The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MC2R  -  melanocortin 2 receptor...

Homo sapiens

Synonyms: ACTH receptor, ACTH-R, ACTHR, Adrenocorticotropic hormone receptor, Adrenocorticotropin receptor, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MC2R


High impact information on MC2R


Chemical compound and disease context of MC2R


Biological context of MC2R

  • Using three markers flanking MC2R gene on chromosome 18, we were able to exclude linkage in a region of 12 centimorgans around the gene [10].
  • OS-3 cells transfected with a cAMP-responsive luciferase reporter plasmid (pCREluc) were unresponsive to ACTH, but cotransfection with a vector expressing human MC2R increased luciferase activity more than 40-fold [11].
  • Conclusions MC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis [4].
  • This assay provides excellent sensitivity in an easily assayed transient transfection system, providing a more rapid and efficient measurement of ACTH receptor activity [11].
  • This study demonstrated for the first time that an E-box (located at -1020 bp) is involved in the repression of hMC2R gene expression in granulosa cells through interactions with several factors, such as activator protein 4, as suggested by electrophoretic mobility shift assay analyses [12].

Anatomical context of MC2R


Associations of MC2R with chemical compounds

  • As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency [4].
  • Sucrose pretreatment blocked receptor desensitization, indicating that hMC2R desensitization and internalization are interrelated [16].
  • Down-regulation of ACTH-receptor expression in normal and neoplastic tissue can be achieved by adrenostatic compounds such as aminoglutethimide and metyrapone [2].
  • Expression of the adrenocorticotropin receptor (MC2-R) is restricted to adrenocortical cells and is up-regulated by both adrenocorticotropin and angiotensin II through the activation of protein kinase A and protein kinase C pathways, respectively [17].
  • After cloning of the promoter region of the human MC2-R gene (hMC2-R), we have shown that cyclic AMP-induced regulation of transcriptional activity of the gene is achieved through two SF1 binding elements located in the proximal promoter [17].
  • ACTH only bound Myc-MC2R in the presence of MRAP [18].
  • We propose a molecular explanation for the reduced activity exhibited by the MC2R alanine 126 by serine mutant [19].

Physical interactions of MC2R


Regulatory relationships of MC2R

  • Addition of ACTH to cells cotransfected with the pCREluc reporter and wild-type MC2R activated luciferase expression with a 50% effective concentration of 5.5 x 10(-9) M ACTH, which is similar to previously reported values [11].

Other interactions of MC2R

  • Inactivating mutations of MC2R lead to hereditary unresponsiveness to ACTH, also known as familial glucocorticoid deficiency (FGD) [11].
  • The novel MC-2 receptor and the MC-1 receptor, described earlier by us (8) showed identical order of affinity for the melanocortin peptides, but the affinities and the fold differences in the affinities to the melanocortin peptides were different when compared to the earlier described MC-1 receptor [3].
  • However, ASIP-[90-132 (L89Y)] was found to be less potent than full-length recombinant ASIP and, surprisingly, only exhibited weak inhibitory activity at the hMC2R [22].
  • By means of RT-PCR, the mRNA of the MC2R, MC3R, and MC4R receptors is undetectable [23].
  • This is the first demonstration that both AP-1 and SF-1 are required for the cAMP-dependent induction of human ACTHR gene [14].

Analytical, diagnostic and therapeutic context of MC2R


  1. Identification of adrenocorticotropin receptor messenger ribonucleic acid in the human pituitary and its loss of expression in pituitary adenomas. Morris, D.G., Kola, B., Borboli, N., Kaltsas, G.A., Gueorguiev, M., McNicol, A.M., Ferrier, R., Jones, T.H., Baldeweg, S., Powell, M., Czirják, S., Hanzély, Z., Johansson, J.O., Korbonits, M., Grossman, A.B. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  2. ACTH-receptor expression, regulation and role in adrenocortial tumor formation. Beuschlein, F., Fassnacht, M., Klink, A., Allolio, B., Reincke, M. Eur. J. Endocrinol. (2001) [Pubmed]
  3. Molecular cloning of a novel human melanocortin receptor. Chhajlani, V., Muceniece, R., Wikberg, J.E. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  4. Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Lin, L., Hindmarsh, P.C., Metherell, L.A., Alzyoud, M., Al-Ali, M., Brain, C.E., Clark, A.J., Dattani, M.T., Achermann, J.C. Clin. Endocrinol. (Oxf) (2007) [Pubmed]
  5. An ACTH receptor on human mononuclear leukocytes. Relation to adrenal ACTH-receptor activity. Smith, E.M., Brosnan, P., Meyer, W.J., Blalock, J.E. N. Engl. J. Med. (1987) [Pubmed]
  6. Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II. Lebrethon, M.C., Naville, D., Begeot, M., Saez, J.M. J. Clin. Invest. (1994) [Pubmed]
  7. Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Clark, A.J., McLoughlin, L., Grossman, A. Lancet (1993) [Pubmed]
  8. Expression of adrenocorticotropin receptor gene in adrenocortical adenomas from patients with Cushing syndrome: possible contribution for the autonomous production of cortisol. Imai, T., Sarkar, D., Shibata, A., Funahashi, H., Morita-Matsuyama, T., Kikumori, T., Ohmori, S., Seo, H. Ann. Surg. (2001) [Pubmed]
  9. Aminoglutethimide suppresses adrenocorticotropin receptor expression in the NCI-h295 adrenocortical tumor cell line. Fassnacht, M., Beuschlein, F., Vay, S., Mora, P., Allolio, B., Reincke, M. J. Endocrinol. (1998) [Pubmed]
  10. Exclusion of the adrenocorticotropin (ACTH) receptor (MC2R) locus in some families with ACTH resistance but no mutations of the MC2R coding sequence (familial glucocorticoid deficiency type 2). Naville, D., Weber, A., Genin, E., Durand, P., Clark, A.J., Bégeot, M. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  11. Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay. Flück, C.E., Martens, J.W., Conte, F.A., Miller, W.L. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  12. An E-box-containing region is involved in the tissue-specific expression of the human MC2R gene. Blondet, A., Doghman, M., Durand, P., Bégeot, M., Naville, D. J. Mol. Endocrinol. (2004) [Pubmed]
  13. The role of the ACTH receptor in adrenal tumors: identification of a novel microsatellite marker. Zwermann, O., Beuschlein, F., Klink, A., Stahl, M., Reincke, M. Horm. Metab. Res. (2004) [Pubmed]
  14. Involvement of AP-1 and steroidogenic factor (SF)-1 in the cAMP-dependent induction of human adrenocorticotropic hormone receptor (ACTHR) promoter. Sarkar, D., Kambe, F., Hayashi, Y., Ohmori, S., Funahashi, H., Seo, H. Endocr. J. (2000) [Pubmed]
  15. Expression and localization of melanocortin-1 receptor in human adipose tissues of severely obese patients. Hoch, M., Eberle, A.N., Wagner, U., Bussmann, C., Peters, T., Peterli, R. Obesity (Silver Spring, Md.) (2007) [Pubmed]
  16. Human melanocortin receptor 2 expression and functionality: effects of protein kinase A and protein kinase C on desensitization and internalization. Kilianova, Z., Basora, N., Kilian, P., Payet, M.D., Gallo-Payet, N. Endocrinology (2006) [Pubmed]
  17. The human MC2-R gene expression: different aspects of its control. Blondet, A., Doghman, M., Penhoat, A., Durand, P., Bégeot, M., Naville, D. Endocr. Res. (2002) [Pubmed]
  18. Differential regulation of the human adrenocorticotropin receptor [melanocortin-2 receptor (MC2R)] by human MC2R accessory protein isoforms alpha and beta in isogenic human embryonic kidney 293 cells. Roy, S., Rached, M., Gallo-Payet, N. Mol. Endocrinol. (2007) [Pubmed]
  19. A novel adrenocorticotropin receptor mutation alters its structure and function, causing familial glucocorticoid deficiency. Artigas, R.A., Gonzalez, A., Riquelme, E., Carvajal, C.A., Cattani, A., Martínez-Aguayo, A., Kalergis, A.M., Pérez-Acle, T., Fardella, C.E. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  20. Three steroidogenic factor-1 binding elements are required for constitutive and cAMP-regulated expression of the human adrenocorticotropin receptor gene. Naville, D., Penhoat, A., Durand, P., Begeot, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  21. Activator protein-1 is necessary for angiotensin-II stimulation of human adrenocorticotropin receptor gene transcription. Naville, D., Bordet, E., Berthelon, M.C., Durand, P., Bégeot, M. Eur. J. Biochem. (2001) [Pubmed]
  22. Functional properties of an agouti signaling protein variant and characteristics of its cognate radioligand. Yang, Y.K., Dickinson, C., Lai, Y.M., Li, J.Y., Gantz, I. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  23. Gamma-MSH peptides in the pituitary: effects, target cells, and receptors. Denef, C., Lu, J., Swinnen, E. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  24. Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management. Wolf, A., Willenberg, H.S., Cupisti, K., Schott, M., Geddert, H., Raffel, A., Bornstein, S.R., Scherbaum, W.A., Knoefel, W.T. Horm. Metab. Res. (2005) [Pubmed]
  25. Novel compound heterozygous mutation of the MC2R gene in a patient with familial glucocorticoid deficiency. Matsuura, H., Shiohara, M., Yamano, M., Kurata, K., Arai, F., Koike, K. J. Pediatr. Endocrinol. Metab. (2006) [Pubmed]
WikiGenes - Universities