SII-SWORD/CoKE huggingface dataset:
Protease-activated receptor 2 (Pro_rcpt_2)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. A GPCR similar to the receptor for the blood clotting enzyme thrombin has been cloned . Like the thrombin receptor, this receptor is activated by N-terminal proteolytic cleavage. Thus, because the physiological agonist at the receptor is unknown, it has been provisionally named proteinase-activated receptor 2 (PAR-2) . Human PAR-2 (hPAR-2) resides both on the plasma membrane and in the Golgi apparatus . hPAR-2 mRNA is highly expressed in human pancreas, kidney, colon, liver and small intestine, and by A549 lung and SW480 colon adenocarcinoma cells . Hybridisation in situ reveals high expression in intestinal epithelial cells throughout the gut , where it is thought that PAR-2 may serve as a trypsin sensor . Its expression by cells and tissues not normally exposed to pancreatic trypsin suggests that other proteases could serve as physiological activators .
Platelet-activating factor receptor (PAF_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Platelet-activating factor (PAF), a unique phospholipid mediator, possesses potent proinflammatory, smooth-muscle contractile and hypotensive activities, and appears to be crucial in the pathogenesis of bronchial asthma and in the lethality of endotoxin and anaphylactic shock . However, little is known of the molecular properties of the PAF receptor and related signal transduction systems . The gene for the human PAF receptor (PAFR) has been isolated, and encodes a protein that is highly similar to the guinea pig PAF receptor. Analysis of somatic cell hybrids suggests that PAFR is encoded by a single gene on human chromosome 1 .
DNA gyrase B subunit, C-terminal (DNA_gyrase_B_C)
Type: Domain

This entry represents the C-terminal of the DNA gyrase B. The N terminus of eukaryotic and prokaryotic DNA topoisomerase II are similar, but they have a different C terminus. The N-terminal of the DNA gyrase B protein is thought to catalyse the ATP-dependent super-coiling of DNA. The C-terminal end supports the complexation with the DNA gyrase A protein and the ATP-independent relaxation. This entry also contains Topoisomerase IV, which is a bacterial enzyme that is closely related to DNA gyrase .
Ornithine/putrescine carbamoyltransferase (Orn/put_carbamltrans)
Type: Family

The ornithine carbamoyltransferases are a family of enzymes that catalyse the production of citrulline from carbamoyl-phosphate and ornithine . This reaction is part of the arginine biosynthetic pathway, and in some organisms the reaction is also part of the arginine deaminase pathway . In most prokaryotes, and some lower eukaryotes, the enzyme is found in the cytoplasm, but in higher eukaryotes, such as mammals, the enzyme is found in the mitochondrial matrix and functions as part of the urea cycle. In most organisms analysed to date, the enzyme has been shown to consist of a trimer of identical or nonidentical subunits . Extensive similarity has been found within the ornithine carbamoyltransferase family, some of the conserved areas being important in catalysis . The C-terminal region of these enzymes contains a highly conserved Cys residue (in a His-Cys-Lys-Pro motif) implicated in ornithine binding .

Putrescine carbamoyltransferase converts carbamoyl putrescine to carbamoyl phosphate and putrescine as part of the agamtine deiminase pathway . It is closely related the the ornithine carbamoyltransferases that function in the arginine deiminase pathway.
Amino acid/polyamine transporter I (AA/rel_permease1)
Type: Family

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related . These proteins include several yeast specific and general amino acid permeases; Emericella nidulans (Aspergillus nidulans) proline transport protein (gene prnB); Trichoderma harzianum amino acid permease INDA1; Salmonella typhimurium L-asparagine permease (gene ansP); and several Escherichia coli and other bacterial permeases and transport proteins. These proteins seem to contain up to 12 transmembrane segments. This entry consists of members of the amino acid-polyamine-organocation (APC) superfamily .

Also included in this entry is the methylthioribose transporter mtrA from Bacillus subtilis, which transports methylthioribose into the cell .
N4/N6-methyltransferase, Type III restriction-modification enzyme EcoPI Mod subunit-like (N4/N6-MTase_EcoPI_Mod-like)
Type: Family

This protein family includes SAM-dependent beta subtype DNA methyltransferases that methylate exocyclic nitrogens and form either N4-methylcytosine (N4-MTases) or N6-methyladenine (N6-MTases) , including Type III restriction-modification enzyme EcoPI Mod subunit from Escherichia phage P1, a component of the beta subtype methylase that binds the system-specific DNA recognition site 5'-AGACC-3' and methylates A-3 of only 1 strand .
DNA-directed DNA-polymerase, family A, mitochondria (DNA-dir_DNA_pol_A_mt)
Type: Family

DNA carries the biological information that instructs cells how to exist in an ordered fashion. Accurate replication is thus one of the most important events in the cell life cycle. This function is mediated by DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP) residues to the 5'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used.

DNA-dependent DNA-polymerases have been grouped into families, denoted A, B and X, on the basis of sequence similarities . Members of family A, which includes bacterial and bacteriophage polymerases, share significant similarity to Escherichia coli polymerase I; hence family A is also known as the pol I family. The bacterial polymerases also contain an exonuclease activity, which is coded for in the N-terminal portion. The yeast gamma polymerases show some similarity to the prokaryotic nuclear polymerases of family A, but their function is restricted to mitochondrial DNA replication and repair .
DNA polymerase A (DNA_polymerase_A)
Type: Family

DNA carries the biological information that instructs cells how to exist in an ordered fashion. Accurate replication is thus one of the most important events in the cell life cycle. This function is mediated by DNA-directed DNA polymerases, which add nucleotide triphosphate (dNTP) residues to the 3'-end of the growing DNA chain, using a complementary DNA as template. Small RNA molecules are generally used as primers for chain elongation, although terminal proteins may also be used. DNA-dependent DNA polymerases have been grouped into families, denoted A, B and X, on the basis of sequence similarities . Members of family A, which includes bacterial and bacteriophage polymerases, share significant similarity to Escherichia coli polymerase I; hence family A is also known as the pol I family. The bacterial polymerases also contain an exonuclease activity, which is coded for in the N-terminal portion. Three motifs, A, B and C , are seen to be conserved across all DNA polymerases, with motifs A and C also seen in RNA polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenow (E. coli) structure. Motif A contains a strictly-conserved aspartate at the junction of a β-strand and an α-helix; motif B contains an α-helix with positive charges; and motif C has a doublet of negative charges, located in a β-turn-beta secondary structure .

This entry represents the DNA-polymerase A family.
Porin, Neisseria sp. type (Porin_Neis)
Type: Family

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.
Aminoacyl-tRNA synthetase, class Ia (aa-tRNA-synth_Ia)
Type: Domain

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 .

The class Ia aminoacyl-tRNA synthetases consist of the isoleucyl, methionyl, valyl, leucyl, cysteinyl, and arginyl-tRNA synthetases; the class Ib include the glutamyl and glutaminyl-tRNA synthetases, and the class Ic are the tyrosyl and tryptophanyl-tRNA synthetases .
Isoleucine-tRNA ligase (Ile-tRNA-ligase)
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 .
Leucine-tRNA ligase (Leu-tRNA-ligase)
Type: Family

Leucine-tRNA ligase (

) is an alpha monomer that belongs to class Ia. The crystal structure of leucine-tRNA ligase from the hyperthermophile Thermus thermophilus has an overall architecture that is similar to that of isoleucine-tRNA ligase, except that the putative editing domain is inserted at a different position in the primary structure. This feature is unique to prokaryote-like leucine-tRNA ligases, as is the presence of a novel additional flexibly inserted domain .

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 .
Valine-tRNA ligase (Valyl-tRNA_ligase)
Type: Family

Valine-tRNA ligase (also known as Valyl-tRNA synthetase) (

) is an alpha monomer that belongs to class Ia aminoacyl-tRNA ligase.

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 .
Aminoacyl-tRNA synthetase, class Ic (aa-tRNA-synth_Ic)
Type: Family

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 .

The class Ia aminoacyl-tRNA synthetases consist of the isoleucyl, methionyl, valyl, leucyl, cysteinyl, and arginyl-tRNA synthetases; the class Ib include the glutamyl and glutaminyl-tRNA synthetases, and the class Ic are the tyrosyl and tryptophanyl-tRNA synthetases .
Tryptophan-tRNA ligase (Trp-tRNA-ligase)
Type: Family

This entry represents tryptophan-tRNA ligase (TrpRS; also known as tryptophanyl-tRNA synthetase) (

). The enzyme is widely distributed, being found in archaea, bacteria and eukaryotes. TrpRS is a homodimer which attaches Tyr to the appropriate tRNA. TrpRS is a class I tRNA synthetase, so it aminoacylates the 2'-OH of the nucleotide at the 3' end of the tRNA. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains class I characteristic 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding .

The class Ia aminoacyl-tRNA synthetases consist of the isoleucyl, methionyl, valyl, leucyl, cysteinyl, and arginyl-tRNA synthetases; the class Ib include the glutamyl and glutaminyl-tRNA synthetases, and the class Ic are the tyrosyl and tryptophanyl-tRNA synthetases .

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 .