SII-SWORD/CoKE huggingface dataset:
Thiol:disulphide interchange protein DsbD (Thiol_diS_interchange_DbsD)
Type: Family

This entry represents the thiol:disulphide interchange protein, DsbD (also known as DipZ). These proteins are thought to facilitate the correct formation of disufide bonds in some periplasmic proteins, as well as for the assembly of the periplasmic c-type cytochromes . DsbD acts by transferring electrons from cytoplasmic thioredoxin to the periplasm. This transfer involves a cascade of disulfide bond formation and reduction steps .
Phenylalanine-tRNA ligase alpha chain 1, bacterial (Phe_tRNA_ligase_alpha1_bac)
Type: Family

Phenylalanine-tRNA ligase (

) is a tetramer of two alpha and two beta chains. This family represents the type 1 alpha chain from bacteria.

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 .
Multidrug resistance protein MdtK (Multidrug-R_MdtK)
Type: Family

This entry represents the multidrug resistance protein MdtK subfamily.

In general, proteins from the MATE family are involved in exporting metabolites across the cell membrane and are often responsible for multidrug resistance (MDR) . These proteins mediate resistance to a wide range of cationic dyes, fluroquinolones, aminoglycosides and other structurally diverse antibodies and drugs. MATE proteins are found in bacteria, archaea and eukaryotes. These proteins are predicted to have 12 α-helical transmembrane regions, some of the animal proteins may have an additional C-terminal helix .
Protein of unknown function UPF0397 (UPF0397)
Type: Family

The proteins in this entry are functionally uncharacterised.
Peroxiredoxin, TDXH subfamily (Peroxiredoxin_TDXH)
Type: Family

Peroxiredoxins are thiol-dependent peroxidases that play an important role in antioxidant defence mechanisms by removing hydrogen peroxide. This group of peroxiredoxins is represented by peroxiredoxins from Pyrococcus horikoshii (PhPrx) and Aeropyrum pernix (ApPrx) . They have a similar structure, though ApPrx has a C-terminal extension that PhPrx does not .
Protein of unknown function UPF0349 (UPF0349)
Type: Family

The proteins in this entry are functionally uncharacterised.
Phenylalanine-tRNA ligase alpha subunit, bacterial/archaeal (Phe_tRNA_ligase_alpha_bac/arc)
Type: Family

Phenylalanine-tRNA ligase (

) is a tetramer of two alpha and two beta subunits. This entry represents the type 2 alpha subunit from bacteria and archaea.

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 .
Phenylalanine-tRNA ligase beta chain 2, archaeal type (Phe_tRNA_ligase_beta2_arc)
Type: Family

Phenylalanine-tRNA ligase (also known as Phenylalanyl-tRNA synthetase) (

) is a tetramer of two alpha and two beta chains. This entry represents the type 2 beta chain from bacteria and archaea.

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 .
Peptidase M48, protease HtpX, putative (Pept_M48_protease_HtpX)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases belong to MEROPS peptidase family M48 (subfamily M48B). The members of this set of proteins are mostly described as probable protease htpX homologue (

).
Disulphide bond formation protein DsbB (Disulphide_bond_form_DsbB)
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 .
Methionine synthase MetE, archaeal (MetE_arc)
Type: Family

This entry represents methionine synthase MetE from Archaea. It catalyses the formation of methionine from methylcobalamin and homocysteine and belongs the vitamin-B12 (cobalamin) independent methionine synthase family .
tRNA (guanine(26)-N(2))-dimethyltransferase, archaeal and bacterial (TRM1_arc_bac)
Type: Family

This entry represents tRNA (guanine(26)-N(2))-dimethyltransferase from archaea and bacteria.

tRNA (guanine(26)-N(2))-dimethyltransferase

uses S-adenosyl-L-methionine to methylate tRNA.
Cardiolipin synthase (Cardiolipin_synthase)
Type: Family

Most bacteria use an enzyme belonging to the phospholipase D family as cardiolipin synthase. In contrast, eukaryotes and most actinobacteria use a cardiolipin synthase of the CDP-alcohol phosphatidyltransferase family .

This entry represents cardiolipin (CL) synthases that belong to the phospholipase D family. They catalyse the reversible phosphatidyl group transfer from one phosphatidylglycerol molecule to another to form cardiolipin (diphosphatidylglycerol) and glycerol . Bacillus subtilis has three genes (clsA, ywjE and ywiE) for CL synthase; the main role in CL synthesis being played by clsA .
NAD-capped RNA hydrolase NudC (RNA_Hydrolase_NudC)
Type: Family

This entry represents NAD-capped RNA hydrolase NudC from bacteria. NudC is a mRNA decapping enzyme that specifically removes the nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs by hydrolysing the diphosphate linkage to produce nicotinamide mononucleotide (NMN) and 5' monophosphate mRNA. This enzyme has preference for mRNAs with a 5'-end purine and catalyses the hydrolysis of a broad range of dinucleotide pyrophosphates. NudC assemblies into a homodimer with the appearance of a butterfly. Each monomer shows two tandem Nudix-fold domains, a N-terminal and a C-terminal, and an extended zinc-binding motif in-between. As a subgroup of the Nudix hydrolase family, NudC has a conserved Nudix motif .
NH(3)-dependent NAD(+) synthetase (NH(3)-dep_NAD(+)_synth)
Type: Family

This entry represents NH(3)-dependent NAD(+) synthetases from prokaryotes.

NAD+ is involved electron transport and redox reactions and in DNA ligation and protein ADP-ribosylation. In yeast and most other organisms, NAD is generated through the de novo pathway and the salvage pathway. In the de novo pathway, quinolinic acid is converted to nicotinic acid mononucleotide (NaMN). In the salvage pathway, NaMN is generated by recycling of nicotinamide. Both pathways converge on NaMN, which is then converted into deamido-NAD+. Subsequently, deamido-NAD+ is converted to NAD+ by NAD+ synthetase .

NAD+ synthetase has been extensively studied in bacteria. It is encoded by nadE gene in E. coli and by outB gene in B. subtilis . These prokaryotic enzymes are ammonia-dependent (containing an ammonia-utilising domain) . However, some prokaryotic NAD(+) synthetases, such as that from Mycobacterium tuberculosis, contain a nitrilase-related domain, are glutamine-dependent, and are not included in this entry .
RNA pyrophosphohydrolase RppH (RppH)
Type: Family

This entry represents an RNA pyrophosphohydrolase belonging to the nudix hydrolase family, RppH subfamily which includes RppH from bacteria and NUD25-27 from plants. RppH accelerates the degradation of transcripts by removing pyrophosphate from the 5'-end of triphosphorylated RNA, leading to a more labile monophosphorylated state that can stimulate subsequent ribonuclease cleavage . NUD25-27 mediate the hydrolysis of some nucleoside diphosphate derivatives. They can use diadenosine 5',5'''-P1P5 pentaphosphate (Ap5A) as substrates .
RNA 2'-phosphotransferase KptA, putative (RNA_2'-PTrans_KptA)
Type: Family

This entry represents KptA, a putative RNA 2'-phosphotransferase. KptA, a functional Tpt1 protein homologue from Escherichia coli is strikingly similar to yeast Tpt1 in its kinetic parameters, although E. coli is not known to have a 2'-phosphorylated RNA substrate .
Putative manganese efflux pump MntP (Put_MntP)
Type: Family

Members of this family probably function as a manganese efflux pump . Escherichia coli MntP (formerly YebN), is upregulated by manganese through transcriptional regulator MntR.
Protein of unknown function UPF0316 (UPF0316)
Type: Family

The proteins in this entry are functionally uncharacterised.
Sulfur carrier protein TusA (Sulphur_carrier_TusA)
Type: Family

This entry represents the TusA family of sulfur carrier proteins. TusA (also known as SirA, UvrY and YhhP) belongs to a group of five proteins (TusA-E) which together are responsible for 2-thiouridylation of 5-methylaminomethyl-2-thiouridine at tRNA wobble positions. TusA accepts sulfur from cysteine desulfurase IscS and transfers it in turn to TusD .
Putative phosphoesterase YjcG (YjcG)
Type: Family

The proteins in this entry are functionally uncharacterised but contains a phosphoesterase HXTX domain found in a number of known and predicted phosphoesterases.
Uncharacterised protein family UPF0353 (UPF0353)
Type: Family

The proteins in this entry are functionally uncharacterised.
Manganese-dependent inorganic pyrophosphatase, probable (Mn-dep_inorganic_PyrPase)
Type: Family

This entry represents probable manganese-dependent inorganic pyrophosphatases that belong to the PPase class C family. This entry includes Manganese-dependent inorganic pyrophosphatase from Methanocaldococcus jannaschii that is characterised .
ATP-dependent Clp protease adaptor protein ClpS (ClpS)
Type: Family

This entry includes ClpS from bacteria and chloroplastic CLPS1/2 from plants. ClpS binds directly to N-terminal destabilising residues through its substrate-binding site distal to the ClpS-ClpA interface, and targets these substrates to the ClpAP protease for degradation .

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.
Uncharacterised protein family UPF0194, membrane protein YbhG (UPF0194_membrane_YbhG)
Type: Family

The proteins in this entry are functionally uncharacterised, but are related to the secretion protein HlyD.
Mevalonate kinase, archaeal (Mevalonate_kinase_arc)
Type: Family

Mevalonate kinase (

) is well-characterised among the Eukaryotes, where it plays a role in the synthesis of isopentanyl pyrophosphate, a common intermediate for a number of pathways including cholesterol biosynthesis. It is also involved in mevalonate catabolism. Close homologues are found in the Archaea. A bacterial example is found in the Borrelia burgdorferi (Lyme disease spirochete), but is not necessarily the same biosynthetic enzyme.

This entry represents archaeal mevalonate kinases. The function of this enzyme is to catalyse the following reaction:

ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
Signal recognition particle, SRP19 subunit, archaeal-type (SRP19_arc-type)
Type: Family

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

This entry represents the SRP19 subunit in Archaea and Fungi. In Fungi it is known as SEC65 subunit.
Nitrobindin, bacteria/plant (Nb(III)_bact/plant)
Type: Family

This entry includes the Nitrobindin family members mostly from bacteria and plants. Mycobacterium tuberculosis Nb (Mt-Nb(III) is a peroxynitrite isomerase, which is a heme-binding protein able to scavenge peroxynitrite and to protect free L-tyrosine against peroxynitrite-mediated nitration, by acting as a peroxynitrite isomerase that converts peroxynitrite to nitrate . This entry also includes ferric nitrobindin-like protein, lacks the conserved His residue that binds heme iron.

Nitrobindins (Nbs) are evolutionary conserved all-β-barrel heme-proteins displaying a highly solvent-exposed heme-Fe(III) atom. Mycobacterium tuberculosis Nb (Mt-Nb(III) and the C terminus of Homo sapiens Nb (Hs-Nb(III)) share this β-barrel structure, suggesting that Nb may act as a sensor possibly modulating the THAP4 transcriptional activity residing in the N-terminal region . Ferric nitrobindin-like proteins that lack the conserved His residue which binds heme iron are also included in the Nb family.
Signal recognition particle, SRP54 subunit (SRP54)
Type: Family

This entry represents the SRP54 subunit of the signal recognition particle protein translocation system.

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

The bacterial homologues of the SRP54 protein and SRP RNA are Ffh and 4.5S RNA. They comprise a minimal bacterial SRP that can target ribosome-nascent chain complexes to the plasma membrane via interaction with FtsY, the bacterial homologue of the SRP receptor .
ATPase, V1 complex, subunit F, bacterial/archaeal (ATPase_V1-cplx_fsu_bac/arc)
Type: Family

This entry represents the F subunit of A/V-type ATP synthases from bacteria and archaea.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
Uncharacterised protein family UPF0313 (UPF0313)
Type: Family

The proteins in this entry are functionally uncharacterised. They contain a radical SAM domain .