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Gene Review

GPR17  -  G protein-coupled receptor 17

Homo sapiens

Synonyms: G-protein coupled receptor 17, P2Y-like receptor, R12, UDP/CysLT receptor, Uracil nucleotide/cysteinyl leukotriene receptor
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Disease relevance of GPR17

  • In vivo inhibition of GPR17 by either CysLT/P2Y receptor antagonists or antisense technology dramatically reduced ischemic damage in a rat focal ischemia model, suggesting GPR17 as the common molecular target mediating brain damage by nucleotides and CysLTs [1].
  • There was a significant genetic correlation between ovarian and breast cancer (R12 = .484) [2].
  • Recombinant human tumor necrosis factor (rhTNF) was pressure-applied onto the the soma of identified neuron R12 in the Aplysia abdominal ganglion. rhTNF induced a slow inward current (ITNF, 80-100 s in duration, 5-10 nA in amplitude) associated with a conductance decrease [3].

High impact information on GPR17

  • Here we show that GPR17, a Gi-coupled orphan receptor at intermediate phylogenetic position between P2Y and CysLT receptors, is specifically activated by both families of endogenous ligands, leading to both adenylyl cyclase inhibition and intracellular calcium increases [1].
  • The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor [1].
  • We have established four hybridoma cells that produce monoclonal antibodies (MoAbs) R2, R4, R6, and R12 directed toward recombinant human erythropoietin (rHuEPO) [4].
  • However, Km values indicated a lower affinity for the enzyme's natural substrates (Km for dihydrofolate [DHF], 3.1 microM for CP1015 and 27.5 microM for R12/T2) and a twofold decrease in the specificity constant [5].
  • In a transformant with only the I100-L mutation (R12/T2) and a D92-A mutation also found in the DHFRs of susceptible isolates, the enzyme was much more resistant to trimethoprim inhibition (50% inhibitory concentration [IC50], 4.2 microM) than was the DHFR from strain CP1015 (IC50, 0.09 microM) [5].

Biological context of GPR17

  • A positive clone, designated hip4, was identified containing an open reading frame of 1,020 bp that had been previously detected in a published genomic clone called R12 [6].

Anatomical context of GPR17

  • Approximately 30% of R8, R10, and R12 patients, and 63% of R14 patients had demonstrable motor block of the lower limbs at 21 hours [7].
  • When serine was introduced instead of N3 to generate a typical PTS1, the SKL motif, at the C-terminus, all of the proteins having mutations at P5, E11, R12, or E15 showed extensive localization in peroxisomes [8].

Associations of GPR17 with chemical compounds

  • The effects of extracellularly applied recombinant human interleukin-2 (rhIL-2) on the gamma-aminobutyric acid (GABA)-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques [9].
  • These data strongly support the hypothesis that mitochondrial Ca(2+) uptake is regulated in part by adenine nucleotides via a P2Y-like receptor mechanism that involves mitochondrial PLC activation [10].
  • After combined general and epidural anesthesia and surgery, 125 patients were randomly assigned to receive either saline or ropivacaine 0.2% at a rate of 6, 8, 10, 12, or 14 mL/h (Groups R6, R8, R10, R12, and R14, respectively) for 21 h [7].
  • Parts of the initially added perchloroethylene, trichloroethylene, R12, R114, diethyl phthalate, dibutyl phthalate and benzylbutyl phthalate were transformed [11].
  • To verify the method, we used it to measure the R12 and R13 Kerr coefficients for a (100)-type single crystal of ferroelectric barium titanate (BaTiO3) at room temperature (23.5 degrees) [12].

Other interactions of GPR17

  • All known P2Y receptors (i.e. P2Y(1,2,4,6,11,12,13,14)) and two P2Y-like receptors (GPR91 and GPR17) were detected in all subjects [13].

Analytical, diagnostic and therapeutic context of GPR17

  • SDS-PAGE and Western blots with monoclonal antibodies T11 and R12 demonstrated that isolated IF consisted of a pair of polypeptides of 54 and 52 kDa [14].
  • Mitochondrial sequence analyses revealed the presence of two haplogroups of R lineage: B5a, and a newly defined clade, R12 [15].
  • Combined endorectal/body-phased-array-coil MRI of the prostate at 1.5 T was retrospectively evaluated twice, with an interval of more than 1 month, by each of two independent radiologists (R1 readings R11 and R12, and R2 readings R21 and R22) in 23 patients (age 51-75 years) who had radical prostatectomy within 1 month of MRI [16].
  • Image analysis of tumors with 99m-Tc-STA-R12, a porphyrin-scintigraphic agent, revealed STA-R12 localization in the tumor tissue alone about 1 h after intravenous infusion [17].
  • Here also, positive response with consensus R12/F12 validates other positive or negative PCR results [18].


  1. The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor. Ciana, P., Fumagalli, M., Trincavelli, M.L., Verderio, C., Rosa, P., Lecca, D., Ferrario, S., Parravicini, C., Capra, V., Gelosa, P., Guerrini, U., Belcredito, S., Cimino, M., Sironi, L., Tremoli, E., Rovati, G.E., Martini, C., Abbracchio, M.P. EMBO J. (2006) [Pubmed]
  2. Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship. Schildkraut, J.M., Risch, N., Thompson, W.D. Am. J. Hum. Genet. (1989) [Pubmed]
  3. Extracellular tumor necrosis factor induces a decreased K+ conductance in an identified neuron of Aplysia kurodai. Sawada, M., Hara, N., Maeno, T. Neurosci. Lett. (1990) [Pubmed]
  4. Characterization and use of monoclonal antibodies directed against human erythropoietin that recognize different antigenic determinants. Goto, M., Murakami, A., Akai, K., Kawanishi, G., Ueda, M., Chiba, H., Sasaki, R. Blood (1989) [Pubmed]
  5. Multiple mutations modulate the function of dihydrofolate reductase in trimethoprim-resistant Streptococcus pneumoniae. Maskell, J.P., Sefton, A.M., Hall, L.M. Antimicrob. Agents Chemother. (2001) [Pubmed]
  6. A novel orphan G protein-coupled receptor primarily expressed in the brain is localized on human chromosomal band 2q21. Bläsius, R., Weber, R.G., Lichter, P., Ogilvie, A. J. Neurochem. (1998) [Pubmed]
  7. Continuous epidural ropivacaine 0.2% for analgesia after lower abdominal surgery. Etches, R.C., Writer, W.D., Ansley, D., Nydahl, P.A., Ong, B.Y., Lui, A., Badner, N., Kawolski, S., Muir, H., Shukla, R., Beattie, W.S. Anesth. Analg. (1997) [Pubmed]
  8. Analyses in transfected cells and in vitro of a putative peroxisomal targeting signal of rat liver serine:pyruvate aminotransferase. Mizuno, T., Ito, K., Uchida, C., Kitagawa, M., Ichiyama, A., Miura, S., Fujita, K., Oda, T. Histochem. Cell Biol. (2002) [Pubmed]
  9. Interleukin-2 inhibits the GABA-induced Cl- current in identified Aplysia neurons. Sawada, M., Hara, N., Ichinose, M. J. Neurosci. Res. (1992) [Pubmed]
  10. Mitochondrial calcium transport is regulated by P2Y(1)- and P2Y(2)-like mitochondrial receptors. Belous, A.E., Jones, C.M., Wakata, A., Knox, C.D., Nicoud, I.B., Pierce, J., Chari, R.S. J. Cell. Biochem. (2006) [Pubmed]
  11. Anaerobic degradation of xenobiotics by organisms from municipal solid waste under landfilling conditions. Ejlertsson, J., Johansson, E., Karlsson, A., Meyerson, U., Svensson, B.H. Antonie Van Leeuwenhoek (1996) [Pubmed]
  12. Method for measuring off-diagonal Kerr coefficients by using polarized light transmission. Melnichuk, M., Wood, L.T. Journal of the Optical Society of America. A, Optics, image science, and vision. (2005) [Pubmed]
  13. P2 receptors in human heart: upregulation of P2X6 in patients undergoing heart transplantation, interaction with TNFalpha and potential role in myocardial cell death. Banfi, C., Ferrario, S., De Vincenti, O., Ceruti, S., Fumagalli, M., Mazzola, A., D' Ambrosi, N., Volontè, C., Fratto, P., Vitali, E., Burnstock, G., Beltrami, E., Parolari, A., Polvani, G., Biglioli, P., Tremoli, E., Abbracchio, M.P. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  14. Evidence for intermediate filaments in squirrelfish erythrophores of Holocentrus ascensionus (Rufus). Stearns, M.E., Wang, M. Exp. Cell Res. (1987) [Pubmed]
  15. Molecular insights into the origins of the Shompen, a declining population of the Nicobar archipelago. Trivedi, R., Sitalaximi, T., Banerjee, J., Singh, A., Sircar, P.K., Kashyap, V.K. J. Hum. Genet. (2006) [Pubmed]
  16. Reproducibility of image interpretation in MRI of the prostate: application of the sextant framework by two different radiologists. Mueller-Lisse, U., Mueller-Lisse, U., Scheidler, J., Klein, G., Reiser, M. European radiology. (2005) [Pubmed]
  17. Tumor-localizing activity of porphyrin and its affinity to LDL, transferrin. Nakajima, S., Takemura, T., Sakata, I. Cancer Lett. (1995) [Pubmed]
  18. Rapid molecular typing of Tuber melanosporum, T. brumale and T. indicum from tree seedlings and canned truffles. Douet, J.P., Castroviejo, M., Mabru, D., Chevalier, G., Dupré, C., Bergougnoux, F., Ricard, J.M., Médina, B. Analytical and bioanalytical chemistry. (2004) [Pubmed]
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