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Gene Review

UTS2R  -  urotensin 2 receptor

Homo sapiens

Synonyms: G-protein coupled receptor 14, GPR14, UR-2-R, UR-II-R, UTR, ...
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Disease relevance of UTS2R


Psychiatry related information on UTS2R

  • In vitro RNA binding experiments demonstrated that Hel-N1 can bind to the 3' untranslated region (3' UTR) of Id mRNA, a transcript that encodes a helix-loop-helix transcriptional repressor that is abundantly expressed in undifferentiated neural precursors [6].
  • The fragile X syndrome is an X linked, semidominant mental retardation disorder caused by the amplification of a CGG repeat in the 5' UTR of the FMR1 gene [7].
  • Association between the 5' UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder [8].
  • No evidence was found for the involvement of variants within the CUX2 coding, or 5' UTR sequence in producing susceptibility to bipolar disorder [9].
  • However, differences in allele frequencies of the 3' UTR single nucleotide polymorphism between the present population and that of Wassink et al. may account for the inability to detect association between WNT2 and autistic disorder in the present data set [10].

High impact information on UTS2R

  • A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis [11].
  • A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations [11].
  • We were surprised to find that mice overexpressing a normal DMPK 3' UTR mRNA reproduced cardinal features of myotonic dystrophy, including myotonia, cardiac conduction abnormalities, histopathology and RNA splicing defects in the absence of detectable nuclear inclusions [12].
  • We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle [13].
  • The IL12B 3' UTR alleles showed different levels of expression in cell lines [14].

Chemical compound and disease context of UTS2R


Biological context of UTS2R


Anatomical context of UTS2R


Associations of UTS2R with chemical compounds

  • Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 [25].
  • Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt) is a new potent and specific antagonist of the human UT receptor [3].
  • A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor [26].
  • Here, we characterise Chinese hamster ovary (CHO) cells expressing the human UT receptor in the following assays; (1) [(125)I]U-II binding, (2) GTPgamma[(35)S] binding, (3) cAMP formation, and (4) intracellular Ca(2+) [27].
  • However, whereas SB-710411 antagonized urotensin-II-induced inositol phosphate formation at the rat UT receptor (pK(b) 6.54+/-0.05), this ligand functioned as an agonist at the monkey UT receptor (pEC(50) 6.56+/-0.35, E(max) 5.27+/-0.65-fold over basal) [28].

Physical interactions of UTS2R

  • Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization [25].

Regulatory relationships of UTS2R

  • Radioligand binding analysis showed high affinity binding of UII to membrane preparations isolated from HEK293 cells stably expressing rat GPR14 [24].

Other interactions of UTS2R


Analytical, diagnostic and therapeutic context of UTS2R


  1. Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese. Suzuki, S., Wenyi, Z., Hirai, M., Hinokio, Y., Suzuki, C., Yamada, T., Yoshizumi, S., Suzuki, M., Tanizawa, Y., Matsutani, A., Oka, Y. Peptides (2004) [Pubmed]
  2. Renal effects of human urotensin-II in rats with experimental congestive heart failure. Ovcharenko, E., Abassi, Z., Rubinstein, I., Kaballa, A., Hoffman, A., Winaver, J. Nephrol. Dial. Transplant. (2006) [Pubmed]
  3. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. Clozel, M., Binkert, C., Birker-Robaczewska, M., Boukhadra, C., Ding, S.S., Fischli, W., Hess, P., Mathys, B., Morrison, K., Müller, C., Müller, C., Nayler, O., Qiu, C., Rey, M., Scherz, M.W., Velker, J., Weller, T., Xi, J.F., Ziltener, P. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  4. Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta. Bousette, N., Patel, L., Douglas, S.A., Ohlstein, E.H., Giaid, A. Atherosclerosis (2004) [Pubmed]
  5. Expression of urotensin II and urotensin II receptor mRNAs in various human tumor cell lines and secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma cells. Takahashi, K., Totsune, K., Murakami, O., Shibahara, S. Peptides (2001) [Pubmed]
  6. Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in vitro to the 3' UTR of mRNA encoding the Id transcriptional repressor. King, P.H., Levine, T.D., Fremeau, R.T., Keene, J.D. J. Neurosci. (1994) [Pubmed]
  7. DNA testing for fragile X syndrome: implications for parents and family. van Rijn, M.A., de Vries, B.B., Tibben, A., van den Ouweland, A.M., Halley, D.J., Niermeijer, M.F. J. Med. Genet. (1997) [Pubmed]
  8. Association between the 5' UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder. Niesler, B., Flohr, T., Nöthen, M.M., Fischer, C., Rietschel, M., Franzek, E., Albus, M., Propping, P., Rappold, G.A. Pharmacogenetics (2001) [Pubmed]
  9. CUX2, a potential regulator of NCAM expression: genomic characterization and analysis as a positional candidate susceptibility gene for bipolar disorder. Jacobsen, N.J., Elvidge, G., Franks, E.K., O'Donovan, M.C., Craddock, N., Owen, M.J. Am. J. Med. Genet. (2001) [Pubmed]
  10. No association between the WNT2 gene and autistic disorder. McCoy, P.A., Shao, Y., Wolpert, C.M., Donnelly, S.L., Ashley-Koch, A., Abel, H.L., Ravan, S.A., Abramson, R.K., Wright, H.H., DeLong, G.R., Cuccaro, M.L., Gilbert, J.R., Pericak-Vance, M.A. Am. J. Med. Genet. (2002) [Pubmed]
  11. A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis. Miyamoto, Y., Mabuchi, A., Shi, D., Kubo, T., Takatori, Y., Saito, S., Fujioka, M., Sudo, A., Uchida, A., Yamamoto, S., Ozaki, K., Takigawa, M., Tanaka, T., Nakamura, Y., Jiang, Q., Ikegawa, S. Nat. Genet. (2007) [Pubmed]
  12. Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy. Mahadevan, M.S., Yadava, R.S., Yu, Q., Balijepalli, S., Frenzel-McCardell, C.D., Bourne, T.D., Phillips, L.H. Nat. Genet. (2006) [Pubmed]
  13. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Clop, A., Marcq, F., Takeda, H., Pirottin, D., Tordoir, X., Bibé, B., Bouix, J., Caiment, F., Elsen, J.M., Eychenne, F., Larzul, C., Laville, E., Meish, F., Milenkovic, D., Tobin, J., Charlier, C., Georges, M. Nat. Genet. (2006) [Pubmed]
  14. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Morahan, G., Huang, D., Ymer, S.I., Cancilla, M.R., Stephen, K., Dabadghao, P., Werther, G., Tait, B.D., Harrison, L.C., Colman, P.G. Nat. Genet. (2001) [Pubmed]
  15. Human urotensin II as a link between hypertension and coronary artery disease. Watanabe, T., Kanome, T., Miyazaki, A., Katagiri, T. Hypertens. Res. (2006) [Pubmed]
  16. De novo myotonic dystrophy mutation in a Nigerian kindred. Krahe, R., Eckhart, M., Ogunniyi, A.O., Osuntokun, B.O., Siciliano, M.J., Ashizawa, T. Am. J. Hum. Genet. (1995) [Pubmed]
  17. 5' UTR of hepatitis A virus RNA: mutations in the 5'-most pyrimidine-rich tract reduce its ability to direct internal initiation of translation. Silveira Carneiro, J., Equestre, M., Pagnotti, P., Gradi, A., Sonenberg, N., Perez Bercoff, R. J. Gen. Virol. (1995) [Pubmed]
  18. Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Torres, E., Vaquero, C., Nicholson, L., Sack, M., Stöger, E., Drossard, J., Christou, P., Fischer, R., Perrin, Y. Transgenic Res. (1999) [Pubmed]
  19. Internal jugular vein thrombosis following in-vitro fertilization in a woman with protein S deficiency and heterozygosity for the prothrombin 3' UTR mutation, despite anticoagulation with heparin. Thomas, R.V., Reid, W., Perry, D.J. Blood Coagul. Fibrinolysis (2001) [Pubmed]
  20. Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerance. Ong, K.L., Wong, L.Y., Man, Y.B., Leung, R.Y., Song, Y.Q., Lam, K.S., Cheung, B.M. Peptides (2006) [Pubmed]
  21. Recent structure-activity studies of the peptide hormone urotensin-II, a potent vasoconstrictor. Grieco, P., Rovero, P., Novellino, E. Current medicinal chemistry. (2004) [Pubmed]
  22. Urotensin-II receptor antagonists. Carotenuto, A., Grieco, P., Rovero, P., Novellino, E. Current medicinal chemistry. (2006) [Pubmed]
  23. Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues. Matsushita, M., Shichiri, M., Imai, T., Iwashina, M., Tanaka, H., Takasu, N., Hirata, Y. J. Hypertens. (2001) [Pubmed]
  24. Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14. Liu, Q., Pong, S.S., Zeng, Z., Zhang, Q., Howard, A.D., Williams, D.L., Davidoff, M., Wang, R., Austin, C.P., McDonald, T.P., Bai, C., George, S.R., Evans, J.F., Caskey, C.T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  25. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Ames, R.S., Sarau, H.M., Chambers, J.K., Willette, R.N., Aiyar, N.V., Romanic, A.M., Louden, C.S., Foley, J.J., Sauermelch, C.F., Coatney, R.W., Ao, Z., Disa, J., Holmes, S.D., Stadel, J.M., Martin, J.D., Liu, W.S., Glover, G.I., Wilson, S., McNulty, D.E., Ellis, C.E., Elshourbagy, N.A., Shabon, U., Trill, J.J., Hay, D.W., Ohlstein, E.H., Bergsma, D.J., Douglas, S.A. Nature (1999) [Pubmed]
  26. Discovery of the first nonpeptide agonist of the GPR14/urotensin-II receptor: 3-(4-chlorophenyl)-3-(2- (dimethylamino)ethyl)isochroman-1-one (AC-7954). Croston, G.E., Olsson, R., Currier, E.A., Burstein, E.S., Weiner, D., Nash, N., Severance, D., Allenmark, S.G., Thunberg, L., Ma, J.N., Mohell, N., O'Dowd, B., Brann, M.R., Hacksell, U. J. Med. Chem. (2002) [Pubmed]
  27. Cell and tissue responses of a range of Urotensin II analogs at cloned and native urotensin II receptors. Evidence for coupling promiscuity. Song, W., McDonald, J., Camarda, V., Calo, G., Guerrini, R., Marzola, E., Thompson, J.P., Rowbotham, D.J., Lambert, D.G. Naunyn Schmiedebergs Arch. Pharmacol. (2006) [Pubmed]
  28. Differential agonistic and antagonistic effects of the urotensin-II ligand SB-710411 at rodent and primate UT receptors. Behm, D.J., Herold, C.L., Camarda, V., Aiyar, N.V., Douglas, S.A. Eur. J. Pharmacol. (2004) [Pubmed]
  29. Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors. Marchese, A., Heiber, M., Nguyen, T., Heng, H.H., Saldivia, V.R., Cheng, R., Murphy, P.M., Tsui, L.C., Shi, X., Gregor, P. Genomics (1995) [Pubmed]
  30. Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy. Langham, R.G., Kelly, D.J., Gow, R.M., Zhang, Y., Dowling, J.K., Thomson, N.M., Gilbert, R.E. Am. J. Kidney Dis. (2004) [Pubmed]
  31. Urotensin II is an autocrine/paracrine growth factor for the porcine renal epithelial cell line, LLCPK1. Matsushita, M., Shichiri, M., Fukai, N., Ozawa, N., Yoshimoto, T., Takasu, N., Hirata, Y. Endocrinology (2003) [Pubmed]
  32. A new ligand for the urotensin II receptor. Camarda, V., Guerrini, R., Kostenis, E., Rizzi, A., Calò, G., Hattenberger, A., Zucchini, M., Salvadori, S., Regoli, D. Br. J. Pharmacol. (2002) [Pubmed]
  33. Urotensin-II blockade with SB-611812 attenuates cardiac dysfunction in a rat model of coronary artery ligation. Bousette, N., Hu, F., Ohlstein, E.H., Dhanak, D., Douglas, S.A., Giaid, A. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  34. Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-protein-coupled receptors from the mouse and monkey. Elshourbagy, N.A., Douglas, S.A., Shabon, U., Harrison, S., Duddy, G., Sechler, J.L., Ao, Z., Maleeff, B.E., Naselsky, D., Disa, J., Aiyar, N.V. Br. J. Pharmacol. (2002) [Pubmed]
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