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Gene Review

GPR68  -  G protein-coupled receptor 68

Homo sapiens

Synonyms: G-protein coupled receptor 68, GPR12A, OGR-1, OGR1, Ovarian cancer G-protein coupled receptor 1, ...
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Disease relevance of GPR68


High impact information on GPR68

  • The specific binding of SPC to OGR1 also activates p42/44 mitogen-activated protein kinases (MAP kinases) and inhibits cell proliferation [3].
  • In accordance with previously published reports, OGR1 was found to evoke strong pH-dependent responses as measured by inositol phosphate accumulation [4].
  • Taken together, these data indicate that OGR1 is expressed early during osteoclastogenesis both in vivo and in vitro and plays a role in osteoclast differentiation [5].
  • Specific inhibition of OGR1 by anti-OGR1 antibody and by small inhibitory RNA inhibited RANKL-induced differentiation of both mouse bone marrow mononuclear cells and RAW cells in vitro, as evidenced by a decrease in tartrate-resistant acid phosphatase-positive osteoclasts [5].
  • Unexpectedly, the acid-induced cAMP accumulation was also largely inhibited by OGR1 siRNA but only slightly by GPR4 siRNA [6].

Biological context of GPR68


Anatomical context of GPR68


Associations of GPR68 with chemical compounds


Other interactions of GPR68

  • As OGR1 and GPR4 were reported as proton-sensing GPCRs (Ludwig, M. G., Vanek, M., Guerini, D., Gasser, J. A., Jones, C. E., Junker, U., Hofstetter, H., Wolf, R. M., and Seuwen, K. (2003) Nature 425, 93-98), we evaluated the proton-sensing function of G2A [12].
  • A novel G protein-coupled receptor, named GPR12A, was cloned by a PCR strategy using degenerate primers designed from sequences conserved among receptors for inflammatory mediators [8].
  • Here we review the status of this field and we confirm that GPR4, OGR1, and TDAG8 should be considered as proton-sensing receptors [13].
  • The cAMP accumulation may occur through OGR1-mediated stimulation of the phospholipase C/cyclooxygenase/PGI(2) pathway [6].

Analytical, diagnostic and therapeutic context of GPR68

  • Strong induction of OGR1 mRNA was also observed by microarray, real-time RT-PCR, and immunoblotting when mouse bone marrow mononuclear cells and RAW 264.7 pre-osteoclast-like cells were treated with RANKL to induce osteoclast differentiation [5].


  1. Identification of human OGR1, a novel G protein-coupled receptor that maps to chromosome 14. Xu, Y., Casey, G. Genomics (1996) [Pubmed]
  2. Proton-sensing G-protein-coupled receptors. Ludwig, M.G., Vanek, M., Guerini, D., Gasser, J.A., Jones, C.E., Junker, U., Hofstetter, H., Wolf, R.M., Seuwen, K. Nature (2003) [Pubmed]
  3. Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Xu, Y., Zhu, K., Hong, G., Wu, W., Baudhuin, L.M., Xiao, Y., Damron, D.S. Nat. Cell Biol. (2000) [Pubmed]
  4. Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Radu, C.G., Nijagal, A., McLaughlin, J., Wang, L., Witte, O.N. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis. Yang, M., Mailhot, G., Birnbaum, M.J., MacKay, C.A., Mason-Savas, A., Odgren, P.R. J. Biol. Chem. (2006) [Pubmed]
  6. Prostaglandin I(2) production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells. Tomura, H., Wang, J.Q., Komachi, M., Damirin, A., Mogi, C., Tobo, M., Kon, J., Misawa, N., Sato, K., Okajima, F. J. Biol. Chem. (2005) [Pubmed]
  7. Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. Zhu, K., Baudhuin, L.M., Hong, G., Williams, F.S., Cristina, K.L., Kabarowski, J.H., Witte, O.N., Xu, Y. J. Biol. Chem. (2001) [Pubmed]
  8. Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue. An, S., Tsai, C., Goetzl, E.J. FEBS Lett. (1995) [Pubmed]
  9. Human resting CD16-, CD16+ and IL-2-, IL-12-, IL-15- or IFN-alpha-activated natural killer cells differentially respond to sphingosylphosphorylcholine, lysophosphatidylcholine and platelet-activating factor. Jin, Y., Damaj, B.B., Maghazachi, A.A. Eur. J. Immunol. (2005) [Pubmed]
  10. TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. Wang, J.Q., Kon, J., Mogi, C., Tobo, M., Damirin, A., Sato, K., Komachi, M., Malchinkhuu, E., Murata, N., Kimura, T., Kuwabara, A., Wakamatsu, K., Koizumi, H., Uede, T., Tsujimoto, G., Kurose, H., Sato, T., Harada, A., Misawa, N., Tomura, H., Okajima, F. J. Biol. Chem. (2004) [Pubmed]
  11. The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand-independent manner. Bektas, M., Barak, L.S., Jolly, P.S., Liu, H., Lynch, K.R., Lacana, E., Suhr, K.B., Milstien, S., Spiegel, S. Biochemistry (2003) [Pubmed]
  12. G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine. Murakami, N., Yokomizo, T., Okuno, T., Shimizu, T. J. Biol. Chem. (2004) [Pubmed]
  13. Receptors for protons or lipid messengers or both? Seuwen, K., Ludwig, M.G., Wolf, R.M. J. Recept. Signal Transduct. Res. (2006) [Pubmed]
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