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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 | 297 | 18p11.2 | MC2R | melanocortin 2 receptor | 8 |
| Mouse | 7 | 296 | 18 41.89 cM | Mc2r | melanocortin 2 receptor | 6 |
| Rat | 7 | 296 | 18p12.1 | Mc2r | melanocortin 2 receptor | |
| Previous and Unofficial Names |
| ACTHR | melanocortin 2 receptor | adrenocorticotropic hormone receptor | melanocortin 2 receptor (adrenocorticotropic hormone) |
| Database Links |
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| Specialist databases | |
| GPCRDB | acthr_human (Hs), acthr_mouse (Mm) |
| Other databases | |
| Alphafold | Q01718 (Hs), Q64326 (Mm) |
| ChEMBL Target | CHEMBL1965 (Hs), CHEMBL2279 (Mm) |
| DrugBank Target | Q01718 (Hs) |
| Ensembl Gene | ENSG00000185231 (Hs), ENSMUSG00000045569 (Mm), ENSRNOG00000016681 (Rn) |
| Entrez Gene | 4158 (Hs), 17200 (Mm), 282839 (Rn) |
| Human Protein Atlas | ENSG00000185231 (Hs) |
| KEGG Gene | hsa:4158 (Hs), mmu:17200 (Mm), rno:282839 (Rn) |
| OMIM | 607397 (Hs) |
| Orphanet | ORPHA123161 (Hs) |
| Pharos | Q01718 (Hs) |
| RefSeq Nucleotide | NM_000529 (Hs), NM_008560 (Mm), NM_001100491 (Rn) |
| RefSeq Protein | NP_000520 (Hs), NP_032586 (Mm), NP_001093961 (Rn) |
| UniProtKB | Q01718 (Hs), Q64326 (Mm) |
| Wikipedia | MC2R (Hs) |
| Associated Proteins |
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| Natural/Endogenous Ligands |
| ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat} |
| Comments: 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) |
| ACTH (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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The MC2 receptor is the primary target for the approved drugs ACTH, cosyntropin, seractide acetate and corticotrophin zinc hydroxide. Radioligands include [125I]ACTH, [125I-Tyr23]ACTH, and [125I](Phe2,Nle4)ACTH(1-24). The MC2 receptor only binds ACTH and does not bind the other melanocortin peptides α-, β-, and γ-MSH. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Human agouti is an selective, endogenous, inverse agonist whose affinity has not yet been established. It is referred to in the literature as agouti-signaling protein (ASP or ASIP). [125I]ASIP [90-132 (L89Y)] has been used as a radioligand [16]. |
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| 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) | Calcium channel |
| References: 5 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Functional Assay Comments | ||||||||||
| For unknown reasons, it has been difficult to express the human MC2 in non-adrenal cell lines [12]. Reference [11] describes the transfection of the human MC2 receptor into murine M3 melanoma cells and HEK293 cells. In the M3 cells, the receptor was expressed in the membrane to form a functional receptor, whereas in HEK293 cells it remained intracellular. |
| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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1. 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]
2. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int, 38 (1): 73-80. [PMID:8932521]
3. Clark AJ, McLoughlin L, Grossman A. (1993) Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet, 341 (8843): 461-2. [PMID:8094489]
4. Kapas S, Cammas FM, Hinson JP, Clark AJ. (1996) Agonist and receptor binding properties of adrenocorticotropin peptides using the cloned mouse adrenocorticotropin receptor expressed in a stably transfected HeLa cell line. Endocrinology, 137 (8): 3291-4. [PMID:8754753]
5. Kojima I, Kojima K, Rasmussen H. (1985) Role of calcium and cAMP in the action of adrenocorticotropin on aldosterone secretion. J Biol Chem, 260 (7): 4248-56. [PMID:2579947]
6. Kubo M, Ishizuka T, Kijima H, Kakinuma M, Koike T. (1995) Cloning of a mouse adrenocorticotropin receptor-encoding gene. Gene, 153 (2): 279-80. [PMID:7875603]
7. Metherell LA, Chapple JP, Cooray S, David A, Becker C, Rüschendorf F, Naville D, Begeot M, Khoo B, Nürnberg P et al.. (2005) Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nat Genet, 37 (2): 166-70. [PMID:15654338]
8. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD. (1992) The cloning of a family of genes that encode the melanocortin receptors. Science, 257 (5074): 1248-51. [PMID:1325670]
9. Naville D, Barjhoux L, Jaillard C, Saez JM, Durand P, Bégeot M. (1997) Stable expression of normal and mutant human ACTH receptor: study of ACTH binding and coupling to adenylate cyclase. Mol Cell Endocrinol, 129 (1): 83-90. [PMID:9175632]
10. 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]
11. Rached M, El Mourabit H, Buronfosse A, Blondet A, Naville D, Begeot M, Penhoat A. (2005) Expression of the human melanocortin-2 receptor in different eukaryotic cells. Peptides, 26 (10): 1842-7. [PMID:15982783]
12. Schimmer BP, Kwan WK, Tsao J, Qiu R. (1995) Adrenocorticotropin-resistant mutants of the Y1 adrenal cell line fail to express the adrenocorticotropin receptor. J Cell Physiol, 163 (1): 164-71. [PMID:7896893]
13. Slominski A, Ermak G, Mihm M. (1996) ACTH receptor, CYP11A1, CYP17 and CYP21A2 genes are expressed in skin. J Clin Endocrinol Metab, 81 (7): 2746-9. [PMID:8675607]
14. Swords FM, Baig A, Malchoff DM, Malchoff CD, Thorner MO, King PJ, Hunyady L, Clark AJ. (2002) Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity. Mol Endocrinol, 16 (12): 2746-53. [PMID:12456795]
15. Xia Y, Wikberg JE. (1996) Localization of ACTH receptor mRNA by in situ hybridization in mouse adrenal gland. Cell Tissue Res, 286 (1): 63-8. [PMID:8781213]
16. 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]
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