SII-SWORD/CoKE huggingface dataset:
Carboxylate/Amino Acid/Amine Transporter (CO/AA/NH_transpt)
Type: Family

Proteins in this entry contain between eight and ten predicted transmembrane regions and are thought to function as transporters. The best characterised of these proteins is PecM (

) from Erwinia chrysanthemi. PecM is an integral membrane protein which influences the activity of the virulence regulator PecS, and appears to be necessary for the complete efflux of blue pigment indigoidine . This entry also includes some proteins predicted to be amino acid metabolite efflux pumps, and several proteins for which no functional predictions have been made.
Signal recognition particle protein (SRP)
Type: Family

This family represents Ffh (Fifty-Four Homologue), the protein component that forms the bacterial (and organellar) signal recognition particle together with a 4.5S RNA . Ffh is a GTPase homologous to eukaryotic SRP54.
L-fucose phosphate aldolase (FucA)
Type: Family

L-fuculose phosphate aldolase converts L-fuculose 1-phosphate to glycerone phosphate + (S)-lactaldehyde. The structure of the class II zinc-ion dependent L-fuculose-1-phosphate aldolase from Escherichia coli has been established at 1.92 A resolution. The homo-tetrameric enzyme has a molecular mass of 4 x 24kDa and follows C(4) symmetry. The four catalytic centres are located in deep clefts at the interfaces of adjacent subunits. The zinc ion is coordinated by three histidines and one glutamate in an almost tetrahedral arrangement. In contrast to numerous other catalytically competent zinc ions, there is no water molecule in the ligand sphere. Sequence homology searches revealed a significant similarity to the bacterial L-ribulose-5-phosphate 4-epimerase,

.

This entry also includes 5-methylthioribulose-1-phosphate/5-deoxyribulose-1-phosphate aldolase which uses 5-methylthioribulose-1-phosphate or 5-deoxyribulose-1-phosphate to produce acetaldehyde and dihydroxyacetone phosphate, with 10-fold greater catalytic efficiency compared to FucA. This enzyme participates in the bifunctional DHAP-shunt salvage pathway for SAM by-products .
Galactose-6-phosphate isomerase subunit LacA (LacA)
Type: Family

Galactose-6-phosphate isomerase (

) is a heteromultimeric protein consisting of subunits LacA and LacB, and catalyses the conversion of D-galactose 6-phosphate to D-tagatose and 6-phosphate in the tagatose 6-phosphate pathway of lactose catabolism . Galactose-6-phosphate isomerase is induced by galactose or lactose. This entry represents the LacA subunit.
Galactose-6-phosphate isomerase subunit LacB (LacB)
Type: Family

Galactose-6-phosphate isomerase (

) is a heteromultimeric protein consisting of subunits LacA and LacB, and catalyses the conversion of D-galactose 6-phosphate to D-tagatose and 6-phosphate in the tagatose 6-phosphate pathway of lactose catabolism . Galactose-6-phosphate isomerase is induced by galactose or lactose. This entry represents the LacB subunit.
Ribose 5-phosphate isomerase B (RpiB)
Type: Family

Ribose 5-phosphate isomerase (

) forms a homodimer and catalyses the interconversion of D-ribose 5-phosphate and D-ribulose 5-phosphate in the non-oxidative branch of the pentose phosphate pathway. This reaction permits the synthesis of ribose from other sugars, as well as the recycling of sugars from nucleotide breakdown. Two unrelated enzymes can catalyse this reaction: RpiA (found in most organisms) and RpiB (found in some bacteria and eukaryotes). RpiB is also involved in metabolism of the rare sugar, allose, in addition to ribose sugars. The structures of RpiA and RpiB are distinct, RpiB having a Rossmann-type α/β/α sandwich topology .

This entry represents the RpiB enzyme. It also includes D-erythrulose-4-phosphate isomerase from Pectobacterium atrosepticum .
6-phosphogluconate dehydratase (6-phosphgluc_deHydtase)
Type: Family

Two dehydratases, dihydroxy-acid dehydratase (gene ilvD or ILV3) and 6-phosphogluconate dehydratase (gene edd) have been shown to be evolutionary related . Dihydroxy-acid dehydratase catalyzes the fourth step in the biosynthesis of isoleucine and valine, the dehydration of 2,3-dihydroxy-isovaleic acid into alpha-ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyzes the first step in the Entner-Doudoroff pathway, the dehydration of 6-phospho-D-gluconate into 6-phospho-2-dehydro-3-deoxy-D-gluconate . Another protein included in this entry is the Escherichia coli hypothetical protein yjhG. The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a
2Fe-2S iron-sulphur cluster .

This family defines the 6-phosphogluconate dehydratases.
Competence protein ComEA (Competence_ComE)
Type: Family

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 .

The development of genetic competence in Bacillus subtilis is a highly regulated adaptive response to stationary-phase stress. For competence to develop, the transcriptional regulator, ComK, must be activated. ComK is required for the expression of genes encoding proteins that function in DNA uptake. In log-phase cultures, ComK is inactive in a complex with MecA and ClpC. The comS gene is induced in response to high culture cell density and nutritional stress and its product functions to release active ComK from the complex. ComK then stimulates the transcription initiation of its own gene as well as that of the late competence operons .

The comE locus is obligatory for bacterial cell competence. comEA and comEC are required for transformability, whereas the products of comEB and of the overlapping comER, which is transcribed in the reverse direction, are dispensable .

ComEA has been shown to be an integral membrane protein, as predicted from hydropathy analysis, with its C-terminal domain outside the cytoplasmic membrane. This C-terminal domain possesses a sequence with similarity to those of several proteins known to be involved in nucleic acid transactions including UvrC and a human protein that binds to the replication origin of the Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) .
Ribose 5-phosphate isomerase, type A (Ribose5P_isomerase_type_A)
Type: Family

Ribose 5-phosphate isomerase, also known as phosphoriboisomerase, catalyses the reversible conversion of D-ribose 5-phosphate to D-ribulose 5-phosphate, the first step in the non-oxidative branch of the pentose phosphate pathway . This reaction enables ribose to be synthesized from sugars, as well as the recycling of sugars during the degradation of nucleotides. There are two unrelated types of ribose 5-phosphate isomerases: type A (RpiA) is the most common and is found in most organisms, while type B (RpiB) is restricted to specific eukaryotic and prokaryotic species. Escherichia coli produces both RpiA and RpiB (also known as AlsB), although RpiA accounts for 99% of total RPI enzymes .

This entry represents type A (RpiA) enzymes found in eukaryotes (plants, Metazoa and fungi), bacteria and archaea.
Acetolactate synthase, small subunit (Acetalactate_synth_ssu)
Type: Family

Acetolactate synthases are a group of biosynthetic enzymes apparently found in plants, fungi and bacteria that are capable of
de novo
synthesis of the branched-chain amino acids . They can all synthesize acetolactate from pyruvate in the biosynthesis of valine, while some are also capable of synthesizing acetohydroxybutyrate from pyruvate and ketobutyrate during the biosynthesis of isoleucine. These enzymes generally require thiamin diphosphate, FAD and a divalent metal ion for catalysis, though some enzymes specific for acetolactate synthesis do not require FAD. They are composed of two subunits, a large catalytic subunit, and a smaller regulatory subunit which binds the natural modulators (valine, and in some cases leucine or isoleucine).

These enzymes are the target for currently-used herbicides such as sulphonylureas and imidazolinones. Their restricted distribution also makes them potential targets for the development of novel antibacterial and antifungal compounds.

This entry represents the small regulatory subunit of acetolactate synthase. It contains an ACT domain, which is a predicted regulatory ligand-binding fold often found in proteins regulated by small-molecule effectors .
Isocitrate dehydrogenase NADP-dependent (Isocitrate_DH_NADP)
Type: Family

Isocitrate dehydrogenase (IDH) is an important enzyme of carbohydrate metabolism which catalyses the oxidative decarboxylation of isocitrate into alpha-ketoglutarate. IDH is either dependent on NAD
+
(

) or on NADP
+
(

). In eukaryotes there are at least three isozymes of IDH: two are located in the mitochondrial matrix (one NAD
+
-dependent, the other NADP
+
-dependent), while the third one (also NADP
+
-dependent) is cytoplasmic. In Escherichia coli the activity of a NADP
+
-dependent form of the enzyme is controlled by the phosphorylation of a serine residue; the phosphorylated form of IDH is completely inactivated.

The eukaryotic, NADP-dependent isocitrate dehydrogenases, are defined by this family that includes cytosolic, mitochondrial, and chloroplast enzymes, as well as bacterial proteins. This family differs considerably from other isocitrate dehydrogenases that are included in a different group together with 3-isopropylmalate dehydrogenases and tartrate dehydrogenases.
UvrABC system, subunit C (UvrC)
Type: Family

In Eubacteria and some Archaea, the first steps in nucleotide excision repair are carried out by the coordinated action of the UvrA, UvrB, and UvrC proteins. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. Upon binding of the UvrA(2)B(2) complex to a putative damaged site, the DNA wraps around one UvrB monomer. DNA wrap is dependent on ATP binding by UvrB and probably causes local melting of the DNA helix, facilitating insertion of UvrB β-hairpin between the DNA strands. Then UvrB probes one DNA strand for the presence of a lesion. If a lesion is found the UvrA subunits dissociate and the UvrB-DNA preincision complex is formed. This complex is subsequently bound by UvrC and the second UvrB is released. If no lesion is found, the DNA wraps around the other UvrB subunit that will check the other stand for damage .

This entry represents UvrC, which is recruited to the UvrB-bound lesion site and cuts the DNA backbone both 5' and 3' to the lesion on the same strand .
3-Dehydro-bile acid delta(4,6)-reductase-like (BaiN-like)
Type: Family

This family of flavoproteins includes 3-dehydro-bile acid delta(4,6)-reductase from Clostridium, which is part of the reductive arm of the bile acid 7-alpha dehydroxylating pathway .
Desulfoferrodoxin (Desulfoferrodoxin_rbo)
Type: Family

Desulfoferrodoxin is a non-haem iron protein which contains two types of iron atoms per molecule, a desulfoferrodoxin-like FES(4) site, and an octahedral coordinated high-spin ferrous site with nitrogen/oxygen-containing ligands. The short N-terminal domain contains four conserved Cys for binding of the ferric iron atom, and is homologous to the small protein desulforedoxin. The remainder of the molecule binds the ferrous iron atom and is similar to neelaredoxin, a monomeric blue non-haem iron protein. The homologue from Treponema pallidum, although essentially a full length homologue, lacks three of the four Cys residues in the N-terminal domain; the domain may have lost ferric binding ability but may have some conserved structural role such as dimerisation, or some new function. This protein is described in some articles as rubredoxin oxidoreductase (rbo), and its gene shares an operon with the rubredoxin gene in Desulfovibrio vulgaris (strain Hildenborough / ATCC 29579 / NCIMB 8303).
Riboflavin biosynthesis protein RibD (Eubact_RibD)
Type: Family

This entry describes the riboflavin biosynthesis protein (ribD) as found in Escherichia coli. The N-terminal domain includes the conserved zinc-binding site region that is shared by proteins such as cytosine deaminase, mammalian apolipoprotein B mRNA editing protein, blasticidin-S deaminase, and Bacillus subtilis competence protein comEB. The C-terminal domain is homologous to the full length of yeast HTP reductase, a protein required for riboflavin biosynthesis. A number of archaeal proteins that may be related to the riboflavin biosynthesis protein contain only the C-terminal domain.
Phosphotransferase system, cellobiose-type IIC component (PTS_IIC_cello)
Type: Family

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), a major carbohydrate active-transport system, catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The phosphotransferase system consists of both the cellobiose-specific and the lactose-specific forms of the phosphotransferase system (PTS) IIC component. The IIC domain catalyses the transfer of a phosphoryl group from the IIB domain to the substrate. When the IIC component and IIB components are in the same polypeptide chain they are designated IIBC.

This family consists of the cellobiose-type IIC component of phosphotransferase systems (PTS), that includes transporters for cellobiose , N,N'-diacetylchitobiose , lichenan and glucomannan .
Competence protein ComEC/Rec2 (Competence_ComEC/Rec2)
Type: Family

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 .

The development of genetic competence in Bacillus subtilis is a highly regulated adaptive response to stationary-phase stress. For competence to develop, the transcriptional regulator, ComK, must be activated. ComK is required for the expression of genes encoding proteins that function in DNA uptake. In log-phase cultures, ComK is inactive in a complex with MecA and ClpC. The comS gene is induced in response to high culture cell density and nutritional stress and its product functions to release active ComK from the complex. ComK then stimulates the transcription initiation of its own gene as well as that of the late competence operons .

This is the DNA internalisation-related competence protein ComEC/Rec2 family. Apparent orthologs are found in 5 species so far (Haemophilus influenzae, Escherichia coli, Bacillus subtilis, Neisseria gonorrhoeae, Streptococcus pneumoniae), of which all but E. coli are model systems for the study of competence for natural transformation. This protein is a predicted multiple membrane-spanning protein likely to be involved in DNA internalisation.
Calcium/proton exchanger CAX-like (CAX-like)
Type: Family

This is a group of calcium/proton exchanger proteins. In Arabidopsis thaliana CAX1 is responsible for maintaining low cytosolic-free Ca2+ concentrations in the plant cells by catalysing pH gradient-energized vacuolar Ca2+ accumulation .
Periplasmic protein thiol:disulphide oxidoreductase DsbE (Periplasmic_diS_OxRdtase_DsbE)
Type: Family

Periplasmic protein thiol:disulphide oxidoreductase is involved in the biogenesis of c-type cytochromes as well as in disulphide bond formation in some periplasmic proteins. This group defines the DsbE (also known as CcmG and CycY) subfamily. DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif . Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c .
Phosphosugar isomerase, KdsD/KpsF-type (KdsD/KpsF-type)
Type: Family

This is a family of closely related proteins with the phosphosugar-binding domain SIS (Sugar ISomerase) followed by two copies of the CBS (named after Cystathionine Beta Synthase) domain. The group includes GutQ, a protein of the glucitol operon and KpsF, a virulence factor involved in capsular polysialic acid biosynthesis in some pathogenic strains of Escherichia coli .
Phosphotransferase system, lactose-specific IIC component (LacE)
Type: Domain

This family of proteins models the IIC domain of the phosphotransferase system (PTS) for lactose. The IIC domain catalyzes the transfer of a phosphoryl group from the IIB domain to lactose. When the IIC component and IIB components are in the same polypeptide chain they are designated IIBC.
tRNA pseudouridine synthase B family (tRNA_PsdUridine_synth_B_fam)
Type: Family

This family, found in archaea and eukaryotes, includes the only archaeal proteins markedly similar to bacterial TruB, the tRNA pseudouridine 55 synthase. However, among two related yeast proteins, the archaeal set matches yeast YLR175w far better than YNL292w. The first, termed centromere/microtubule binding protein 5 (CBF5), is an apparent rRNA pseudouridine synthase, while the second is the exclusive tRNA pseudouridine 55 synthase for both cytosolic and mitochondrial compartments. It is unclear whether archaeal proteins found by this entry modify tRNA, rRNA, or both.

Yeast CBF5 plays a central role in ribosomal RNA processing. It is a probable catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Its pseudouridine ('psi') residues may serve to stabilise the conformation of rRNAs. It may function as a pseudouridine synthase. It is also a centromeric DNA-CBF3-binding factor which is involved in mitotic chromosome segregation .
tRNA-guanine transglycosylase (TGT)
Type: Family

Queuine is a hypermodified base that occurs in the wobble position of the anticodon of tRNAs Asp, Asn, His and Tyr. Queuine is incorporated into tRNA via a base exchange reaction with guanine catalysed by queuine tRNA-ribosyltransferase (also known as tRNA-guanine transglycosylase). In eukaryotes, queuine is directly exchanged into tRNA while in eubacteria, a queuine precursor (preQ1) is incorporated and ultimately modified to queuine . Archaea contain a closely related enzyme (

) that catalyses a base exchange of guanine for an archaeosine precursor . This precursor is then subsequently converted to the archaeal-specific modified base archaeosine. Some archaea, such as Archaeoglobus fulgidus, contain both these enzymes.

The eukaryotic tRNA-guanine transglycosylase exists as a heterodimer of a catalytic subunit (QTRT1) and another subunit known as queuine tRNA-ribosyltransferase domain-containing 1 (QTRTD1), whereas the eubacteria enzyme is homodimeric .
tRNA-guanine(15) transglycosylase (TgtA)
Type: Family

This tRNA-guanine transglycosylase (tgt) from archaea differs from the tgt of E. coli and other Bacteria in the site of action and the modification that results. It exchanges 7-cyano-7-deazaguanine (preQ0) with guanine at position 15 of archaeal tRNA; this nucleotide is subsequently converted to archaeosine, found exclusively in the Archaea. This enzyme from Haloferax volcanii has been purified, characterised, and partially sequenced and is the basis for identifying this family. In contrast, bacterial tgt catalyzes the exchange of preQ0 or preQ1 for the guanine base at position 34; this nucleotide is subsequently modified to queuosine. Archeoglobus fulgidus has both enzymes, while some other Archaea have just this one .
Error-prone DNA polymerase/DNA polymerase III subunit alpha DnaE/PolC (DnaE2/DnaE/PolC)
Type: Family

All proteins in this family for which functions are known are DNA polymerases. The group includes the error-prone DNA polymerase (DnaE2), involved in damage-induced mutagenesis and translesion synthesis (TLS), DNA polymerase III PolC-type, and the alpha subunit of DNA polymerase III (DnaE) (

). DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity.
UV excision repair protein Rad23 (Rad23)
Type: Family

All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. Rad23 contains a ubiquitin-like domain that interacts with catalytically active proteasomes and two ubiquitin (Ub)-associated (UBA) sequences that bind Ub. Rad23 interacts with ubiquitinated cellular proteins through the synergistic action of its UBA domains.

In humans, Rad23 complexes with the XPC protein.
UvrABC system, subunit B (UvrB)
Type: Family

In Eubacteria and some Archaea, the first steps in nucleotide excision repair are carried out by the coordinated action of the UvrA, UvrB, and UvrC proteins. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. Upon binding of the UvrA(2)B(2) complex to a putative damaged site, the DNA wraps around one UvrB monomer. DNA wrap is dependent on ATP binding by UvrB and probably causes local melting of the DNA helix, facilitating insertion of UvrB β-hairpin between the DNA strands. Then UvrB probes one DNA strand for the presence of a lesion. If a lesion is found the UvrA subunits dissociate and the UvrB-DNA preincision complex is formed. This complex is subsequently bound by UvrC and the second UvrB is released. If no lesion is found, the DNA wraps around the other UvrB subunit that will check the other stand for damage .

This entry represents the UvrB subunit. UvrB shares structural similarity with helicases and have ATPase activity .
AP endonuclease 1 (AP_endonuc_1)
Type: Family

AP endonucleases can be classified into two families based on sequence similarity. This family contains members of AP endonuclease family 1. They are endonucleases that remove the damaged DNA at cytosines and guanines by cleaving on the 3'-side of the AP site by a beta-elimination reaction . The proteins contain glutamate which has been shown in the Escherichia coli enzyme to bind a divalent metal ion such as magnesium or manganese.

DNA damaging agents such as the anti-tumour drugs bleomycin and neocarzinostatin or those that generate oxygen radicals produce a variety of lesions in DNA. Amongst these is base-loss which forms apurinic/apyrimidinic (AP) sites or strand breaks with atypical 3' termini. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3' terminus of DNA strand breaks.
Glutamine synthetase type I (Gln_synth_I)
Type: Family

Glutamine synthetase type I (or glutamate-ammonia ligase) has a dodecameric form, which can be subdivided into 1-alpha and 1-beta forms. The phylogeny of the 1-alpha and 1-beta forms appears polyphyletic. Escherichia coli, Synechocystis sp. (strain PCC 6803), Aquifex aeolicus, and the crenarcheon Sulfolobus acidocaldarius have form 1-beta, while Bacillus subtilis, Thermotoga maritima, and various euryarchaea has form 1-alpha. The 1-beta dodecamer from the crenarcheon S. acidocaldarius differs from that in E. coli in that it is not regulated by adenylation.