G protein-coupled receptor 75, member of the class A family of seven-transmembrane G protein-coupled receptors
G-protein coupled receptor 75 (GPR75) is an atypical chemokine receptor that is expressed by mouse and human islets. Although GPR75 shows low sequence homology to C-C chemokine receptors, chemokine (C-C motif) ligand 5 (CCL5) has been shown to act as an endogenous ligand for GPR75. CCL5 plays a key role in recruiting lymphocytes to sites of inflammatory and infection through promiscuous binding to the C-C chemokine G-protein-coupled receptors. Although categorized as a member of the rhodopsin-like class A GPCRs, GPR75 contains HRL-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. 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, which then activate the heterotrimeric G proteins. GPR75 is coupled to the G-protein G(q), which elevates intracellular calcium.