SII-SWORD/CoKE huggingface dataset:
Hemolysin A /rRNA methyltransferase TlyA (Hemolysin_A/TlyA)
Type: Family

Haemolysins are exotoxins that attack blood cell membranes and cause cell rupture. The mechanism of action is not well defined. Hemolysin A is induced by sodium ribonucleate, and is produced by pathogenic bacterial strains. Haemolysin A from Treponema hyodysenteriae causes swine dysentery . The homologous protein from Mycobacterium tuberculosis is known as 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA and exhibits haemolytic activity in vitro. It catalyses the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA .
Translation elongation factor EF1A, eukaryotic/archaeal (Transl_elong_EF1A_euk/arc)
Type: Family

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

EF-Tu (also known as EF-1alpha or EF1A) is a G-protein. It forms a ternary complex of EF-Tu (EF1A)-GTP-aminoacyltRNA. The binding of aminoacyl-tRNA stimulates GTP hydrolysis by EF-Tu (EF1A), causing a conformational change in EF-Tu (EF1A) that causes EF-Tu (EF1A)-GDP to detach from the ribosome, leaving the aminoacyl-tRNA attached at the A-site. Only the cognate aminoacyl-tRNA can induce the required conformational change in EF-Tu (EF1A) through its tight anticodon-codon binding . EF-Tu (EF1A)-GDP is returned to its active state, EF-Tu (EF1A)-GTP, through the action of another elongation factor, EF1B (also known as EF-Ts or EF-1beta/gamma/delta).

This entry represents EF1A proteins from in eukaryotic (eEF1alpha) and archaeal (aEF1alpha) organisms, these proteins being more closely related to one another than to EF1A (or EF-Tu) from bacteria (

).

Archaeal EF1-alpha is not only involved in translation elongation. It interacts with Pelota, a mRNA surveillance protein involved in no-go mRNA decay and non-stop mRNA decay; and with RF1, a tRNA-mimicking protein which recognises stop codons and catalyses polypeptide-chain release. Through these interactions archaeal EF1-alpha also has a role in translational termination and mRNA surveillance pathways .
Translation elongation factor EFG/EF2 (Transl_elong_EFG/EF2)
Type: Family

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

EF-G is a large, five-domain GTPase that promotes the directional movement of mRNA and tRNAs on the ribosome in a GTP-dependent manner. Unlike other GTPases, but by analogy to the myosin motor, EF-G performs its function of powering translocation in the GDP-bound form; that is, in a kinetically stable ribosome-EF-G(GDP) complex formed by GTP hydrolysis on the ribosome. The complex undergoes an extensive structural rearrangement, in particular affecting the small ribosomal subunit, which leads to mRNA-tRNA movement. Domain 4, which extends from the 'body' of the EF-G molecule much like a lever arm, appears to be essential for the structural transition to take place. In a hypothetical model, GTP hydrolysis induces a conformational change in the G domain of EF-G, which affects the interactions with neighbouring domains within EF-G. The resulting rearrangement of the domains relative to each other generates conformational strain in the ribosome to which EF-G is fixed. Because of structural features of the tRNA-ribosome complex, this conformational strain results in directional tRNA-mRNA movement. The functional parallels between EF-G and motor proteins suggest that EF-G differs from classical G-proteins in that it functions as a force-generating mechanochemical device rather than a conformational switch .

Every completed bacterial genome has at least one copy, but some species have additional EF-G-like proteins. The closest homologue to canonical (e.g. Escherichia coli) EF-G in the spirochetes clusters as if it is derived from mitochondrial forms, while a more distant second copy is also present. Synechocystis sp. (strain PCC 6803)
has a few proteins more closely related to EF-G than to any other characterised protein. Two of these resemble E. coli EF-G more closely than does the best match from the spirochetes; it may be that both function as authentic EF-G.
Translation elongation factor EFTu/EF1A, bacterial/organelle (Transl_elong_EFTu/EF1A_bac/org)
Type: Family

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

EF-Tu (also known as EF-1alpha or EF1A) is a G-protein. It forms a ternary complex of EF-Tu (EF1A)-GTP-aminoacyltRNA. The binding of aminoacyl-tRNA stimulates GTP hydrolysis by EF-Tu (EF1A), causing a conformational change in EF-Tu (EF1A) that causes EF-Tu (EF1A)-GDP to detach from the ribosome, leaving the aminoacyl-tRNA attached at the A-site. Only the cognate aminoacyl-tRNA can induce the required conformational change in EF-Tu (EF1A) through its tight anticodon-codon binding . EF-Tu (EF1A)-GDP is returned to its active state, EF-Tu (EF1A)-GTP, through the action of another elongation factor, EF1B (also known as EF-Ts or EF-1beta/gamma/delta).

This entry represents EF1A (or EF-Tu) proteins found primarily in bacteria, mitochondria and chloroplasts. Eukaryotic and archaeal EF1A (

) are excluded from this entry. When bound to GTP, EF-Tu can form a complex with any (correctly) aminoacylated tRNA except those for initiation and for selenocysteine, in which case EF-Tu is replaced by other factors .
Translation elongation factor EF1B, beta chain, archaeal (Transl_elong_EF1B_B_arc)
Type: Family

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .

This entry represents the beta (EF-1beta, also known as EF1B-alpha) chain of EF1B proteins from archaea (aEF-1beta). The beta chain has exchange activity, which mainly resides in its C-terminal region. In archaea, EF1B is a dimer .
Translation elongation factor EFG/EF2, archaeal (Transl_elong_EFG/EF2_arc)
Type: Family

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF2 (EF-G) is a G-protein. It brings about the translocation of peptidyl-tRNA and mRNA through a ratchet-like mechanism: the binding of GTP-EF2 to the ribosome causes a counter-clockwise rotation in the small ribosomal subunit; the hydrolysis of GTP to GDP by EF2 and the subsequent release of EF2 causes a clockwise rotation of the small subunit back to the starting position . This twisting action destabilises tRNA-ribosome interactions, freeing the tRNA to translocate along the ribosome upon GTP-hydrolysis by EF2. EF2 binding also affects the entry and exit channel openings for the mRNA, widening it when bound to enable the mRNA to translocate along the ribosome.

This entry represents archaeal EF2 proteins (also known as aEF2), which are more similar to eukaryotic EF2 than to bacterial EF2 (or EFG), both in sequence similarity and in sharing with eukaryotes the property of having a diphthamide (modified His) residue at a conserved position. The diphthamide can be ADP-ribosylated by diphtheria toxin in the presence of NAD.
Translation initiation factor aIF-2, archaea (TF_aIF-2_arc)
Type: Family

In archaea, at least four initiation factors are required for the initiation of protein biosynthesis: aIF-1, aIF-1A, aIF-2, and aIF-5B. aIF-2 promotes the GTP-dependent binding of the initiator tRNA to the small subunit of the ribosome . This GTPase is a is a heterotrimer formed by three subunits .

This entry represents the Probable translation initiation factor IF-2 mostly found in archaea (aIF-2).
PA2G4 family (PA2G4)
Type: Family

Proteins of this family have been identified in a number of species as a nuclear protein with a cell cycle dependence. Various names have been given to members of this family which include cell cycle protein p38-2G4, also known as proliferation-associated protein PA2G4 , curved DNA-binding protein , proliferation-associated protein A, and ErbB3-binding protein 1 (Ebp1) . They constitute the proliferation-associated PA2G4 family, which is structurally homologous to the type II methionine aminopeptidases, but without methionine aminopeptidase activity . ErbB3 binding protein-1 (Ebp1) is a potential regulator of ErbB3 signaling, and is implicated in cell growth, apoptosis and differentiation in many cell types .

These proteins are classified as non-peptidase homologues in the MEROPS peptidase family M24 (clan MG).
Glucosamine-6-phosphate isomerase (Glucosamine6P_isomerase)
Type: Family

Glucosamine-6-phosphate isomerase, aslo known as Glucosamine-6-phosphate deaminase (

), catalyses the conversion of D-glucosamine 6-phosphate (GlcN6P) to D-fructose 6-phosphate and ammonium. This is the last step in the pathway for N-acetylglucosamine (GlcNAC) utilization in bacteria such as Escherichia coli (gene nagB) or in fungi such as Candida albicans (Yeast) (gene NAG1). The structure of this enzyme from E. coli (NagB) is described as a modified NAD-binding domain, and undergoes allosteric conformational changes that regulate its function . The reaction steps involve opening of the pyranose ring of the substrate and a sequence of general base-catalysed reactions to bring about isomerisation and deamination .

This family also includes a closely related pair of proteins from Bacillus subtilis, one of which is uncharacterised but included as a member of the orthologous set.
Peptide chain release factor 3 (PrfC)
Type: Family

Peptide chain release factor 3 (RF-3, PrfC) is a GTPase found in a broad range of bacteria that accelerates dissociation of class I release factors (RF1 and RF2) from the ribosome following peptide release . In addition to its contribution to translation termination by recycling the class I release factors, RF3 has also been implicated in dissociation of peptidyl-tRNAs from elongating ribosomes and in a post-peptidyltransferase quality control (post-PT QC) mechanism that selectively terminates ribosomes carrying erroneous peptides .
Acetyl-CoA carboxylase, biotin carboxylase (Acetyl_CoA_COase_biotin_COase)
Type: Family

This family represents the biotin carboxylase subunit found usually as a component of acetyl-CoA carboxylase. Acetyl-CoA carboxylase (

) is a heterohexamer of biotin carboxyl carrier protein, biotin carboxylase (

), and two subunits of carboxyl transferase in a 2:2 complex. In the first step of long-chain fatty acid synthesis, biotin carboxylase catalyses the carboxylation of the carrier protein and then the transcarboxylase transfers the carboxyl group to form malonyl-coA. Homologous domains are found in eukaryotic forms of acetyl-CoA carboxylase and in a number of other carboxylases (e.g. pyruvate carboxylase). In some systems, the biotin carboxyl carrier protein and this protein (biotin carboxylase) may be shared by different carboxyltransferases. However, this model is not intended to identify the biotin carboxylase domain of propionyl-coA carboxylase. The model should hit the full length of proteins, except for chloroplast transit peptides in plants. If it hits a domain only of a longer protein, there may be a problem with the identification.
L-asparaginase, type II (AsnASE_II)
Type: Family

L-asparaginase catalyses the conversion of L-asparagine to L-aspartate. Two related families of asparaginase (L-asparagine amidohydrolase,

) are designated type I and type II according to the terminology in Escherichia coli, which has both: L-asparaginase I is a low-affinity enzyme found in the cytoplasm, while L-asparaginase II is a high-affinity periplasmic enzyme synthesized with a cleavable signal sequence. This family describes L-asparaginases related to type II of E. coli. Both the cytoplasmic and the cell wall asparaginases of Saccharomyces cerevisiae belong to this set. Type II L-asparaginase acts as a tetramer, which is actually a dimer of two tightly bound dimers . A conserved threonine residue is thought to supply the nucleophile hydroxy-group that attacks the amide bond. Many bacterial L-asparaginases have both L-asparagine and L-glutamine hydrolysis activities, to a different degree, and some of them are annotated as asparaginase/glutaminase .

Type II L-asparaginases are potent antileukemic agents and have been used in the treatment of acute lymphoblastic leukemia (ALL), but not without severe side effects . Tumour cells appear to have a heightened dependence on exogenous L-aspartate, and depleting their surroundings of L-aspartate may starve cancerous ALL cells .
Diphthine synthase (Dphthn_synthase)
Type: Family

Diphthine synthase (

), also known as diphthamide biosynthesis S-adenosylmethionine-dependent methyltransferase, participates in the modification of a specific histidine residue in elongation factor 2 (EF-2) of eukaryotes and archaea to diphthamide. It is required for the methylation step in dipthamide biosynthesis.

This entry also includes diphthine methyl ester synthase (

) from Saccharomyces cerevisiae (a product of the DPH5 gene), which is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes methylations of a modified histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester: the second step of diphthamide biosynthesis .
1-acyl-sn-glycerol-3-phosphate acyltransferase (AGP_acyltrans)
Type: Domain

This domain describes the core homologous region of a collection of related proteins, several of which are known to act as 1-acyl-sn-glycerol-3-phosphate acyltransferases (

). Proteins scoring above the trusted cut-off are likely to have the same general activity, which is to convert acyl-CoA and 1-acyl-SN-glycerol 3-phosphate to CoA and 1,2-diacyl-SN-glycerol 3-phosphate. However, there is variation among characterised members as to whether the acyl group can be donated by acyl carrier protein or coenzyme A, and in the length and saturation of the donated acyl group . 1-acyl-sn-glycerol-3-phosphate acyltransferase is also called 1-AGP acyltransferase, lysophosphatidic acid acyltransferase, and LPA acyltransferase.
Hydroxymethylglutaryl-CoA reductase, bacterial-type (HMG_CoA_Rdtase_bac-typ)
Type: Family

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).

This entry represents class II HMG-CoA reductases, as well as some class I enzymes from archaea. This family was built from two class II NAD-dependent enzymes from organisms closely related to Pseudomonas mevalonii, a bacterium that can use mevalonate as its sole carbon source. Some archaeal HMG-CoA reductases were found to be of bacterial origin .
Hydroxymethylglutaryl-CoA reductase, eukaryotic/archaeal type (HMG_CoA_Rdtase_eu_arc)
Type: Family

This entry represents class I HMG-CoA reductase enzymes.

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).
Glucose-6-phosphate dehydrogenase assembly protein OpcA (G6PDH_assembly_OpcA)
Type: Family

OpcA protein may play a role in the functional assembly of glucose-6-phosphate dehydrogenase . The opcA gene is found immediately downstream of zwf, the glucose-6-phosphate dehydrogenase (G6PDH) gene, in a number of species, including Mycobacterium tuberculosis, Streptomyces coelicolor, Nostoc punctiforme (strain ATCC 29133/PCC 73102), and Synechococcus sp. (strain PCC 7942). In the latter, disruption of opcA was shown to block assembly of G6PDH into active oligomeric forms.
Methyltransferase HemK-like (HemK-like)
Type: Family

This entry includes HemK (also known as PrmC) from Escherichia coli. HemK methylates the class 1 translation termination release factors RF1/PrfA and RF2/PrfB on the glutamine residue of the universally conserved GGQ motif . Its homologue in Saccharomyces cerevisiae, Mtq1, is a methyltransferase that methylates MRF1 on 'Gln-287' using S-adenosyl L-methionine as methyl donor . Homologues are found, usually in a single copy, in nearly all completed genomes, but varying somewhat in apparent domain architecture. Both Escherichia coli and Haemophilus influenzae have two members rather than one. The members from the Mycoplasmas have an additional C-terminal domain.
Eukaryotic/archaeal PrmC-related (PrmC-related)
Type: Family

These proteins exhibit homology to the Saccharomyces cerevisiae Mtq2 (also know as PrmC ). Mtq2 methylates eRF1 on 'Gln-182' using S-adenosyl L-methionine as methyl donor. eRF1 needs to be complexed to eRF3 in its GTP-bound form to be efficiently methylated . In bacteria, the methylation of RF1/RF2 by PrmC is important for normal growth, to increase the affinity of RF1/RF2 for ribosomes and to enhance translation termination . Human homologue of Mtq2 is called hemK methyltransferase family member 2 (HEMK2, also known as N6AMT1), which is an N6-adenine-specific DNA methyltransferase .
Oxygen-independent coproporphyrinogen III oxidase HemN (Coprogen_oxidase_HemN)
Type: Family

This family represents HemN, the oxygen-independent coproporphyrinogen III oxidase that replaces HemF function under anaerobic conditions. HemN catalyses the anaerobic transformation of coproporhyrinogen-III into protoporphyrinogen-IX during porphyrin biosynthesis. Several species, including Escherichia coli, Helicobacter pylori, and Aquifex aeolicus, have both a member of this family and a member of another, closely related family for which there is no evidence of coproporphyrinogen III oxidase activity,

. Members of this family have a perfectly conserved motif PYRT[SC]YP in a region N-terminal to the region of homology with the related uncharacterised protein.