SII-SWORD/CoKE huggingface dataset:
Cholecystokinin receptor type A (Cholcy_rcpt_A)
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 .

Cholecystokinins (CCKs) and gastrins are naturally-occurring peptides that share a common C-terminal sequence, GWMDF; full biological activity resides in this region. In the periphery, the principal physiological actions of CCK include gall bladder contraction, pancreatic enzyme secretion and regulation of secretion/absorption in the gastrointestinal tract. In the CNS, CCK induces analgesia, satiety and a decrease in exploratory behaviour. In mesolimbic and mesocortical neurons, CCK coexists with dopamine. It is found throughout the digestive tract, with high concentrations in the duodenum and jejunum. It is also found in peripheral nerves to other smooth muscles and to secretory glands, and is one of the most abundant peptides in the brain. The highest levels of the CCKA receptor are found in peripheral tissues, notably the pancreas, stomach, intestine and gall bladder. It has only a limited distribution in the brain. The receptor has been implicated in the pathogenesis of schizophrenia, Parkinson's disease, drug addiction and feeding disorders.
Large ribosomal subunit protein uL3 (Ribosomal_uL3)
Type: Family

Ribosomal protein L3 (also known as uL3) is one of the proteins from the large ribosomal subunit. In Escherichia coli, L3 is known to bind to the 23S rRNA and may participate in the formation of the peptidyltransferase centre of the ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities includes bacterial, red algal, cyanelle, mammalian, yeast and Arabidopsis thaliana L3 proteins; archaeal Haloarcula marismortui HmaL3 (HL1), and yeast mitochondrial YmL9 .

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 .
G protein-coupled receptor 12 (GPR12)
Type: Family

G protein-coupled receptor 12 (GPR12) was initially isolated from a rat pituitary library, and is found in discrete regions of the brain, pituitary and testis, but is absent in other tissues . Three human homologues (GPR12, GPR6 and GPR3) have also been isolated . The 3 genes have been localised to human chromosomal regions 13q12, 6q21
and 1p34.3-p36.1 respectively.

This entry represents G protein-coupled receptor 12. It is an orphaned receptor, with no endogenous ligand having yet been identified.
ROK family (ROK)
Type: Family

A family of bacterial proteins has been described which groups transcriptional repressors, sugar kinases and yet uncharacterised open reading frames . This family, known as ROK (Repressor, ORF, Kinase) includes the xylose operon repressor, xylR, from Bacillus subtilis, Lactobacillus pentosus and Staphylococcus xylosus; N-acetylglucosamine repressor, nagC, from Escherichia coli; glucokinase

from Streptomyces coelicolor; fructokinase

from Pediococcus pentosaceus, Streptococcus mutans and Zymomonas mobilis; allokinase

and mlc from E. coli; and E. coli hypothetical proteins yajF and yhcI and the corresponding Haemophilus influenzae proteins. The repressor proteins (xylR and nagC) from this family possess an N-terminal region not present in the sugar kinases and which contains an helix-turn-helix DNA-binding motif.
PKD domain (PKD_dom)
Type: Domain

The polycystic kidney disease (PKD) domain is an 80-90 amino acid module originally found in 16 copies in the extracellular segment of polycystin-1, a large cell surface glycoprotein. Polycystin-1 is encoded by the PKD1 gene, which is mutated in autosomal dominant polycystic kidney disease (ADPKD).
Although its function is unknown, it may be involved in protein-protein and protein-carbohydrate interactions based on its predicted domain structure. One or more copies of the PKD domain are also found in several other extracellular proteins from higher organisms, eubacteria, and archaebacteria. Singles copies of the PKD domain are found in the melanocytes heavily glycosylated cell-surface proteins Pmel 17, MMP and Nmp. Some bacterial collagenases and proteases also contain a single PKD domain adjacent to their catalytic domains, whereas four copies are present in the heavily glycosylated surface layer protein of archaebacteria . The PKD modules are often observed, within a same protein sequence, in association with FnIII domains .

The most conserved motif is the WDFGDGS sequence that is found in the central part of many PKD domains and could play a structural role . Determination of the solution structure of the first PKD domain from human polycystin-1 has shown that the module is built from two β-sheet, one of three strands and one of four strands, which are packed face-to-face .
Glycoside hydrolase family 38, N-terminal domain (Glyco_hydro_38_N)
Type: Domain

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 38

comprises enzymes with only one known activity; alpha-mannosidase (

) (

).

Lysosomal alpha-mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme catalyses the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a lysosomal storage disease characterised by the accumulation of unbranched oligo-saccharide chains.

This entry represents the N-terminal domain of the glycoside hydrolase 38 family protein.
Movement protein (MPV)
Type: Family

This entry includes movement proteins from various viruses, including Movement protein (also known as Protein 3A) from Bromoviruses and Cucumoviruses, whose genomes contain 3 RNA segments. The third segment (RNA 3) contains two proteins, the coat protein and the 3A protein. Protein 3A has been shown to be involved in cell-to-cell movement of the virus . The protein family also includes NSm protein from Tomato spotted wilt virus which is involved in tubule formation, movement and symptomatology .
Major outer membrane protein, Chlamydia (Major_OMP_Chlamydia)
Type: Family

The major outer membrane protein of Chlamydia contains four symmetrically spaced variable domains (VDs I to IV). This protein maintains the structural rigidity of the outer membrane and facilitates porin formation, permitting diffusion of solutes through the intracellular reticulate body membrane. It is believed to play a role in pathogenesis and possibly adhesion. Along with the lipopolysaccharide, the major out membrane protein (MOMP) makes up the surface of the elementary body cell. Disulphide bond interactions within and between MOMP molecules and other components form high molecular weight oligomers. The MOMP is the protein used to determine the different serotypes.
Helicase, superfamily 3, single-stranded DNA/RNA virus (Helicase_SF3_ssDNA/RNA_vir)
Type: Domain

Helicases have been classified in 5 superfamilies (SF1-SF5). All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) and Walker B (Mg2+-binding aspartic acid) motifs. Superfamily 3 consists of helicases encoded mainly by small DNA viruses and some large nucleocytoplasmic DNA viruses . Small viruses are very dependent on the host-cell machinery to replicate. SF3 helicase in small viruses is associated with an origin-binding domain. By pairing a domain that recognises the ori with a helicase, the virus can bypass the host-cell-based regulation pathway and initiate its own replication. The protein binds to the viral ori leading to origin unwinding. Cellular replication proteins are then recruited to the ori and the viral DNA is replicated.

In SF3 helicases the Walker A and Walker B motifs are separated by spacers of rather uniform, and relatively short, length. In addition to the A and B motifs this family is characterised by a third motif (C) which resides between the B motif and the C terminus of the conserved region. This motif consists of an Asn residue preceded by a run of hydrophobic residues .

Several structures of SF3 helicases have been solved . They all possess the same core α/β fold, consisting of a five-stranded parallel β-sheet flanked on both sides by several α-helices. In contrast to SF1 and SF2 helicases, which have RecA-like core folds, the strand connectivity within the α/β core domain is that of AAA+ proteins . The SF3 helicase proteins assemble into a hexameric ring.

Some proteins known to contain an SF3 helicase domain are listed below:

Polyomavirus large T antigen. It initiates DNA unwinding and replication via interactions with the viral origin of replication.

Papillomavirus E1 protein. An ATP-dependent DNA helicase required for initiation of viral DNA replication.

Parvovirus Rep/NS1 protein, which is also required for the initiation of viral replication.

Poxviridae and other large DNA viruses D5 protein.

Bacteriophage DNA primase/helicase protein.

Bacterial prophage DNA primase/helicase protein.

The entry represents the core α/β fold of the SF3 helicase domain found predominantly in DNA viruses.
Ubiquitin-conjugating (UBC), catalytic core domain (UBC)
Type: Domain

This entry represents the catalytic core domain of E2 ubiquitin-conjugating enzymes and similar sequences mainly found in eukaryotes. It is an α/β domain.

Ubiquitin-conjugating enzymes (UBC or E2 enzymes) (

)
catalyse the covalent attachment of ubiquitin to target proteins. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1,

), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3,

,

), which work sequentially in a cascade . The E1 enzyme mediates an ATP-dependent transfer of a thioester-linked ubiquitin molecule to a cysteine residue on the E2 enzyme. The E2 enzyme then either transfers the ubiquitin moiety directly to a substrate, or to an E3 ligase, which can also ubiquitinylate a substrate.

There are several different E2 enzymes (over 30 in humans), which are broadly grouped into four classes, all of which have a core catalytic domain (containing the active site cysteine), and some of which have short N- and C-terminal amino acid extensions: class I enzymes consist of just the catalytic core domain (UBC), class II possess a UBC and a C-terminal extension, class III possess a UBC and an N-terminal extension, and class IV possess a UBC and both N- and C-terminal extensions. These extensions appear to be important for some subfamily function, including E2 localisation and protein-protein interactions . In addition, there are proteins with an E2-like fold that are devoid of catalytic activity (such as protein crossbronx from flies), but which appear to assist in poly-ubiquitin chain formation.
7TM GPCR, serpentine receptor class g (Srg) (7TM_GPCR_serpentine_rcpt_Srg)
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 nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to sense and respond to several hundred different chemicals because each neuron detects several stimuli . Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' . Chemoreception in C. elegans is mediated by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). More than 1300 potential chemoreceptor genes have been identified in C. elegans, which are generally prefixed sr for serpentine receptor. The receptor superfamilies include Sra (Sra, Srb, Srab, Sre), Str (Srh, Str, Sri, Srd, Srj, Srm, Srn) and Srg (Srx, Srt, Srg, Sru, Srv, Srxa), as well as the families Srw, Srz, Srbc, Srsx and Srr . Many of these proteins have homologues in Caenorhabditis briggsae.

This entry represents serpentine receptor class g (Srg) from the Srg superfamily . Srg receptors contain seven hydrophobic, putative transmembrane, regions and can be distinguished from other 7TM GPCR receptors by their own characteristic TM signatures.
5-Hydroxytryptamine 1A receptor (5HT1A_rcpt)
Type: Family

5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics .

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel , all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family , and they activate an intracellular second messenger cascade to produce their responses.

The 5-HT1 receptors are a subfamily of 5-HT receptors that were originally classified according to their inhibition of adenylyl cyclase, degree of sequence similarity and their overlapping pharmacological specificities. The subfamily is comprised of five different receptors 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, and they can couple to Gi/Go and mediate inhibitory neurotransmission, although signalling via other transduction systems are known. One of the 5-HT1 receptors, the 5-HT1E receptor, is yet to achieve receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR), since a robust response mediated via the protein has not been reported in the literature.

5-HT1A receptors are the most widespread of all the 5-HT receptors. They are found pre-and post-synaptically : in the raphe nuclei they are somatodendritic and act as autoreceptors to inhibit cell firing; whereas postsynaptic 5-HT1A receptors are present in a number of limbic structures, particularly the hippocampus . 5-HT1A receptors are involved in many neuromodulative processes, and are potential anxiolytic and hypertensive targets . Receptor antagonists like buspirone and flesinoxan have been shown to relieve anxiety and depression . Other 5-HT1A receptor agonists decrease blood pressure and heart rate via a central mechanism, by inducing peripheral vasodilation . This also increases heat dissipation from the organism, causing a decrease in body temperature . 5-HT1A receptors have been implicated in the neuroendocrine regulation of adrenocorticotrophic hormone (ACTH) . In the CNS, 5-HT1A receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and in the raphe nucleus in high densities, whilst lower amounts also exist in the basal ganglia and thalamus .
Neuropeptide Y receptor family (NPY_rcpt)
Type: Family

Neuropeptide Y (NPY) acts as a neurotransmitter in the brain and in the autonomic nervous system. In the brain it is thought to have several functions, including increasing food intake and storage of energy as fat , facilitation of learning and memory via the modulation of hippocampal activity , inhibition of anxiety , presynaptic inhibition of neurotransmitter release in the CNS and periphery , and modulation of circadian rhythm . In the periphery, NPY stimulates vascular smooth muscle contraction , modulates the release of pituitary hormones , pain transmission , inhibition of insulin release and modulation of renal function . NPY has also been implicated in the pathophysiology of hypertension , congestive heart failure and appetite regulation and controlling epileptic seizures . Signalling responses appear to be restricted to certain cell types and in the autonomic system it is mainly produced by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue . These include inhibition of Ca2+ channels, such as in neurones , and activation and inhibition of K+ channels, such as in cardiomyocytes and vascular smooth muscle cells .

The various functions of NPY are mediated by neuropeptide Y receptors, which are members of rhodopsin-like G-protein coupled receptors, they are also activated by peptide YY and the pancreatic polypeptide . There are five pharmacologically distinct neuropeptide Y receptor subtypes ; neuropeptide Y receptor Y1 (Y1), neuropeptide Y receptor Y2 (Y2), neuropeptide Y receptor Y4 (Y4), neuropeptide Y receptor Y5 (Y5) and neuropeptide Y receptor Y6 (Y6).

This entry represents neuropeptide Y receptor family.
Proteolipid membrane potential modulator (PMP3)
Type: Family

Proteolipid membrane potential modulator is an evolutionarily conserved proteolipid in the plasma membrane which, in S. pombe, is transcriptionally regulated by the Spc1 stress MAPK (mitogen-activated protein kinases) pathway. It functions to modulate the membrane potential, particularly to resist high cellular cation concentration. In eukaryotic organisms, stress-activated mitogen-activated protein kinases play crucial roles in transmitting environmental signals that will regulate gene expression for allowing the cell to adapt to cellular stress. Pmp3-like proteins are highly conserved in bacteria, yeast, nematode and plants .

Proteins in this entry include the PMP3 as well as several other proteins that have been shown to be evolutionary related. These are small proteins of from 52 to 140 amino-acid resiudes that contain two transmembrane domains and belong to the UPF0057 (PMP3) protein family.
Free Met sulfoxide reductase conserved site (FRMsr_CS)
Type: Conserved_site

Free methionine-R-sulfoxide reductases are a family of GAF domain-containing proteins that have been shown to catalyse the reversible oxidation-reduction of the R-enantiomer of free methionine sulfoxide to methionine . This entry represents a conserved site within the GAF domain section of these proteins.