaction 3-phospho-serine + H2O = L-serine + phosphate, which is the last step in the biosynthesis of serine from carbohydrates. The reaction proceeds via the formation of a phosphoryl-enzyme intermediate. It acts as a homodimer, and requires magnesium as a cofactor .
ZPR1-like, archaea (ZPR1-like_arc)
Type: Family

This entry represents a group of ZPR1-like proteins predominantly found in archaea, including the poorly characterised ZPR1-like proteins PH1223 and MJ0530. ZPR1 was shown experimentally to bind zinc. ZPR1 binds the tyrosine kinase domain of epidermal growth factor receptor but is displaced by receptor activation and autophosphorylation after which it redistributes in part to the nucleus. The function of ZPR1 from archaea and eukaryotes is not yet clear. However, Zpr1 from yeast acts as a protein folding chaperone for elongation factor 1-alpha .
Branched-chain amino acid transport, AzlC (Brnchd-chn_aa_trnsp_AzlC)
Type: Family

The gene encoding the AzlC protein is a part of the azl operon which is involved in branched-chain amino acid transport . AzlCD is a bipartite histidine exporter consisting of AzlC and AzlD subunits . Overexpression of this gene results in resistance to a leucine analog, 4-azaleucine.
Dethiobiotin synthase BioD (DTB_synth_BioD)
Type: Family

BioD is involved in biotin biosynthesis and catalyses the reaction (CO2 + 7,8-diaminononanoate + ATP = dethiobiotin + phosphate + ADP) . It binds ATP and requires magnesium as a co-factor.

Proteins in this entry also include bifunctional proteins, such as BioCD from Bordetella avium, BioDA from Aspergillus nidulans , and BIO3-BIO1 protein from plants. They are also involved in the biotin biosynthesis .
Restriction endonuclease, type I, HsdR (Restrct_endonuc_typeI_HsdR)
Type: Family

This entry represents the R subunit (HsdR) of type I restriction endonucleases. The restriction subunit (R) is required for both nuclease and ATPase activity, but not for modification. After locating a non-methylated recognition site, the enzyme complex serves as a molecular motor that translocates DNA in an ATP-dependent manner until a collision occurs that triggers cleavage . Members of this family are assumed to differ from each other in DNA site specificity. Cryo-electron microscopy structures of a representative type I R-M system highlight the importance of the Intrinsic flexibility of the individual subunits for the functionality of this system .
Cell envelope-related transcriptional attenuator domain (LytR_CpsA_psr)
Type: Domain

This entry describes a domain (known as LCP domain) that is found in the predicted extracellular domain of a number of proteins involved in cell wall biosynthesis . One of these is protein Psr, described as a penicillin binding protein 5 (PDP-5) synthesis repressor. Another is Bacillus subtilis LytR, described as a transcriptional attenuator of itself and the LytABC operon, where LytC is N-acetylmuramoyl-L-alanine amidase. A third is CpsA, a putative regulatory protein involved in exocellular polysaccharide biosynthesis. These proteins share the property of having a short putative N-terminal cytoplasmic domain and transmembrane domain forming a signal-anchor . Studies in Corynebacterium glutamicum revealed that this domain contains conserved aspartate and arginine residues and mutations in this domain are detrimental for the bacterium growth .
DNA polymerase II large subunit DP2 (PolC_DP2)
Type: Family

This family represents the large subunit, DP2, of a two subunit novel archaebacterial replicative DNA polymerase first characterised for Pyrococcus furiosus . The orthologue from Methanococcus jannaschii has also been characterised .
Ribonuclease II/ribonuclease R (RNase_II/RNase_R)
Type: Family

This family is defined to identify a pair of paralogous 3'->5' exoribonucleases in Escherichia coli, plus the set of proteins apparently orthologous to one or the other in other eubacteria. VacB was characterised originally as required for the expression of virulence genes, but is now recognised as the exoribonuclease RNase R (Rnr). Its paralog in Escherichia coli and Haemophilus influenzae is designated exoribonuclease II (Rnb) . Both are involved in the degradation of mRNA, and consequently have strong pleiotropic effects that may be difficult to disentangle. Both these proteins share domain-level similarity (RNB, S1) with a considerable number of other proteins, and full-length similarity scoring below the trusted cut-off to proteins associated with various phenotypes but uncertain biochemistry; it may be that these latter proteins are also 3' exoribonucleases.
ComEC/Rec2-related protein (ComEC_N)
Type: Domain

This family is defined to identify a pair of paralogous 3' exoribonucleases in Escherichia coli, plus the set of proteins apparently orthologous to one or the other in other eubacteria. VacB was characterised originally as required for the expression of virulence genes, but is now recognised as the exoribonuclease RNase R (Rnr). Its paralog in Escherichia coli and Haemophilus influenzae is designated exoribonuclease II (Rnb). Both are involved in the degradation of mRNA, and consequently have strong pleiotropic effects that may be difficult to disentangle. Both these proteins share domain-level similarity (RNB, S1) with a considerable number of other proteins, and full-length similarity scoring below the trusted cut off to proteins associated with various phenotypes but uncertain biochemistry; it may be that these latter proteins are also 3' exoribonucleases.

Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions .
Monothiol glutaredoxin-related (Monothiol_GRX-rel)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This family groups proteins from different organisms which are related to monothiol glutaredoxins. Monothiol glutaredoxins occur in different subcellular compartments; for instance, yeast Grx3 and Grx4 are nuclear proteins, whereas Grx5 is mitochondrially localized . They share a common basic structural motif and biochemical mechanism of action, while participating in a diversity of cellular functions as protein redox regulators.
Sodium/potassium/calcium exchanger (K/Na/Ca-exchanger)
Type: Family

This entry represents the potassium-dependent sodium/calcium exchanger protein family (NCKX), also known as solute carrier family 24 (SLC24) .
Mg chelatase-related protein (Mg_chelat-rel)
Type: Family

This family of proteins are variously described as 'hypothetical protein yifB', 'competence protein', 'hypothetical protein' or 'Mg chelatase-related protein'. Sequence comparison shows that YifB is closest to the chelatase family . This family includes ComM, a protein that is induced during competence development .
Helicase SMUBP-2/Hcs1-like (SMUBP-2/Hcs1-like)
Type: Family

Proteins in this entry belong to the DNA2/NAM7 helicase family, including SMUBP-2 from humans, DNA polymerase alpha-associated DNA helicase A (also konwn as Hcs1) from budding yeasts and some putative helicases from prokaryotes.
Cobyrinate/Hydrogenobyrinate a,c-diamide synthase CbiA/CobB (CbiA/CobB_synth)
Type: Family

This family describes cobyrinic acid a,c-diamide synthase CbiA protein of cobalamin biosynthesis. It is responsible for the amidation of cobyrinic acid to cobyrinic acid a,c-diamide via the intermediate formation of cobyrinic acid c-monoamide or hydrogenobrynic acid. NH(2) groups are provided by glutamine and one molecule of ATP hydrogenolyzed for each amidation . This entry also includes the hydrogenobyrinate a,c-diamide synthase CobB that catalyzes the ATP-dependent amidation of the two carboxylate groups at positions a and c of hydrogenobyrinate, using either L-glutamine or ammonia as the nitrogen source .
Cobalamin biosynthesis CobD/CbiB (Cobalamin_biosynth_CobD/CbiB)
Type: Family

This entry represents the CbiB protein, which is involved in cobalamin biosynthesis and porphyrin biosynthesis. It converts cobyric acid to cobinamide by the addition of aminopropanol on the F carboxylic group. It is part of the cob operon .

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .
CO dehydrogenase/acetyl-CoA synthase delta subunit (CO_DH/Ac-CoA_synth_dsu)
Type: Family

This is the small subunit of the ACDS complex that catalyses the reversible cleavage of acetyl-CoA, allowing growth on acetate as sole source of carbon and energy. ACDS complex is a heterodimer which catalyses the reaction CO + H2O + Acceptor = CO2 + Reduced acceptor and is involved in the synthesis of acetyl-CoA from CO2 and H2. This subunit probably maintains the overall quaternary structure of the ACDS complex.
Clp protease, ATP-binding subunit ClpX (Clp_protease_ATP-bd_su_ClpX)
Type: Family

ClpX is a member of the HSP (heat-shock protein) 100 family. Gel filtration and electron microscopy showed that ClpX subunits associate to form a six-membered ring that is stabilised by binding of ATP or nonhydrolysable analogs of ATP . It functions as an ATP-dependent molecular chaperone and is the regulatory subunit of the ClpXP protease .

ClpXP is involved in DNA damage repair, stationary-phase gene expression, and ssrA-mediated protein quality control. To date more than 50 proteins include transcription factors, metabolic enzymes, and proteins involved in the starvation and oxidative stress responses have been identified as substrates .

The N-terminal domain of ClpX is a C4-type zinc binding domain (ZBD) involved in substrate recognition. ZBD forms a very stable dimer that is essential for promoting the degradation of some typical ClpXP substrates such as lO and MuA .
Magnesium/cobalt transport protein CorA (Mg/Co-transport_prot_CorA)
Type: Family

The CorA transport system is a primary Mg2+ transporter for Bacteria and Archaea. Some members in this family may have a function other than Mg2+ transport . Prokaryotic CorA can be classified into two sub-groups: (1) T. maritima type (group A) (2) E. coli and S.typhimurium type (group B) .
Succinate dehydrogenase/fumarate reductase iron-sulphur protein (Succ_DH/fum_Rdtase_Fe-S)
Type: Family

Succinate dehydrogenase and fumarate reductase are reverse directions of the same enzymatic interconversion, succinate + FAD+ = fumarate + FADH2 (

). In Escherichia coli, the forward and reverse reactions are catalyzed by distinct complexes: fumarate reductase operates under anaerobic conditions and succinate dehydrogenase operates under aerobic conditions. This group also includes a region of the B subunit of a cytosolic archaeal fumarate reductase.
Glycolate oxidase subunit GlcD (GlcD)
Type: Family

The glc locus of Escherichia coli encodes the subunits of glycolate oxidase and the glc regulator protein. The subunit GlcD is similar to that of several D-lactate dehydrogenases, including that of E. coli. Glycolate oxidase has been found to have some D-lactate dehydrogenase activity.
Heat shock protein HslU (HslU)
Type: Family

This family of proteins represent HslU, a bacterial clpX homologue, which is an ATPase and chaperone belonging to the AAA Clp/Hsp100 family and a component of the eubacterial proteasome.
Leucyl-tRNA synthetase, class Ia, archaeal/eukaryotic cytosolic (Leu-tRNA-synth_Ia_arc/euk)
Type: Family

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Leucyl tRNA synthetase (

) is an alpha monomer that belongs to class Ia. There are two different families of leucyl-tRNA synthetases. This family includes both archaeal and cytosolic eukaryotic leucyl-tRNA synthetases.
MauM/NapG ferredoxin-type protein (MauM_NapG)
Type: Family

MauM ferredoxin-type protein is involved in methylamine utilization . NapG ferredoxin-type protein is associated with nitrate reductase activity . The two proteins are highly similar.