SII-SWORD/CoKE huggingface dataset:
DNA-(apurinic or apyrimidinic site) endonuclease (APNUC_T5)
Type: Family

This family represents the DNA-(apurinic or apyrimidinic site) endonuclease from T5-like phages. It performs endonucleolytic cleavage at abasic sites, which are generated by the base-excision activity of host Ung. The cleavage generates a 5'-deoxyribose phosphate and 3'-hydroxyl end. The sites are specifically recognized through the formation of a complex with host Ung. The viral endonucleolytic activity damages the host DNA, blocks host DNA replication and induces cell division arrest. This may provide an advantage for the phage and save nucleotides for the viral replication since specifically targets the host DNA, which possesses more misincorporated uracils than the viral genome .
Eukaryotic elongation factor 2 kinase, alpha-kinase domain (eEF2K_a_kinase_dom)
Type: Domain

This entry represents the alpha-kinase catalytic domain of eukaryotic elongation factor-2 kinase (eEF2K) and similar sequences, mainly found in animals.

Eukaryotic elongation factor-2 kinase (eEF2K) is also called calcium/calmodulin (CaM)-dependent eEF2K. It phosphorylates eukaryotic elongation factor-2 (EEF2) at a single site, leading to its inactivation and inability to bind ribosomes, and slowing down the elongation stage of protein synthesis. It has been linked to many human diseases including cardiovascular conditions (atherosclerosis) and pulmonary arterial hypertension, as well as solid tumours and neurological disorders . eEF2K is an atypical protein kinase containing a CaM binding region, an alpha-kinase catalytic domain, and TPR-like Sel1 repeats at the C-terminal. Alpha-kinase is an atypical protein kinase catalytic domain with no detectable similarity to conventional protein serine/threonine kinases. These proteins target both protein sequences that adopt an α-helical conformation and residues in non-helical regions .
DUF11 repeat (DUF11_rpt)
Type: Repeat

This entry represents a conserved repeat of about 53 amino acids that is part of the DUF11 domain (

). Examples containing this repeat include a 132-residue region found repeated in three of the five longest proteins of Bacillus anthracis, a 131-residue repeat in a cell wall-anchored protein of Enterococcus faecalis (Streptococcus faecalis), and a 120-residue repeat in Methanobacterium sp. A similar region is found in some Chlamydia trachomatis outer membrane proteins. In Methanothermobacter sp. CaT2, a DUF11-containing repeat hypothetical protein encoded by MTCT_1020, plays a key role as a membrane-bound adhesion protein in the aggregation of CaT2. DUF11-containing repeat domains are not involved in aggregation, but may be important for stabilizing the surface cell wall structures of CaT2 .
Cell division protein FtsX, proteobacteria (FtsX_proteobact)
Type: Family

This entry represents Cell division protein FtsX and similar proteins predominantly found in proteobacteria.

FtsX is an integral membrane protein encoded in the same operon as signal recognition particle docking protein FtsY and FtsE. FtsE is a hydrophilic nucleotide-binding protein that associates with the inner membrane by means of association with FtsX; FtsE mutants are viable only in high salt, supporting possible roles in cell division or in transport . FtsX belongs to a family of predicted permeases and may play a role in the insertion of proteins required for potassium transport, cell division, and other activities . FtsX is involved in sporulation in the Gram-positive bacterium Bacillus subtilis .
Probable 3-phenylpropionic acid transporter (HcaT)
Type: Family

This entry represents a group of permeases, including probable 3-phenylpropionic acid transporter HcaT from Escherichia coli , and and similar sequences from gammaproteobacteria.
Molybdenum cofactor biosynthesis C, bacteria/eukaryotes (MoaC_bact/euk)
Type: Family

This entry represents molybdenum cofactor biosynthesis C (MoaC) proteins from bacteria and eukaryotes. Members of this family are involved in molybdenum cofactor (Moco) biosynthesis, an essential cofactor of a diverse group of redox enzymes. MoaC is a small hexameric protein that converts, together with MoaA, a guanosine derivative to the precursor Z by inserting the carbon-8 of the purine between the 2' and 3' ribose carbon atoms, which is the first of three phases of Moco biosynthesis .
Orotidine 5'-phosphate decarboxylase, archaeal (OMPdecase_arc)
Type: Family

This entry represents orotidine 5'-phosphate decarboxylases (OMPdecases) found in archaea.

Orotidine 5'-phosphate decarboxylase (OMPdecase) (

) catalyses the last step in the
de novo
biosynthesis of pyrimidines, the decarboxylation of OMP into UMP. In higher eukaryotes OMPdecase is part, with orotate phosphoribosyltransferase, of a bifunctional enzyme, while the prokaryotic and fungal OMPdecases are monofunctional proteins.

Some parts of the sequence of OMPdecase are well conserved across species. The best conserved region is located in the N-terminal half of OMPdecases and is centred around a lysine residue which is essential for the catalytic function of the enzyme.

OMPdecases adopt classical TIM-barrel fold with an active site located at one side of the barrel .
Orotidine 5'-phosphate decarboxylase, bacterial (OMPdecase_bac)
Type: Family

This entry represents orotidine 5'-phosphate decarboxylases (OMPdecases) found in bacteria.

Orotidine 5'-phosphate decarboxylase (OMPdecase) (

) catalyses the last step in the
de novo
biosynthesis of pyrimidines, the decarboxylation of OMP into UMP. In higher eukaryotes OMPdecase is part, with orotate phosphoribosyltransferase, of a bifunctional enzyme, while the prokaryotic and fungal OMPdecases are monofunctional proteins.

Some parts of the sequence of OMPdecase are well conserved across species. The best conserved region is located in the N-terminal half of OMPdecases and is centred around a lysine residue which is essential for the catalytic function of the enzyme.

OMPdecases adopt classical TIM-barrel fold with an active site located at one side of the barrel .
1-pyrroline-5-carboxylate dehydrogenase, bacillales (RocA_bacillales)
Type: Family

This entry represents a group of 1-pyrroline-5-carboxylate dehydrogenases (RocA) specific to Bacillales , aldehyde dehydrogenases that catalyses the oxidation of glutamate semialdehyde to glutamate , utilizing NAD as the electron acceptor. These enzymes play important roles in cellular redox control, superoxide generation, and apoptosis.
Internalin A (InlA)
Type: Family

Internalins, as found in the intracellular human pathogen Listeria monocytogenes, are paralogous surface or secreted proteins with an N-terminal signal peptide, leucine-rich repeats, and usually a C-terminal LPXTG processing and cell surface anchoring site. This family represents Internalin A (InlA), a class 1 (LPXTG-type) internalin .
Deacetylase EF_0837-like (EF_0837-like)
Type: Family

This entry represents a group of proteins from proteobacteria and bacilli, including Deacetylase EF_0837 from Enterococcus faecalis, an esterase that can catalyse the deacetylation of acetyl-(R)-mandelate, but with very low efficiency in vitro . These proteins resemble aminohydrolases (see

), including dihydroorotases.
Sactionine bond-forming enzyme CteB-like, SPASM domain (SPASM_CteB-like)
Type: Domain

This entry represents the C-terminal iron-sulfur cluster-binding SPAM domain of CteB and similar sequences mainly found in Clostridia but also in other prokaryotic species.

Sactionine bond-forming enzyme CteB from Clostridium thermocellum (

) is a radical S-adenosylmethionine (SAM) enzyme that catalyses the formation of the requisite thioether bridge between a cysteine and the α-carbon of an opposing amino acid that is required in sactipeptide biosynthesis. Radical SAM enzymes are characterised by a conserved CxxxCxxC motif, which coordinates the conserved iron-sulfur cluster that is involved in the reductive cleavage of SAM and generates a 5'-deoxyadenosyl radical, which in turn abstracts a hydrogen from the appropriately positioned carbon atom of the substrate. Radical SAM (RS) enzymes with a C-terminal SPASM domain contain at least one other iron-sulfur cluster. CteB contains two auxillary 4Fe-4S clusters in its SPASM domain .
FxsC, N-terminal domain (FxsC_N)
Type: Domain

This entry represents the TIR-like domain found at the N-terminal of FxsC proteins from actinomycetes, which occur in the context of FxSxx-COOH class RiPP precursors (FxsA) and their radical SAM/SPASM domain maturases (FxsB). Most but not all members have an additional C-terminal domain (see

) .
Allantoinase, bacteria (Allantoinase_bact)
Type: Family

This entry represents bacterial allantoinase, which catalyses the conversion of allantoin (5-ureidohydantoin) to allantoic acid by hydrolytic cleavage of the five-member hydantoin ring . The proteins in this family are all in the vicinity of other genes involved in the processes of xanthine/urate/allantoin catabolism.
Translesion DNA synthesis-associated protein ImuA (ImuA_translesion)
Type: Family

A three-gene cassette encoding ImuA, ImuB, and ImuC (referring to inducible mutagenesis) is induced by DNA damage, is capable of DNA synthesis across DNA damage lesions, and consequently is associated with mutagenesis. This family represents ImuA (previously misnamed SulA in Pseudomonas putida) which shows some homology to SulA itself and to RecA. ImuB resembles Y-family polymerases but may be catalytically inactive. ImuC is a C-family polymerase, and catalytically active .
Plasmid replication protein RepC (RepABC_RepC)
Type: Family

This family represents homologues of replication protein C (RepC). repABC plasmids are widely distributed among alphaproteobacteria; all repABC operons contain at least three protein-encoding genes: repA, repB and repC. The first two genes encode proteins involved in plasmid segregation, whereas repC encodes a protein crucial for replication. The origin of replication maps within the repC gene . This entry represents the plasmid replication protein RepC, which is rate limiting for pT181 replication and it is likely that pT181 replication is regulated at the level of RepC synthesis .
Quinone oxidoreductase-like (QOR-like)
Type: Family

This family includes quinone oxidoreductases (QOR) from bacteria and fungi predominantly, with some uncharacterised plant sequences. QOR catalyses the conversion of a quinone NAD(P)H to a hydroquinone NAD(P) . Quinones are cyclic diones derived from aromatic compounds. Membrane bound QOR acts in the respiratory chains of bacteria and mitochondria. QOR reduces quinones through a semi-quinone intermediate via a NAD(P)H-dependent single electron transfer. QOR is a member of the medium chain dehydrogenase/reductase family, but lacks the zinc-binding sites of the prototypical alcohol dehydrogenases of this group . The N-terminal catalytic domain has a distant homology to GroES. These proteins form homodimers, and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding .

This family also includes 2-haloacrylate reductase, which catalyses the NADPH-dependent reduction of a carbon-carbon double bond in organohalogen compounds. Although it has significant sequence similarity to QOR, Burkholderia 2-haloacrylate reductase does not act on the quinones 1,4-benzoquinone and 1,4-naphthoquinone .
Peptidase M17, peptidase B-like, N-terminal domain (M17_PepB-like_N)
Type: Domain

This entry represents the N-terminal domain found in Peptidase B from Escherichia coli and other members of the family of M17 peptidases from gammaproteobacteria. M17 peptidases are a diverse metalloprotease family that consist of conserved C-terminal LAP domain and more divergent N-terminal domain. This N-terminal domain adopts α/β fold comprising a mixed β-sheet with α-helices packed on one side . The number of strands in the β-sheet and the α-helices can vary in different M17 peptidases. It is involved in dimeric interactions.

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

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
Ribosomal protein L36, bacteria (Ribosomal_L36_bact)
Type: Family

This entry represents the typical 50S ribosomal protein L36 mainly from proteobacteria, bacteroidetes and actinobacteria. This entry also includes a few proteins from algae.

Ribosomal protein bL36 (also known as L36) is the smallest protein from the large subunit of the prokaryotic ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities can be grouped into: bacterial L36; algal and plant chloroplast L36; Cyanelle L36; fungal and animal L36. L36 is a small basic and cysteine-rich protein of around 40 amino-acid residues probably involved in late assembly of the 50S particle, in vitro translation and cell growth. This protein shows a zinc-binding CxxC motif. Its paralogue encoded by ykgO (as named in Escherichia coli), lacks the zinc-binding site and replaces RpmJ when zinc availability is low .
GPR1/FUN34/YaaH conserved region (GPR1_FUN34_YAAH)
Type: Conserved_site

This entry represents a conserved region found in a group of evolutionary related proteins that includes Yarrowia lipolytica (Candida lipolytica) glyxoxylate pathway regulator GPR1 , Saccharomyces cerevisiae Ady2 and FUN34 (also known as Ato2); fission yeast Mug86 (also known as SpAC5D6.09c); Escherichia coli SatP (YaaH) ; and Aspergillus nidulans AcpA (AN5226). They contain six transmembrane regions that are involved in transport. This entry represents a region found in the first transmembrane helix (

).

Saccharomyces cerevisiae Ady2 is necessary for the expression of an acetate permease . Gpr1p affects sensitivity to acetic acid in the yeast Yarrowia lipolytica . AcpA may be an acetate transporter that is essential for acetate permease activity in the hyphal fungus Aspergillus nidulans . SatP is involved in the uptake of acetate and succinate .
Succinate-acetate/proton symporter SatP (SatP)
Type: Family

This family includes succinate-acetate/proton symporter SatP from E. coli (also known as YaaH). It mediates the uptake of acetate and succinate and this transport is energetically dependent on the proton motive force . Structural studies of SatP revealed that it forms an hexameric channel structure. It has six transmembrane helices (TM) surrounding the central channel pore in each protomer and three conserved hydrophobic residues, FLY, located in the middle of the TM for pore constriction. There are three conserved polar residues in the TM1 that faces to the periplasmic side, and are closely associated with acetate translocation activity .

This entry also includes MM_0903 from Methanosarcina mazei (

), which is involved in aceticlastic methanogenesis and other uncharacterised proteins from archaea and eukaryotes.
L-glyceraldehyde 3-phosphate reductase (GAP_reductase)
Type: Family

This entry represents a group of bacterial proteins, including L-glyceraldehyde 3-phosphate reductase from Escherichia coli (GAP reductase), which catalyses the stereospecific, NADPH-dependent reduction of L-glyceraldehyde 3-phosphate (L-GAP). Its physiological role is the detoxification of L-GAP, which may be formed by non-enzymatic racemisation of GAP. Also involved in the stress response as a methylglyoxal reductase which converts the toxic metabolite methylglyoxal to acetol in vitro and in vivo .
IS1182 transposase (IS1182_transpos)
Type: Family

Members of this family are transposases of the IS1182 family. About two-thirds of the members of this family have an extra domain between the middle and the C-terminal domain, about 50 amino acids in size and containing four invariant Cys residues.
Acyl-CoA dehydrogenase FadE (FadE)
Type: Family

This entry represents acyl-coenzyme A dehydrogenase FadE, mainly found in gammaproteobacteria. FadE catalyses the dehydrogenation of acyl-coenzyme A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation .
HTH-type transcriptional regulator RpiR-like (RpiR-like)
Type: Family

This entry represents HTH-type transcriptional regulator RpiR-like family of proteins which includes RpiR, MurR, HexR and some uncharacterised transcriptional regulators mainly from bacteria.

These proteins consist of two domains, a N-terminal helix-turn-helix (HTH) DNA-binding domain and a C-terminal sugar isomerase (SIS) domain that may bind phosphosugars. In E. coli, RpiR negatively regulates the expression of rpiB gene. Both rpiB and rpiA are ribose phosphate isomerases that catalyze the reversible reactions of ribose 5-phosphate into ribulose 5-phosphate . HexR binds to the promoters of the central metabolic operons and thus it is involved in glucose-responsive regulation . In addition, HexR also regulates genes involved in nitrogen metabolism, redox potential, and denitrification, suggesting that HexR may play an important role in connecting these major pathways in responses to environmental adaptation. In gammaproteobacteria P. putida and Shewanella oneidensis, binding of the 2-dehydro-3-deoxyphosphogluconate (KDPG) metabolic intermediate of glycolysis was reported to dissociate HexR from its target DNA . The transcriptional repressor MurR controls the expression of murP and murQ, which are involved in transporting and metabolizing N-acetylmuramic acid (MurNAc) generating N-acetylmuramic acid-6-phosphate (MurNAc-6-P) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P), both are able to bind to MurR and weaken the DNA binding ability of MurR .
ABC transporter, ATP-binding protein MalK/UgpC-like (ABC_transpr_MalK/UgpC-like)
Type: Family

This family includes bacterial and archaeal ATP-binding proteins that are part of ABC transporter complexes which mediate the uptake of different substrates, including sugar/oligosaccharides and glycerol-3-phosphate. These complexes are composed of two ATP-binding proteins, two transmembrane proteins and a solute-binding protein. Proteins in this entry are the ATPases responsible for the energy coupling to the transport system and include MalK, UgpC, SugC, MsiK, MsmK, AglK, GgtA, among others . These proteins have a similar structure despite low sequence conservation. The maltose/maltodextrin import ATP-binding protein MalK is an extensively studied protein part of the ABC transporter complex, involved in maltose/maltodextrin import . It functions in the MalKFGE ABC transporter complex to transport maltose into the cell by using ATP hydrolysis. MalK is the cytoplasmic nucleotide-binding protein of the multi-subunit complex in which MalF and MalG, the two transmembrane proteins, are present in single copies, and MalK as a homodimer .
ISAs1 transposase (ISAs1_transpos)
Type: Family

This entry represents a group of poorly characterised bacterial sequences that belong to the transposase 11 family, including Putative transposase YncI from Escherichia coli.
Transposase IS110-like (Transpos_IS110)
Type: Family

Proteins of this family are DEDD (Asp, Glu, Asp, Asp) type transposases, which are encoded by the IS110 family elements .
Ribosome-associated ATPase RbbA (ABC2_perm_RbbA)
Type: Family

This entry includes the ribosome-associated ATPase RbbA from E. coli and its homologues, found in proteobacteria. RbbA binds to 70S and 30S ribosomal particles and its ATPase activity is ribosome-dependent . This ATPase stimulates protein synthesis and ribosome-dependent ATP hydrolysis . RbbA is specifically inhibited by hygromycin B, an antibiotic that impairs translational fidelity and translocation of mRNA on ribosomes. RbbA contains two N-terminal ATP-binding domains that are similar to ABCF-type ATPases known to bind to the ribosomal E-site.
Tn3-like transposase (Tn3-like_transpos)
Type: Family

This entry includes transposases of Tn3, Tn21, Tn1721, Tn2501, Tn3926 transposons from Escherichia coli and similar bacterial sequences. The specific binding of the Tn3 transposase to DNA has been demonstrated. Sequence analysis has suggested that the invariant triad of Asp689, Asp765, Glu895 (numbering as in Tn3) may correspond to the D-D-35-E motif previously implicated in the catalytic performance of numerous transposases .
IS1634 transposase (IS1634_transpos)
Type: Family

Members of this protein family are DDE type transposases encoded by the IS1634 family elements, which were firstly identified and characterised in Mycoplasma mycoides .
Transposase IS630-like (Transpos_IS630-like)
Type: Family

This family represents a group of largely uncharacterised proteins found in bacteria, eukaryotes and some archaeal species, including transposase IS630 from Shigella sonnei.
IS481-like transposase (IS481-like_transpos)
Type: Family

This entry represents a group of proteins from bacteria, including the probable transcription factor YagA from Escherichia coli and different IS481-like transposases.
Metalloprotease PmbA (PmbA)
Type: Family

This entry represents a group of proteins from bacteria and archaea, including metalloprotease PmbA (also known as TldE) from Escherichia coli. PmbA is involved in proteolytic processing of the antibiotic Microcin B17. It suppresses the inhibitory activity of the carbon storage regulator (CsrA) .
IS4-like transposase (IS4-like_transpos)
Type: Family

This entry represents a group of proteins mainly found in proteobacteria and cyanobacteria that contain the domain

.
Type VII secretion system-associated protein (T7SS_assoc)
Type: Family

Members of this family are almost exclusively found in Actinomycetes, in the context of type VII secretion systems (T7SS). Several paralogs may accompany a single T7SS. A few members of this family are large proteins with additional domains that add or remove, ADP-ribosylations, suggesting that all family members may have effector activity as well, and that the longer members of the family are multifunctional effector proteins.
DsrMKJOP redox complex, subunit DsrM (DsrM)
Type: Family

This family represents a group of prokaryotic proteins, including the DsrM subunit of the DsrMKJOP complex from Desulfovibrio desulfuricans (

), which is predicted to consist of five membrane-spanning helices which contain histidine residues that can potentially coordinate two heme groups. This membrane-bound redox complex is involved in sulfate reduction in sulfate-reducing organisms (SROs) . The dsrM gene encodes a cytochrome b reductase, which shares similarity to the b-type cytochrome subunit of nitrate reductase from various organisms, such as NarI of nitrate reductase of Escherichia coli. HmeC also belongs to this family. This protein is a subunit of HmeACDE, which is found in sulfate-reducing archaeon Archaeoglobus fulgidus .