SII-SWORD/CoKE huggingface dataset:
Cannabinoid receptor type 2 (Canbinoid_rcpt_2)
Type: Family

Cannabinoid receptors are a class of cell membrane receptors that belong to the rhodopsin-like G-protein coupled receptor (GPCR) family . Typical of G protein-coupled receptors, cannabinoid receptors contain seven transmembrane spanning domains . Cannabinoid receptors are activated by three major groups of ligands: endocannabinoids, such as N-arachidonoylethanolamine and 2-arachidonoyl glycerol (produced by the mammalian body), plant cannabinoids, such as tetrahydrocannabinol (produced by the plant
Cannabis sativa
) and synthetic cannabinoids, such as HU-210 . Currently, two known cannabinoid receptor subtypes have been identified, CB1 receptor and CB2 receptor , and are phylogenetically restricted to the chordate branch of the animal kingdom . The International Union of Basic and Clinical Pharmacology (IUPHAR) has identified five pharmacological targets that could be used to find new cannabinoid receptors or channels , which has resulted in a number of cannabinoid receptors being considered. TRP vanilloid 1, which is thought to function as an ionotropic cannabinoid receptor , and some deorphanised GPCRs : GPR18, GPR55, GPR119. However, according to the criteria, no channel, non-CB1/CB2 established receptor or deorphanised receptor can currently be classified fully as a novel cannabinoid receptor .

This entry represents cannabinoid receptor 2 (CB2), which is found primarily in immune tissue , specifically T cells of the immune system, on macrophages and B cells, and in hematopoietic cells . The CB2 receptor is closely related to CB1 receptor exhibiting 68% homology . The CB2 receptor has been shown to bind cannabinoid and aminoalkylindole compounds and to signal a response through the inhibition of adenylate cyclase . The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG) . The primary effect of the CB2 receptor is mainly on the immunological activity of leukocytes , and it has specifically been implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, and induction of cell migration . CB2 receptors may have possible therapeutic roles in the treatment of neurodegenerative disorders such as Alzheimer's disease .
Glycoside hydrolase, family 14 (Glyco_hydro_14)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 14

comprises enzymes with only one known activity; beta-amylase (

). A Glu residue has been proposed as a catalytic residue, but it is not known if it is the nucleophile or the proton donor.

Beta-amylase is an enzyme that hydrolyses 1,4-alpha-glucosidic linkages in starch-type polysaccharide substrates so as to remove successive maltose units from the non-reducing ends of the chains. Beta-amylase is present in certain bacteria as well as in plants.

Three highly conserved sequence regions are found in all known beta-amylases. The first of these regions is located in the N-terminal section of the enzymes and contains an aspartate which is known to be involved in the catalytic mechanism . The second, located in a more central location, is centred around a glutamate which is also involved in the catalytic mechanism .

The 3D structure of a complex of soybean beta-amylase with an inhibitor (alpha-cyclodextrin) has been determined to 3.0A resolution by X-ray diffraction . The enzyme folds into large and small domains: the large domain has a (β/α)8 super-secondary structural core, while the smaller is formed from two long loops extending from the β3 and β4 strands of the (β/α)8 fold. The interface of the two domains, together with shorter loops from the (β α)8 core, form a deep cleft, in which the inhibitor binds. Two maltose molecules also bind in the cleft, one sharing a binding site with alpha-cyclodextrin, and the other sitting more deeply in the cleft .
Phosphoribosylglycinamide formyltransferase, active site (GART_AS)
Type: Active_site

Phosphoribosylglycinamide formyltransferase (

) (GART) catalyses the third step in
de novo
purine biosynthesis, the transfer of a formyl group to 5'-phosphoribosylglycinamide. In higher eukaryotes, GART is part of a multifunctional enzyme polypeptide that catalyses three of the steps of purine biosynthesis. In bacteria, plants and yeast, GART is a monofunctional protein of about 200 amino-acid residues.

In the Escherichia coli enzyme, an aspartic acid residue has been shown to be involved in the catalytic mechanism. The region around this active site residue is well conserved in GART from prokaryotic and eukaryotic sources.

Mammalian formyltetrahydrofolate dehydrogenase (

) is a cytosolic enzyme responsible for the NADP-dependent decarboxylative reduction of 10-formyltetrahydrofolate into tetrahydrofolate. It is a protein of about 900 amino acids consisting of three domains; the N-terminal domain (200 residues) is structurally related to GARTs.

E. coli methionyl-tRNA formyltransferase (

) (gene fmt) is the enzyme responsible for modifying the free amino group of the aminoacyl moiety of methionyl-tRMA(fMet). The central part of fmt seems to be evolutionary related to GART's active site region.

This signature contains the Asp active site residue.
Bombesin receptor-like (Bombsn_rcpt-like)
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 .

This family represents a group of animal proteins that play important roles in both physiological state and diseases . Proteins in this family are frequently overexpressed by common tumors. Consequently, they are considered a possible therapeutic target in several tumors, particularly in prostate, breast, and lung cancer, but its role in some CNS/neural tumors (gliomas, neuroblastomas, medulloblastomas) may also be of interest .
L-lactate/malate dehydrogenase (L-lactate/malate_DH)
Type: Family

This family contains both lactate and malate dehydrogenases. Malate dehydrogenases catalyse the interconversion of malate to oxaloacetate. The enzyme participates in the citric acid cycle.

L-lactate dehydrogenase (

) (LDH) catalyses the reversible NAD-dependent interconversion of pyruvate to L-lactate. In vertebrate muscles and in lactic acid bacteria it represents the final step in anaerobic glycolysis. This tetrameric enzyme is present in prokaryotic and eukaryotic organisms. In vertebrates there are three isozymes of LDH: the M form (LDH-A), found predominantly in muscle tissues; the H form (LDH-B), found in heart muscle and the X form (LDH-C), found only in the spermatozoa of mammals and birds. In birds and crocodilian eye lenses, LDH-B serves as a structural protein and is known as epsilon-crystallin .

L-2-hydroxyisocaproate dehydrogenase (

) (L-hicDH) catalyses the reversible and stereospecific interconversion between 2-ketocarboxylic acids and L-2-hydroxy-carboxylic acids. L-hicDH is evolutionary related to LDH's.
HIV negative factor Nef (HIV_Nef)
Type: Family

Human immunodeficiency virus 1 (HIV-1) negative factor (Nef protein) accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases .
Phosphotriesterase (Phosphotriesterase)
Type: Family

Bacteria such as Brevundimonas diminuta (Pseudomonas diminuta) harbour a plasmid that carries the gene for phosphotriesterase (PTE also known as parathion hydrolase;

). This enzyme has attracted interest because of its potential use in the detoxification of chemical waste and organophosphate warfare agents such as VX, soman, and sarin, and its ability to degrade agricultural pesticides such as parathion. It acts specifically on synthetic organophosphate triesters and phosphorofluoridates. It does not seem to have a naturally occurring substrate and may thus have optimally evolved for utilising paraoxon.

PTE exists as a homodimer with one active site per monomer. The active site is located next to a binuclear metal centre, at the C-terminal end of a TIM α-β barrel motif. The native enzyme contains two zinc ions at the active site however these can be replaced with other metals such as cobalt, cadmium, nickel or manganese and the enzyme remains active .

PTE belongs to a family of enzymes that possess a binuclear zinc metal centre at their active site. The two zinc ions are coordinated by six different residues, six of which being histidines. This family so far includes, in addition to the parathion hydrolase, the following proteins:

Sulfolobus solfataricus aryldialkylphosphatase that has a low paraoxonase activity .

E. coli php (phosphotriesterase homology) protein. The substrate of php is not yet known .

Mycobacterium tuberculosis phosphotriesterase homology protein Rv0230C.

Phospho-furanose lactonase from Mycoplasma .

Animal phosphotriesterase related protein (PTER) (RPR-1).
Bombesin receptor type 3 (Bombesin_rcpt_3)
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 .

Bombesins are peptide neurotransmitters whose biological activity resides in a common C-terminal sequence, WAXGHXM. In the periphery, bombesin-related peptides stimulate smooth muscle and glandular secretion. In the brain, these peptides are believed to play a role in homeostasis, thermo-regulation and metabolism, and have been reported to elicit analgesia and excessive grooming, together with central regulation of a variety of peripheral effects.

Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The preproNMB gene transcript encodes a precursor of 117 amino acids, which is metabolised to neuromedin B. Receptors for these peptides have widespread distribution in peripheral tissue. High levels are found in smooth muscle and in the brain.

The recently-identified BRS-3 bombesin receptor subtype is found in germ cells in testis and in uteri of pregnant animals; it is also present in a variety of lung carcinoma cell lines. The receptor is believed to play a role in sperm cell division and maturation. Its action is mediated by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system.
Influenza matrix M1, N-terminal (Flu_matrix_M1_N)
Type: Domain

Matrix protein (M1) of influenza virus is a bifunctional membrane/RNA-binding protein that mediates the encapsidation of RNA-nucleoprotein cores into the membrane envelope. It is therefore required that M1 binds both membrane and RNA simultaneously . M1 is comprised of two domains connected by a linker sequence. The N-terminal domain has a multi-helical structure that can be divided into two subdomains . The C-terminal domain also contains an α-helical structure.
Zinc finger, Btk motif (Znf_Btk_motif)
Type: Conserved_site

The Btk-type zinc finger or Btk motif (BM) is a conserved zinc-binding motif containing conserved cysteines and a histidine that is present in certain eukaryotic signalling proteins. The motif is named after Bruton's tyrosine kinase (Btk), an enzyme which is essential for B cell maturation in humans and mice . Btk is a member of the Tec family of protein tyrosine kinases (PTK). These kinases contain a conserved Tec homology (TH) domain between the N-terminal pleckstrin homology (PH) domain (

) and the Src homology 3 (SH3) domain (

). The N-terminal of the TH domain is highly conserved and known as the Btf motif, while the C-terminal region of the TH domain contains a proline-rich region (PRR). The Btk motif contains a conserved His and three Cys residues that form a zinc finger (although these differ from known zinc finger topologies), while PRRs are commonly involved in protein-protein interactions, including interactions with G proteins . The TH domain may be of functional importance in various signalling pathways in different species . A complete TH domain, containing both the Btk and PRR regions, has not been found outside the Tec family; however, the Btk motif on its own does occur in other proteins, usually C-terminal to a PH domain (note that although a Btk motif always occurs C-terminal to a PH domain, not all PH domains are followed by a Btk motif).

The crystal structures of Btk show that the Btk-type zinc finger has a globular core, formed by a long loop which is held together by a zinc ion, and that the Btk motif is packed against the PH domain . The zinc-binding residues are a histidine and three cysteines, which are fully conserved in the Btk motif .
Peptidase S10, serine carboxypeptidase (Peptidase_S10)
Type: Family

This group of serine peptidases belong to MEROPS peptidase family S10 (clan SC). The type example is carboxypeptidase Y from Saccharomyces cerevisiae (Baker's yeast) .

All known carboxypeptidases are either metallo carboxypeptidases or serine carboxypeptidases (

and

). The catalytic activity of the serine carboxypeptidases, like that of the trypsin family serine proteases, is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which is itself hydrogen-bonded to a serine . The sequences surrounding the active site serine and histidine residues are highly conserved in all the serine carboxypeptidases.
Nucleoside diphosphate kinase (Nucleoside_diP_kinase)
Type: Family

Nucleoside diphosphate kinases (

) (NDK) are enzymes required for the synthesis of nucleoside triphosphates (NTP) other than ATP. They provide NTPs for nucleic acid synthesis, CTP for lipid synthesis, UTP for polysaccharide synthesis and GTP for protein elongation, signal transduction and microtubule polymerisation.

NDK are proteins of 17 Kd that act via a ping-pong mechanism in which a histidine residue is phosphorylated, by transfer of the terminal phosphate group from ATP. In the presence of magnesium, the phosphoenzyme can transfer its phosphate group to any NDP, to produce an NTP.

NDK isozymes have been sequenced from prokaryotic and eukaryotic sources. It has also been shown that the Drosophila awd (abnormal wing discs) protein, is a microtubule-associated NDK. Mammalian NDK is also known as metastasis inhibition factor nm23. The sequence of NDK has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism .
Synaptotagmin (Synaptotagmin)
Type: Domain

Synaptotagmins are synaptic vesicle membrane proteins found in abundance in nerve cells and some endocrine cells . The amino acid sequence of synaptotagmin comprises a single transmembrane region with a short vesicular N-terminal region, and a cytoplasmic C-terminal region containing 2 internal repeats similar to the C2 regulatory domain of protein kinase C. The protein is believed to be important in the docking and fusion of synaptic vesicles with the plasma membrane, i.e. with neurotransmitter release .

The 2 synaptotagmin C2 domains have been shown to have different functions: C2A binds phospholipid in a calcium-dependent manner, while C2B binds inositol polyphosphate and phospholipid irrespective of the presence of Ca
2+
. The structure of C2 domains in synaptotagmin I has been deduced: the C2 polypeptide forms an 8-stranded β-sandwich constructed around a conserved 4-stranded motif, designated a C2 key . The calcium binding region is a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif, while the site of phospholipid interaction is thought to be a polybasic sequence on the hairpin loop connecting strands 3 and 4 .
23S rRNA (uracil(1939)-C(5))-methyltransferase RlmD (23S_rRNA_MeTrfase_RlmD)
Type: Family

This family represents the RlmD (also known as rumA / ygcA) RNA uridine methyltransferase. In E. coli, methyltransferases are responsible for converting uridine to thymidine in rRNA and tRNAs. Among them, TrmA is responsible for tRNA U54 methylation. RlmD (assigned as YgcA previously) was first identified as a methyltransferase through its homology to the TrmA family. RlmD was then found acting as a methyltransferase on the 23S RNA for the conserved U1939 .
Peptidase M3A/M3B catalytic domain (Pept_M3A_M3B_dom)
Type: Domain

This group of metallopeptidases belong to MEROPS peptidase family M3 (clan MA(E)), subfamilies M3A and M3B. The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.

The Thimet oligopeptidase family, is a large family of archaeal, bacterial and eukaryotic oligopeptidases that cleave medium sized peptides. The group contains:

Mitochondrial intermediate peptidase (

)

Neurolysin, mitochondrial precursor, (

)

Thimet oligopeptidase (

)

Dipeptidyl carboxypeptidase (

)

Oligopeptidase A (

)

Oligoendopeptidase F
Ribonuclease T2-like (RNase_T2-like)
Type: Family

Ribonuclease T2 (RNase T2) is a widespread family of secreted RNases found in every organism examined thus far. This family includes RNase Rh, RNase MC1, RNase LE, and self-incompatibility RNases (S-RNases) . Plant T2 RNases are expressed during leaf senescence in order to scavenge phosphate from ribonucleotides. They are also expressed in response to wounding or pathogen invasion. S-RNases are thought to prevent self-fertilization by acting as selective cytotoxins of "self" pollen. Generally, RNases have two distinct binding sites: the primary site (B1 site) and the subsite (B2 site), for nucleotides located at the 5'- and 3'- terminal ends of the sissile bond, respectively.

The fungal ribonucleases T2 from Aspergillus oryzae, M from Aspergillus saitoi and Rh from Rhizopus niveus are structurally and functionally related 30 Kd glycoproteins that cleave the 3'-5' internucleotide linkage of RNA via a nucleotide 2',3'-cyclic phosphate intermediate (

). Two histidines residues have been shown to be involved in the catalytic mechanism of RNase T2 and Rh. These residues and the region around them are highly conserved in a number of other RNAses that have been found to be evolutionary related to these fungal enzymes.
Large ribosomal subunit protein eL37 (Ribosomal_eL37)
Type: Family

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of sequence similarities. This family represents the large ribosomal subunit protein eL37 (also known as L37) , which consists of proteins of 56 to 96 amino-acid residues that share a highly conserved region located in the N-terminal part.

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 .