MC<sub>5</sub> receptor | Melanocortin receptors | IUPHAR/BPS Guide to PHARMACOLOGY

MC5 receptor

Target id: 286

Nomenclature: MC5 receptor

Family: Melanocortin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for MC5 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 325 18p11.2 MC5R melanocortin 5 receptor 5
Mouse 7 325 18 E2 Mc5r melanocortin 5 receptor 6,14
Rat 7 325 18q12.1 Mc5r melanocortin 5 receptor 8
Previous and Unofficial Names
MC5R | melanocortin receptor 5
Database Links
Specialist databases
GPCRDB mc5r_human (Hs), mc5r_mouse (Mm), mc5r_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat}
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 ligands (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
Ligand Sp. Action Affinity Units Reference
SHU9119 Hs Partial agonist 9.0 pKd 18
pKd 9.0 [18]
[125I]NDP-MSH Hs Full agonist 8.6 pKd 12
pKd 8.6 (Kd 2.8x10-9 M) [12]
α-MSH {Sp: Human, Mouse, Rat} Hs Full agonist 6.9 pKd 15
pKd 6.9 [15]
setmelanotide Hs Agonist 6.4 pKi 13
pKi 6.4 (Ki 4.3x10-7 M) [13]
ACTH {Sp: Human} Hs Agonist <5.0 pKi 19
pKi <5.0 (Ki >1x10-5 M) [19]
PG-901 Hs Full agonist 10.5 pIC50 7
pIC50 10.5 [7]
MT-II Hs Full agonist 9.0 pIC50 15
pIC50 9.0 [15]
afamelanotide Hs Full agonist 9.0 pIC50 15
pIC50 9.0 [15]
Agonist Comments
α-MSH, NDP-MSH, MT-II and ACTH (1-24) are > 10-fold more potent at the rhesus MC5 than human MC5 [9].
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
HS024 Hs Antagonist 8.5 pKd 10
pKd 8.5 [10]
agouti {Sp: Mouse} Mm Inverse agonist 4.9 pKd 11
pKd 4.9 [11]
Ac-c[Cys-Glu-His-D-Phe-Arg-Trp-D-Cys]-Pro-Pro-Lys-Asp-NH2 Hs Antagonist 8.0 pIC50 1
pIC50 8.0 [1]
agouti-related protein {Sp: Human} Hs Inverse agonist 6.5 pIC50 22
pIC50 6.5 [22]
View species-specific antagonist tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  14
Secondary Transduction Mechanisms
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:  16
Tissue Distribution
Adrenal gland, fat cells, kidney, leukocytes, lung, lymph node, mammary gland, ovary, pituitary, testis and uterus.
Species:  Human
Technique:  PCR and hybridisation.
References:  4
Adipose tissue.
Species:  Mouse
Technique:  RT-PCR and Northern Blotting.
References:  2
Harderian, preputial and lacrimal glands.
Species:  Mouse
Technique:  Radioligand binding.
References:  3
Exocrine glands: Extraorbital lacrimal, Harderian, preputial, and prostate glands.
Pancreas, adrenal glands, esophagus and thymus.
Species:  Rat
Technique:  RNase protection assay.
References:  20
Expression Datasets

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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
Measurement of Ca2+ in a HEK 293 cell line transfected with the MC5 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Mobilization of [Ca2+]i.
References:  16
Measurement of cAMP in cell lines transfected with the MC5 receptor.
Species:  Human
Tissue:  HEK 293 and COS cells.
Response measured:  Intracellular cAMP accumulation.
References:  14
Measurment of cAMP levels in cells transfected with the MC5 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in cAMP.
References:  21
Measurment of cAMP levels and leptin expression in 3T3-L1 adipocyte cells expressing both MC2 and MC5 receptors.
Species:  Human
Tissue:  3T3-L1 cell line.
Response measured:  Increase in cAMP production and decrease in leptin expression.
References:  17
Measurement of cAMP accumulation in CHO cells stably transfected with the rat MC5 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Increase in cAMP accumulation.
References:  8
Physiological Functions
Sebum production.
Species:  Mouse
Tissue:  Hair follicle-associated sebaceous glands.
References:  3
Physiological Consequences of Altering Gene Expression
Mice with targeted deletion of the MC5 receptor have a defect in water and thermoregulation secondary to their decreased production of sebaceous lipids.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  3
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
involves: 129S4/SvJaeSor * 129S6/SvEvTac
MGI:99420  MP:0001777 abnormal body temperature regulation PMID: 9413988 
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
involves: 129S4/SvJaeSor * 129S6/SvEvTac
MGI:99420  MP:0000367 abnormal coat/ hair morphology PMID: 9413988 
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
involves: 129S4/SvJaeSor * 129S6/SvEvTac
MGI:99420  MP:0003859 abnormal Harderian gland physiology PMID: 9413988 
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
B6.129S4-Mc5r
MGI:99420  MP:0003859 abnormal Harderian gland physiology PMID: 9413988 
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
involves: 129S4/SvJaeSor * 129S6/SvEvTac
MGI:99420  MP:0001348 abnormal lacrimal gland physiology PMID: 9413988 
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
involves: 129S4/SvJaeSor * 129S6/SvEvTac
MGI:99420  MP:0002992 abnormal sebaceous lipid secretion PMID: 9413988 
Mc5rtm1Cone Mc5rtm1Cone/Mc5rtm1Cone
B6.129S4-Mc5r
MGI:99420  MP:0003862 decreased aggression towards males PMID: 14733892 

References

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1. Balse-Srinivasan P, Grieco P, Cai M, Trivedi D, Hruby VJ. (2003) Structure-activity relationships of novel cyclic α-MSH/β-MSH hybrid analogues that lead to potent and selective ligands for the human MC3R and human MC5R. J. Med. Chem., 46: 3728-3733. [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: 2043-2050. [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: 789-798. [PMID:9413988]

4. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int., 38: 73-80. [PMID:8932521]

5. Chhajlani V, Muceniece R, Wikberg JES. (1993) Molecular cloning of a novel human melanocortin receptor. Biochem. Biophys. Res. Commun., 195: 866-873. [PMID:8396929]

6. 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: 1214-1220. [PMID:8185570]

7. 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: 5287-5294. [PMID:12431055]

8. 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: 1007-1014. [PMID:8179577]

9. 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: 47-59. [PMID:10711496]

10. 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: 5006-5014. [PMID:9832440]

11. Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO. (1998) Melanocortin receptor binding determinants in the agouti protein. Biochemistry, 37 (4): 991-7. [PMID:9454589]

12. 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: 85-95. [PMID:15840392]

13. 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]

14. 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]

15. MacNeil DJ, Howard AD, Guan X, Fong TM, Nargund RP, Bednarek MA, Goulet MT, Weinberg DH, Strack AM, Marsh DJ, Chen HY, Shen CP, Chen AS, Rosenblum CI, MacNeil T, Tota M, MacIntyre ED, Van der Ploeg LH. (2002) The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur. J. Pharmacol., 440: 141-157. [PMID:12007532]

16. 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: 11-19. [PMID:11161002]

17. 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: 99-109. [PMID:12644303]

18. Schioth 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: 191-196. [PMID:10657491]

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. 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: 2348-2355. [PMID:9564844]

21. Yang Y-K Dickinson C, Lae Y-M, Li J-Y, Ira Gantz I. (2001) Functional properties of an agouti signaling protein variant and binding characteristics of its cognate radioligand. Am. J. Physiol. Regul. Integr. Comp. Physiol., 281: 1877-1886. [PMID:11705773]

22. 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: 148-155. [PMID:9892020]

Contributors

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How to cite this page

Tung M. Fong, Helgi Schiöth, Ira Gantz, Roger D. Cone, Sadaf Farooqi, Carrie Haskell-Luevano, Victor J. Hruby, Kathleen G. Mountjoy, Jeffrey B. Tatro, Jarl E. S. Wikberg.
Melanocortin receptors: MC5 receptor. Last modified on 20/02/2018. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=286.