G Protein Coupled Receptor 68 (GPR68)

It was isolated by degenerate PCR from an ovarian cell line cDNA library. The 365-amino acid predicted protein contains 7 hydrophobic transmembrane domains and is 54% identical to the human orphan receptor GPR4.OGR1, which had previously been described as a receptor for sphingosylphosphorylcholine, acts as a proton-sensing receptor stimulating inositol phosphate formation. The receptor is inactive at pH 7.8 and fully activated at pH 6.8. Site-directed mutagenesis showed that histidines at the extracellular surface are involved in pH sensing. These include histidines 17, 20, 84, 269, and 169. Mutation of these amino acids resulted in receptors that failed to stimulate inositol phosphate formation at pH 6.8 but on exposure to more acidic pH activity, could be restored.