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Not curated in GtoImmuPdb
Target id: 286
Nomenclature: MC5 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 | 325 | 18p11.21 | MC5R | melanocortin 5 receptor | 5 |
| Mouse | 7 | 325 | 18 41.46 cM | Mc5r | melanocortin 5 receptor | 7,15 |
| Rat | 7 | 325 | 18q12.1 | Mc5r | melanocortin 5 receptor | 9 |
| Previous and Unofficial Names |
| MC5R | melanocortin receptor 5 |
| Database Links |
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| Specialist databases | |
| GPCRdb | mc5r_human (Hs), mc5r_mouse (Mm), mc5r_rat (Rn) |
| Other databases | |
| Alphafold | P33032 (Hs), P41149 (Mm), P35345 (Rn) |
| ChEMBL Target | CHEMBL4608 (Hs), CHEMBL4489 (Mm), CHEMBL2701 (Rn) |
| Ensembl Gene | ENSG00000176136 (Hs), ENSMUSG00000007480 (Mm), ENSRNOG00000016685 (Rn) |
| Entrez Gene | 4161 (Hs), 17203 (Mm), 25726 (Rn) |
| Human Protein Atlas | ENSG00000176136 (Hs) |
| KEGG Gene | hsa:4161 (Hs), mmu:17203 (Mm), rno:25726 (Rn) |
| OMIM | 600042 (Hs) |
| Pharos | P33032 (Hs) |
| RefSeq Nucleotide | NM_005913 (Hs), NM_013596 (Mm), NM_013182 (Rn) |
| RefSeq Protein | NP_005904 (Hs), NP_038624 (Mm), NP_037314 (Rn) |
| UniProtKB | P33032 (Hs), P41149 (Mm), P35345 (Rn) |
| Wikipedia | MC5R (Hs) |
| 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: α-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) |
| α-MSH (POMC, P01189) > β-MSH (POMC, P01189) > ACTH (POMC, P01189) > γ-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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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| α-MSH, NDP-MSH, MT-II and ACTH (1-24) are > 10-fold more potent at the rhesus MC5 than human MC5 [10]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | 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: 15 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| G protein (identity unknown) | Other - See Comments |
| Comments: Melanocortin activation of the MC5 mobilizes intracellular calcium via an incompletely understood pathway(s). | |
| References: 17 | |
| 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
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||
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1. Balse-Srinivasan P, Grieco P, Cai M, Trivedi D, Hruby VJ. (2003) Structure-activity relationships of novel cyclic alpha-MSH/beta-MSH hybrid analogues that lead to potent and selective ligands for the human MC3R and human MC5R. J Med Chem, 46 (17): 3728-33. [PMID:12904077]
2. Boston BA, Cone RD. (1996) Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. Endocrinology, 137 (5): 2043-50. [PMID:8612546]
3. Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, Cone RD. (1997) Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell, 91 (6): 789-98. [PMID:9413988]
4. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int, 38 (1): 73-80. [PMID:8932521]
5. Chhajlani V, Muceniece R, Wikberg JE. (1993) Molecular cloning of a novel human melanocortin receptor. Biochem Biophys Res Commun, 195 (2): 866-73. [PMID:8396929]
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. Gantz I, Shimoto Y, Konda Y, Miwa H, Dickinson CJ, Yamada T. (1994) Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochem Biophys Res Commun, 200 (3): 1214-20. [PMID:8185570]
8. 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]
9. Griffon N, Mignon V, Facchinetti P, Diaz J, Schwartz JC, Sokoloff P. (1994) Molecular cloning and characterization of the rat fifth melanocortin receptor. Biochem Biophys Res Commun, 200 (2): 1007-14. [PMID:8179577]
10. Huang RR, Singh G, Van der Ploeg LH, Fong TM. (2000) Species-dependent pharmacological properties of the melanocortin-5 receptor. J Recept Signal Transduct Res, 20 (1): 47-59. [PMID:10711496]
11. 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]
12. Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO. (1998) Melanocortin receptor binding determinants in the agouti protein. Biochemistry, 37 (4): 991-7. [PMID:9454589]
13. 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]
14. 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]
15. Labbe O, Desarnaud F, Eggerickx D, Vassart G, Parmentier M. (1994) Molecular cloning of a mouse melanocortin 5 receptor gene widely expressed in peripheral tissues. Biochemistry, 33: 4543-4549. [PMID:8161509]
16. 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]
17. 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]
18. Norman D, Isidori AM, Frajese V, Caprio M, Chew SL, Grossman AB, Clark AJ, Michael Besser G, Fabbri A. (2003) ACTH and alpha-MSH inhibit leptin expression and secretion in 3T3-L1 adipocytes: model for a central-peripheral melanocortin-leptin pathway. Mol Cell Endocrinol, 200 (1-2): 99-109. [PMID:12644303]
19. 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]
20. 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]
21. van der Kraan M, Adan RA, Entwistle ML, Gispen WH, Burbach JP, Tatro JB. (1998) Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology, 139 (5): 2348-55. [PMID:9564844]
22. 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]
23. Yang YK, Thompson DA, Dickinson CJ, Wilken J, Barsh GS, Kent SB, Gantz I. (1999) Characterization of Agouti-related protein binding to melanocortin receptors. Mol Endocrinol, 13 (1): 148-55. [PMID:9892020]
