SII-SWORD/CoKE huggingface dataset:
Isoleucine-tRNA ligase, type 2 (Ile-tRNA-ligase_type2)
Type: Family

Isoleucine-tRNA ligase (also known as Isoleucyl-tRNA synthetase)(

) is an alpha monomer that belongs to class Ia. The enzyme, isoleucine-tRNA ligase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the ligase itself rapidly hydrolyses only the valylated products as shown from the crystal structures.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

In eukaryotes, two forms of isoleucine-tRNA synthetase exist, a cytoplasmic form and a mitochondrial form . Type 2 includes bacterial, archaeal and cytoplasmic (gene iars1) isoleucine-tRNA ligases.
Metallothionein domain superfamily, vertebrate (Metalthion_dom_sf_vert)
Type: Homologous_superfamily

Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, nickel, etc. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds . An empirical classification into three classes has been proposed by Fowler and coworkers and Kojima . Members of class I are defined to include polypeptides related in the positions of their cysteines to equine MT-1B, and include mammalian MTs as well as from crustaceans and molluscs. Class II groups MTs from a variety of species, including sea urchins,
fungi, insects and cyanobacteria. Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units .

This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Subsequently, a new classification was proposed on the basis of sequence similarity derived from phylogenetic relationships, which basically proposes an MT family for each main taxonomic group of organisms .

This superfamily represents the domain found in vertebrates .
Transcription regulator HTH, PurR (Tscrpt_reg_HTH_PurR)
Type: Family

This entry represents the bacterial helix-turn-helix transcriptional repressor PurR family.

The purR gene encodes a transcriptional repressor of the HTH-type, which is responsible for controlling the syntehsis of enzymes involved in purine biosynthesis . PurR is dimeric and consists of an N-terminal domain for DNA binding and a C-terminal domain that is responsible for corepressor (hypoxanthine and guanine) binding.

The LacI/GalR family, which includes the LacL superfamily, represents one of the largest and most diverse groups of bacterial transcriptional regulators. These proteins play crucial roles in regulating various aspects of bacterial metabolism, particularly carbohydrate utilisation . Characterised by a conserved N-terminal helix-turn-helix (HTH) DNA-binding motif

and a C-terminal regulatory domain that binds effector molecules

, members of this family can function as both repressors and activators, though most act as repressors . They typically respond to specific effector molecules, often sugars or metabolites, which modulate their DNA-binding affinity and consequently their regulatory activity. This allows bacteria to fine-tune gene expression in response to environmental conditions and available carbon sources . Some well-characterised members of this family include:

LacI (lactose operon repressor) in Escherichia coli

GalR (galactose operon repressor) in Escherichia coli

PurR (purine biosynthesis repressor) in various bacteria

CcpA (catabolite control protein A) in Gram-positive bacteria

FruR (fructose repressor) in Enterobacteriaceae
Processive diacylglycerol beta-glucosyltransferase (Pro_diacylglycrl_glcsylTrfase)
Type: Family

This entry represents a family of bacterial processive diacylglycerol glucosyltransferases. This enzyme is involved in the synthesis of bilayer and non-bilayer-forming membrane biolipids. It successively transfers up to three glycosyl residues to diacylglycerol, forming mono-, di- and triglycosyldiacylglycerol. Diglycosyldiacylglycerol is the predominant glycolipid found in Bacillales .
Digeranylgeranylglycerophospholipid reductase (DGGGPL_reductase)
Type: Family

This entry represents a family of archaeal geranylgeranyl glycerophospholipid reductases. They are responsible for the reduction of 2,3-digeranylgeranylglycerophospholipids into 2,3-diphytanylglycerophospholipids during the biosynthesis of archaeal membrane lipids . They are also able to catalyze the reduction of 2,3-di-O-geranylgeranylglyceryl phosphate analogues such as 2,3-di-O-phytyl-sn-glyceryl phosphate, 3-O-(2,3-di-O-phytyl-sn-glycero-phospho)-sn-glycerol and 2,3-di-O-phytyl-sn-glycero-phosphoethanolamine.
Small ribosomal subunit protein uS2, flavodoxin-like domain superfamily (Ribosomal_uS2_flav_dom_sf)
Type: Homologous_superfamily

This entry represents a flavodoxin-like domain superfamily found in ribosomal protein uS2.

This entry represents the family of ribosomal uS2 proteins. They are required for the assembly of different ribosomal subunits and are widely distributed among all living organisms .

Ribosomal uS2 family in humans includes three members:

Small ribosomal subunits uS2 (also known as RPSA).

Small ribosomal subunits uS2B (also known as RPSA2).

Small ribosomal subunits uS2m in mitochondria (also known as MRPS2).

Ribosomal protein SA (RPSA), previously named 37 kDa laminin receptor precursor/67 kDa laminin receptor (LRP/LR), has been characterised as a multifunctional protein that plays multiple roles in different pathological processes .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
D-galactonate dehydratase (Galactonate_deHydtase)
Type: Family

This entry represents a family of bacterial D-galactonate dehydratases which catalyse the dehydration of D-galactonate to 2-keto-3-deoxy-D-galactonate .
2-keto-3-deoxy-L-rhamnonate aldolase (KDR_aldolase)
Type: Family

This entry represents a family of bacterial 2-keto-3-deoxy-L-rhamnonate aldolases. They are responsible for reversible retro-aldol cleavage of 2-keto-3-deoxy-L-rhamnonate (KDR) to pyruvate and lactaldehyde .
Haloalkane dehalogenase, subfamily 2 (Haloalkane_dehalogenase_2)
Type: Family

Haloalkane dehalogenases catalyse the hydrolytic cleavage of carbon-halogen bonds in halogenated aliphatic compounds, leading to the formation of the corresponding primary alcohols, halide ions and protons . These enzymes can be divided into two subfamilies which differ in the amino acids and the topology of their catalytic triads. Subfamily 1 seems to have a preference for short-chain haloalkanes as substrates, whereas subfamily 2 seems to prefer long-chains.

This entry represents the subfamily 2 haloalkane dehalogenases.
Peptidase PrsW, archaeal/bacterial (Peptidase_PrsW_arch/bac)
Type: Family

This entry represents the archaeal and bacterial peptidase PrsW, which is involved in intramembrane proteolysis and antimicrobial peptide resistance .
Flagellar regulator Flk (Flagellar_regulator_Flk)
Type: Family

This group represents a flagellar regulator Flk. It is involved in coupling flgM translation to flagellar ring assembly .
Membrane-associated protein TcaA (Mem_prot_TcaA)
Type: Family

TcaA is a bacterial membrane protein that plays a role in resistance to glycopeptide antibiotics .
Folylpolyglutamate synthase, eukaryota (Folylpolyglutamate_synth_euk)
Type: Family

Folylpolyglutamate synthase

(FPGS) is an ATP-dependent enzyme that is responsible for the addition of a polyglutamate tail to folate and folate derivatives . It plays a key role in the retention of the intracellular folate pool. In some bacteria, such as Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (FPGS activity) are catalyzed by the same enzyme, FolC .

The crystal structure of the MgATP complex of the enzyme from Lactobacillus casei reveals FPGS to be a modular protein, consisting of two domains, one with a typical mononucleotide-binding fold and the other similar to the folate-binding enzyme dihydrofolate reductase. The active site of the enzyme is located in a large interdomain cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C domain, a cavity likely to be the folate binding site has been identified, and inspection of this cavity and the surrounding protein structure suggests that the glutamate tail of the substrate may project into the active site. A further feature of the structure is a well defined ω-loop, which contributes both to the active site and to interdomain interactions .

This entry represents the eukaryotic FPGS enzymes.
Golgi SNAP receptor complex, subunit 1 (Golgi_SNAP_su1)
Type: Family

This entry contains proteins involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. The Golgi SNAP receptor complex subunit 1 interacts with GABARAPL2 . It is aslo identified in a unique SNARE complex composed of the Golgi SNAREs GOSR2, STX5 and YKT6 .
Riboflavin kinase domain, CTP-dependent (Riboflavin_kinase_CTP-dep)
Type: Domain

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (

), which converts it into FMN, and FAD synthetase (

), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme , the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family . The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases .

This entry represents a CTP-dependent riboflavin kinase domain, found primarily in archaea, that catalyses the phosphorylation of riboflavin to form flavin mononucleotide in riboflavin biosynthesis. Its structure resembles a RIFT barrel, structurally similar to but topologically distinct from bacterial and eukaryotic examples . The N-terminal is a winged helix-turn-helix DNA-binding domain, and the C-terminal half is most similar in sequence to a group of cradle-loop barrels.
Low specificity L-threonine aldolase-like (Low_specificity_L-TA-like)
Type: Family

This group represents Low specificity threonine aldolases (

) which catalyse the conversion of L-threonine or L-allo-threonine into glycine and acetaldehyde. Pyridoxal 5'-phosphate is a cofactor in the reaction . The entry also includes L-allo-threonine aldolase which acts on L-allo-threonine but not L-threonine or L-serine . These family also includes closely related members, such as aldolase vrtJ from Penicillium aethiopicum and alanine racemase TOXG . Aldolase vrtJ is part of the gene cluster that mediates the biosynthesis of viridicatumtoxin, a tetracycline-like fungal meroterpenoid with a unique, fused spirobicyclic ring system .
Uncharacterised protein family SanA (Uncharacterised_SanA)
Type: Family

Members of this entry have no known function and contains the protein SanA.
Lipoprotein NlpI (Lipoprotein_NlpI)
Type: Family

This entry represents a group of uncharacterised proteins, which includes lipoprotein NlpI.
CoA-transferase family III domain 1 superfamily (CoA-Trfase_III_dom_1_sf)
Type: Homologous_superfamily

CoA-transferases are found in organisms from all kingdoms of life. They catalyse reversible transfer reactions of coenzyme A groups from CoA-thioesters to free acids. There are at least three families of CoA-transferases, which differ in sequence and reaction mechanism:

Family I consists of CoA-transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most use succinyl-CoA or acetyl-CoA as CoA donors.

Family II consists of the homodimeric alpha-subunits of citrate lyase and citramalate lyase (

,

). These enzymes catalyse the transfer of acyl carrier protein (ACP) with a covalently bound CoA derivative, but can accept free CoA thioesters as well.

Family III consists of formyl-CoA:oxalate CoA-transferase , succinyl-CoA:(R)-benzylsuccinate CoA-transferase , (E)-cinnamoyl-CoA:(R)-phenyllactate CoA-transferase , succinyl-CoA:mesaconate CoA-transferase and butyrobetainyl-CoA:(R)-carnitine CoA-transferase . These CoA-transferases occur in prokaryotes and eukaryotes, and catalyse CoA-transfer reactions in a highly substrate-and stereo-specific manner .

This superfamily represents the structural domain 1 of family III CoA-transferases.
Exodeoxyribonuclease I (Exodeoxyribonuclease_I)
Type: Family

This entry represents exodeoxyribonuclease I. It functions as a DNA deoxyribophosphodiesterase that releases deoxyribose-phosphate moieties following the cleavage DNA at an apurinic/apyrimidinic (AP) site by either an AP endonuclease AP lyase; exonucleolytic cleavage in the 3'- to 5'-direction yields nucleoside 5'-phosphates .
Protein-glutamine gamma-glutamyltransferase, animal (Transglutaminase_animal)
Type: Family

This entry includes a group of transglutaminases from animals.
Transcription regulator HTH, RhaS (Tscrpt_reg_HTH_RhaS)
Type: Family

This entry represents the HTH transcriptional activator RhaS. It is responsible for activation of rhaBAD and rhaT operons and therefore is involved in the control of rhamnose metabolism.
Phosphatidylinositol-4/5-phosphate 5/4-kinase (PInositol-4/5-P-5/4-kinase)
Type: Family

This entry includes type I and type II phosphatidylinositol-phosphate-kinases (PIPKs) . Type I (phosphatidylinositol-4-phosphate 5-kinase/PIP5K) and type II (phosphatidylinositol-5-phosphate 4-kinase/PIP4K) PIPKs catalyse the formation of phosphoinositol-4,5-bisphosphate via the phosphorylation of phosphatidylinositol-4-phosphate and phosphatidylinositol-5-phosphate, respectively, all of which are involved in the phosphoinositide signalling pathway .
Small ribosomal subunit protein mS23, conserved domain (Ribosomal_mS23_dom)
Type: Domain

This entry represents a domain found in the mitochondrial small ribosomal subunit protein mS23. The function of this conserved region is not known.

In Saccharomyces cerevisiae (Baker's yeast) the mature mitochondrial ribosomes consist of a small (37S) and a large (54S) subunit. The 37S subunit contains at least 33 different proteins and 1 molecule of RNA (15S). The 54S subunit contains at least 45 different proteins and 1 molecule of RNA (21S) .
Peptidase M4 (Peptidase_M4)
Type: Family

This group of metallopeptidases that belong to the MEROPS peptidase family M4 (thermolysin family, clan MA(E)). The protein fold of the peptidase domain of thermolysin (MEROPS identifier M04.001), is the type example for members of the clan MA. The thermolysin family is composed only of secreted eubacterial endopeptidases. The zinc-binding residues of thermolysin are H-142, H-146 and E-166, with E-143 acting as the catalytic residue. Thermolysin also contains four calcium-binding sites, which contribute to its unusual thermostability. The family also includes enzymes from a number of pathogens, including Legionella and Listeria, and the protein pseudolysin (MEROPS identifier M04.005), all with a substrate specificity for an aromatic residue in the P1' position. Three-dimensional structure analysis has shown that the enzymes undergo a hinge-bend motion during catalysis. Pseudolysin has a broader specificity, acting on large molecules such as elastin and collagen, possibly due to its wider active site cleft .

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 .
Nitrophorin (Nitrophorin)
Type: Family

Nitrophorins are haemoproteins found in saliva of blood-feeding insects . Saliva of the blood-sucking bug Rhodnius prolixus (Triatomid bug) contains four homologous nitrophorins, designated NP1 to NP4 in order of their relative abundance in the glands . As isolated, nitrophorins contain nitric oxide (NO) ligated to the ferric (FeIII) haem iron. Histamine, which is released by the host in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site. Dilution, binding of histamine and increase in pH (from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.

The salivary nitrophorin from the hemipteran Cimex lectularius (Bed bug) has no sequence similarity to R. prolixus nitrophorins. It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent evolution .

3-D structures of several nitrophorin complexes are known . The nitrophorin structures reveal lipocalin-like eight-stranded β-barrel, three α-helices and two disulphide bonds, with haem inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin, in a similar fashion (see for review). The haem iron is ligated to His59. The position of His59 is restrained through water-mediated hydrogen bond to the carboxylate of Asp70. The His59-Fe bond is bent ~15 degrees out of the imidazole plane. Asp70 forms an unusual hydrogen bond with one of the haem propionates, suggesting the residue has an altered pKa. In NP1-histamine structure, the planes of His59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidised cytochrome b5.

This entry represents the nitrophorin family.
Porin domain superfamily (Porin_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain found in porins.

Porins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts, where they form ion-selective channels for small hydrophilic molecules (up to ~600 D) . X-ray structure analyses of several bacterial porins have revealed a large 16-stranded anti-parallel β-barrel structure enclosing the transmembrane pore, by contrast with all other integral membrane proteins described to date, which are α-helical. Three subunits form a trimer; the 3-fold axis is approximately parallel to the barrel axes and is assumed to be perpendicular to the membrane plane.

From the range of porins now known, similarities have been observed between porins from different species, and between porins of different specificity within the same species. But most porins cannot be related to each other on the basis of sequence alone, and this is reflected in the lengths of the known porin sequences, which range from 282-483 residues/monomer.