Recombinant Human Psychosine receptor (GPR65) Protein

Function

Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:15326175, PubMed:15618224, PubMed:20855608, PubMed:33478938, PubMed:37722051, PubMed:39753132, PubMed:40211064). Activated by an optimal pH of 7.4 (PubMed:39753132). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:15326175, PubMed:15618224, PubMed:37722051, PubMed:39753132). GPR65 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (PubMed:15618224, PubMed:37722051, PubMed:39753132). May also act as a receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (PubMed:11309421, PubMed:15326175). Plays a role in immune response by maintaining lysosome function and regulating T-cell metabolism (PubMed:27287411). Acts as a regulator of inflammation by mediating pH-sensing of extracellular acidification which takes place in inflamed tissues: activation regulates endo-lysosomal function of immune cells and T-cell metabolism (By similarity). Constitutively active in endosomes and stimulates adenylate cyclase production from endosomes independently from extracellular pH changes (PubMed:39753132)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Early endosome membrane (Multi-pass membrane protein); Late endosome membrane (Multi-pass membrane protein)

Tissue Specificity

Predominantly expressed in thymus, spleen, lymph nodes, small intestine, lung, placenta and peripheral blood leukocytes

• Kyaw H. et al. Cloning, characterization, and mapping of human homolog of mouse T-cell death-associated gene. — DNA Cell Biol. (1998)
• Heilig R. et al. The DNA sequence and analysis of human chromosome 14. — Nature (2003)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Im D.-S. et al. Identification of a molecular target of psychosine and its role in globoid cell formation. — J. Cell Biol. (2001)
• Wang J.Q. et al. TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. — J. Biol. Chem. (2004)
• Ishii S. et al. Identification of T cell death-associated gene 8 (TDAG8) as a novel acid sensing G-protein-coupled receptor. — J. Biol. Chem. (2005)
• Ihara Y. et al. The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor. — Proc. Natl. Acad. Sci. U.S.A. (2010)
• Huang X.P. et al. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. — Nature (2015)