IUPHAR/BPS Guide to Pharmacology CITE
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Type VI RTKs: PTK7/CCK4 in GtoPdb v.2025.3
Get PDFThe PTK7 receptor is associated with polarization of epithelial cells and the development of neural structures. Sequence analysis suggests that the gene product is catalytically inactive as a protein kinase, hence acting as a pseudokinase. There is, however, evidence for a role in Wnt signalling [2], as well as an ability to form heteromers with other RTKs, such as VEGFR2 and ROR2
3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.4
Get PDFSmall G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases
Formylpeptide receptors in GtoPdb v.2025.1
Get PDFThe formylpeptide receptors (nomenclature agreed by the NC-IUPHAR Subcommittee on the formylpeptide receptor family [150]) respond to exogenous ligands such as the bacterial product fMet-Leu-Phe (fMLF) and endogenous ligands such as lipoxin A4 (LXA4), 15-epi-lipoxin A4, annexin I , cathepsin G, amyloid β42, serum amyloid A and spinorphin, derived from β-haemoglobin. FPR1 also serves as a plague receptor for selective destruction of human immune cells by Y. pestis [135]. The FPR1/2 agonists \u27compound 17b\u27 and \u27compound 43\u27 have shown cardiac protective functions [149, 64]
SLC28 and SLC29 families of nucleoside transporters in GtoPdb v.2025.1
Get PDFNucleoside transporters are divided into two families, the sodium-dependent, concentrative solute carrier family 28 (SLC28) and the equilibrative, solute carrier family 29 (SLC29). The endogenous substrates are typically nucleosides, although some family members can also transport nucleobases and organic cations [1]
SLC8 family of sodium/calcium exchangers in GtoPdb v.2025.1
Get PDFThe sodium/calcium exchangers (NCX) use the extracellular sodium concentration to facilitate the extrusion of calcium out of the cell. Alongside the plasma membrane Ca2+-ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA), as well as the sodium/potassium/calcium exchangers (NKCX, SLC24 family), NCX allow recovery of intracellular calcium back to basal levels after cellular stimulation. When intracellular sodium ion levels rise, for example, following depolarisation, these transporters can operate in the reverse direction to allow calcium influx and sodium efflux, as an electrogenic mechanism. Structural modelling suggests the presence of 9 TM segments, with a large intracellular loop between the fifth and sixth TM segments [1]
Hydrolases & Lipases in GtoPdb v.2024.4
Get PDFListed 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
Carnitine palmitoyltransferases in GtoPdb v.2024.4
Get PDFThe CPT1 enzymes convert long chain (greater than ∼C12) acyl-CoA molecules to acylcarnitine derivatives to facilitate their transport from the cytosol into the mitochondrial matrix via the carnitine/acylcarnitine carrier (CACT; SLC25A20). The acylcarnitines are converted back to acyl-CoA by CPT2 to support the fatty acid oxidation (FAO) cycle in the mitochondria. CPT1s are allosterically inhibited by malonyl-CoA
E3 ubiquitin ligase components in GtoPdb v.2023.2
Get PDFUbiquitination (a.k.a. ubiquitylation) is a protein post-translational modification that typically requires the sequential action of three enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin ligases) [30]. Ubiquitination of proteins can target them for proteasomal degradation, or modulate cellular processes including cell cycle progression, transcriptional regulation, DNA repair and signal transduction. E3 ubiquitin ligases, of which there are >600 in humans, are a family of highly heterogeneous proteins and protein complexes that recruit ubiquitin-loaded E2 enzymes to mediate transfer of the ubiquitin molecule from the E2 to protein substrates. Target substrate specificity is determined by a substrate recognition subunit within the E3 complex. E3 ligases are being exploited as pharmacological targets to facilitate targeted protein degradation (TPD), as an alternative to small molecule inhibitors [3], through the development of proteolysis targeting chimeras (PROTACs) and molecular glues
Complement peptide receptors in GtoPdb v.2023.1
Get PDFComplement peptide receptors (nomenclature as agreed by the NC-IUPHAR subcommittee on Complement peptide receptors [113]) are activated by the endogenous ~75 amino-acid anaphylatoxin polypeptides C3a and C5a, generated upon stimulation of the complement cascade. C3a and C5a exert their functions through binding to their receptors (C3a receptor, C5a receptor 1 and C5a receptor 2), causing cell recruitment and triggering cellular degranulation that contributes to local inflammation
Apelin receptor in GtoPdb v.2023.1
Get PDFThe apelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the apelin receptor [73] and subsequently updated [75]) responds to apelin, a 36 amino-acid peptide derived initially from bovine stomach. apelin-36, apelin-13 and [Pyr1]apelin-13 are the predominant endogenous ligands which are cleaved from a 77 amino-acid precursor peptide (APLN, Q9ULZ1) [88]. A second family of peptides discovered independently and named Elabela [13] or Toddler, that has little sequence similarity to apelin, is present, and functional at the apelin receptor in the adult cardiovascular system [97, 71]. The enzymatic pathways generating biologically active apelin and Elabela isoforms have not been determined but both propeptides include sites for potential proprotein convertase processing [81]. Structure-activity relationship Elabela analogues have been described [65, 90]. The stoichiometry of apelin receptor-heterotrimeric G protein complexes has been studied using cryogenic-electron microscopy [98]