G protein-coupled receptors 3, 6, 12, and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors
GPR3, GPR6, and GPR12 form a subfamily of constitutively active G-protein coupled receptors with dual coupling to G(s) and G(i) proteins. These three orphan receptors are involved in the regulation of cell proliferation and survival, neurite outgrowth, cell clustering, and maintenance of meiotic prophase arrest. They constitutively activate adenylate cyclase to a similar degree as that seen with fully activated G(s)-coupled receptors, and are also able to constitutively activate inhibitory G(i/o) proteins. Lysophospholipids such as sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine have been detected as the high-affinity ligands for Gpr6 and Gpr12, respectively, which show high sequence homology with GPR3. Also included in this subfamily is GPRx, also known as GPR185, which involved in the maintenance of meiotic arrest in frog oocytes.