SII-SWORD/CoKE huggingface dataset:
Protamine-2 (PRM2)
Type: Family

The protamines are a diverse family of small arginine-rich proteins that are synthesized in the late-stage spermatids of many animals and plants. They bind to DNA, condensing the spermatid genome into a genetically inactive state. The two protamines found in mammals, P1 and P2, are the most widely studied. Both P1 and P2 have been shown to be required for normal sperm function in primates and many rodents .
Inositol 1,4,5-trisphosphate receptor (InsP3_rcpt)
Type: Family

The inositol 1,4,5-trisphosphate (IP3)3 receptors (IP3R) are tetrameric intracellular Ca2 release channels on the endoplasmic membrane that are activated by the ligand IP3 . The mammalian IP3R family consists of three isoforms (IP3R1, IP3R2, and IP3R3). They form homotetrameric or heterotetrameric channels . They contain three functional domains: an N-terminal IP3-binding domain, a channel-forming domain localized to the C terminus, and a regulatory/coupling domain connecting these two domains .

This entry also includes Inositol 1,4,5-trisphosphate receptor-like protein A (iplA) which is the only gene known in the Dicyostelium genome that shares homology with IP3-receptors of higher eukaryotes and its gene product exerts a crucial role in the control of basal [Ca2+]i and of agonist induced Ca2+-fluxes .
Receptor L-domain (Rcpt_L-dom)
Type: Domain

The structure for the first three domains of the extracellular portion of IGF-1R (type-1 insulin-like growth-factor receptor) has been solved and consists of two L-domains and a cysteine rich region (L1-Cys-rich-L2). The L-domains each consist of a single-stranded right-handed β-helix. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain with modules associated in an unusual manner. The three domains surround a central space of sufficient size to accommodate a ligand molecule .

This entry represents the L-domain. This domain can also be found in insulin receptor(IR) and epidermal growth-factor receptor (EGFR) family members, and in yeast cell surface GPI proteins PST1 and ECM33 .
Bradykinin receptor family (Brdyknn_rcpt)
Type: Family

Bradykinins are a family of short, structurally similar peptides that activate sensory fibres, contract venous smooth muscle, stimulate release of cytokines, induce connective tissue proliferation and mediate endothelium-dependent vasodilation . Bradykinin antagonists are used in the treatment of inflammation, asthma, mild pain and endotoxic shock.

Bradykinin receptors are members of the seven transmembrane, rhodopsin-like G-protein coupled receptor family and are widespread in peripheral tissues. There are two bradykinins receptor subtypes: B1 and B2. It has also been proposed there could be further subtypes of the bradykinin receptor, including a tracheal B3 receptor but these, as yet have not been confirmed .

This entry represents the bradykinin receptor family.
Dopamine D5 receptor (Dopamine_D5_rcpt)
Type: Family

Dopamine receptors are members of the rhodopsin-like G-protein coupled receptor family and are prominent in the vertebrate central nervous system (CNS). Dysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders , including social phobia , Tourette's syndrome , Parkinson's disease , schizophrenia , neuroleptic malignant syndrome , attention-deficit hyperactivity disorder (ADHD) and drug and alcohol dependence . As a result, dopamine receptors are common drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors .

There are at least five different known subtypes of dopamine receptors designated D1, D2, D3, D4 and D5 . They are distinguished by their G-protein coupling, ligand specificity, anatomical distribution and physiological effects. Dopamine receptors are divided into two further subfamilies. The D1-like family consists of D1 and D5 receptors, which couple to Gs and mediate excitatory neurotransmission. The D2-like family, meanwhile, consists of D2, D3 and D4 receptors, which couple to Gi/Go and mediate inhibitory neurotransmission. Although dopamine receptors are widely distributed in the brain, they are found in different locations that have different receptor type densities, presumably reflecting different functional roles . D1 and D2 receptor subtypes are found at 10-100 times the levels of the D3, D4, D5 subtypes .

This entry represents the dopamine D5 receptors (also known as D1B). They are found in greatest abundance in the caudate-putamen, nucleus accumbens and olfactory tubercle, with lower levels in the frontal cortex, habenula, amygdala, hypothalamus and thalamus. In the periphery,
binding sites are found in the kidney, heart, liver and parathyroid gland. In humans, the pulmonary artery expresses D1, D2, D4, and D5 and receptor subtypes, which may account for vasodilatory effects of dopamine in the blood . In rats, dopamine D5 receptors are present on the smooth muscle of the blood vessels in most major organs .
Outer membrane protein OmpA-like, transmembrane domain (OmpA-like_TM_dom)
Type: Domain

The ompA-like transmembrane domain is present in a number of different outer membrane proteins of several Gram-negative bacteria. Many of the proteins having this domain in the N-terminal also have the conserved bacterial outer membrane protein domain

at the C terminus. The outer membrane protein A of Escherichia coli (OmpA), is one of the most studied proteins in this group . It has a multifunctional role. OmpA is required for the action of colicins K and L and for the stabilisation of mating aggregates in conjugation. It also serves as a receptor for a number of T-even like phages and can act as a porin with low permeability that allows slow penetration of small solutes .

OmpA consists of a regular, extended eight-stranded β-barrel and appears to be constructed like an inverse micelle with large water-filled cavities, but does not form a pore. The cavities seem to be highly conserved during evolution. The structure corroborates the concept that all outer membrane proteins consist of β-barrels . The β-barrel membrane anchor appears to be the outer membrane equivalent of the single-chain α-helix anchor of the inner membrane.
Endothelin receptor family (Endthln_rcpt)
Type: Family

Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C and phospholipase D, as well as cytosolic protein kinase activation. The play an important role in the regulation of the cardiovascular system and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels . As a result, endothelins are implicated in a number of vascular diseases, including the heart, general circulation and brain . Endothelins stimulate the contraction in almost all other smooth muscles (e.g., uterus, bronchus, vas deferens, stomach) and stimulate secretion in several tissues e.g., kidney, liver and adrenals . Endothelins have also been implicated in a variety of pathophysiological conditions associated with stress including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure .

Two endothelin receptor subtypes have been isolated and identified, endothelin A receptor(ETA) and endothelin B receptor (ETB) , and are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (GPCRA) which stimulate multiple effectors via several types of G protein . ETA and ETB receptors are both widely distributed, ETA receptors are mainly located on vascular smooth muscle cells, whereas ETB receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain, e.g. cerebral cortex, cerebellum and glial cells . ETA receptors are considered to be the primary vasoconstrictor and growth-promoting receptor, and the binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure . Endothelin B receptor on the other hand not only inhibits cell growth and vasoconstriction in the vascular system but also functions as a "clearance receptor". This receptor-mediated clearance mechanism is particularly important in the lung, which clears about 80% of circulating endothelin-1 .
Both receptors are localised to non-vascular structures such as epithelial cells as well as occurring in the central nervous system (CNS) on glial cells and neurones, where they are thought to mediate neurotransmission and vascular functions .
Tripartite terminase subunit 1 (UL28/UL56)
Type: Family

In herpesviruses the terminase complex is a genome-packaging motor formed by a small (S-terminase) and a large terminase subunit (L-terminase), plus a third terminase subunit known as T-terminase. The S-terminase subunit, pUL28 in HSV-1 and pUL56 in HCMV , binds packaging initiation sites on viral genome . These proteins play a central role in viral genome cleavage and packaging .
Muscarinic acetylcholine receptor M5 (Musac_Ach_M5_rcpt)
Type: Family

Muscarinic acetylcholine receptors are members of rhodopsin-like G-protein coupled receptor family. They play several important roles; they mediate many of the effects of acetylcholine in the central and peripheral nervous system and modulate a variety of physiological functions, such as airway, eye and intestinal smooth muscle contraction, heart rate and glandular secretions. The receptors have a widespread tissue distribution and are a major drug target in human disease. They may be effective therapeutic targets in Alzheimer's disease, schizophrenia, Parkinson's disease and chronic obstructive pulmonary disease .

The muscarinic acetylcholine M5 receptor is primarily found in the CNS , but is also found in esophageal smooth muscle and in the heart . Binding of acetylcholine to the receptor triggers a number of cellular responses, such as adenylate cyclase inhibition , phosphoinositide degradation , and potassium channel modulation . The receptor has been shown to stimulate gastric acid secretion .
Histamine H2 receptor (Histamine_H2_rcpt)
Type: Family

Histamine plays an important role in a variety of pathophysiological conditions. In allergic conditions, histamine is released from basophils and mast cells and is responsible for symptoms of allergic conditions of the skin and airways. In the gastric mucosa, gastric induced histamine release stimulates parietal cells to secrete gastric acid. In the central nervous system (CNS), histamine is synthesized in specific neurons that are localized in the posterior hypothalamus. These neurons are involved in a variety of important physiological functions, including the regulation of the sleep-wake cycle, cardiovascular control, regulation of the hypothalamic pituitary adrenal-axis, learning and memory .

Histamine exerts its biological effects by binding to and activating four distinct separate rhodopsin-like G protein-coupled receptors-histamine H1 receptor, histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Each of the histamine receptors produce a functional response, but their mechanism differs. The H1 receptor couples to Gq/11 stimulating phospholipase C, whereas the H2 receptor interacts with Gs to activate adenylyl cyclase . The H3 and H4 receptors couple to Gi proteins to inhibit adenylyl cyclase, and to stimulate MAPK in the case of the H3 receptor .

This entry represents the histamine H2 receptor (also known as HH2R). It is located in parietal cells found in the stomach and in the heart and has a limited distribution in vascular smooth muscle and cells of the immune system. H2 receptors primarily stimulate gastric acid secretion and vasodilation, H2 antagonists are therefore used in the clinical treatment of peptic ulceration and asthma . Activation of the H2 receptor results in physiological responses, including stimulation of suppressor T cells, decrease in neutrophil and basophil chemotaxis and activation, proliferation of lymphocytes and activity of natural killer cells . H2 receptors are a potent stimulant of cAMP production and increases intracellular Ca2+ concentrations and releases Ca2+ from the intracellular stores . A combination of both H1 and H2 antihistamines block all the systemic activities of histamine so the activation of the H2 receptor is likely to contribute to the increased vascular permeability prompted by H1 receptor stimulation. Thus, a combination of H1 and H2 receptor activation contributes to nasal airway swelling and rhinorrhea .
RNA recognition motif domain (RRM_dom)
Type: Domain

Many eukaryotic proteins containing one or more copies of a putative RNA-binding domain of about 90 amino acids are known to bind single-stranded RNAs . The largest group of single strand RNA-binding proteins is the eukaryotic RNA recognition motif (RRM) family that contains an eight amino acid RNP-1 consensus sequence . RRM proteins have a variety of RNA binding preferences and functions, and include heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing (SR, U2AF, Sxl), protein components of small nuclear ribonucleoproteins (U1 and U2 snRNPs), and proteins that regulate RNA stability and translation (PABP, La, Hu) . The RRM in heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) appears to have two RRM-like domains with specialised features for protein recognition . The motif also appears in a few single stranded DNA binding proteins.

The typical RRM consists of four anti-parallel β-strands and two α-helices arranged in a β-α-β-β-α-β fold with side chains that stack with RNA bases. Specificity of RNA binding is determined by multiple contacts with surrounding amino acids. A third helix is present during RNA binding in some cases . The RRM is reviewed in a number of publications .

This entry also includes some bacterial putative RNA-binding proteins.
5-Hydroxytryptamine 1D receptor (5HT1D_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.

This entry represents 5-HT1D receptor. It shares almost identical pharmacology with 5-HT1B receptor, but they differ in their level of expression: the level of 5-HT1D expression is very low compared with that of 5-HT1B receptors . 5-HT1D receptors are found in neurons in the CNS and in vascular smooth muscles in the periphery, and affect locomotion and anxiety . In the brain they are involved in vascular vasoconstriction and, as a result, 5-HT1D receptors are the therapeutic targets of the anti-migraine 'triptans' (e.g. sumitriptan and zolmitriptan), which are used to treat acute migraine attack . 5-HT1D receptors are also implicated in feeding behaviour, anxiety, depression. It has also been suggested that 5-HT1D receptors have a stimulatory effect on growth hormone secretion, possibly by inhibiting hypothalamic somatostatin release .
Ketol-acid reductoisomerase, C-terminal (KARI_C)
Type: Domain

Ketol-acid reductoisomerase (KARI; (

)), also known as acetohydroxy acid isomeroreductase (AHIR or AHAIR), catalyses the conversion of acetohydroxy acids into dihydroxy valerates in the second step of the biosynthetic pathway for the essential branched-chain amino acids valine, leucine, and isoleucine. KARI catalyses an unusual two-step reaction consisting of an alkyl migration in which the substrate, either 2-acetolactate (AL) or 2-aceto-2-hydroxybutarate (AHB), is converted to 3-hydoxy-3-methyl-2- oxobutyrate or 3-hydoxy-3-methyl-2-pentatonate, followed by a NADPH-dependent reduction to give 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3- methylvalerate respectively .

KARI is present only in bacteria, fungi, and plants, but not in animals. KARIs are divided into two classes on the basis of sequence length and oligomerisation state. Class I KARIs are ~340 amino acid residues in length and include all fungal KARIs, whereas class II KARIs are ~490 residues long and include all plant KARIs. Bacterial KARIs can be either class I or class II. KARIs are composed of two types of domains, an N-terminal Rossmann fold domain and one or two C-terminal knotted domains. Two intertwinned knotted domains are required for function, and in the short-chain or class I KARIs, each polypeptide chain has one knotted domain. As a result, dimerisation of two monomers forms two complete KARI active sites. In the long-chain or class II KARIs, a duplication of the knotted domain has occurred and, as a result, the protein does not require dimerisation to complete its active site .

The α-helical KARI C-terminal knotted domain can be described as a six-helix core in which helices coil like cable threads around each other, thus forming a bundle .
Beta 1 adrenoceptor (ADRB1_rcpt)
Type: Family

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 .

This entry represents the beta 1 adrenoceptors, which are located mainly in cardiac tissue , where they increase cardiac output by altering the heart rate and force of contraction and in kidney, where they enhance renin . Beta 1 adrenoceptors are also found in the liver, lung and brain and the sphincter part of the gastrointestinal tract . They also causes amylase secretion from the salivary glands . Presynaptically, their activation causes an increase in noradrenaline release.
Large ribosomal subunit protein eL36 (Ribosomal_eL36)
Type: Family

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. The eL36 (also known as L36e) ribosomal family consists of mammalian , Caenorhabditis elegans and Drosophila L36, Candida albicans L39, and yeast YL39 ribosomal proteins .

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 .
Nitrogenase/oxidoreductase, component 1 (Nase/OxRdtase_comp1)
Type: Domain

Enzymes belonging to this family include cofactor-requiring nitrogenases and protochlorophyllide reductase. The key enzymatic reactions in nitrogen fixation are catalysed by the nitrogenase complex, which has two components, the iron protein (component 2), and a component (component 1) which is either a molybdenum-iron, vanadium-iron or iron-iron protein. The enzyme (

) forms a hexamer of two alpha, two beta and two delta chains. Protochlorophyllide reductase (

) is involved in the light-dependent accumulation of chlorophyll, probably at the step of reduction of protochlorophyllide to chlorophyllide.