ACTH receptor

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Melanocortin 2 receptor (adrenocorticotropic hormone)
Symbols MC2R ; ACTHR
External IDs OMIM607397 MGI96928 HomoloGene444 IUPHAR: 283 ChEMBL: 1965 GeneCards: MC2R Gene
RNA expression pattern
PBB GE MC2R 208568 at tn.png
PBB GE MC2R 217434 at tn.png
More reference expression data
Species Human Mouse
Entrez 4158 17200
Ensembl ENSG00000185231 ENSMUSG00000045569
UniProt Q01718 Q64326
RefSeq (mRNA) NM_000529 NM_001271716
RefSeq (protein) NP_000520 NP_001258645
Location (UCSC) Chr 18:
13.88 – 13.92 Mb
Chr 18:
68.41 – 68.43 Mb
PubMed search [1] [2]

The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH.[1]


Both human and bovine ACTH receptors are synthesized as 297 residue long proteins. There is 81% homology between human and bovine sequences.[2] The full length sequence includes seven hydrophobic domains that are predicted as transmembrane segments.[2] In the third intracellular loop of the receptor a protein kinase A and protein kinase c phosphorylation motifs have been detected.[2]

Tissue and subcellular localization[edit]

ACTH receptor is found in the zona fasciculata of the human adrenal cortex. Binding of the receptor by ACTH stimulates the production of cortisol. (By contrast, aldosterone production from the zona glomerulosa is stimulated primarily by angiotensin II.)

Protein recognition at the receptor uses energy obtained from the dephosphorylation of ATP to cAMP by adenylate cyclase. ACTH receptors are located on the plasma membrane, and are G protein-coupled receptors.

The ACTH receptor uses cAMP as a secondary messenger.[3][4]


Mutations in this receptor cause familial glucocorticoid deficiency type 1, in which patients have high levels of serum ACTH and low levels of cortisol.[5][6]

See also[edit]


  1. ^ Beuschlein F, Fassnacht M, Klink A, Allolio B, Reincke M (2001). "ACTH-receptor expression, regulation and role in adrenocortial tumor formation". Eur. J. Endocrinol. 144 (3): 199–206. doi:10.1530/eje.0.1440199. PMID 11248736. 
  2. ^ a b c Raikhinstein M, Zohar M, Hanukoglu I (February 1994). "cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone (ACTH) receptor". Biochim. Biophys. Acta 1220 (3): 329–32. doi:10.1016/0167-4889(94)90157-0. PMID 8305507. 
  3. ^ Hanukoglu I, Feuchtwanger R, Hanukoglu A (Nov 1990). "Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells.". J Biol Chem 265 (33): 20602–8. PMID 2173715. 
  4. ^ Elias LL, Clark AJ (October 2000). "The expression of the ACTH receptor". Braz. J. Med. Biol. Res. 33 (10): 1245–8. doi:10.1590/S0100-879X2000001000015. PMID 11004726. 
  5. ^ Clark AJ, McLoughlin L, Grossman A (February 1993). "Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor". Lancet 341 (8843): 461–2. doi:10.1016/0140-6736(93)90208-X. PMID 8094489. 
  6. ^ Tsigos C, Arai K, Hung W, Chrousos GP (November 1993). "Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene". J. Clin. Invest. 92 (5): 2458–61. doi:10.1172/JCI116853. PMC 288430. PMID 8227361. 

Further reading[edit]

  • Cone RD, Mountjoy KG, Robbins LS et al. (1993). "Cloning and functional characterization of a family of receptors for the melanotropic peptides.". Ann. N. Y. Acad. Sci. 680: 342–63. doi:10.1111/j.1749-6632.1993.tb19694.x. PMID 8390157. 
  • Allolio B, Reincke M (1997). "Adrenocorticotropin receptor and adrenal disorders.". Horm. Res. 47 (4-6): 273–8. doi:10.1159/000185476. PMID 9167964. 
  • Tatro JB (1997). "Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides.". Neuroimmunomodulation 3 (5): 259–84. doi:10.1159/000097281. PMID 9218248. 
  • 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. doi:10.1126/science.1325670. PMID 1325670. 
  • Clark AJ, McLoughlin L, Grossman A (1993). "Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor.". Lancet 341 (8843): 461–2. doi:10.1016/0140-6736(93)90208-X. PMID 8094489. 
  • Tsigos C, Arai K, Hung W, Chrousos GP (1993). "Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene.". J. Clin. Invest. 92 (5): 2458–61. doi:10.1172/JCI116853. PMC 288430. PMID 8227361. 
  • Gantz I, Tashiro T, Barcroft C et al. (1994). "Localization of the genes encoding the melanocortin-2 (adrenocorticotropic hormone) and melanocortin-3 receptors to chromosomes 18p11.2 and 20q13.2-q13.3 by fluorescence in situ hybridization.". Genomics 18 (1): 166–7. doi:10.1006/geno.1993.1448. PMID 8276410. 
  • Gantz I, Konda Y, Tashiro T et al. (1993). "Molecular cloning of a novel melanocortin receptor.". J. Biol. Chem. 268 (11): 8246–50. PMID 8463333. 
  • Naville D, Barjhoux L, Jaillard C et al. (1996). "Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency.". J. Clin. Endocrinol. Metab. 81 (4): 1442–8. doi:10.1210/jc.81.4.1442. PMID 8636348. 
  • Naville D, Jaillard C, Barjhoux L et al. (1997). "Genomic structure and promoter characterization of the human ACTH receptor gene.". Biochem. Biophys. Res. Commun. 230 (1): 7–12. doi:10.1006/bbrc.1996.5911. PMID 9020063. 
  • Yang YK, Ollmann MM, Wilson BD et al. (1997). "Effects of recombinant agouti-signaling protein on melanocortin action.". Mol. Endocrinol. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374. 
  • Naville D, Barjhoux L, Jaillard C et al. (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. doi:10.1016/S0303-7207(97)04043-4. PMID 9175632. 
  • Penhoat A, Naville D, Jaillard C et al. (1997). "Presence of multiple functional polyadenylation signals in the 3'-untranslated region of human corticotropin receptor cDNA.". Biochim. Biophys. Acta 1356 (3): 249–52. doi:10.1016/S0167-4889(97)00031-1. PMID 9194567. 
  • Ishii T, Ogata T, Sasaki G et al. (2000). "Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH.". Clin. Endocrinol. (Oxf) 53 (3): 389–92. doi:10.1046/j.1365-2265.2000.01040.x. PMID 10971458. 
  • Flück CE, Martens JW, Conte FA, Miller WL (2002). "Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.". J. Clin. Endocrinol. Metab. 87 (9): 4318–23. doi:10.1210/jc.2002-020501. PMID 12213892. 
  • Swords FM, Baig A, Malchoff DM et al. (2003). "Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity.". Mol. Endocrinol. 16 (12): 2746–53. doi:10.1210/me.2002-0099. PMID 12456795. 
  • Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Roy S, Rached M, Gallo-Payet N (July 2007). "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". Mol. Endocrinol. 21 (7): 1656–69. doi:10.1210/me.2007-0041. PMID 17456795. 

External links[edit]