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Gene Review

P2RY13  -  purinergic receptor P2Y, G-protein coupled...

Homo sapiens

Synonyms: FKSG77, G-protein coupled receptor 86, G-protein coupled receptor 94, GPCR1, GPR86, ...
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Disease relevance of P2RY13


Psychiatry related information on P2RY13

  • Many drugs of abuse signal through receptors that couple to G proteins (GPCRs), so the factors that control GPCR signaling are likely to be important to the understanding of drug abuse [6].
  • Given the complexity of neurological disorders such as ischemic stroke, Alzheimer's disease and epilepsy, exploitation mGlu receptor-associated GPCR interactions may prove efficacious in the treatment of such disorders [7].

High impact information on P2RY13

  • Future high-resolution structural studies of rhodopsin and other GPCRs will form a basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction [8].
  • Significantly, GPCR-containing CCPs are also functionally distinct, as their surface residence time is regulated locally by GPCR cargo via PDZ-dependent linkage to the actin cytoskeleton [9].
  • Our results reveal a novel function of betaarr1 as a cytoplasm-nucleus messenger in GPCR signaling and elucidate an epigenetic mechanism for direct GPCR signaling from cell membrane to the nucleus through signal-dependent histone modification [10].
  • (2005) provide evidence that beta-arrestin 1 moves to the nucleus in response to GPCR stimulation, where it regulates gene expression by facilitating histone acetylation at specific gene promoters [11].
  • A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription [10].

Chemical compound and disease context of P2RY13


Biological context of P2RY13

  • We show that inhibition of proHB-EGF processing blocks GPCR-induced EGFR transactivation and downstream signals [17].
  • GPCR desensitization occurs as a consequence of G protein uncoupling in response to phosphorylation by both second messenger-dependent protein kinases and G protein-coupled receptor kinases (GRKs) [18].
  • The focus of this review is the current and evolving understanding of the contribution of GRKs, beta-arrestins, and endocytosis to GPCR-specific patterns of desensitization and resensitization [18].
  • ALX at the level of DNA has sequence homology to the N-formylpeptide receptor and as an orphan GPCR was initially referred to as the N-formylpeptide receptor-like 1 [19].
  • Allosteric sites on GPCRs represent novel drug targets because allosteric modulators possess a number of theoretical advantages over classic orthosteric ligands, such as a ceiling level to the allosteric effect and a potential for greater GPCR subtype-selectivity [20].

Anatomical context of P2RY13

  • GPR94 was expressed in the frontal cortex, caudate putamen and thalamus of brain while GPR95 was expressed in the human prostate and rat stomach and fetal tissues [21].
  • Our data suggest that OA1 represents the first example of an exclusively intracellular GPCR and support the hypothesis that GPCR-mediated signal transduction systems also operate at the internal membranes in mammalian cells [22].
  • A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs [23].
  • Another ArfGAP, Git2, was found to be a component of the Gbetagamma-mediated directional sensing machinery, while simultaneously playing an essential role in the suppressive control of superoxide production, which is mediated by vesicle transport in GPCR-stimulated neutrophils [24].
  • Over the past three years, three types of scaffolds for GPCR-directed complex assembly have been identified: transactivated receptor tyrosine kinases (RTKs), integrin-based focal adhesions, and GPCRs themselves [25].

Associations of P2RY13 with chemical compounds

  • Two other novel GPCR genes, GPR94 and GPR95, encoded a subfamily with the genes encoding the UDP-glucose and P2Y(12) receptors (sharing >50% identities in the TM regions) [21].
  • We provide here structural evidence that the protein product of the ocular albinism type 1 gene (OA1), a pigment cell-specific integral membrane glycoprotein, represents a novel member of the GPCR superfamily and demonstrate that it binds heterotrimeric G proteins [22].
  • MAP kinase activation may result from stimulation of either tyrosine-kinase (RTK) receptors, which possess intrinsic tyrosine kinase activity, or G-protein-coupled receptors (GPCR) [26].
  • Conversely, stimulating ligand-gated channels, particularly those that are permeable to Ca(2+), indirectly produces effects on GPCRs and/or on GPCR-activated signaling cascades [27].
  • Transient expression of either Gq- or Gi-coupled receptors in COS-7 cells allowed GPCR agonist-induced EGFR transactivation, and lysophosphatidic acid (LPA)-generated signals involved the docking protein Gab1 [28].

Other interactions of P2RY13


Analytical, diagnostic and therapeutic context of P2RY13

  • Graded reductions in GPCR expression can be achieved through antisense strategies or total gene ablation or replacement can be achieved through gene targeting strategies, and exogenous expression of wild-type or mutant GPCR isoforms can be accomplished with transgenic technologies [34].
  • Here, we report the molecular cloning of a novel GPCR for LTB(4), designated BLT2, which binds LTB(4) with a Kd value of 23 nM compared with 1.1 nM for BLT1, but still efficiently transduces intracellular signaling [35].
  • Techniques: GPCR assembly, pharmacology and screening by flow cytometry [36].
  • Many attempts have been made to design universal ligand-screening systems such that any GPCR can be screened using a common assay end-point [37].
  • Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues [38].


  1. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. Gschwind, A., Hart, S., Fischer, O.M., Ullrich, A. EMBO J. (2003) [Pubmed]
  2. A central role of EGF receptor transactivation in angiotensin II -induced cardiac hypertrophy. Shah, B.H., Catt, K.J. Trends Pharmacol. Sci. (2003) [Pubmed]
  3. p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling. Sheffler, D.J., Kroeze, W.K., Garcia, B.G., Deutch, A.Y., Hufeisen, S.J., Leahy, P., Brüning, J.C., Roth, B.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils. McMeekin, S.R., Dransfield, I., Rossi, A.G., Haslett, C., Walker, T.R. Blood (2006) [Pubmed]
  5. The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner. Alberich Jordà, M., Rayman, N., Tas, M., Verbakel, S.E., Battista, N., van Lom, K., Löwenberg, B., Maccarrone, M., Delwel, R. Blood (2004) [Pubmed]
  6. Regulators of G protein signaling (RGS proteins): novel central nervous system drug targets. Neubig, R.R. J. Pept. Res. (2002) [Pubmed]
  7. Emerging signalling and protein interactions mediated via metabotropic glutamate receptors. Moldrich, R.X., Beart, P.M. Current drug targets. CNS and neurological disorders. (2003) [Pubmed]
  8. Rhodopsin: structural basis of molecular physiology. Menon, S.T., Han, M., Sakmar, T.P. Physiol. Rev. (2001) [Pubmed]
  9. Cargo regulates clathrin-coated pit dynamics. Puthenveedu, M.A., von Zastrow, M. Cell (2006) [Pubmed]
  10. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Kang, J., Shi, Y., Xiang, B., Qu, B., Su, W., Zhu, M., Zhang, M., Bao, G., Wang, F., Zhang, X., Yang, R., Fan, F., Chen, X., Pei, G., Ma, L. Cell (2005) [Pubmed]
  11. Beta-arrestin goes nuclear. Beaulieu, J.M., Caron, M.G. Cell (2005) [Pubmed]
  12. Lysophosphatidic acid-induced squamous cell carcinoma cell proliferation and motility involves epidermal growth factor receptor signal transactivation. Gschwind, A., Prenzel, N., Ullrich, A. Cancer Res. (2002) [Pubmed]
  13. Pleiotropic coupling of G protein-coupled receptors to the mitogen-activated protein kinase cascade. Role of focal adhesions and receptor tyrosine kinases. Della Rocca, G.J., Maudsley, S., Daaka, Y., Lefkowitz, R.J., Luttrell, L.M. J. Biol. Chem. (1999) [Pubmed]
  14. The synthetic peptide derived from the NH2-terminal extracellular region of an orphan G protein-coupled receptor, GPR1, preferentially inhibits infection of X4 HIV-1. Jinno-Oue, A., Shimizu, N., Soda, Y., Tanaka, A., Ohtsuki, T., Kurosaki, D., Suzuki, Y., Hoshino, H. J. Biol. Chem. (2005) [Pubmed]
  15. Differential regulation of estrogen receptor alpha, glucocorticoid receptor and retinoic acid receptor alpha transcriptional activity by melatonin is mediated via different G proteins. Kiefer, T.L., Lai, L., Yuan, L., Dong, C., Burow, M.E., Hill, S.M. J. Pineal Res. (2005) [Pubmed]
  16. Involvement of metabotropic glutamate receptor 1, a G protein coupled receptor, in melanoma development. Marín, Y.E., Chen, S. J. Mol. Med. (2004) [Pubmed]
  17. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Prenzel, N., Zwick, E., Daub, H., Leserer, M., Abraham, R., Wallasch, C., Ullrich, A. Nature (1999) [Pubmed]
  18. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Ferguson, S.S. Pharmacol. Rev. (2001) [Pubmed]
  19. The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo. Chiang, N., Serhan, C.N., Dahlén, S.E., Drazen, J.M., Hay, D.W., Rovati, G.E., Shimizu, T., Yokomizo, T., Brink, C. Pharmacol. Rev. (2006) [Pubmed]
  20. G protein-coupled receptor allosterism and complexing. Christopoulos, A., Kenakin, T. Pharmacol. Rev. (2002) [Pubmed]
  21. Discovery and mapping of ten novel G protein-coupled receptor genes. Lee, D.K., Nguyen, T., Lynch, K.R., Cheng, R., Vanti, W.B., Arkhitko, O., Lewis, T., Evans, J.F., George, S.R., O'Dowd, B.F. Gene (2001) [Pubmed]
  22. Ocular albinism: evidence for a defect in an intracellular signal transduction system. Schiaffino, M.V., d'Addio, M., Alloni, A., Baschirotto, C., Valetti, C., Cortese, K., Puri, C., Bassi, M.T., Colla, C., De Luca, M., Tacchetti, C., Ballabio, A. Nat. Genet. (1999) [Pubmed]
  23. A receptor in pituitary and hypothalamus that functions in growth hormone release. Howard, A.D., Feighner, S.D., Cully, D.F., Arena, J.P., Liberator, P.A., Rosenblum, C.I., Hamelin, M., Hreniuk, D.L., Palyha, O.C., Anderson, J., Paress, P.S., Diaz, C., Chou, M., Liu, K.K., McKee, K.K., Pong, S.S., Chaung, L.Y., Elbrecht, A., Dashkevicz, M., Heavens, R., Rigby, M., Sirinathsinghji, D.J., Dean, D.C., Melillo, D.G., Patchett, A.A., Nargund, R., Griffin, P.R., DeMartino, J.A., Gupta, S.K., Schaeffer, J.M., Smith, R.G., Van der Ploeg, L.H. Science (1996) [Pubmed]
  24. ArfGAP family proteins in cell adhesion, migration and tumor invasion. Sabe, H., Onodera, Y., Mazaki, Y., Hashimoto, S. Curr. Opin. Cell Biol. (2006) [Pubmed]
  25. Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Luttrell, L.M., Daaka, Y., Lefkowitz, R.J. Curr. Opin. Cell Biol. (1999) [Pubmed]
  26. Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. van Biesen, T., Hawes, B.E., Luttrell, D.K., Krueger, K.M., Touhara, K., Porfiri, E., Sakaue, M., Luttrell, L.M., Lefkowitz, R.J. Nature (1995) [Pubmed]
  27. D1 and NMDA receptors hook up: expanding on an emerging theme. Salter, M.W. Trends Neurosci. (2003) [Pubmed]
  28. Signal characteristics of G protein-transactivated EGF receptor. Daub, H., Wallasch, C., Lankenau, A., Herrlich, A., Ullrich, A. EMBO J. (1997) [Pubmed]
  29. Involvement of multiple P2Y receptors and signaling pathways in the action of adenine nucleotides diphosphates on human monocyte-derived dendritic cells. Marteau, F., Communi, D., Boeynaems, J.M., Suarez Gonzalez, N. J. Leukoc. Biol. (2004) [Pubmed]
  30. Agonists and antagonists for P2 receptors. Jacobson, K.A., Costanzi, S., Joshi, B.V., Besada, P., Shin, D.H., Ko, H., Ivanov, A.A., Mamedova, L. Novartis Found. Symp. (2006) [Pubmed]
  31. Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. von Kügelgen, I. Pharmacol. Ther. (2006) [Pubmed]
  32. Transcriptional changes in multiple system atrophy and Parkinson's disease putamen. Vogt, I.R., Lees, A.J., Evert, B.O., Klockgether, T., Bonin, M., Wüllner, U. Exp. Neurol. (2006) [Pubmed]
  33. P2 receptor mRNA expression profiles in human lymphocytes, monocytes and CD34+ stem and progenitor cells. Wang, L., Jacobsen, S.E., Bengtsson, A., Erlinge, D. BMC Immunol. (2004) [Pubmed]
  34. G protein-coupled receptors: functional and mechanistic insights through altered gene expression. Rohrer, D.K., Kobilka, B.K. Physiol. Rev. (1998) [Pubmed]
  35. A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. Yokomizo, T., Kato, K., Terawaki, K., Izumi, T., Shimizu, T. J. Exp. Med. (2000) [Pubmed]
  36. Techniques: GPCR assembly, pharmacology and screening by flow cytometry. Waller, A., Simons, P.C., Biggs, S.M., Edwards, B.S., Prossnitz, E.R., Sklar, L.A. Trends Pharmacol. Sci. (2004) [Pubmed]
  37. Chimaeric G alpha proteins: their potential use in drug discovery. Milligan, G., Rees, S. Trends Pharmacol. Sci. (1999) [Pubmed]
  38. Trace amines: identification of a family of mammalian G protein-coupled receptors. Borowsky, B., Adham, N., Jones, K.A., Raddatz, R., Artymyshyn, R., Ogozalek, K.L., Durkin, M.M., Lakhlani, P.P., Bonini, J.A., Pathirana, S., Boyle, N., Pu, X., Kouranova, E., Lichtblau, H., Ochoa, F.Y., Branchek, T.A., Gerald, C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
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