SII-SWORD/CoKE huggingface dataset:
Ion-translocating oxidoreductase complex subunit E (RnfE)
Type: Family

The six-subunit complex RnfABCDGE in Rhodobacter capsulatus (Rhodopseudomonas capsulata) encodes a NADH oxidoreductase responsible for electron transport to nitrogenase, necessary for nitrogen fixation . A closely related complex in Escherichia coli, RsxABCDGE (Reducer of SoxR), reduces the 2Fe-2S-containing superoxide sensor SoxR, active as a transcription factor when oxidized . The Rnf complex is ferredoxin:NAD+ oxidoreductase that appears to pump different ions in different bacteria. In Clostridium ljungdahlii and Desulfovibrio alaskensis functions as a proton pump whose activity is important for growth , whereas in Acetobacterium woodii functions as a Na(+)-translocating electron transport chain .

This family represents the subunit E of Rnf complexes.
Cysteine desulfurase-related, unknown function (Cys_dSase-rel_unknwn_funct)
Type: Family

This entry describes a subfamily of probable pyridoxal phosphate-dependent enzymes in the aminotransferase class V family. Related families contain members active as cysteine desulfurases, selenocysteine lyases, or both. The members of this family form a distinct clade and all are shorter at the N terminus. The function of members of this family are unknown.
Cysteine desulfurase, SufS (Cys_dSase_SufS)
Type: Family

Cysteine desulfurases are pyridoxal-phosphate enzymes which catalyse the removal of sulphur from L-cysteine to form L-alanine and elemental sulphur. These enzymes have been shown to play an important role in the biosynthesis of iron-sulphur clusters, thionucleosides in tRNA, thiamine, biotin, lipoate and molydopterin .

This entry represents a subfamily of NifS-related cysteine desulfurases that are often involved in iron-sulphur cluster formation, which is needed for nitrogen fixation and other vital functions . Many of these enzymes, in addition to cysteine desulfurase activity, also show selenocysteine lyase activity where L-selenocysteine is converted to L-alanine and selenide . Some of these enzymes are much more specific for selenocysteine than cysteine and are thus believed to function in selenium metabolism rather than sulphur metabolism.

Structural studies of the Escherichia coli and Synechocystis enzymes indicate that they are homodimers which show a similar fold to other members of the alpha family of pyridoxal-phosphate enzymes .
Ubiquinone biosynthesis hydroxylase UbiH/COQ6 (UbiH/COQ6)
Type: Family

This entry represents a family of FAD-dependent hydroxylases (monooxygenases), which are all believed to act in the aerobic ubiquinone biosynthesis pathway . In Escherichia coli, three enzyme activities have been described: UbiI, UbiH and UbiF . UbiH and UbiF are similar to one another and form the basis of this subfamily. UbiI (also known as visC) is highly similar to UbiF, adjacent to UbiH and, when mutated, results in a phenotype similar to that of UbiH (also known as visB) . Several other species appear to have three homologues in this family, although they assort themselves differently on phylogenetic trees (e.g. Xylella and Mesorhizobium) making it difficult to ascribe a specific activity to each one. Eukaryotes appear to have only a single homologue in this subfamily (COQ6, ) which complements UbiH, but also possess a non-orthologous gene, COQ7 which complements UbiF.
Beta-phosphoglucomutase (Beta-PGM)
Type: Family

This entry represents the beta-phosphoglucomutase (Beta-PGM) enzyme which catalyses the interconversion of beta-D-glucose-1-phosphate and beta-D-glucose-6-phosphate. The 6-phosphate is capable of non-enzymatic anomerisation (alpha to beta or vice versa) while the 1-phosphate is not. A separate enzyme is responsible for the isomerisation of the alpha anomers. Beta-D-glucose-1-phosphate results from the phosphorolysis of maltose (

), trehalose (

) or trehalose-6-phosphate (

). Alternatively, these reactions can be run in the synthetic direction to create the disaccharides. All sequenced genomes which contain a member of this family also appear to contain at least one putative maltose or trehalose phosphorylase. Three species, Lactococcus, Enterococcus and Neisseria appear to contain a pair of paralogous beta-PGM's.

Beta-PGM is a member of the haloacid dehalogenase superfamily of hydrolase enzymes. These enzymes are characterised by a series of three catalytic motifs positioned within an α-β (Rossman) fold . Beta-PGM contains an inserted α helical domain in between the first and second conserved motifs and thus is a member of subfamily IA of the superfamily . The third catalytic motif comes in three variants, the third of which, containing a conserved DD or ED, is the only one found here as well as in several other related enzymes.
Phosphotransferase system, sucrose-specific IIBC component (PTS_IIBC_sucr)
Type: Domain

This entry represents the fused enzyme II B and C components of the sucrose-specific PTS sugar transporter system . Sucrose is converted to sucrose-6-phosphate in the process of translocation into the cell. Some of these transporters lack their own IIA domains and instead use the glucose IIA protein (IIAglc or Crr). The exceptions to this rule are Staphylococci, Streptococci, Lactococci, Lactobacilli, etc. which contain their own A domain as a C-terminal fusion.
Phosphotransferase system, N-acetylglucosamine-specific IIBC component (PTS_IIBC_nag)
Type: Domain

This entry represents the combined B and C domains of the PTS transport system enzyme II specific for N-acetylglucosamine transport . Many of the genes in this family also include an A domain as part of the same polypeptide and thus should be given the name 'PTS system, N-acetylglucosamine-specific IIABC component'. This family is most closely related to the glucose-specific PTS enzymes.
Phosphotransferase system, alpha-glucoside-specific IIBC component (PTS_IIBC_a_glc)
Type: Family

This entry represents the fused PTS enzyme II B and C domains. A gene from Clostridium has been partially characterised as a maltose transporter, while genes from Fusobacterium and Klebsiella have been proposed to transport the five non-standard isomers of sucrose.
Beta-phosphoglucomutase hydrolase (B-phosphoglucomutase_hydrolase)
Type: Domain

Phosphoglucomutases interconvert D-glucose 1-phosphate and D-glucose 6-phosphate, a reaction which is important for energy metabolism in many organisms and for cell wall biosynthesis in bacteria . Beta-phosphoglucomutases are monomeric enzymes which interconvert the beta anomers of these compounds using Mg2+ as a cofactor.

This entry groups together three clades: the characterised beta-phosphoglucomutases (bPGMs) (including those from Escherichia coli, Bacillus subtilis and Lactococcus lactis, a clade of putative bPGMs from mycobacteria and a clade including the uncharacterised E. coli and Haemophilus influenzae yqaB genes which may prove to be beta-mutases of a related 1-phosphosugar. All of these are members of the larger Haloacid dehalogenase (HAD) subfamily IA and include the 'variant 3' Glu-Asp version of the third conserved HAD domain.

The Lactococcus enzyme has been crystallised and studied in detail . It is composed of two distinct regions, an α/β core domain similar to that found in other HAD family members, and a helical cap domain. The core domain contains a central six-stranded parallel β sheet surrounded by six α helices, while the cap domain consists of an antiparallel four α-helix bundle. Overall, the monomer forms a "kidney-bean" shape similar to that observed in other HAD family members such as phosphoserine phosphatase. The active site of the enzyme is located at the interface of the two domains.
Aromatic-L-amino-acid decarboxylase (Aromatic_deC)
Type: Family

A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group . Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine ; tyrosine decarboxylase, which
converts tyrosine into tyramine; and histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine . These enzymes belong to the group II decarboxylases .
Class I and II aminoacyl-tRNA synthetase, tRNA-binding arm (tRNA-bd_arm)
Type: Homologous_superfamily

This superfamily represents an α-helical tRNA-binding arm found in class I and II aminoacyl-tRNA synthetase enzymes, as well as in the methicillin resistance protein FemA.

The tRNA-binding arm domain is conserved between class I and class II aminoacyl-tRNA synthetase enzymes (

), consisting of two α helices in an antiparallel hairpin with a left-handed twist. The appended tRNA-binding domains recognise a small number of nucleotides that are conserved specifically in each cognate tRNA species for the discrimination between the cognate and noncognate tRNAs . These nucleotides are called identity elements, and constitute the identity set. The tRNA-binding arm occurs as the C-terminal domain in some class I enzymes, such as valyl-tRNA synthetase, and as the N-terminal domain in some class II enzymes, such as phenylalanyl-tRNA synthetase.

The methicillin resistance protein, FemA (factors essential for methicillin resistance), contains a probable tRNA-binding arm that is similar in structure to those found in tRNA synthetases. In FemA, the tRNA-binding arm is inserted into the C-terminal NAT-like domain, and is thought to bind tRNA-glycine. FemA, along with FemB and FemX, plays a vital role in peptidoglycan biosynthesis specific to Staphylococci .
Small ribosomal subunit protein uS13-like, H2TH (Ribosomal_uS13-like_H2TH)
Type: Homologous_superfamily

This superfamily represents the H2TH motif found in the small ribosomal subunit protein uS13.

Small ribosomal subunit protein uS13 was previously known as Ribosomal protein S13 . In Escherichia coli, S13 is known to be involved in binding fMet-tRNA and, hence, in the initiation of translation. S13 contains thee helices and a β-hairpin in the core of the protein, which form a helix-two turns-helix (H2TH) motif, and a non-globular C-terminal extension.

This H2TH motif can be found in other proteins as well. In the DNA repair protein, MutM (formamidopyrimidine DNA glycosylase; Fpg), the middle domain contains the H2TH motif. MutM is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidatively damaged bases (N-glycosylase activity) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity) . Other repair enzymes, such as E. coli Endonuclease VIII that excises oxidized pyrimidines from DNA, also contain a DNA-binding H2TH motif within the middle domain. The H2TH domains of these repair proteins are only peripherally involved in binding DNA; their primary function may be simply to position the N-terminal lobe and C-terminal zinc finger domain of the glycosylases for interactions with DNA.

The middle domain of topoisomerase IV-B subunit contains a H2TH motif that is structurally related to the DNA repair proteins. Although the H2TH domain appears to be retained in all archaeal and plant type IIB topoisomerases identified to date, it has no known function and has not been observed in other topoisomerase families .
Cytochrome c/b562 (Cyt_c/b562)
Type: Homologous_superfamily

Cytochromes are haem-containing proteins that function as electron carriers during electron transfer reactions. Cytochromes can be divided into types depending upon how the haem atom is bound: in c-type cytochromes the haem is covalently attached to the polypeptide, while in b-type cytochromes the haem is not covalently attached. A four-helical bundle motif is found in several cytochromes, including the cytochrome c family (

), cytochrome b562 (

), and cytochrome b559, despite having very low sequence similarities. Cytochromes c and b562 are found in many bacteria and are probably involved in nitric oxide transfer . These proteins exhibit a reduction potential in the range of around 8mV to 400mV, which sets the energy yield possible in metabolism and is also a key determinant of the rate at which redox reactions proceed .
SinR repressor/SinI anti-repressor, dimerisation domain (SinR/SinI_dimer_dom)
Type: Domain

The SinR repressor is part of a group of Sin (sporulation inhibition) proteins in Bacillus subtilis that regulate the commitment to sporulation in response to extreme adversity . SinR is a tetrameric repressor protein that binds to the promoters of genes essential for entry into sporulation and prevents their transcription. This repression is overcome through the activity of SinI, which disrupts the SinR tetramer through the formation of a SinI-SinR heterodimer, thereby allowing sporulation to proceed. The SinR structure consists of two domains: a dimerisation domain stabilised by a hydrophobic core, and a DNA-binding domain that is identical to domains of the bacteriophage 434 CI and Cro proteins that regulate prophage induction. The dimerisation domain is a four-helical bundle formed from two helices from the C-terminal residues of SinR and two helices from the central residues of SinI. These regions in SinR and SinI are similar in both structure and sequence. The interaction of SinR monomers to form tetramers is weaker than between SinR and SinI, since SinI can effectively disrupt SinR tetramers.

This entry represents the dimerisation domain in both SinI and SinR proteins.
Lambda repressor-like, DNA-binding domain superfamily (Lambda_DNA-bd_dom_sf)
Type: Homologous_superfamily

Bacteriophage lambda C1 repressor controls the expression of viral genes as part of the lysogeny/lytic growth switch. C1 is essential for maintaining lysogeny, where the phage replicates non-disruptively along with the host. If the host cell is threatened, then lytic growth is induced. The Lambda C1 repressor consists of two domains connected by a linker: an N-terminal DNA-binding domain that also mediates interactions with RNA polymerase, and a C-terminal dimerisation domain . The DNA-binding domain consists of four helices in a closed folded leaf motif. Several different phage repressors from different helix-turn-helix families contain DNA-binding domains that adopt a similar topology. These include the Lambda Cro repressor, Bacteriophage 434 C1 and Cro repressors, P22 C2 repressor, and Bacteriophage Mu Ner protein.

The DNA-binding domain of Bacillus subtilis spore inhibition repressor SinR is identical to that of phage repressors . SinR represses sporulation, which only occurs in response to adverse conditions. This provides a possible evolutionary link between the two adaptive responses of bacterial sporulation and prophage induction.

Other DNA-binding domains also display similar structural folds to that of Lambda C1. These include bacterial regulators such as the purine repressor (PurR), the lactose repressor (Lacr) and the fructose repressor (FruR), each of which has an N-terminal DNA-binding domain that exhibits a fold similar to that of lambda C1, except that they lack the first helix . POU-specific domains found in transcription factors such as in Oct-1, Pit-1 and Hepatocyte nuclear factor 1a (LFB1/HNF1) display four-helical fold DNA-binding domains similar to that of Lambda C1 . The N-terminal domain of cyanase has an α-helix bundle motif similar to Lambda C1, but it probably does not bind DNA. Cyanase is an enzyme found in bacteria and plants that catalyses the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide in response to extracellular cyanate .
Ribbon-helix-helix (Ribbon_hlx_hlx)
Type: Homologous_superfamily

This superfamily represents domains with a ribbon-helix-helix core topology consisting of four helices in an open array of two hairpins. Such domains are found in several bacterial and phage repressors, including the Escherichia coli methionine repressor (MetJ), which when combined with S-adenosylmethionine (SAM) represses the expression of the methionine regulon and of enzymes involved in SAM synthesis . Other bacterial and phage repressors containing domains with a similar fold include the bacterial plasmid-encoded repressors CopG (

), the bacterial omega transcription repressor , and the phage repressors Arc and Mnt . These repressors are usually obligate dimers, which pair through a single N-terminal strand, and possess a C-terminal helix-turn-helix unit .
Glutathione S-transferase, C-terminal-like (Glutathione-S-Trfase_C-like)
Type: Domain

In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophillic compounds by catalysing their conjugation to glutathione. GST is found as a domain in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of cephalopods is also a GST . Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family . GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold. Each monomer is composed of a distinct N-terminal sub-domain, which adopts the thioredoxin fold, and a C-terminal all-helical sub-domain, which adopts a 4-helical bundle fold. This entry is the C-terminal domain.

Glutaredoxin 2 (Grx2), glutathione-dependent disulphide oxidoreductases, is structurally similar to GSTs, even though they lack any sequence similarity. Grx2 is also composed of N and C-terminal subdomains. It is thought that the primary function of Grx2 is to catalyse reversible glutathionylation of proteins with glutathione in cellular redox regulation including the response to oxidative stress. Grx2 is dissimilar to other glutaredoxins apart from containing the conserved active site residues .
SNARE (SNARE)
Type: Homologous_superfamily

Soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins are a family of membrane-associated proteins characterised by an α-helical coiled-coil domain called the SNARE motif . These proteins are classified as v-SNAREs and t-SNAREs based on their localisation on vesicle or target membrane; another classification scheme defines R-SNAREs and Q-SNAREs, as based on the conserved arginine or glutamine residue in the centre of the SNARE motif. SNAREs are localised to distinct membrane compartments of the secretory and endocytic trafficking pathways, and contribute to the specificity of intracellular membrane fusion processes.

The t-SNARE domain consists of a 4-helical bundle with a coiled-coil twist. The SNARE motif contributes to the fusion of two membranes. SNARE motifs fall into four classes: homologues of syntaxin 1a (t-SNARE), VAMP-2 (v-SNARE), and the N- and C-terminal SNARE motifs of SNAP-25. It is thought that one member from each class interacts to form a SNARE complex.

The SNARE motif represented in this entry is found in the N-terminal domains of certain syntaxin family members: syntaxin 1a, which is required for neurotransmitter release, syntaxin 6, which is found in endosomal transport vesicles , yeast Sso1p , and Vam3p, a yeast syntaxin essential for vacuolar fusion . The SNARE motifs in these proteins share structural similarity, despite having a low level of sequence similarity.
p53, tetramerisation domain (p53_tetrameristn)
Type: Domain

This entry represents the tetramerisation domain of p53. The tetramerisation domain of human p53 extends from residues 325 to 356, and has a 4-helical bundle fold. The tetramerisation domain is essential for DNA binding, protein-protein interactions, post-translational modifications, and p53 degradation .

The p53 tumour suppressor is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating non-transformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumour suppressor in some, but probably not all, tumour types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. p53 can be divided into different functional domains: an N-terminal transactivation domain (

), a proline-rich domain, a DNA-binding domain (

) which contains a conserved site (

), a tetramerisation domain (

) and a C-terminal regulatory region.
Integration host factor (IHF)-like DNA-binding domain superfamily (IHF-like_DNA-bd_dom_sf)
Type: Homologous_superfamily

Integration host factor (IHF) (

,

) is a small heterodimeric protein that binds the minor groove of DNA in a sequence-specific manner and induces a large bend. This bending stabilises distinct DNA conformations that are required during several bacterial processes, such as recombination, transposition, replication and transcription . The core structure of IHF consists of a partly opened 4-helical bundle that is capped with a β-sheet.

Prokaryotic protein HU and the bacteriophage SPO1 transcription factor TF1 are closely related to IHF. These proteins are collectively referred to as type II DNA-binding proteins (DBPII), forming a group of basic, dimeric proteins found in all bacteria that are able to bind DNA to induce and stabilise DNA bending. HU plays a structural role in replication initiation, transcription regulation, site-specific recombination, and the compaction of the bacterial genome . TF1 is essential for viral multiplication .

The DNA-binding domain of the TraM protein (

), an essential component of the DNA transfer machinery of the conjugative resistance plasmid R1, appears to have a similar structure to DBPII .
RuvA domain 2-like (RuvA_2-like)
Type: Homologous_superfamily

In prokaryotes, RuvA, RuvB, and RuvC process the universal DNA intermediate of homologous recombination, termed Holliday junction. The tetrameric DNA helicase RuvA specifically binds to the Holliday junction and facilitates the isomerization of the junction from the stacked folded configuration to the square-planar structure . In the RuvA tetramer, each subunit consists of three domains, I, II and III, where I and II form the major core that is responsible for Holliday junction binding and base pair rearrangements of Holliday junction executed at the crossover point, whereas domain III regulates branch migration through direct contact with RuvB. Domain 2 has a SAM (sterile alpha motif)-like α-bundle fold that occurs as a duplication containing two helix-hairpin-helix (HhH) motifs.

The C-terminal domain (CTD) of the excision repair protein UvrC shows structural similarity to RuvA domain 2. The CTD of UvrC is essential for 5' incision in the prokaryotic nucleotide excision repair process, and acts to mediate structure-specific binding to single-stranded-double-stranded junction DNA .

Domain III of NAD+-dependent DNA ligase consists of a duplication of two RuvA-like domains (four HhH motifs), and also contains a zinc-finger subdomain. DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD+ as a cofactor .