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Calcium-sensing receptor in GtoPdb v.2025.3
Full text linkThe calcium-sensing receptor (CaS, provisional nomenclature as recommended by NC-IUPHAR [49] and subsequently updated [81]) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L-amino acids (particularly L-Trp and L-Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [82]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [14, 115], L-amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [36, 49, 65, 113, 114]. Indeed, L-amino acids have been identified as "co-agonists", with both concomitant calcium and L-amino acid binding required for full receptor activation [155, 57]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [18] or decreased extracellular ionic strength [114] while sensitivity is decreased by pathophysiological phosphate concentrations [20]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS
Melatonin receptors in GtoPdb v.2025.3
Full text linkMelatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [40]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon
Neuropeptide Y receptors in GtoPdb v.2025.3
Full text linkNeuropeptide Y (NPY) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Neuropeptide Y Receptors [159]) are activated by the endogenous peptides neuropeptide Y, neuropeptide Y-(3-36), peptide YY, PYY-(3-36) and pancreatic polypeptide (PP). The receptor originally identified as the Y3 receptor has been identified as the CXCR4 chemokine recepter (originally named LESTR, [140]). The y6 receptor is a functional gene product in mouse, absent in rat, but contains a frame-shift mutation in primates producing a truncated non-functional gene [85]. Three-dimensional structures have been determined for subtype active receptors Y1, Y2 and Y4 [216, 115] and inactive antagonist bound Y1 and Y2 receptors [245, 215]. Many of the agonists exhibit differing degrees of selectivity dependent on the species examined. For example, the potency of PP is greater at the rat Y4 receptor than at the human receptor [63]. In addition, many agonists lack selectivity for individual subtypes, but can exhibit comparable potency against pairs of NPY receptor subtypes, or have not been examined for activity at all subtypes. [125I]-PYY or [125I]-NPY can be used to label Y1, Y2, Y5 and y6 subtypes non-selectively, while [125I][cPP(1-7), NPY(19-23), Ala31, Aib32, Gln34]hPP may be used to label Y5 receptors preferentially (note that cPP denotes chicken peptide sequence and hPP is the human sequence)
Voltage-gated calcium channels (CaV) in GtoPdb v.2025.3
Full text linkCa2+ channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [136] and approved by the NC-IUPHAR Subcommittee on Ca2+ channels [75]. Most Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high- to moderate-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I-IV), each repeat having six transmembrane domains (S1-S6) forming a voltage-sensing domain (VSD, S1-S4) coupled to a pore-forming module (S5, S6 and their connecting linker that contains the selectivity filter. Voltage-dependent gating is driven by voltage-induced transmembrane movements of the S4-helix enabled by conserved positive charges interacting with negative counter-charges within the VSD [74]. All of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2-δ subunits. CACHD1 is an α2δ-like protein that modulates Cav3 channel activity [100]. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Cav1.1 channel. The α2-δ1 and α2-δ2 subunits bind gabapentin and pregabalin [92]
3A. Estrogen receptors in GtoPdb v.2025.3
Full text linkEstrogen receptor (ER) activity regulates diverse physiological processes via transcriptional modulation of target genes [2]. The selection of target genes and the magnitude of the response, be it induction or repression, are determined by many factors, including the effect of the hormone ligand and DNA binding on ER structural conformation, and the local cellular regulatory environment. The cellular environment defines the specific complement of DNA enhancer and promoter elements present and the availability of coregulators to form functional transcription complexes. Together, these determinants control the resulting biological response
SLC1 family of amino acid transporters in GtoPdb v.2025.3
No full textThe SLC1 family of sodium dependent transporters includes the plasma membrane located glutamate transporters and the neutral amino acid transporters ASCT1 and ASCT2 [3, 54, 40, 41, 9]
Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family in GtoPdb v.2025.3
No full textThe TAM receptor family, named from the first letter of each of its constituents, respond to growth arrest specific protein 6 and protein S. These ligands are secreted plasma proteins which undergo vitamin K-dependent post-translational modifications generating carboxyglutamate-rich domains which are able to bind to negatively-charged surfaces of apoptotic cells. Members of this RTK family represented a novel structural motif, when originally sequenced
Type III receptor serine/threonine kinases in GtoPdb v.2025.3
Full text linkType III serine/threonine kinase is often referred to as an accessory protein. While it has no known enzymatic activity, it can regulate the signalling of RSTKs [3, 2]
Hydrolases & Lipases in GtoPdb v.2025.3
Full text linkListed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins
