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NMU1 receptor

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Target not currently curated in GtoImmuPdb

Target id: 298

Nomenclature: NMU1 receptor

Family: Neuromedin U receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 426 2q37.1 NMUR1 neuromedin U receptor 1 3,30,38
Mouse 7 428 1 C5 Nmur1 neuromedin U receptor 1 38
Rat 7 425 9q35 Nmur1 neuromedin U receptor 1 13
Gene and Protein Information Comments
For human NMU1, sequences encoding both 403 and 426 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 [3].
Previous and Unofficial Names Click here for help
GPR66 [12,18,32] | FM-3 [12-13,32-33,38] | NmU-R1 [32] | SNORF62 [30]
Database Links Click here for help
Specialist databases
GPCRdb nmur1_human (Hs), nmur1_mouse (Mm)
Other databases
Alphafold Q9HB89 (Hs), O55040 (Mm), Q9JJI5 (Rn)
ChEMBL Target CHEMBL1075178 (Hs), CHEMBL3351216 (Mm)
Ensembl Gene ENSG00000171596 (Hs), ENSMUSG00000026237 (Mm), ENSRNOG00000018521 (Rn)
Entrez Gene 10316 (Hs), 14767 (Mm), 65276 (Rn)
Human Protein Atlas ENSG00000171596 (Hs)
KEGG Gene hsa:10316 (Hs), mmu:14767 (Mm), rno:65276 (Rn)
OMIM 604153 (Hs)
Pharos Q9HB89 (Hs)
RefSeq Nucleotide NM_006056 (Hs), NM_010341 (Mm), NM_023100 (Rn)
RefSeq Protein NP_006047 (Hs), NP_034471 (Mm), NP_075588 (Rn)
UniProtKB Q9HB89 (Hs), O55040 (Mm), Q9JJI5 (Rn)
Wikipedia NMUR1 (Hs)
Natural/Endogenous Ligands Click here for help
neuromedin S-33 {Sp: Human}
neuromedin S-36 {Sp: Mouse} , neuromedin S-36 {Sp: Rat}
neuromedin U-25 {Sp: Human}
neuromedin U-23 {Sp: Mouse} , neuromedin U-23 {Sp: Rat}

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]neuromedin U-25 (human) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist 9.9 – 10.1 pKd 1,4
⤷ pKd 9.9 – 10.1 [1,4]
[125I]neuromedin U-23 (rat) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist 9.1 – 9.5 pKd 13,30
⤷ pKd 9.1 – 9.5 [13,30]
[125I]neuromedin U-8 (pig) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist 8.6 pKd 30
⤷ pKd 8.6 [30]
neuromedin U-23 {Sp: Rat} Peptide Click here for species-specific activity table Hs Agonist 10.1 pKi 1
⤷ pKi 10.1 [1]
neuromedin U-25 {Sp: Pig} Peptide Click here for species-specific activity table Hs Agonist 9.6 pKi 1
⤷ pKi 9.6 [1]
neuromedin U-25 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 9.5 pKi 1
⤷ pKi 9.5 [1]
neuromedin U-8 {Sp: Pig} Peptide Click here for species-specific activity table Hs Agonist 8.8 pKi 1
⤷ pKi 8.8 [1]
neuromedin U-8 {Sp: Dog} Peptide Click here for species-specific activity table Hs Agonist 8.5 pKi 1
⤷ pKi 8.5 [1]
neuromedin S-33 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 10.2 pEC50 24
⤷ pEC50 10.2 [24]
compound 5d [PMID: 25815150] Peptide Hs Full agonist 10.1 pEC50 35
⤷ pEC50 10.1 (EC50 8.3x10-11 M) [35]
CPN-267 Peptide Primary target of this compound Hs Agonist 9.6 pEC50 37
⤷ pEC50 9.6 (EC50 2.5x10-10 M) [37]
neuromedin U-8 {Sp: Pig} Peptide Click here for species-specific activity table Hs Full agonist 9.0 – 10.0 pEC50 1,13,30
⤷ pEC50 9.0 – 10.0 [1,13,30]
neuromedin U-23 {Sp: Rat} Peptide Click here for species-specific activity table Hs Full agonist 8.7 – 9.1 pEC50 1,13,30
⤷ pEC50 8.7 – 9.1 [1,13,30]
neuromedin U-25 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.4 – 9.4 pEC50 1,4,13,30
⤷ pEC50 8.4 – 9.4 [1,4,13,30]
HAS-NMU Peptide Click here for species-specific activity table Hs Full agonist 8.5 – 9.0 pEC50 28
⤷ pEC50 8.5 – 9.0 [28]
neuromedin U-25 {Sp: Pig} Peptide Click here for species-specific activity table Hs Full agonist 8.3 – 8.9 pEC50 1,13,30
⤷ pEC50 8.3 – 8.9 [1,13,30]
compound 8d [PMID: 24999562] Peptide Hs Full agonist 8.0 – 9.0 pEC50 36
⤷ pEC50 8.0 – 9.0 [36]
CPN-223 Peptide Hs Partial agonist 8.5 pEC50 34
⤷ pEC50 8.5 (EC50 3.2x10-9 M) [34]
PEG40-NMU Peptide Click here for species-specific activity table Hs Full agonist 7.0 – 8.0 pEC50 15
⤷ pEC50 7.0 – 8.0 [15]
NM4-C16 Peptide Click here for species-specific activity table Hs Full agonist 6.3 pEC50 20
⤷ pEC50 6.3 [20]
neuromedin S-33 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 10.0 pIC50 24
⤷ pIC50 10.0 [24]
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 NMU1 selectivity [35-37] (see General Introduction).
Primary Transduction Mechanisms Click here for help
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 [1,4,6,41].
References:  1,4,6,30,33,41
Tissue Distribution Click here for help
Significant levels in adipose tissue, duodenum, jejunum, small intestine, adrenal cortex, bone marrow and testis. Moderate amounts found in spleen, stomach, lung, trachea, mammary gland, kidney, pancreas, prostate, uterus, heart and placenta. Transcripts also observed in considerable levels in human ileum smooth muscle, caecum, gallbladder, long saphenous vein and all colon segments. In the cardiovascular system, mRNA and protein are mainly in the left ventricle, coronary artery and saphenous vein.
Species:  Human
Technique:  Northern blot, quantitative PCR, in situ hybridization, Western blot.
References:  11-13,16,22,30,33
A similar pattern to that of human.
Expression in thymus, peripheral blood leukocytes (particularly B and T cells), lung, stomach, spleen, mesenteric lymphnodes, peyer's patches, spinal cord.
Some have failed to show NMUR1 expression in human and mouse brains, others have shown low levels with widespread expression. Highest levels in the cerebellum, dorsal root ganglion, hippocampus and spinal cord (levels 5-25 fold less than in periphery).
Species:  Mouse
Technique:  Northern blots, quantitative PCR, in situ hybridization
References:  8,12-13,30,33
A similar pattern to that of human.
Highest levels of mRNA in duodenum, jejunum, ileum, lung and spleen; moderate levels in femur, caecum, colon and rectum. Transcripts and protein in the medullary and cortical areas of adrenal gland. mRNA and protein in pancreatic islets.
Expressed in approximately 25% of small/medium diameter neurones within the dorsal root ganglia.
Species:  Rat
Technique:  Northern blot, quantitative PCR, in situ hybridization, Western blot.
References:  9,11,14,17,31,39-40,42
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Cells transfected with NMU1.
Species:  Mouse
Tissue:  HEK-293 cells.
Response measured:  Increase in intracellular calcium.
References:  10
Cells transfected with NMU1.
Species:  Human
Tissue:  CHO, HEK-293 and COS-7 cells.
Response measured:  Increase in intracellular calcium, inositol phosphate generation, inhibition of forskolin-stimulated cAMP generation, ERK activation, G-protein activation.
References:  1,4,9,12-13,18,30,33
Physiological Functions Comments
Evidence exists across species for involvement of NMU1 in a range of physiological aspects including:
  • Contraction: human ileum and urinary bladder [19], gall bladder, ascending colon and long saphenous vein [16], coronary artery, mammary artery and saphenous vein [22], rat uterus smooth muscle [21], rat stomach-fundus [2], lower esophageal sphincter and ileum [29], colon [5], mouse gall bladder, stomach-fundus, uterus, lower esophageal sphincter [29] and forestomach [7].
  • Stress response [31,39,42].
  • Inhibition of gastric acid secretion and gastric emptying [23].
  • Inflammatory and immunological responses [25-27].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Nmur1tm1Lex Nmur1tm1Lex/Nmur1tm1Lex
Not Specified		 MGI:1341898  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 16474416 
Nmur1tm1Rtor|Nmur2tm1Rtor Nmur1tm1Rtor/Nmur1tm1Rtor,Nmur2tm1Rtor/Nmur2tm1Rtor
involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6NCr * C57BL/6NTac		 MGI:1341898  MGI:2441765  MP:0001973 increased thermal nociceptive threshold PMID: 17379411 
Nmur1tm1Sjab Nmur1tm1Sjab/Nmur1tm1Sjab
involves: 129P2/OlaHsd * C57BL/6		 MGI:1341898  MP:0002169 no abnormal phenotype detected PMID: 19070594 

References

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1. Aiyar N, Disa J, Foley JJ, Buckley PT, Wixted WE, Pullen M, Shabon U, Dul E, Szekeres PG, Elshourbagy NA et al.. (2004) Radioligand binding and functional characterization of recombinant human NmU1 and NmU2 receptors stably expressed in clonal human embryonic kidney-293 cells. Pharmacology, 72 (1): 33-41. [PMID:15292653]

2. Benito-Orfila MA, Domin J, Nandha KA, Bloom SR. (1991) The motor effect of neuromedin U on rat stomach in vitro. Eur J Pharmacol, 193 (3): 329-33. [PMID:2055247]

3. 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]

4. Brighton PJ, Szekeres PG, Wise A, Willars GB. (2004) Signaling and ligand binding by recombinant neuromedin U receptors: evidence for dual coupling to Galphaq/11 and Galphai and an irreversible ligand-receptor interaction. Mol Pharmacol, 66 (6): 1544-56. [PMID:15331768]

5. Brighton PJ, Wise A, Dass NB, Willars GB. (2008) Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue. J Pharmacol Exp Ther, 325 (1): 154-64. [PMID:18180374]

6. Chen RX, Liu F, Li Y, Liu GA. (2012) Neuromedin S increases L-type Ca(2+) channel currents through G(i)α-protein and phospholipase C-dependent novel protein kinase C delta pathway in adult rat ventricular myocytes. Cell Physiol Biochem, 30 (3): 618-30. [PMID:22832358]

7. Dass NB, Bassil AK, North-Laidler VJ, Morrow R, Aziz E, Tuladhar BR, Sanger GJ. (2007) Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation. Br J Pharmacol, 150 (4): 502-8. [PMID:17211455]

8. Domin J, Al-Madani AM, Desperbasques M, Bishop AE, Polak JM, Bloom SR. (1990) Neuromedin U-like immunoreactivity in the thyroid gland of the rat. Cell Tissue Res, 260 (1): 131-5. [PMID:2340578]

9. Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Habata Y, Hinuma S, Onda H, Nishimura O, Fujino M. (2000) Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3. J Biol Chem, 275 (28): 21068-74. [PMID:10783389]

10. Funes S, Hedrick JA, Yang S, Shan L, Bayne M, Monsma Jr FJ, Gustafson EL. (2002) Cloning and characterization of murine neuromedin U receptors. Peptides, 23 (9): 1607-15. [PMID:12217421]

11. Gartlon J, Szekeres P, Pullen M, Sarau HM, Aiyar N, Shabon U, Michalovich D, Steplewski K, Ellis C, Elshourbagy N et al.. (2004) Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats. Psychopharmacology (Berl.), 177 (1-2): 1-14. [PMID:15205870]

12. Hedrick JA, Morse K, Shan L, Qiao X, Pang L, Wang S, Laz T, Gustafson EL, Bayne M, Monsma FJ Jr. (2000) Identification of a human gastrointestinal tract and immune system receptor for the peptide neuromedin U. Mol Pharmacol, 58: 870-875. [PMID:10999960]

13. 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]

14. 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]

15. 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]

16. Jones NA, Morton MF, Prendergast CE, Powell GL, Shankley NP, Hollingsworth SJ. (2006) Neuromedin U stimulates contraction of human long saphenous vein and gastrointestinal smooth muscle in vitro. Regul Pept, 136 (1-3): 109-16. [PMID:16782214]

17. Kaczmarek P, Malendowicz LK, Pruszynska-Oszmalek E, Wojciechowicz T, Szczepankiewicz D, Szkudelski T, Nowak KW. (2006) Neuromedin U receptor 1 expression in the rat endocrine pancreas and evidence suggesting neuromedin U suppressive effect on insulin secretion from isolated rat pancreatic islets. Int J Mol Med, 18 (5): 951-5. [PMID:17016626]

18. 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]

19. Maggi CA, Patacchini R, Giuliani S, Turini D, Barbanti G, Rovero P, Meli A. (1990) Motor response of the human isolated small intestine and urinary bladder to porcine neuromedin U-8. Br J Pharmacol, 99 (1): 186-8. [PMID:2331570]

20. Micewicz ED, Bahattab OS, Willars GB, Waring AJ, Navab M, Whitelegge JP, McBride WH, Ruchala P. (2015) Small lipidated anti-obesity compounds derived from neuromedin U. Eur J Med Chem, 101: 616-26. [PMID:26204509]

21. Minamino N, Kangawa K, Matsuo H. (1985) Neuromedin U-8 and U-25: novel uterus stimulating and hypertensive peptides identified in porcine spinal cord. Biochem Biophys Res Commun, 130 (3): 1078-85. [PMID:3839674]

22. Mitchell JD, Maguire JJ, Kuc RE, Davenport AP. (2009) Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system. Cardiovasc Res, 81 (2): 353-61. [PMID:18987052]

23. Mondal MS, Date Y, Murakami N, Toshinai K, Shimbara T, Kangawa K, Nakazato M. (2003) Neuromedin U acts in the central nervous system to inhibit gastric acid secretion via CRH system. Am J Physiol Gastrointest Liver Physiol, 284 (6): G963-9. [PMID:12584108]

24. Mori K, Miyazato M, Ida T, Murakami N, Serino R, Ueta Y, Kojima M, Kangawa K. (2005) Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. EMBO J, 24 (2): 325-35. [PMID:15635449]

25. Moriyama M, Fukuyama S, Inoue H, Matsumoto T, Sato T, Tanaka K, Kinjyo I, Kano T, Yoshimura A, Kojima M. (2006) The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia. Am J Physiol Lung Cell Mol Physiol, 290 (5): L971-7. [PMID:16373672]

26. Moriyama M, Matsukawa A, Kudoh S, Takahashi T, Sato T, Kano T, Yoshimura A, Kojima M. (2006) The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock. Biochem Biophys Res Commun, 341 (4): 1149-54. [PMID:16466693]

27. Moriyama M, Sato T, Inoue H, Fukuyama S, Teranishi H, Kangawa K, Kano T, Yoshimura A, Kojima M. (2005) The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. J Exp Med, 202 (2): 217-24. [PMID:16009716]

28. Neuner P, Peier AM, Talamo F, Ingallinella P, Lahm A, Barbato G, Di Marco A, Desai K, Zytko K, Qian Y et al.. (2014) Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide. J Pept Sci, 20 (1): 7-19. [PMID:24222478]

29. Prendergast CE, Morton MF, Figueroa KW, Wu X, Shankley NP. (2006) Species-dependent smooth muscle contraction to Neuromedin U and determination of the receptor subtypes mediating contraction using NMU1 receptor knockout mice. Br J Pharmacol, 147 (8): 886-96. [PMID:16474416]

30. 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]

31. Rucinski M, Ziolkowska A, Neri G, Trejter M, Zemleduch T, Tyczewska M, Nussdorfer GG, Malendowicz LK. (2007) Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat. Int J Mol Med, 20 (2): 255-9. [PMID:17611645]

32. Shan L, Qiao X, Crona JH, Behan J, Wang S, Laz T, Bayne M, Gustafson EL, Monsma Jr FJ, Hedrick JA. (2000) Identification of a novel neuromedin U receptor subtype expressed in the central nervous system. J Biol Chem, 275 (50): 39482-6. [PMID:11010960]

33. Szekeres PG, Muir AI, Spinage LD, Miller JE, Butler SI, Smith A, Rennie GI, Murdock PR, Fitzgerald LR, Wu Hl et al.. (2000) Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3. J Biol Chem, 275 (27): 20247-50. [PMID:10811630]

34. Takayama K, Mori K, Asari T, Sohma Y, Nomura E, Sasaki Y, Taguchi A, Taniguchi A, Miyazato M, Minamino N et al.. (2020) Design and synthesis of peptidic partial agonists of human neuromedin U receptor 1 with enhanced serum stability. Bioorg Med Chem Lett, 30 (18): 127436. [PMID:32721452]

35. Takayama K, Mori K, Sohma Y, Taketa K, Taguchi A, Yakushiji F, Minamino N, Miyazato M, Kangawa K, Hayashi Y. (2015) Discovery of potent hexapeptide agonists to human neuromedin u receptor 1 and identification of their serum metabolites. ACS Med Chem Lett, 6 (3): 302-7. [PMID:25815150]

36. 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]

37. Takayama K, Mori K, Tanaka A, Nomura E, Sohma Y, Mori M, Taguchi A, Taniguchi A, Sakane T, Yamamoto A et al.. (2017) Discovery of a Human Neuromedin U Receptor 1-Selective Hexapeptide Agonist with Enhanced Serum Stability. J Med Chem, 60 (12): 5228-5234. [PMID:28548497]

38. Tan CP, McKee KK, Liu Q, Palyha OC, Feighner SD, Hreniuk DL, Smith RG, Howard AD. (1998) Cloning and characterization of a human and murine T-cell orphan G-protein-coupled receptor similar to the growth hormone secretagogue and neurotensin receptors. Genomics, 52 (2): 223-9. [PMID:9782091]

39. 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]

40. 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]

41. Zhang Y, Jiang D, Zhang Y, Jiang X, Wang F, Tao J. (2012) Neuromedin U type 1 receptor stimulation of A-type K+ current requires the βγ subunits of Go protein, protein kinase A, and extracellular signal-regulated kinase 1/2 (ERK1/2) in sensory neurons. J Biol Chem, 287 (22): 18562-72. [PMID:22493291]

42. Ziolkowska A, Macchi C, Trejter M, Rucinski M, Nowak M, Nussdorfer GG, Malendowicz LK. (2008) Effects of neuromedin-U on immature rat adrenocortical cells: in vitro and in vivo studies. Int J Mol Med, 21 (3): 303-7. [PMID:18288377]

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