SII-SWORD/CoKE huggingface dataset:
Signal transduction response regulator, phosphate regulon transcriptional regulatory protein PhoB (Sig_transdc_resp-reg_PhoB)
Type: Family

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .

This entry represents the signal transduction regulatory protein PhoB. PhoB is a DNA-binding response regulator protein acting with PhoR in a 2-component system responding to phosphate ion. PhoB acts as a positive regulator of gene expression for phosphate-related genes such as phoA, phoS, phoE and ugpAB as well as itself . It is often found proximal to genes for the high-affinity phosphate ABC transporter (pstSCAB;

) and presumably regulates these as well.
Phenylacetate-CoA ligase (PA_CoA_ligase)
Type: Family

This entry represents Phenylacetate-coenzyme A ligase (PaaK) found mainly in bacteria and archaea.

Phenylacetate-CoA ligase (PA-CoA ligase) catalyses the first step in aromatic catabolism of phenylacetic acid (PA) into phenylacetyl-CoA (PA-CoA) . Often located in a conserved gene cluster with enzymes involved in phenylacetic acid activation (paaG/H/I/J), phenylacetate-CoA ligase has been found among the proteobacteria as well as in Gram-positive prokaryotes . In the B-subclass proteobacterium Azoarcus evansii, phenylacetate-CoA ligase has been shown to be induced under aerobic and anaerobic growth conditions. It remains unclear however, whether this induction is due to the same enzyme or to another isoenzyme restricted to specific anaerobic growth conditions .
1,2-phenylacetyl-CoA epoxidase, subunit A (PaaA)
Type: Family

This entry represents 1,2-phenylacetyl-CoA epoxidase, subunit A (also known as PaaA). E. coli PaaA and PaaC are components of 1,2-phenylacetyl-CoA epoxidase multicomponent enzyme system which catalyses the reduction of phenylacetyl-CoA (PA-CoA) to form 1,2-epoxyphenylacetyl-CoA. PaaA is the catalytic subunit involved in the incorporation of one atom of molecular oxygen into phenylacetyl-CoA .
1,2-phenylacetyl-CoA epoxidase, subunit C (PaaC)
Type: Family

This entry represents 1,2-phenylacetyl-CoA epoxidase, subunit C (also known as PaaC). E. coli PaaA and PaaC are components of 1,2-phenylacetyl-CoA epoxidase multicomponent enzyme system which catalyses the reduction of phenylacetyl-CoA (PA-CoA) to form 1,2-epoxyphenylacetyl-CoA. PaaC may be essential for structural integrity of the alpha subunit .
1,2-phenylacetyl-CoA epoxidase, subunit D (PaaD-like)
Type: Family

This entry represents the 1,2-phenylacetyl-CoA epoxidase, subunit D (also know as PaaD) and related bacterial proteins. PaaD ia a component of 1,2-phenylacetyl-CoA epoxidase multicomponent enzyme system which catalyses the reduction of phenylacetyl-CoA (PA-CoA) to form 1,2-epoxyphenylacetyl-CoA. The subunit D may have a function related to the maturation of the monooxygenase complex, rather than direct involvement in catalysis. PaaD could assist either in maturation of PaaE or PaaA .

Phenylacetate-CoA oxygenase is comprised of a five gene complex responsible for the hydroxylation of phenylacetate-CoA (PA-CoA) as the second catabolic step in phenylacetic acid (PA) degradation . Although the exact function of this enzyme has not been determined, it has been shown to be required for phenylacetic acid degradation and has been proposed to function in a multicomponent oxygenase acting on phenylacetate-CoA .
1,2-phenylacetyl-CoA epoxidase, subunit E (PaaE)
Type: Family

This entry represents the 1,2-phenylacetyl-CoA epoxidase, subunit E (also know as PaaE) and related bacterial proteins. PaaE ia a component of 1,2-phenylacetyl-CoA epoxidase multicomponent enzyme system which catalyses the reduction of phenylacetyl-CoA (PA-CoA) to form 1,2-epoxyphenylacetyl-CoA. The subunit E is a reductase with a preference for NADPH and FAD, capable of reducing cytochrome c .

Phenylacetate-CoA oxygenase is comprised of a five gene complex responsible for the hydroxylation of phenylacetate-CoA (PA-CoA) as the second catabolic step in phenylacetic acid (PA) degradation . Although the exact function of this enzyme has not been determined, it has been shown to be required for phenylacetic acid degradation and has been proposed to function in a multicomponent oxygenase acting on phenylacetate-CoA .
Periplasmic nitrate reductase c-type cytochrome, NapC/NirT (NO3Rdtase_cyt_c_NapC/NirT)
Type: Family

This entry contains NapC, a predicted membrane-anchored four-heme c-type cytochrome that forms one component of the periplasmic nitrate reductase along with NapA, NapB, NapD, NapE, and NapF subunits. A single known exception at this time is NirT, which is instead a component of a nitrite reductase. This family excludes TorC subunits of trimethylamine N-oxide (TMAO) reductases .
Ferredoxin-type protein, NapH/MauN family (NapH_MauN)
Type: Family

Most members of this family are the NapH protein, found next to NapG in operons that encode the periplasmic nitrate reductase . Some species with this reductase lack NapC but accomplish electron transfer to NapAB in some other manner, likely to involve NapH, NapG, and/or some other protein. A few members of this protein are designated MauN and are found in methylamine utilization operons in species that appear to lack a periplasmic nitrate reductase .
Trimethylamine-N-oxide reductase TorA (TorA)
Type: Family

This very narrowly defined family represents trimethylamine-N-oxide (TMAO) reductase TorA. TorA typically is located in the periplasm, has a Tat (twin-arginine translocation)-dependent signal sequence, and is encoded in a torCAD operon. TorA reduces TMAO into trimethylamine; an anaerobic reaction coupled to energy-yielding reactions . The torC gene, located upstream from torA encodes a pentahemic c-type cytochrome, likely to be involved in electron transfer to the TorA terminal reductase .
Anaerobic dimethyl sulphoxide reductase, subunit A, DmsA/YnfE (Anaer_DMSO_reductase)
Type: Family

Many bacterial species are capable of anaerobic growth by using dimethylsulphoxide (DMSO) as the terminal electron acceptor, with DMSO reductase as the terminal elctron transfer enzyme. In Escherichia coli and many other Gram-negative bacteria DMSO reductase is a membrane-bound enzyme composed of three subunits; a catalytic molybdenum-containing subunit (DmsA), an electron transfer subunit containing a [4Fe-4S] cluster (DmsB), and a hydrophobic membrane-spanning anchor subunit which attaches the enzyme to the cytoplasmic membrane (DmsC) . It is generally thought now that DmsAB faces the periplasm, contradicting previous results suggesting a cytoplasmic location. The N-terminal region of DmsA contains a "twin-arginine" signal sequence, suggesting export to the periplasm occurs via the TAT secretion pathway.

This entry represents known and predicted bacterial DmsA proteins. Several species contain one or more paralogs of DmsA. In
E. coli
, the two paralogs of DmsA, YnfE and YnfF, are encoded within the ynfEFGHI operon . YnfE and YnfF cannot form a functional complex with DmsBC, but YnfFGH can restore growth on DMSO when DmABC is deleted. The function of YnfE is not known and it appears to prevent formation of the YnfFGH complex if present.
Bacterial surface protein 26-residue repeat (Liste_lipo_26)
Type: Repeat

This entry describes a tandem peptide repeat sequence of 25 or 26 residues, found in predicted surface proteins (often lipoproteins) mainly from Listeria monocytogenes, Listeria innocua, Enterococcus faecalis (Streptococcus faecalis), Lactobacillus plantarum, Mycoplasma spp., Helicobacter hepaticus, and other species. DNA sequences describing the protein repeats are described as having dyad symmetry, lead to the name PARCEL (Palindromic Amphipathic Repeat Coding ELement) .
Structural maintenance of chromosomes protein, prokaryotic (SMC_prok)
Type: Family

The SMC (structural maintenance of chromosomes) family of proteins, exist in virtually all organisms, including bacteria and archaea. The SMC proteins are essential for successful chromosome transmission during replication and segregation of the genome in all organisms. They function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression .

SMCs are generally present as single proteins in bacteria, and as at least six distinct proteins in eukaryotes. The proteins range in size from approximately 110 to 170kDa, and share a five-domain structure, with globular N- and C-terminal domains separated by a long (circa 100 nm or 900 residues) coiled coil segment in the centre of which is a globular ''hinge'' domain, characterised by a set of four highly conserved glycine residues that are typical of flexible regions in a protein. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T), which has been shown by mutational studies to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif (XXXXD, where X is any hydrophobic residue), and a LSGG motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases .

This entry represents the SMC protein from bacteria and archaea .
Cytidylate kinase, archaeal-type (Cyt_kin_arch)
Type: Family

Proteins in this family are believed to be cytidylate kinase. Members of this family are found in the archaea and in spirochaetes, and differ considerably from the common bacterial form of cytidylate kinase described by

.
Selenoprotein, Rdx-type (Selenoprotein_Rdx-typ)
Type: Family

This entry represents the Rdx family of selenoproteins, which includes mammalian selenoproteins SelW, SelV, SelT and SelH, bacterial SelW-like proteins and cysteine-containing proteins of unknown function in all three domains of life. Mammalian Rdx12 and its fish selenoprotein orthologues are also members of this family . These proteins possess a thioredoxin-like fold and a conserved CXXC or CxxU (U is selenocysteine) motif near the N terminus, suggesting a redox function. Rdx proteins can use catalytic cysteine (or selenocysteine) to form transient mixed disulphides with substrate proteins. Selenium (Se) plays an essential role in cell survival and most of the effects of Se are probably mediated by selenoproteins.

Selenoprotein W (SelW) plays an important role in protection of neurons from oxidative stress during neuronal development .
2-oxoacid:acceptor oxidoreductase, gamma subunit, pyruvate/2-ketoisovalerate (PorC_KorC)
Type: Domain

A number of anaerobic and microaerophilic species lack pyruvate dehydrogenase and have instead a four subunit, oxygen-sensitive pyruvate oxidoreductase, with either ferredoxins or flavodoxins (Helicobacter pylori (Campylobacter pylori)) used as the acceptor. Several related four-subunit enzymes may exist in the same species. This entry describes the gamma subunit. In Pyrococcus furiosus, enzymes active on pyruvate and 2-ketoisovalerate share a common gamma subunit .
Pyruvate-flavodoxin oxidoreductase (Pyrv_flavodox_OxRed)
Type: Family

The oxidative decarboxylation of pyruvate to acetyl-CoA, a central step in energy metabolism, can occur by two different mechanisms . In mitochondria and aerobic bacteria this reaction is catalysed by the multienzyme complex pyruvate dehydrogenase using NAD as electron acceptor. In anaerobic organisms, however, this reaction is reversibly catalysed by a single enzyme using either ferrodoxin or flavodoxin as the electron acceptor.

Pyruvate:ferrodoxin/flavodoxin reductases (PFORs) in this entry occur in both obligately and facultatively anaerobic bacteria and also some eukaryotic microorganisms. These proteins are single-chain enzymes containing a thiamin pyrophosphate cofactor for the cleavage of carbon-carbon bonds next to a carbonyl group, and iron-sulphur clusters for electron transfer. The Desulfovibrio africanus enzyme is currently the only PFOR whose three dimensional structure is known . It is a homodimer where each subunit contains one thiamin pyrophosphate cofactor and two ferrodoxin-like 4Fe-S clusters and an atypical 4Fe-S cluster. Each monomer is composed of seven domains - domains I, II and VI make intersubunit contacts, while domains III, IV and V are located at the surface of the dimer, and domain VII forms a long arm extending over the other subunit. The cofactor is bound at the interface of domains I and VI and is proximal to the atypical 4Fe-S bound by domain VI, while the ferrodoxin-like 4Fe-S clusters are bound by domain V. Comparison of this enzyme with the multi-chain PFORs shows a correspondence between the domains in this enzyme and the subunits of the multi-chain enzymes.
2-oxoacid:acceptor oxidoreductase, beta subunit (OFOB)
Type: Family

A number of anaerobic and microaerophilic bacterial species lack pyruvate dehydrogenase and have instead a much smaller enzyme complex consisting of a 2-oxoacid oxidoreductase with either ferredoxin or flavodoxin used as the acceptor. 2-oxoacid oxidoreductases are also found in the Archaea. The enzyme complex can comprise one (alpha2), two (alpha2-beta2), or four distinct subunits . 2-oxoacid oxidoreductases catalyse CoA-dependent oxidative decarboxylation of 2-oxoacids . Halobacterium salinarum (and most halophilic archaea) contains two 2-oxoacid:ferredoxin oxidoreductases. One (Kor) functions as an oxoglutarate-ferredoxin oxidoreductase , whereas the other (Por) has been characterised as a pyruvate-ferredoxin oxidoreductase .
Translation elongation factor P-like, YeiP (Transl_elong_p-like_YeiP)
Type: Family

This entry represents homologues of elongation factor P (

) and are probable translation factors. Members of this family are found only in some gammaproteobacteria, including Escherichia coli (YeiP) and Vibrio cholerae.
2-oxoacid:acceptor oxidoreductase, delta subunit, pyruvate/2-ketoisovalerate (PorD_KorD)
Type: Family

A number of anaerobic and microaerophilic species lack pyruvate dehydrogenase and have instead a four subunit, oxygen-sensitive pyruvate oxidoreductase, with either ferredoxins or flavodoxins used as the acceptor. Several related four-subunit enzymes may exist in the same species. This entry describes the delta subunits, representing mostly pyruvate, 2-ketoisovalerate, and 2-oxoglutarate specific enzymes. The delta subunit is the smallest and resembles ferredoxins.
Glutaredoxin, eukaryotic/virial (Glutaredoxin_euk/vir)
Type: Domain

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 entry is found in eukaryotic glutaredoxins and includes sequences from fungi, plants and metazoans as well as viruses .
Glutaredoxin, GrxC (GRX_bact)
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 subfamily of bacterial glutaredoxins (GRX) includes Escherichia coli Grx1 (GrxC1) and Grx3 (GrxC). GrxC appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulphides .
Glutaredoxin-2 (Grx2)
Type: Family

This family includes the highly abundant Escherichia coli GrxB (Grx2) glutaredoxin which is notably longer than either GrxA or GrxC . Unlike the other two E. coli glutaredoxins, Grx2 appears to be unable to reduce ribonucleotide reductase , and may have more to do with resistance to redox stress . Purified Grx2 exhibits glutathione S-transferase activity indicating that it may have a dual-function as glutaredoxin and glutathione S-transferase .
Glutaredoxin, GrxA (GRXA)
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 entry includes the Escherichia coli glyutaredoxin GrxA which appears to have primary responsibility for the reduction of ribonucleotide reductase .
Disulfide oxidoreductase TON_0319-like (TON_0319-like)
Type: Family

This group of proteins found in bacteria and archaea contains a C-terminal domain with homology to bacterial and eukaryotic glutaredoxins, including a CPYC motif. Many members of this family are selenoproteins. Member protein TON_0319 from Thermococcus onnurineus (

) was shown modulate the redox state of the CxxC disulfide of SurR, a transcription factor involved in the sulfur response .

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.