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Gene Review

NMUR1  -  neuromedin U receptor 1

Homo sapiens

Synonyms: (FM-3), FM-3, FM3, G-protein coupled receptor 66, G-protein coupled receptor FM-3, ...
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Disease relevance of NMUR1


Psychiatry related information on NMUR1

  • 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 NMUR1

  • 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 NMUR1


Biological context of NMUR1


Anatomical context of NMUR1


Associations of NMUR1 with chemical compounds

  • Neuromedin U induced specific and evident elevation of extracellular acidification rates, arachidonic acid metabolite release, and intracellular Ca(2+) mobilization in Chinese hamster ovary cells expressing human FM-3 [19].
  • In adult females, hypothalamic expression of NMS (which was confined to suprachiasmatic nucleus) and NMU2R significantly varied during the estrous cycle (maximum at proestrus) and was lowered after ovariectomy and enhanced after progesterone supplementation [26].
  • 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 [27].
  • 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) [28].
  • 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 [29].

Physical interactions of NMUR1

  • NMU binds to GPR66-expressing cells with high specificity to induce intracellular calcium mobilization [30].

Regulatory relationships of NMUR1


Other interactions of NMUR1


Analytical, diagnostic and therapeutic context of NMUR1

  • 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 [33].
  • 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 [34].
  • Techniques: GPCR assembly, pharmacology and screening by flow cytometry [35].
  • Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues [36].
  • In the present study we demonstrate the formation of an agonist-induced multimeric complex containing a GPCR, betaarrestin 2, and the beta2-adaptin subunit of AP-2. beta2-Adaptin binds betaarrestin 2 in a yeast two-hybrid assay and coimmunoprecipitates with betaarrestins and beta2AR in an agonist-dependent manner in HEK-293 cells [37].


  1. Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias. Shetzline, S.E., Rallapalli, R., Dowd, K.J., Zou, S., Nakata, Y., Swider, C.R., Kalota, A., Choi, J.K., Gewirtz, A.M. Blood (2004) [Pubmed]
  2. 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]
  3. A central role of EGF receptor transactivation in angiotensin II -induced cardiac hypertrophy. Shah, B.H., Catt, K.J. Trends Pharmacol. Sci. (2003) [Pubmed]
  4. 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]
  5. 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]
  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. The neuromedin u-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Takahashi, K., Furukawa, C., Takano, A., Ishikawa, N., Kato, T., Hayama, S., Suzuki, C., Yasui, W., Inai, K., Sone, S., Ito, T., Nishimura, H., Tsuchiya, E., Nakamura, Y., Daigo, Y. Cancer Res. (2006) [Pubmed]
  18. Post-translational proteolytic processing of the calcium-independent receptor of alpha-latrotoxin (CIRL), a natural chimera of the cell adhesion protein and the G protein-coupled receptor. Role of the G protein-coupled receptor proteolysis site (GPS) motif. Krasnoperov, V., Lu, Y., Buryanovsky, L., Neubert, T.A., Ichtchenko, K., Petrenko, A.G. J. Biol. Chem. (2002) [Pubmed]
  19. Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3. Fujii, R., Hosoya, M., Fukusumi, S., Kawamata, Y., Habata, Y., Hinuma, S., Onda, H., Nishimura, O., Fujino, M. J. Biol. Chem. (2000) [Pubmed]
  20. The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia. Moriyama, M., Fukuyama, S., Inoue, H., Matsumoto, T., Sato, T., Tanaka, K., Kinjyo, I., Kano, T., Yoshimura, A., Kojima, M. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  21. Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats. Gartlon, J., Szekeres, P., Pullen, M., Sarau, H.M., Aiyar, N., Shabon, U., Michalovich, D., Steplewski, K., Ellis, C., Elshourbagy, N., Duxon, M., Ashmeade, T.E., Harrison, D.C., Murdock, P., Wilson, S., Ennaceur, A., Atkins, A., Heidbreder, C., Hagan, J.J., Hunter, A.J., Jones, D.N. Psychopharmacology (Berl.) (2004) [Pubmed]
  22. Neuromedin U stimulates contraction of human long saphenous vein and gastrointestinal smooth muscle in vitro. Jones, N.A., Morton, M.F., Prendergast, C.E., Powell, G.L., Shankley, N.P., Hollingsworth, S.J. Regul. Pept. (2006) [Pubmed]
  23. Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3. Szekeres, P.G., Muir, A.I., Spinage, L.D., Miller, J.E., Butler, S.I., Smith, A., Rennie, G.I., Murdock, P.R., Fitzgerald, L.R., Wu, H., McMillan, L.J., Guerrera, S., Vawter, L., Elshourbagy, N.A., Mooney, J.L., Bergsma, D.J., Wilson, S., Chambers, J.K. J. Biol. Chem. (2000) [Pubmed]
  24. Regulation of gonadotropin secretion and puberty onset by neuromedin U. Fukue, Y., Sato, T., Teranishi, H., Hanada, R., Takahashi, T., Nakashima, Y., Kojima, M. FEBS Lett. (2006) [Pubmed]
  25. Identification of a novel neuromedin U receptor subtype expressed in the central nervous system. Shan, L., Qiao, X., Crona, J.H., Behan, J., Wang, S., Laz, T., Bayne, M., Gustafson, E.L., Monsma, F.J., Hedrick, J.A. J. Biol. Chem. (2000) [Pubmed]
  26. Neuromedin s as novel putative regulator of luteinizing hormone secretion. Vigo, E., Roa, J., López, M., Castellano, J.M., Fernandez-Fernandez, R., Navarro, V.M., Pineda, R., Aguilar, E., Diéguez, C., Pinilla, L., Tena-Sempere, M. Endocrinology (2007) [Pubmed]
  27. 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]
  28. 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]
  29. Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Luttrell, L.M., Daaka, Y., Lefkowitz, R.J. Curr. Opin. Cell Biol. (1999) [Pubmed]
  30. Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3). Kojima, M., Haruno, R., Nakazato, M., Date, Y., Murakami, N., Hanada, R., Matsuo, H., Kangawa, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  31. Identification and functional characterization of a novel subtype of neuromedin U receptor. Hosoya, M., Moriya, T., Kawamata, Y., Ohkubo, S., Fujii, R., Matsui, H., Shintani, Y., Fukusumi, S., Habata, Y., Hinuma, S., Onda, H., Nishimura, O., Fujino, M. J. Biol. Chem. (2000) [Pubmed]
  32. Multiple alternative splicing forms of human RAD17 and their differential response to ionizing radiation. Chen, M.S., Higashikubo, R., Laszlo, A., Roti Roti, J. Gene (2001) [Pubmed]
  33. G protein-coupled receptors: functional and mechanistic insights through altered gene expression. Rohrer, D.K., Kobilka, B.K. Physiol. Rev. (1998) [Pubmed]
  34. 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]
  35. 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]
  36. 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]
  37. The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Laporte, S.A., Oakley, R.H., Zhang, J., Holt, J.A., Ferguson, S.S., Caron, M.G., Barak, L.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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