7tm Receptors

Abstract

Overview:The completion of the Human Genome Project allowed the identification of a large family of proteins with a common motif of seven groups of 20-24 hydrophobic amino acids arranged as a helices. Approximately 800 of these seven transmembrane (7TM) receptors have been identified of which over 300 are non-olfactory receptors (see Fredriksson et al., 2003; Lagerstrom and Schioth, 2008). Subdivision on the basis of sequence homology allows the definition of rhodopsin, secretin, adhesion, glutamate and Frizzled receptor families. NC-IUPHAR recognizes Classes A, B, and C, which equate to the rhodopsin, secretin and glutamate receptor families.The nomenclature of 7TM receptors is commonly used interchangeably with G protein-coupled receptors, although the former nomenclature allows for signalling of 7TM receptors through pathways not involving G proteins. For example, adiponectin and membrane progestin receptors appear to signal independently of G proteins and appear to reside in membranes in an inverted fashion compared with conventional 7TM receptors. Additionally, the NPR3 natriuretic peptide receptor has a single transmembrane domain structure, but appears to couple to G proteins to generate cellular responses. The 300+ non-olfactory 7TM receptors are the targets for the majority of drugs in clinical usage (Overington et al., 2006), although only a minority of these receptors are exploited therapeutically. Further ReadingFoord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP et al. (2005) . Preliminary pairingsWhile the remainder of this section focuses on those 7TM receptors for which there is substantial pharmacological information, or interest, listed below are a number of putative 7TM receptors identified by IUPHAR , for which only preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. Gene SymbolEnsembl ID Other names Putative endogenous ligand Comment GPR1 ENSG00000183671 -Appears to act as a co-receptor for HIV (Shimizu et al., 1999) GPR3 ENSG00000181773 ACCA Fails to respond to a variety of lipid-derived agents (Yin et al., 2009) Has been reported to activate adenylyl cyclase constitutively through Gs (Eggerickx et al., 1995). Gene disruption results in premature ovarian aging (Ledent et al., 2005) and reduced b-amyloid deposition (Thathiah et al., 2009) in mice GPR4 ENSG00000177464 Protons (Ludwig et al., 2003; Tobo et al., 2007) An initial report suggesting activation by lysophosphatidylcholine, sphingosylphosphorylcholine (Zhu et al., 2001) has been retracted (Zhu et al., 2005). Gene disruption is associated with increased perinatal mortality and impaired vascular proliferation (Yang et al., 2007 Has also been reported to respond to the phosphodiesterase inhibitor zaprinast (Taniguchi et al., 2006) and the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (Taniguchi et al., 2008) GPR37 ENSG00000170775 PAELR, EDNRLB Head activator peptide (Rezgaoui et al., 2006) Reported to a...