Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- References
- Contributors
- How to cite this page
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 | |
| 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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| View species-specific agonist tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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 | Adenylate 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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References
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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