SII-SWORD/CoKE huggingface dataset:
HTH-type transcriptional repressor NanR (Tscrpt_reg_NanR)
Type: Family

The nan operon encodes a group of proteins that are involved in sialic acid utilisation. Expression of the operon appears to be subject to negative control by the transcriptional repressor, NanR. Sialic acid may induce the nan operon by binding to this repressor .

NanR possesses an N-terminal DNA binding domain, containing a helix-turn-helix (HTH) motif, and a C-terminal domain that may be involved in ligand binding.
Global transcriptional regulator Spx (Spx)
Type: Family

Spx is a global transcriptional regulator that plays a key role in stress response . It acts as an "anti-alpha" factor and interacts with the RNA polymerase alpha subunit C-terminal domain. RNA polymerase is therefore prevented from responding to certain activator proteins such as ResD and ComA . Spx is a negative regulator of competence . It was previously known as YjbD .
Probable [Fe-S]-dependent transcriptional repressor (FeoC)
Type: Family

Bacteria commonly utilise a unique type of transporter, called Feo, to specifically acquire the ferrous (Fe2+) form of iron from their environment. Enterobacterial Feo systems are composed of three proteins: FeoA, a small, soluble SH3-domain protein probably located in the cytosol; FeoB, a large protein which likely functions as the Fe2+ permease; and FeoC, a small protein apparently functioning as an [Fe-S]-dependent transcriptional repressor of the feoABC operon .

This entry represents the FeoC protein.
Pyrophosphatase PpaX (Pyrophosphatase_Ppax)
Type: Family

Microorganisms that can utilise halogenated compounds as growth substrates produce enzymes that cleave carbon-halogen bonds and are commonly called dehalogenases. The hydrolytic dehalogenases catalyse a nucleophilic displacement reaction, with water as the sole co-substrate . They are divided into haloalkane dehalogenases and haloacid dehalogenases (HAD). HADs belong to a large superfamily of hydrolases with diverse substrate specificity, which also includes epoxide hydrolases, phosphoglycolate phosphatases, histidinol phosphate phosphatases, nitrophenyl phosphatases and numerous other proteins .

This entry represents the pyrophosphatase PpaX subfamily of the HAD superfamily. These enzymes hydrolyse pyrophosphate formed during P-Ser-HPr dephosphorylation by HPrK/P . They may play a role in controlling the intracellular pyrophosphate pool.
Polyisoprenyl-teichoic acid--peptidoglycan teichoic acid transferase TagU (TagU)
Type: Family

This entry represents polyisoprenyl-teichoic acid--peptidoglycan teichoic acid transferase TagU. TagU was previously known as bacterial transcriptional regulator LytR, and was originally described a 35kDa protein which is responsible for attenuation of expression of both itself and the lytABC operon. LytABC form an N-acetylmuramoyl-L-alanine amidase, which is one of the two major autolysins of B. subtilis . This protein has since been proposed to catalyse the transfer of the anionic cell wall polymers (APs) from their lipid-linked precursor to the cell wall peptidoglycan (PG) within cell wall teichoic acid biosynthesis, hence the new name of polyisoprenyl-teichoic acid--peptidoglycan teichoic acid transferase TagU .
Uncharacterised nudix hydrolase NudL (Nudix_NudL)
Type: Family

NudL probably mediates the hydrolysis of some nucleoside diphosphate derivatives, but the function of this protein is currently unknown.
Antiholin-like protein LrgA (Antiholin-like_LrgA)
Type: Family

This entry contains bacterial antiholin-like LrgA proteins, which have been shown to modulate murein hydrolase activity . Together with holin-like CidA, LrgA function to control cell death and lysis during biofilm development .
Spermidine export protein MdtI (Spermidine_export_MdtI)
Type: Family

Spermidine export protein MdtI catalyzes the excretion of spermidine. It can also confer resistance to deoxycholate and SDS . It is integral to membrane .
Maltoporin (Maltoporin)
Type: Family

Maltoporin (LamB) is involved in the transport of maltose and maltodextrins . It forms homotrimers composing three 18-stranded antiparallel β-barrels, containing three independent channels .
3-phenylpropionate/cinnamic acid dioxygenase, ferredoxin subunit (HcaC)
Type: Family

Phenylpropanoid compounds are widely available in natural environments, and they can originate from putrefaction of proteins in soil or as breakdown products of several constituents of plants, such as lignin, various oils, and resins. Microbial catabolism of phenylpropanoid compounds plays an important role not only in the natural degradative cycle of these aromatic molecules but also in their industrial applications such as wine making, aging, and storage. In particular, degradation of cinnamic acid (CI), 3-phenylpropionic acid (PP), and their hydroxylated derivatives has been reported in several bacteria, including Pseudomonas species , Arthrobacter species , Escherichia coli (strain K12) , and Rhodococcus globerulus .

This entry represents the ferredoxin subunit (HcaC). It has been suggested that residues in the central portion of this subunit may be involved in the coordination of a Rieske-type [2Fe-2S] cluster .
Spermidine export protein MdtJ (Spermidine_export_MdtJ)
Type: Family

Spermidine export protein MdtJ catalyzes the excretion of spermidine. It can also confer resistance to deoxycholate and SDS . It is induced by spermidine.
Lipoate-protein ligase A (Lipoate_ligase_A)
Type: Family

Lipoate-protein ligase A catalyzes both the ATP-dependent activation of exogenously supplied lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of lipoate-dependent enzymes . It is also able to catalyze very poorly the transfer of lipoyl and octanoyl moiety from their acyl carrier protein .
Iron-sulfur cluster repair protein YftE (FeS-repair_YftE)
Type: Family

YtfE was is also known as regulator of cell morphogenesis and NO signaling because it is involved in anaerobic NO protection . It is part of a family of di-iron proteins involved in the repair of iron-sulphur clusters .
Aquaporin Z (Aquaporin_Z)
Type: Family

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .

This entry represents aquaporin Z, a major water channel protein in bacteria. It mediates water influx in response to large changes in cellular osmorality .
3-phenylpropionate/cinnamic acid dioxygenase, ferredoxin--NAD(+) reductase subunit (HcaD)
Type: Family

Phenylpropanoid compounds are widely available in natural environments, and they can originate from putrefaction of proteins in soil or as breakdown products of several constituents of plants, such as lignin, various oils, and resins. Microbial catabolism of phenylpropanoid compounds plays an important role not only in the natural degradative cycle of these aromatic molecules but also in their industrial applications such as wine making, aging, and storage. In particular, degradation of cinnamic acid (CI), 3-phenylpropionic acid (PP), and their hydroxylated derivatives has been reported in several bacteria, including Pseudomonas species , Arthrobacter species , Escherichia coli (strain K12) , and Rhodococcus globerulus .

This entry represents the ferredoxin reductase subunit of PP/CI dioxygenase.
MSF-type transporter YcaD (MFS_YcaD)
Type: Family

Among the different families of transporter, only two occur ubiquitously in all classifications of organisms. These are the ATP-Binding Cassette (ABC) superfamily and the Major Facilitator Superfamily (MFS). The MFS transporters are single-polypeptide secondary carriers capable only of transporting small solutes in response to chemiosmotic ion gradients .

This entry represents the uncharacterised major facilitator superfamily protein YcaD from enterobacteria.
Transcription regulator HTH, YidZ (Tscrpt_reg_YidZ)
Type: Family

YidZ is a HTH-type transcription regulator involved in anaerobic NO protection .
Xanthine-guanine phosphoribosyltransferase (Xanthine_Guanine_PRibTrfase)
Type: Family

Xanthine-guanine phosphoribosyltransferases, part of the purine salvage pathway, catalyse the transfer of the phosphoribosyl group from 5-phospho-alpha-D-ribosyl 1-pyrophosphate to xanthine, guanine and (to a leser extent) hypoxanthine to form GMP, XMP, and IMP, respectively . This enzyme uses magnesium as a cofactor and belong to the wider purine/pyrimidinephosphoribosyltransferase family.
Replication factor C small subunit, archaeal (Rep_factor-C_ssu_arc)
Type: Family

Replication factor C (RFC) is a multimeric AAA+ protein complex that loads the DNA polymerase processivity clamp PCNA (Proliferating Cell Nuclear Antigen) onto DNA using ATP to drive the reaction . PCNA functions at multiple levels in directing DNA metabolic pathways . When bound to DNA, PCNA organises various proteins involved in DNA replication, DNA repair, DNA modification, and chromatin modelling.

In contrast to eukaryotic RFC, which has been shown to contain five distinct polypeptides, archaeal RFC contains only two types of subunit - large and small. The exact subunit stoichiometry in archaea is unclear. In Methanobacterium thermoautotrophicum, RFC is reported to be a heterohexamer, composed of four small and two large subunits . In Sulfolobus solfataricus, meanwhile, it is reported to be a heteropentamer of four small subunits and one large .

This entry represents the archaeal RFC small subunit.
Co-chaperone DjlA (DjlA)
Type: Family

This entry represents the DnaJ-like regulatory co-chaperone DjlA found in bacteria. These proteins interact directly with DnaK for induction of wcaABCDE operon, which is involved in the synthesis of a colanic acid polysaccharide capsule .
RbsD-like superfamily (RbsD-like_sf)
Type: Homologous_superfamily

RbsD is a component of the ribose operon. It was originally thought to be a high affinity ribose transport protein, but further analysis shows that it is a D-ribose pyranase

. It catalyses the interconversion of beta-pyran and beta-furan forms of D-ribose. It also catalyzes the conversion between beta-allofuranose and beta-allopyranose.

FucU is a component of the fucose operon and is a L-fucose mutarotase

, involved in the anomeric conversion of L-fucose. It also exhibits a pyranase activity for D-ribose .

Both have been classified in the RbsD/FucU family of proteins. Members of this family are ubiquitous having been found in organisms from eubacteria to mammals.

The crystal structure of Bacillus subtilis RbsD reveals a 3 layers (α-β-α) subunit that associates into a homodecameric assembly .
L-fucose mutarotase (L-fucose_mutarotase)
Type: Family

FucU is a component of the fucose operon and is a L-fucose mutarotase

, involved in the anomeric conversion of L-fucose. It also exhibits a pyranase activity for D-ribose .
FAD/NAD(P)-binding domain (FAD/NAD-binding_dom)
Type: Domain

This entry describes the FAD binding domain which has a nested NADH binding domain and is found in both class I and class II oxidoreductases. this domain seems to include contains the pair of redox-active cysteines involved in the transfer of reducing equivalents from the FAD cofactor to the substrate.

FAD flavoproteins belonging to the family of pyridine nucleotide-disulphide oxidoreductases (glutathione reductase, trypanothione reductase, lipoamide dehydrogenase, mercuric reductase, thioredoxin reductase, alkyl hydroperoxide reductase) share sequence similarity with a number of other flavoprotein oxidoreductases, in particular with ferredoxin-NAD+ reductases involved in oxidative metabolism of a variety of hydrocarbons (rubredoxin reductase, putidaredoxin reductase, terpredoxin reductase, ferredoxin-NAD+ reductase components of benzene 1,2-dioxygenase, toluene 1,2-dioxygenase, chlorobenzene dioxygenase, biphenyl dioxygenase), NADH oxidase and NADH peroxidase . Comparison of the crystal structures of human glutathione reductase and Escherichia coli thioredoxin reductase reveals different locations of their active sites, suggesting that the enzymes diverged from an ancestral FAD/NAD(P)H reductase and acquired their disulphide reductase activities independently .

Despite functional similarities, oxidoreductases of this family show no sequence similarity with adrenodoxin reductases and flavoprotein pyridine nucleotide cytochrome reductases (FPNCR) . Assuming that disulphide reductase activity emerged later, during divergent evolution, the family can be referred to as FAD-dependent pyridine nucleotide reductases, FADPNR.

To date, 3D structures of glutathione reductase , thioredoxin reductase , mercuric reductase , lipoamide dehydrogenase , trypanothione reductase and NADH peroxidase have been solved. The enzymes share similar tertiary structures based on a doubly-wound α/β fold, but the relative orientations of their FAD- and NAD(P)H-binding domains may vary significantly. By contrast with the FPNCR family, the folds of the FAD- and NAD(P)H-binding domains are similar, suggesting that the domains evolved by gene duplication .
Heme A synthase, type 2 (HemeA_Synthase_type2)
Type: Family

Heme A synthase catalyzes the oxidation of the C8 methyl side group on heme O porphyrin ring into a formyl group .

This entry represents the type 2 subfamily, found in some bacteria and eukaryota.
Heme A synthase, type 1 (HemeA_Synthase_type1)
Type: Family

Heme A synthase catalyzes the oxidation of the C8 methyl side group on heme O porphyrin ring into a formyl group .

The type 1 subfamily of this enzyme is found in Gram-positive bacteria. Bacillus subtilis CatA is involved in sporulation .
Glyoxylate/hydroxypyruvate reductase B (Glyo/OHPyrv_Rdtase_B)
Type: Family

Glyoxylate/hydroxypyruvate reductase B catalyzes the NADPH-dependent reduction of glyoxylate and hydroxypyruvate into glycolate and glycerate, respectively .
3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase, Firmicutes (THcHDO_hydrolase_firmi)
Type: Family

3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolase is involved in the cleavage of the C1-C2 bond of 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione (THcHDO) to yield 5-deoxy-glucuronate (5DG) .

This entry consists of 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione hydrolases from Gram-positive bacteria (Firmicutes).
tRNA-modifying protein YgfZ (tRNA-modifying_YgfZ)
Type: Family

YgfZ is a folate-binding protein involved in regulating the level of ATP-dnaA and in the modification of some tRNAs. It is probably a key factor in regulatory networks that act via tRNA modification, such as initiation of chromosomal replication .
Holin-like protein CidA (Holin-like_CidA)
Type: Family

This entry represents CidA, which increases the activity of extracellular murein hydrolases possibly by mediating their export via hole formation. It is inhibited by the antiholin-like proteins LrgAB. In an unstressed cell, the LrgAB products probably inhibit the function of the CidAB proteins. When a cell is stressed by the addition of antibiotics or by other factors in the environment, the CidAB proteins possibly oligomerise within the bacterial cell membrane, creating lesions that disrupt the proton motive force, which in turn results in loss of cell viability. These lesions are also hypothesised to regulate the subsequent cell lysis by either allowing the murein hydrolases access to the cell wall substrate and/or regulating their activity by a possible change in the cell wall pH that results from loss of membrane potential .
Transcriptional repressor HTH, NsrR (Tscrpt_rep_HTH_NsrR)
Type: Family

The HTH-type transcriptional repressor NsrR is a nitric oxide-sensitive repressor of genes involved in protecting the cell against nitrosative stress, such as ytfE, hmpA and ygbA. It may require iron for activity. NsrR does not regulate its own transcription .
CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, bacterial (PGP_synthase_bac)
Type: Family

CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase (

), also known as phosphatidylglycerophosphate synthase, glycerophosphate phosphatidyltransferase and PGP synthase, catalyses the conversion of CDP-diacylglycerol and glycerol-3-phosphate to CMP and 3-(3-phosphatidyl)-glycerol 1-phosphate in the committed step to the synthesis of acidic phospholipids. It is an integral membrane protein. A number of related enzymes are quite similar in both sequence and catalytic activity, including Saccharomyces cerevisiae (Baker's yeast) YDL142c, now known to be a cardiolipin synthase. There may be problems with incorrect transitive annotation of near homologues as authentic CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase.

This entry represents a family of bacterial CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferases .
DNA integrity scanning protein, DisA (DNA_integrity_scanning_protein)
Type: Family

DNA integrity scanning protein (DisA) participates in a DNA-damage check-point that is active prior to asymmetric division when DNA is damaged. DisA forms globular foci that rapidly scan along the chromosomes during sporulation, searching for lesions. When a lesion is present, disA pauses at the lesion site. This triggers a cellular response that culminates in a temporary block in sporulation initiation .
Transcriptional repressor HTH, FabR (Tscrpt_reg_HTH_FabR)
Type: Family

This entry is represented by the transcriptional repressor FabR found in Gammaproteobacteria. Members of this family contain one HTH TetR-type DNA-binding domain. FabR represses the transcription of FabB, which is involved in unsaturated fatty acid (UFA) biosynthesis. By controlling UFA production, FabR directly influences the physical properties of the membrane bilayer .
Solute-binding protein family 5, conserved site (SBP_5_CS)
Type: Conserved_site

This entry represents a conserved site located near the N-terminal end of bacterial solute-binding proteins from family 5.

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .

On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped into eight families or clusters, which generally correlate with the nature of the solute bound. This entry represents a conserved site found in the extracellular solute-binding protein family 5 members from Gram-positive bacteria, Gram-negative bacteria and archaea.

Family 5 members include:

Periplasmic oligopeptide-binding proteins (gene oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (genes oppA, amiA or appA).

Periplasmic dipeptide-binding proteins of Escherichia coli (gene dppA) and of Bacillus subtilis (gene dppE).

Periplasmic murein peptide-binding protein of E. coli (gene mppA).

Periplasmic peptide-binding proteins sapA of E. coli, Salmonella typhimurium and Haemophilus influenzae.

Periplasmic nickel-binding protein (gene nikA) of Escherichia coli.

Heme-binding lipoprotein (gene hbpA or dppA) from H. influenzae.

Lipoprotein xP55 from Streptomyces lividans.

H. influenzae hypothetical protein HI0213.

Hypothetical protein y4tO from Rhizobium sp. strain NGR234 symbiotic plasmid.

Hypothetical protein y4wM from Rhizobium strain NGR234 symbiotic plasmid.
D-phenylhydantoinase (D_phenylhydantoinase)
Type: Family

D-phenylhydantoinase catalyses the stereospecific hydrolysis of the cyclic amide bond of D-hydantoin derivatives with an aromatic side chains at the 5'-position. It has no activity on dihydropyrimidines. The physiological function of this enzyme is unknown .
Transcriptional regulator SgrR (Tscrpt_reg_SgrR)
Type: Family

This entry represents the transcriptional regulator SgrR, which contains 1 HTH MarR-type DNA-binding domain. SgrR activates the small RNA gene SgrS under glucose-phosphate stress conditions as well as YfdZ. It represses its own transcription under both stress and non-stress conditions. It also might act as a sensor of the intracellular accumulation of phosphoglucose by binding these molecules in its C-terminal solute-binding domain.
Transcriptional regulator HTH-type, MalT (Tscrpt_reg_HTH_MalT)
Type: Family

This entry represents the transcription regulator MalT, which contains one HTH LuxR-type DNA-binding domain. MalT positively regulates the transcription of the maltose regulon whose gene products are responsible for uptake and catabolism of malto-oligosaccharides. It binds and recognises a DNA motif: 5'-GGA[TG]GA-3', called the MalT box.

MalT is a monomer in solution but oligomerises to an active state in the presence of the positive effectors ATP and maltotriose. It interacts with MalY, MalK and Aes, all of which negatively regulate MalT activity by antagonising maltotriose binding.
Nucleoid occlusion factor SlmA (NO_SlmA)
Type: Family

This entry represents SlmA, which is a cell-division inhibitor required for nucleoid occlusion (NO) that contains 1 HTH TetR-type DNA-binding domain , and similar sequences from gammaproteobacteria. It participates in the proper positioning of the FtsZ/septal ring at midcell during cell division, functioning as a DNA-associated division inhibitor directly involved in preventing Z ring assembly on portions of the membrane surrounding the nucleoid .
5-deoxy-glucuronate isomerase, Bacilli (IolB_Bacilli)
Type: Family

Members of this family include several bacterial myo-inositol catabolism (IolB) proteins. The Bacillus subtilis inositol operon (iolABCDEFGHIJ) is involved in myo-inositol catabolism. Glucose repression of the iol operon induced by inositol is exerted through catabolite repression mediated by CcpA and the iol induction system mediated by IolR . IolB catalyses the isomerisation of 5-deoxy-D-glucuronic acid to produce 2-deoxy-5-keto-D-gluconic acid .

The entry represents IolB from Bacilli.
Cell division protein ZapA, eubacteria (Cell_div_ZapA_eubact)
Type: Family

This entry represents ZapA, an activator of cell division through the inhibition of FtsZ GTPase activity, therefore promoting FtsZ assembly into bundles of protofilaments necessary for the formation of the division Z ring. ZapA is recruited early at mid-cell but it is not essential for cell division.