SII-SWORD/CoKE huggingface dataset:
Uteroglobin (Uteroglobin)
Type: Family

Uteroglobin (blastokinin or Clara cell protein CC10) is a mammalian steroid-inducible secreted protein originally isolated from the uterus of rabbits during early pregnancy . The mucosal epithelia of several organs that communicate with the external environment express uteroglobin. Its tissue-specific expression is regulated by steroid hormones, and is augmented in the uterus by non-steroidal prolactin. Uteroglobin may be a multi-functional protein with anti-inflammatory/immunomodulatory properties, acting to inhibit phospholipase A2 activity , and binding to (and possibly sequestering) several hydrophobic ligands such as progesterone, retinols, polychlorinated biphenyls, phospholipids and prostaglandins . In addition, uteroglobin has anti-chemotactic, anti-allergic, anti-tumourigenic and embryo growth-stimulatory properties. Uteroglobin may have a homeostatic role against oxidative damage, inflammation, autoimmunity and cancer . However, the true biological function of uteroglobin is poorly understood. Uteroglobin consists of a disulphide-linked homodimer with a large hydrophobic pocket located between the two dimers . Each monomer being composed of four helices that do not form a canonical four helix-bundle motif but rather a boomerang-shaped structure in which helices H1, H3, and H4 are able to bind a homodimeric partner . The hydrophobic pocket binds steroids, particularly progesterone, with high specificity. It is a member of the secretoglobin superfamily.

This entry represents uteroglobin proteins from several mammalian species .
SNF2, N-terminal (SNF2_N)
Type: Domain

This domain is found in proteins involved in a variety of processes including transcription regulation (e.g., SNF2, STH1, brahma, MOT1), DNA repair (e.g., ERCC6, RAD16, RAD5), DNA recombination (e.g., RAD54), and chromatin unwinding (e.g., ISWI) as well as a variety of other proteins with little functional information (e.g., lodestar, ETL1) . SNF2 functions as the ATPase component of the SNF2/SWI multisubunit complex, which utilises energy derived from ATP hydrolysis to disrupt histone-DNA interactions, resulting in the increased accessibility of DNA to transcription factors .
Rap/Ran-GAP domain (Rap/Ran_GAP_dom)
Type: Domain

Structural domains comprising this superfamily share the structure of two shown to be homologous GTPase activating proteins for Rap and Ran. Both are Ras-like guanine-nucleotide-binding proteins (GNBPs) involved in a variety of signal-transduction processes and their activity is regulated by GEFs and GAPs.

Rap small G proteins have been implicated in various cellular processes such as exocytosis, cAMP signalling, cell adhesion and cell proliferation. Rap proteins acts as molecular switches, with an active GTP-bound form and an inactive GDP-bound form . The inactive GDP bound form is promoted by GTPase-activating proteins (GAPs). GAP proteins specific for Rap contain a conserved region of around 200 amino-acid residues, the RapGAP domain. This domain can accelerate the GTP hydrolysis activity of Rap by five orders of magnitude .

Ran, also known as GTP-binding nuclear protein, is on the other hand essential for the translocation of RNA and proteins through the nuclear pore complex and has been implicated in the control of DNA synthesis and cell cycle progression.
Beta 2 adrenoceptor (ADRB2_rcpt)
Type: Family

This entry represents the beta 2 receptor; it mediates relaxation of smooth muscle including vascular beds, bronchus, intestine and uterus . Beta 2 adrenoceptors, also mediate glycogenlysis and glucogenesis in the liver , regulate cell metabolism in skeletal muscle and inhibit the activity of leukocytes and other blood cells. The receptors are found in the heart, where they are involved in increased cardiac output, although to a lesser extent than beta 1 adrenoceptor. The receptors are located presynaptically in nerves, where they facilitate neurotransmitter release, and in the brain, where they regulate a variety of physiological processes .

The adrenoceptors (or adrenergic receptors) are rhodopsin-like G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system, effect blood pressure, myocardial contractile rate and force, airway reactivity, and a variety of metabolic and central nervous system functions. The clinical uses of adrenergic compounds are vast. Agonists and antagonists interacting with adrenoceptors have proved useful in the treatment of a variety of diseases, including hypertension, angina pectoris, congestive heart failure, asthma, depression, benign prostatic hypertrophy, and glaucoma. These drugs are also useful in several other therapeutic situations including shock, premature labour and opioid withdrawal, and as adjuncts to general anaesthetics.

There are three classes of adrenoceptors, based on their sequence similarity, receptor pharmacology and signalling mechanisms . These three classes are alpha 1 (a Gq coupled receptor), alpha 2 (a Gi coupled receptor) and beta (a Gs coupled receptor), and each can be further divided into subtypes . The different subtypes can coexist in some tissues, but one subtype normally predominates.

There are three subtypes of beta adrenoceptors (beta 1-3), the division is mainly based on their affinities to adrenergic agonists and antagonists. All three subtypes act in the main by activating a Gs protein , activating adenylate cyclase activity. The beta 2 subtype also couples to Gi/o protein . Beta adrenoceptor selective agonists (beta blockers) are used in the treatment of asthma, angina, cardiac conditions and have proven useful in the treatment of migraine, anxiety disorders and hyperthyroidism, and, when applied topically, are useful in the treatment of glaucoma .
Ser/Thr protein kinase, TGFB receptor (TGFB_receptor)
Type: Family

Transforming growth factor-beta (TGF-beta) forms a family with other growth factors. The receptors for most of the members of this growth factor family are related. These proteins are receptor-type kinases of Ser/Thr type, which have a single transmembrane domain and a specific hydrophilic Cys-rich ligand-binding domain . The C-terminal part of the extracellular domain is conserved. Some of the receptors of this family contain subclass-specific N-terminal extensions of this homology domain. The type I receptors also possess 7 extracellular residues preceding the cysteine box.
Glycoside hydrolase, family 45 (Glyco_hydro_45)
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 45

comprises enzymes with only one known activity; endoglucanase (

).

The microbial degradation of cellulose and xylans requires several types of enzymes such as endoglucanases, cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Fungi and bacteria produce a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family K or as the glycosyl hydrolases family 45 . The best conserved regions in these enzymes is located in the N-terminal section. It contains an aspartic acid residue which has been shown to act as a nucleophile in the catalytic mechanism. This also has several cysteines that are involved in forming disulphide bridges.
Bleomycin resistance protein (Bleomycin-R)
Type: Family

Bleomycin (Blm) is a glycopeptide antibiotic produced naturally by actinomycetes. It is a strong DNA-cutting agent and thus finds use as a potent anti-cancer drug. The DNA-cutting mechanism is complex, involving concomitant oxidation of FeII and reduction of oxygen. In addition to iron, Blm binds other transition metals: cobalt, nickel, copper and zinc. Actinomycetes have developed a defence mechanism against this lethal compound, producing a protein that confers resistance to Blm through drug sequestering. The crystal structure of the bleomycin resistance protein reveals 2 identically-folded halves, each having an α/β fold but showing no sequence similarity . Each half comprises a 4-stranded β-sheet and a short α-helix (3 turns). The sheets within each half lie roughly at right-angles and are related by an approximate 2-fold axis. The crystal packing shows compact dimers that have a hydrophobic interface and are involved in mutual chain exchange.
Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily (Flavivir/Alphavir_Ig-like_sf)
Type: Homologous_superfamily

This immuniglobulin-like domain superfamily is found in polyproteins from Flavivirus and Alphavirus.

Flaviruses are small, enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Yellow fever virus, West Nile virus, Tick-borne encephalitis virus, Japanese encephalitis virus, and Dengue virus 2 . Flaviviruses consist of three structural proteins: the core nucleocapsid protein C (

), and the envelope glycoproteins M (

) and E. Glycoprotein E is a class II viral fusion protein that mediates both receptor binding and fusion. Class II viral fusion proteins are found in flaviviruses and alphaviruses, and are structurally distinct from class I fusion proteins from influenza-type viruses and retroviruses. Glycoprotein E is comprised of three domains: domain I (dimerisation domain) is an 8-stranded β barrel, domain II (central domain) is an elongated domain composed of twelve β strands and two α helices, and domain III (immunoglobulin-like domain) is an IgC-like module with ten β strands. This entry represents the Ig-like domain III, which contains a putative receptor-binding loop .
GPCR, family 3 (GPCR_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 .

GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length . Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors . As these receptors regulate many important physiological processes they are potentially promising targets for drug development.
Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain (PI3K_Ras-bd_dom)
Type: Domain

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that phosphorylate 4,5-bisphonate (PI(4,5) P2 or PIP2) at the 3-position of the inositol ring, and thus generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which, in turns, initiates a vast array of signaling events. PI3Ks can be grouped into three classes based on their domain organisation. Class I PI3Ks are heterodimers consisting of a p110 catalytic subunit and a regulatory subunit of either the p85 type (associated with the class IA p110 isoforms p110alpha, p110beta or p110delta) or the p101 type (associated with the class IB p110 isoform p110gamma). Common to all catalytic subunits are an N-terminal adaptor-binding domain (ABD) that binds to p85, a Ras- binding domain (RBD), a putative membrane-binding domain (C2), a helical domain of unknown function, and a kinase catalytic domain. Class II PI3Ks lack the ABD domain and are distinguished by a carboxy terminal C2 domain. Class III enzymes lack the ABD and RBD domains .

PI3K RBD is a small globular domain of about 100 residues in length with an α/β-sandwich topology. The PI3K RBD domain consists of a five-stranded mixed β-sheet flanked by two α-helices .
Glutamyl-tRNA reductase (4pyrrol_synth_GluRdtase)
Type: Family

Delta-aminolevulinic acid (ALA) is the obligatory precursor for the synthesis of all tetrapyrroles including porphyrin derivatives such as chlorophyll and heme. ALA can be synthesized via two different pathways: the Shemin (or C4) pathway which involves the single step condensation of succinyl-CoA and glycine and which is catalyzed by ALA synthase and via the C5 pathway from the five-carbon skeleton of glutamate. The C5 pathway operates in the chloroplast of plants and algae, in cyanobacteria, in some eubacteria and in archaebacteria .

The initial step in the C5 pathway is carried out by glutamyl-tRNA reductase (GluTR) which catalyzes the NADP-dependent conversion of glutamate- tRNA(Glu) to glutamate-1-semialdehyde (GSA) with the concomitant release of tRNA(Glu) which can then be recharged with glutamate by glutamyl-tRNA synthetase .

This entry represents glutamyl-tRNA reductase (

), which required NADPH as a coenzyme . This entry also includes the multifunctional siroheme biosynthesis protein HemA from
Clostridium josui
which besides acting as a glutamyl-tRNA reductase also converts precorrin-2 to sirohydrochlorin and sirohydrochlorin to siroheme .
7TM GPCR, serpentine receptor class a (Sra) (7TM_GPCR_serpentine_rcpt_Sra)
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 a (Sra) from the Sra superfamily . Sra receptors contain 6-7 hydrophobic, putative transmembrane, regions and can be distinguished from other 7TM GPCR receptors by their own characteristic TM signatures.
Hyperglycemic hormone type 1 (Hyperglycemic1)
Type: Family

Hyperglycemic hormone, which controls blood sugar levels, is an abundant peptide in the sinus glands of isopods and decapods . The peptide is a potent secretagogue, releasing digestive enzymes from the hepatopancreas. It may act as a stress hormone. The peptide contains around 70 amino acid residues, and includes six cysteine residues involved in disulphide bond formation . The sequences show a high degree of similarity to the American lobster molt-inhibiting hormone , which also shows hyperglycemic hormone activity.

Sequence analysis reveals at least 2 discrete sequence families, characterised by distinctive N- and C-terminal signatures: broadly, the families represent separate groups of the crustacean hyperglycemic-like hormones and the molt-inhibiting-like hormones. The positions of five of the six cysteine residues are conserved between these families, the first Cys being displaced by one residue position.

This entry represents the type 1 that includes the crustacean hyperglycemic-like hormones.
Metallothionein, family 15, plant (Metalthion_15p)
Type: Family

Members of this family are metallothioneins. These proteins are cysteine rich proteins that bind to heavy metals. Members of this family appear to be closest to Class II metallothioneins.
Large envelope protein S (HBV_HBSAG)
Type: Family

This entry represents the large envelope protein S from hepatitis B virus. The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein .
Neuropeptide Y1 receptor (NPY1_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 the neuropeptide Y1 receptor, which is present in smooth muscle such as the intestine and blood vessels . The Y1 receptor are believed to have a predominantly postsynaptic location, and are involved in the inhibition of adenylyl cyclase through a pertussis-toxin-sensitive G-protein, probably of the Gi protein class . There is also evidence that Y1 can stimulate an increase in intracellular calcium independently of the phosphoinositide pathway .
Peptide chain release factor class I (Pep_chain_release_fac_I)
Type: Domain

Peptide chain release factors (RFs) are required for the termination of protein biosynthesis . At present two classes of RFs can be distinguished. Class I RFs bind to ribosomes that have encountered a stop codon at their decoding site and induce release of the nascent polypeptide. Class II RFs are GTP-binding proteins that interact with class I RFs and enhance class I RF activity. In prokaryotes there are two class I RFs that act in a codon specific manner : RF-1(gene prfA) mediates UAA and UAG-dependent termination while RF-2 (gene prfB) mediates UAA and UGA-dependent termination. RF-1 and RF-2 are structurally and evolutionary related proteins which have been shown to be part of a larger family .
MHC class II, beta chain, N-terminal (MHC_II_b_N)
Type: Domain

This entry represents the N-terminal domain (also called beta-1 domain) of the beta chain of class II MHC glycoproteins from vertebrates.

Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.

Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) .

MHC class II molecules are comprised of two membrane-spanning chains, alpha and beta, of similar size. Both chains consist of two globular domains (N-and C-terminal), and a transmembrane segment to anchor them to the membrane . A groove in the structure acts as the peptide-binding site.