G protein-coupled receptor 162, member of the class A family of seven-transmembrane G protein-coupled receptors
This subgroup represents the orphan G-protein coupled receptor 162 (GPR162), also called A-2 or GRCA, with unknown endogenous ligand and function. Phylogenetical analysis indicates that GPR162 and GPR153 share a common evolutionary ancestor due to a gene duplication event. Although categorized as members of the rhodopsin-like class A GPCRs, both GPR162 and GPR153 contain HRM-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors and important for efficient G protein-coupled signal transduction. Moreover, the LPxF motif, a variant of NPxxY motif that plays a crucial role during receptor activation, is found at the end of TM7 in GPR162 and GPR153. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.