Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Agonists
- Antagonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Phenotypes, Alleles and Disease Models
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 415 | 5q33.1 | NMUR2 | neuromedin U receptor 2 | 4,19,44,49 |
| Mouse | 7 | 395 | 11 B1.3 | Nmur2 | neuromedin U receptor 2 | 10 |
| Rat | 7 | 395 | 10q22 | Nmur2 | neuromedin U receptor 2 | 19 |
| Gene and Protein Information Comments | ||||||
| For human NMU2, sequences encoding both 412 and 415 amino acids have been reported as a consequence of the presence of two potential translation initiation sites. It is unclear which form is expressed physiologically, although there is circumstantial evidence to favour the shorter form [4]. There is evidence for the existence of receptor haplotypes [3]. |
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| Previous and Unofficial Names |
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| FM-4 [19] | FM4 [55] | SNORF72 [44] | NMU-R2 [49] | TGR-1 [18] | |
| Database Links |
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| Specialist databases | |
| GPCRDB | nmur2_human (Hs) |
| Other databases | |
| ChEMBL Target | CHEMBL1075144 (Hs), CHEMBL3351217 (Mm) |
| Ensembl Gene | ENSG00000132911 (Hs), ENSMUSG00000037393 (Mm), ENSRNOG00000014081 (Rn) |
| Entrez Gene | 56923 (Hs), 216749 (Mm), 64042 (Rn) |
| Human Protein Atlas | ENSG00000132911 (Hs) |
| KEGG Gene | hsa:56923 (Hs), mmu:216749 (Mm), rno:64042 (Rn) |
| OMIM | 605108 (Hs) |
| Pharos | Q9GZQ4 (Hs) |
| RefSeq Nucleotide | NM_020167 (Hs), NM_153079 (Mm), NM_022275 (Rn) |
| RefSeq Protein | NP_064552 (Hs), NP_694719 (Mm), NP_071611 (Rn) |
| UniProtKB | Q9GZQ4 (Hs), Q8BZ39 (Mm), Q9ESQ4 (Rn) |
| Wikipedia | NMUR2 (Hs) |
| Natural/Endogenous Ligands |
| neuromedin S-33 {Sp: Human} |
| neuromedin S-36 {Sp: Mouse} , neuromedin S-36 {Sp: Rat} |
| neuromedin U-25 {Sp: Human} |
| neuromedin U-23 {Sp: Rat} |
Download all structure-activity data for this target as a CSV file 
| Agonists | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 1) pIC50 for neuromedin S is determined against 50pM [125I-Tyr0]-neuromedin S 2) Agonism and pEC50 values are based on Ca2+ signaling by recombinant receptors expressed in cell lines. 3) Modified peptide ligands and non-peptide ligands have emerged that have high potency and improved pharmacokinetic features. These include compounds with NMU2 selectivity [30-32,47,51] (see General Introduction). NY0116 exhibits very slight NMU2 selectivity compared to NMU1, but interactions with other GPCRs cannot be excluded. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: Coupling to Gi/G0 G proteins has been identified as evidenced by inhibition of forskolin-induced cAMP accumulation [1,5,7,18,20,60]. | |
| References: 1,5,7,44,49-50,60 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions Comments | |
Evidence across species (human, rat, mouse) for involvement in a range of patho-physiological aspects including:
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| Phenotypes, Alleles and Disease Models
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References
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2. Bechtold DA, Ivanov TR, Luckman SM. (2009) Appetite-modifying actions of pro-neuromedin U-derived peptides. Am. J. Physiol. Endocrinol. Metab., 297 (2): E545-51. [PMID:19531638]
3. Bhattacharyya S, Luan J, Farooqi IS, Keogh J, Montague C, Brennand J, Jorde L, Wareham NJ, O'Rahilly S. (2004) Studies of the neuromedin U-2 receptor gene in human obesity: evidence for the existence of two ancestral forms of the receptor. J. Endocrinol., 183 (1): 115-20. [PMID:15525579]
4. Brighton PJ, Szekeres PG, Willars GB. (2004) Neuromedin U and its receptors: structure, function, and physiological roles. Pharmacol. Rev., 56 (2): 231-48. [PMID:15169928]
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18. Hosoya M, Moriya T, Kawamata Y, Ohkubo S, Fujii R, Matsui H, Shintani Y, Fukusumi S, Habata Y, Hinuma S et al.. (2000) Identification and functional characterization of a novel subtype of neuromedin U receptor. J. Biol. Chem., 275 (38): 29528-32. [PMID:10887190]
19. Howard AD, Wang R, Pong SS, Mellin TN, Strack A, Guan XM, Zeng Z, Williams Jr DL, Feighner SD, Nunes CN et al.. (2000) Identification of receptors for neuromedin U and its role in feeding. Nature, 406 (6791): 70-4. [PMID:10894543]
20. Hsu SH, Luo CW. (2007) Molecular dissection of G protein preference using Gsalpha chimeras reveals novel ligand signaling of GPCRs. Am. J. Physiol. Endocrinol. Metab., 293 (4): E1021-9. [PMID:17652154]
21. Ingallinella P, Peier AM, Pocai A, Marco AD, Desai K, Zytko K, Qian Y, Du X, Cellucci A, Monteagudo E et al.. (2012) PEGylation of Neuromedin U yields a promising candidate for the treatment of obesity and diabetes. Bioorg. Med. Chem., 20 (15): 4751-9. [PMID:22771182]
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23. Jethwa PH, Small CJ, Smith KL, Seth A, Darch SJ, Abbott CR, Murphy KG, Todd JF, Ghatei MA, Bloom SR. (2005) Neuromedin U has a physiological role in the regulation of food intake and partially mediates the effects of leptin. Am. J. Physiol. Endocrinol. Metab., 289 (2): E301-5. [PMID:16014357]
24. Jethwa PH, Smith KL, Small CJ, Abbott CR, Darch SJ, Murphy KG, Seth A, Semjonous NM, Patel SR, Todd JF et al.. (2006) Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat. Endocrinology, 147 (6): 2886-92. [PMID:16556758]
25. Kamisoyama H, Honda K, Saneyasu T, Sugahara K, Hasegawa S. (2007) Central administration of neuromedin U suppresses food intake in chicks. Neurosci. Lett., 420 (1): 1-5. [PMID:17445984]
26. Ketterer K, Kong B, Frank D, Giese NA, Bauer A, Hoheisel J, Korc M, Kleeff J, Michalski CW, Friess H. (2009) Neuromedin U is overexpressed in pancreatic cancer and increases invasiveness via the hepatocyte growth factor c-Met pathway. Cancer Lett., 277 (1): 72-81. [PMID:19118941]
27. Kojima M, Haruno R, Nakazato M, Date Y, Murakami N, Hanada R, Matsuo H, Kangawa K. (2000) Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3). Biochem. Biophys. Res. Commun., 276 (2): 435-8. [PMID:11027493]
28. Kowalski TJ, Spar BD, Markowitz L, Maguire M, Golovko A, Yang S, Farley C, Cook JA, Tetzloff G, Hoos L et al.. (2005) Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice. J. Endocrinol., 185 (1): 151-64. [PMID:15817836]
29. Liu JJ, Payza K, Huang J, Liu R, Chen T, Coupal M, Laird JM, Cao CQ, Butterworth J, Lapointe S et al.. (2009) Discovery and pharmacological characterization of a small-molecule antagonist at neuromedin U receptor NMUR2. J. Pharmacol. Exp. Ther., 330 (1): 268-75. [PMID:19369576]
30. Ma ML, Li M, Gou JJ, Ruan TY, Jin HS, Zhang LH, Wu LC, Li XY, Hu YH, Wen K et al.. (2014) Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor. Bioorg. Med. Chem., 22 (21): 6117-23. [PMID:25262941]
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32. Meng T, Su HR, Binkert C, Fischli W, Zhou L, Shen JK, Wang MW. (2008) Identification of non-peptidic neuromedin U receptor modulators by a robust homogeneous screening assay. Acta Pharmacol. Sin., 29 (4): 517-27. [PMID:18358099]
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36. Nakahara K, Kojima M, Hanada R, Egi Y, Ida T, Miyazato M, Kangawa K, Murakami N. (2004) Neuromedin U is involved in nociceptive reflexes and adaptation to environmental stimuli in mice. Biochem. Biophys. Res. Commun., 323 (2): 615-20. [PMID:15369794]
37. Nakazato M, Hanada R, Murakami N, Date Y, Mondal MS, Kojima M, Yoshimatsu H, Kangawa K, Matsukura S. (2000) Central effects of neuromedin U in the regulation of energy homeostasis. Biochem. Biophys. Res. Commun., 277 (1): 191-4. [PMID:11027662]
38. Nandha KA, Benito-Orfila MA, Jamal H, Akinsanya KO, Bloom SR, Smith DM. (1999) Effect of steroids and the estrous cycle on uterine neuromedin U receptor expression. Peptides, 20 (10): 1203-9. [PMID:10573292]
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43. Quan H, Funabashi T, Furuta M, Kimura F. (2003) Effects of neuromedin U on the pulsatile LH secretion in ovariectomized rats in association with feeding conditions. Biochem. Biophys. Res. Commun., 311 (3): 721-7. [PMID:14623332]
44. Raddatz R, Wilson AE, Artymyshyn R, Bonini JA, Borowsky B, Boteju LW, Zhou S, Kouranova EV, Nagorny R, Guevarra MS et al.. (2000) Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. J. Biol. Chem., 275 (42): 32452-9. [PMID:10899166]
45. Rucinski M, Ziolkowska A, Tyczewska M, Szyszka M, Malendowicz LK. (2008) Neuromedin U directly stimulates growth of cultured rat calvarial osteoblast-like cells acting via the NMU receptor 2 isoform. Int. J. Mol. Med., 22 (3): 363-8. [PMID:18698496]
46. Sakamoto T, Mori K, Miyazato M, Kangawa K, Sameshima H, Nakahara K, Murakami N. (2008) Involvement of neuromedin S in the oxytocin release response to suckling stimulus. Biochem. Biophys. Res. Commun., 375 (1): 49-53. [PMID:18675786]
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51. Takayama K, Mori K, Taketa K, Taguchi A, Yakushiji F, Minamino N, Miyazato M, Kangawa K, Hayashi Y. (2014) Discovery of selective hexapeptide agonists to human neuromedin u receptors types 1 and 2. J. Med. Chem., 57 (15): 6583-93. [PMID:24999562]
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53. Torres R, Croll SD, Vercollone J, Reinhardt J, Griffiths J, Zabski S, Anderson KD, Adams NC, Gowen L, Sleeman MW et al.. (2007) Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses. Pain, 130 (3): 267-78. [PMID:17379411]
54. Trejter M, Neri G, Rucinski M, Majchrzak M, Nussdorfer GG, Malendowicz LK. (2008) Neuromedin-U stimulates enucleation-induced adrenocortical regeneration in the rat. Int. J. Mol. Med., 21 (6): 683-7. [PMID:18506360]
55. Vigo E, Roa J, López M, Castellano JM, Fernandez-Fernandez R, Navarro VM, Pineda R, Aguilar E, Diéguez C, Pinilla L et al.. (2007) Neuromedin s as novel putative regulator of luteinizing hormone secretion. Endocrinology, 148 (2): 813-23. [PMID:17110433]
56. Wren AM, Small CJ, Abbott CR, Jethwa PH, Kennedy AR, Murphy KG, Stanley SA, Zollner AN, Ghatei MA, Bloom SR. (2002) Hypothalamic actions of neuromedin U. Endocrinology, 143 (11): 4227-34. [PMID:12399416]
57. Yang G, Su J, Yao Y, Lei Z, Zhang G, Li X. (2010) The regulatory mechanism of neuromedin S on luteinizing hormone in pigs. Anim. Reprod. Sci., 122 (3-4): 367-74. [PMID:21071159]
58. Yu XH, Cao CQ, Mennicken F, Puma C, Dray A, O'Donnell D, Ahmad S, Perkins M. (2003) Pro-nociceptive effects of neuromedin U in rat. Neuroscience, 120 (2): 467-74. [PMID:12890516]
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