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Not curated in GtoImmuPdb
Target id: 284
Nomenclature: MC3 receptor
Family: Melanocortin receptors
Annotation status:
Annotated and reviewed, awaiting update
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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 | 323 | 20q13.2 | MC3R | melanocortin 3 receptor | 9,28 |
Mouse | 7 | 323 | 2 94.8 cM | Mc3r | melanocortin 3 receptor | 8 |
Rat | 7 | 323 | 3q42 | Mc3r | melanocortin 3 receptor | 7,24 |
Previous and Unofficial Names ![]() |
γ-MSH receptor | melanocortin receptor 3 |
Database Links ![]() |
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Specialist databases | |
GPCRdb | mc3r_mouse (Mm), mc3r_rat (Rn) |
Other databases | |
Alphafold | P41968 (Hs), P33033 (Mm), P32244 (Rn) |
ChEMBL Target | CHEMBL4644 (Hs), CHEMBL4774 (Mm), CHEMBL4023 (Rn) |
Ensembl Gene | ENSG00000124089 (Hs), ENSMUSG00000038537 (Mm), ENSRNOG00000004451 (Rn) |
Entrez Gene | 4159 (Hs), 17201 (Mm), 29310 (Rn) |
Human Protein Atlas | ENSG00000124089 (Hs) |
KEGG Gene | hsa:4159 (Hs), mmu:17201 (Mm), rno:29310 (Rn) |
OMIM | 155540 (Hs) |
Orphanet | ORPHA220900 (Hs) |
Pharos | P41968 (Hs) |
RefSeq Nucleotide | NM_019888 (Hs), NM_008561 (Mm), NM_001025270 (Rn) |
RefSeq Protein | NP_063941 (Hs), NP_032587 (Mm), NP_001020441 (Rn) |
UniProtKB | P41968 (Hs), P33033 (Mm), P32244 (Rn) |
Wikipedia | MC3R (Hs) |
Associated Proteins ![]() |
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Natural/Endogenous Ligands ![]() |
ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat} |
agouti {Sp: Mouse} |
agouti-related protein {Sp: Human} |
β-MSH {Sp: Human} |
α-MSH {Sp: Human, Mouse, Rat} |
γ-MSH {Sp: Human, Mouse, Rat} |
β-MSH {Sp: Mouse} , β-MSH {Sp: Rat} |
Comments: γ-MSH is the principal endogenous agonist. Endogenous antagonists are agouti and agouti-related protein. For representations of the rodent orthologues of these peptides see agouti (mouse), agouti (rat) and agouti-related protein (mouse). |
Potency order of endogenous agonists (Human) |
γ-MSH (POMC, P01189), β-MSH (POMC, P01189) > ACTH (POMC, P01189), α-MSH (POMC, P01189) |
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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Commonly used radioligands include [125I]NDP-MSH and [125I]AGRP(86-132). |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific antagonist tables |
Primary Transduction Mechanisms ![]() |
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Transducer | Effector/Response |
Gs family | Adenylyl cyclase stimulation |
References: 9 |
Secondary Transduction Mechanisms ![]() |
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Transducer | Effector/Response |
G protein (identity unknown) | Other - See Comments |
Comments: Melanocortin activation of the MC3 mobilizes intracellular calcium via an incompletely understood pathway(s). | |
References: 20,29 |
Tissue Distribution ![]() |
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Expression Datasets ![]() |
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Functional Assays ![]() |
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Physiological Functions ![]() |
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Physiological Consequences of Altering Gene Expression ![]() |
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Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology ![]() |
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1. Adan RA, Szklarczyk AW, Oosterom J, Brakkee JH, Nijenhuis WA, Schaaper WM, Meloen RH, Gispen WH. (1999) Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat. Eur J Pharmacol, 378: 249-258. [PMID:10493100]
2. Boman A, Jonassen TEN, Lundstedt T. (2007) Phenyl pyrrole aminoguanidine derivatives. Patent number: WO2007141343A1. Assignee: Action Pharma A/S. Priority date: 09/06/2006. Publication date: 13/12/2007.
3. Butler AA, Kesterson RA, Khong K, Cullen MJ, Pelleymounter MA, Dekoning J, Baetscher M, Cone RD. (2000) A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology, 141 (9): 3518-21. [PMID:10965927]
4. Chen AS, Marsh DJ, Trumbauer ME, Frazier EG, Guan XM, Yu H, Rosenblum CI, Vongs A, Feng Y, Cao L et al.. (2000) Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet, 26 (1): 97-102. [PMID:10973258]
5. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int, 38 (1): 73-80. [PMID:8932521]
6. Conde-Frieboes K, Thøgersen H, Lau JF, Sensfuss U, Hansen TK, Christensen L, Spetzler J, Olsen HB, Nilsson C, Raun K et al.. (2012) Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective α-melanocyte-stimulating hormone (α-MSH) analogues. J Med Chem, 55 (5): 1969-77. [PMID:22335602]
7. Daniels D, Suzuki A, Shapiro E, Luo L, Yee DK, Fluharty SJ. (2005) Rattus norvegicus melanocortin 3 receptor: a corrected sequence. Peptides, 26 (10): 1835-41. [PMID:15985309]
8. Desarnaud F, Labbe O, Eggerickx D, Vassart G, Parmentier M. (1994) Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene. Biochem J, 299 ( Pt 2): 367-73. [PMID:8172596]
9. Gantz I, Konda Y, Tashiro T, Shimoto Y, Miwa H, Munzert G, Watson SJ, DelValle J, Yamada T. (1993) Molecular cloning of a novel melanocortin receptor. J Biol Chem, 268 (11): 8246-50. [PMID:8463333]
10. Grieco P, Balse PM, Weinberg D, MacNeil T, Hruby VJ. (2000) D-Amino acid scan of gamma-melanocyte-stimulating hormone: importance of Trp(8) on human MC3 receptor selectivity. J Med Chem, 43 (26): 4998-5002. [PMID:11150170]
11. Grieco P, Cai M, Han G, Trivedi D, Campiglia P, Novellino E, Hruby VJ. (2007) Further structure-activity studies of lactam derivatives of MT-II and SHU-9119: their activity and selectivity at human melanocortin receptors 3, 4, and 5. Peptides, 28 (6): 1191-6. [PMID:17482720]
12. Grieco P, Lavecchia A, Cai M, Trivedi D, Weinberg D, MacNeil T, Van der Ploeg LH, Hruby VJ. (2002) Structure-activity studies of the melanocortin peptides: discovery of potent and selective affinity antagonists for the hMC3 and hMC4 receptors. J Med Chem, 45 (24): 5287-94. [PMID:12431055]
13. Hruby VJ, Lu D, Sharma SD, Castrucci AL, Kesterson RA, al-Obeidi FA, Hadley ME, Cone RD. (1995) Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J Med Chem, 38 (18): 3454-61. [PMID:7658432]
14. Kask A, Mutulis F, Muceniece R, Pähkla R, Mutule I, Wikberg JE, Rägo L, Schiöth HB. (1998) Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology, 139 (12): 5006-14. [PMID:9832440]
15. Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO. (1998) Melanocortin receptor binding determinants in the agouti protein. Biochemistry, 37 (4): 991-7. [PMID:9454589]
16. Kopanchuk S, Veiksina S, Petrovska R, Mutule I, Szardenings M, Rinken A, Wikberg JE. (2005) Co-operative regulation of ligand binding to melanocortin receptor subtypes: evidence for interacting binding sites. Eur J Pharmacol, 512 (2-3): 85-95. [PMID:15840392]
17. Kumar KG, Sutton GM, Dong JZ, Roubert P, Plas P, Halem HA, Culler MD, Yang H, Dixit VD, Butler AA. (2009) Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides, 30 (10): 1892-900. [PMID:19646498]
18. Liang J, Li L, Jin X, Xu B, Pi L, Liu S, Zhu W, Zhang C, Luan B, Gong L et al.. (2018) Pharmacological effect of human melanocortin-2 receptor accessory protein 2 variants on hypothalamic melanocortin receptors. Endocrine, 61 (1): 94-104. [PMID:29704154]
19. MacNeil DJ, Howard AD, Guan X, Fong TM, Nargund RP, Bednarek MA, Goulet MT, Weinberg DH, Strack AM, Marsh DJ et al.. (2002) The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur J Pharmacol, 440 (2-3): 141-57. [PMID:12007532]
20. Mountjoy KG, Kong PL, Taylor JA, Willard DH, Wilkison WO. (2001) Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells. Physiol Genomics, 5 (1): 11-9. [PMID:11161002]
21. Ni XP, Pearce D, Butler AA, Cone RD, Humphreys MH. (2003) Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest, 111 (8): 1251-8. [PMID:12697744]
22. Nickolls SA, Cismowski MI, Wang X, Wolff M, Conlon PJ, Maki RA. (2003) Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity. J Pharmacol Exp Ther, 304 (3): 1217-27. [PMID:12604699]
23. Oosterom J, Nijenhuis WA, Schaaper WM, Slootstra J, Meloen RH, Gispen WH, Burbach JP, Adan RA. (1999) Conformation of the core sequence in melanocortin peptides directs selectivity for the melanocortin MC3 and MC4 receptors. J Biol Chem, 274 (24): 16853-60. [PMID:10358030]
24. Roselli-Rehfuss L, Mountjoy KG, Robbins LS, Mortrud MT, Low MJ, Tatro JB, Entwistle ML, Simerly RB, Cone RD. (1993) Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci USA, 90 (19): 8856-60. [PMID:8415620]
25. Rosenfeld RD, Zeni L, Welcher AA, Narhi LO, Hale C, Marasco J, Delaney J, Gleason T, Philo JS, Katta V et al.. (1998) Biochemical, biophysical, and pharmacological characterization of bacterially expressed human agouti-related protein. Biochemistry, 37 (46): 16041-52. [PMID:9819197]
26. Schioth HB, Muceniece R, Wikberg JE, Chhajlani V. (1995) Characterisation of melanocortin receptor subtypes by radioligand binding analysis. Eur J Pharmacol, 288 (3): 311-317. [PMID:7774675]
27. Schiöth HB, Muceniece R, Mutulis F, Bouifrouri AA, Mutule I, Wikberg JE. (1999) Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119. Neuropeptides, 33 (3): 191-6. [PMID:10657491]
28. Schiöth HB, Muceniece R, Wikberg JE, Szardenings M. (1996) Alternative translation initiation codon for the human melanocortin MC3 receptor does not affect the ligand binding. Eur J Pharmacol, 314 (3): 381-4. [PMID:8957262]
29. Wachira SJ, Hughes-Darden CA, Taylor CV, Ochillo R, Robinson TJ. (2003) Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways. Neuropeptides, 37 (4): 201-10. [PMID:12906838]
30. Yang YK, Dickinson C, Lai YM, Li JY, Gantz I. (2001) Functional properties of an agouti signaling protein variant and characteristics of its cognate radioligand. Am J Physiol Regul Integr Comp Physiol, 281 (6): R1877-86. [PMID:11705773]