SII-SWORD/CoKE huggingface dataset:
Small ribosomal subunit protein uS19 (Ribosomal_uS19)
Type: Family

This entry represents the small ribosomal subunit protein uS19 family.

The small subunit ribosomal proteins can be categorised as: primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins. The small ribosomal subunit protein S19 contains 88-144 amino acid residues. In Escherichia coli, S19 is known to form a complex with S13 that binds strongly to 16S ribosomal RNA. Experimental evidence has revealed that S19 is moderately exposed on the ribosomal surface, and is designated a secondary rRNA binding protein. S19 belongs to a family of ribosomal proteins that includes: eubacterial S19; algal and plant chloroplast S19; cyanelle S19; archaebacterial S19; plant mitochondrial S19; and eukaryotic S15 ('rig' protein).

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 .
Pancreatic trypsin inhibitor Kunitz domain (Kunitz_BPTI)
Type: Domain

The majority of the sequences having this domain belong to the MEROPS inhibitor family I2, clan IB; the Kunitz/bovine pancreatic trypsin inhibitor family, they inhibit proteases of the S1 family and are restricted to the metazoa with a single exception: Amsacta moorei entomopoxvirus. They are short (~50 residue) α/β proteins with few secondary structures. The fold is constrained by 3 disulphide bonds. The type example for this family is aprotinin (bovine pancreatic trypsin inhibitor) (or basic protease inhibitor), but the family includes numerous other members , such as snake venom basic protease; mammalian inter-alpha-trypsin inhibitors; trypstatin, a rodent mast cell inhibitor of trypsin; a domain found in an alternatively-spliced form of Alzheimer's amyloid beta-protein; domains at the C-termini of the alpha(1) and alpha(3) chains of type VII and type VI collagens; and tissue factor pathway inhibitor precursor.

The pancreatic trypsin inhibitor (Kunitz) family is one of the numerous families of serine proteinase inhibitors. The basic structure of such a type of inhibitor is shown in the following schematic representation:

+-----------------------+
| +--------+ |
| | **|******* |
xxCxxC#xxxCxxxCxxxxxxCxxxxCxx
| |
+----------+

{------50 residues------}

'C': conserved cysteine involved in a disulfide bond.
'#': active site residue.
'*': position of the pattern.
3-beta hydroxysteroid dehydrogenase/isomerase (3Beta_OHSteriod_DH/Estase)
Type: Domain

The enzyme 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3 beta-HSD) catalyses the oxidation and isomerisation of 5-ene-3 beta-hydroxypregnene and 5-ene-hydroxyandrostene steroid precursors into the corresponding 4-ene-ketosteroids necessary for the formation of all classes of steroid hormones.
Catalase haem-binding site (Catalase_haem_BS)
Type: Binding_site

Catalases (

) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen, serving to protect cells from its toxic effects . Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. Most catalases are mono-functional, haem-containing enzymes, although there are also bifunctional haem-containing peroxidase/catalases (

) that are closely related to plant peroxidases, and non-haem, manganese-containing catalases (

) that are found in bacteria . Based on a phylogenetic analysis, catalases can be classified into clade 1, 2 and 3. Clade 1 contains small subunit catalases from plants and a subset of bacteria; clade 2 contains large subunit catalases from fungi and a second subset of bacteria; and clade 3 contains small subunit catalases from bacteria, fungi, protists, animals, and plants .

Mono-functional, haem-containing catalases have a core that includes a haem-containing active site deeply buried in a β-barrel structure with two or three channels providing access to the haem. This entry covers a tyrosine residue that serves as the haem proximal side ligand and includes a conserved arginine that participates in haem-binding.
Tyrosinase copper-binding domain (Tyrosinase_Cu-bd)
Type: Domain

Tyrosinase (

) is a copper monooxygenases that catalyses the hydroxylation of monophenols and the oxidation of o-diphenols to o-quinols. This enzyme, found in prokaryotes as well as in eukaryotes, is involved in the formation of pigments such as melanins and other polyphenolic compounds. Tyrosinase binds two copper ions (CuA and CuB). Each of the two copper ions has been shown to be bound by three conserved histidines residues. The regions around these copper-binding ligands are well conserved and also shared by some hemocyanins, which are copper-containing oxygen carriers from the hemolymph of many molluscs and arthropods . At least two proteins related to tyrosinase are known to exist in mammals, and include TRP-1 (TYRP1) , which is responsible for the conversion of 5,6-dihydro-xyindole-2-carboxylic acid (DHICA) to indole-5,6-quinone-2-carboxylic acid; and TRP-2 (TYRP2) , which is the melanogenic enzyme DOPAchrome tautomerase (

) that catalyses the conversion of DOPAchrome to DHICA. TRP-2 differs from tyrosinases and TRP-1 in that it binds two zinc ions instead of copper . Other proteins that belong to this family are plant polyphenol oxidases (PPO) (

), which catalyze the oxidation of mono- and o-diphenols to o-diquinones ; and Caenorhabditis elegans hypothetical protein C02C2.1.
Muscarinic acetylcholine receptor M1 (Musac_Ach_M1_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 .

Muscarinic acetylcholine receptor M1 it is common in exocrine glands and the CNS , being is particularly abundant in the cerebal cortex and hippocampus . The receptors have also been also found on esophageal smooth muscle and bladder tissue . Their distribution largely overlaps with that of M3 and M4 receptors. M1 receptors are involved in mediating higher cognitive processes, such as learning and memory . They also play a role in regulation of locomotor activity and in salivation .
Blood group Rhesus C/E/D polypeptide (RhesusRHD)
Type: Family

Proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen Facts Book Academic Press, London / San Diego, (1997)]. The RH(CE) polypeptide (Rhesus C/E antigens) and RH(D) polypeptide (Rhesus D antigen) belong to the Rh blood group system and are associated with antigens that include C/c, E/e, D, f, C(e), C(w), C(x), V, E(w), G, Tar, VS, D(w), cE, amongst others.

The Rh (Rhesus) blood group system is important in clinical medicine by virtue of being involved in haemolytic disease of the newborn, transfusion reactions, autoimmune haemolytic anaemias, and haemolytic reactions of non-immune origin . The RH locus from RH(D)-positive donors contains 2 homologous structural genes, one of which encodes the D protein that carries the major antigen of the Rh system. Hydropathy analysis of the RhD gene product reveals 13 hydrophobic domains, all of which have been assumed to be transmembrane (TM) .

The proteins in this entry are related to ammonium transport .
Cannabinoid receptor family (Cnbnoid_rcpt)
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 the cannabinoid receptor family, which includes cannabinoid receptor 1 and cannabinoid receptor 2.
5-hydroxytryptamine receptor family (5HT_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.

This entry represents the 5-hydroxytryptamine receptor family.
5-Hydroxytryptamine 6 receptor (5HT6_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.

5-HT6 receptors are positively coupled to adenylyl cyclase. They are expressed almost exclusively in the brain and prominently expressed in the caudate nucleus . Based on their abundance in extrapyramidal, limbic and cortical regions of the brain, it has been suggested that the 5-HT6 receptors play a role in functions like motor control, emotionality, cognition and memory . Blockade of central 5-HT6 receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas , whereas activation enhances GABAergic signaling in a widespread manner . Antagonism of 5-HT6 receptors also facilitates dopamine and norepinephrine release in the frontal cortex , while stimulation has the opposite effect .

5-HT6 receptors have high affinity for several typical and atypical antipsychotic agents, including clozapine, olanzapine fluperlapine and seroquel . This attribute has led to speculation of potential involvement of the 5-HT6 receptor in the pathogenesis of psychiatric disorders. 5-HT6 receptor antagonists have been demonstrated to be active in rodent models of depression, anxiety and obsessive-compulsive disorder, and such agents may be useful treatments for these conditions . There is also some evidence of enhanced retention of spatial learning following treatment with such compounds . However, it should be noted that the rodent brain has a notably different regional pattern of 5-HT6 receptor expression in comparison to humans, and little data has been generated in actual clinical populations.
Adrenoceptor family (ADR_fam)
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.

This entry represents the adrenoceptor family.
Anaphylatoxin chemotactic receptor, C3a/C5a1/C5a2 (Anphylx_rcpt_C3a/C5a1-2)
Type: Family

The activation of the complement cascade produces a number of small fragments that are bioactive: potent chemoattractants and secretagogues that act on immune and non-immune cells . Similar peptides can also be released by the actions of non-complement proteases, for instance during clotting . Initially these were termed anaphylatoxins because of their effect on mast cell histamine release, but were reclassified as complement component peptides. They include C3a and C5a, which are involved immune response , neural development and organ regeneration . A third peptide, C4a, has a similar structure, but it is inactive in humans . Since the primary function of complement component peptides is in inflammation, they are important targets for the development of anti-inflammatory therapies .

The anaphylatoxin chemotactic receptors (also known as complement peptide receptors) are a group of rhodopsin-like G-protein coupled receptors (GPCRs) . There are three subtypes: C3a anaphylatoxin chemotactic receptor (C3AR1) , C5a anaphylatoxin chemotactic receptor (C5AR1) and C5a anaphylatoxin chemotactic receptor C5L2 (C5AR2) . Both C3AR1 and C5AR1 receptors are classical GPCRs. However, C5AR2 appears to be permanently uncoupled from G proteins but can associate with beta-arrestin . Nevertheless, it has been shown that activation of both C5AR1 and C5AR2 is required for a full pro-inflammatory response, particularly in mice . Several receptor antagonists have been reported , although none, so far, have been show to be effective in humans.

This entry represents C3a anaphylatoxin chemotactic receptors and C5a anaphylatoxin chemotactic receptor 1/2.
CC chemokine receptor 1 (Chemokine_CCR1)
Type: Family

Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role . They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system , and endothelial cells, where they may act as either angiogenic or angiostatic factors .

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors . Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells . Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).

CC chemokine receptors are a subfamily of the chemokine receptors that specifically bind and respond to cytokines of the CC chemokine family. There are currently ten members of the CC chemokine receptor subfamily, named CCR1 to 10. The receptors receptors are found in monocytes, lymphocytes, basophils and eosinophils.

This entry represents CC chemokine receptor 1 (CCR1). In humans, it is found on peripheral blood lymphocytes and monocytes . Immunologically mediated inflammatory disease indications have been suggested for CCR1 , including cardiac allograft rejection and glomerulonephritis . Following interaction with specific CC chemokine ligands, CCR1 triggers a flux in intracellular calcium ions . This causes cell responses, including the recruitment of mononuclear phagocytes into the CNS, leading to chemotaxis .