ACTH receptor

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Melanocortin 2 receptor (adrenocorticotropic hormone)
Identifiers
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
Orthologs
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]

Structure[edit]

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]

Pathology[edit]

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]

References[edit]

  1. ^ Beuschlein F, Fassnacht M, Klink A, Allolio B, Reincke M (Mar 2001). "ACTH-receptor expression, regulation and role in adrenocortial tumor formation". European Journal of Endocrinology / European Federation of Endocrine Societies 144 (3): 199–206. doi:10.1530/eje.0.1440199. PMID 11248736. 
  2. ^ a b c Raikhinstein M, Zohar M, Hanukoglu I (Feb 1994). "cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone (ACTH) receptor". Biochimica Et Biophysica 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" (PDF). The Journal of Biological Chemistry 265 (33): 20602–8. PMID 2173715. 
  4. ^ Elias LL, Clark AJ (Oct 2000). "The expression of the ACTH receptor". Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas / Sociedade Brasileira De Biofísica ... [Et Al.] 33 (10): 1245–8. doi:10.1590/S0100-879X2000001000015. PMID 11004726. 
  5. ^ Clark AJ, McLoughlin L, Grossman A (Feb 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 (Nov 1993). "Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene". The Journal of Clinical Investigation 92 (5): 2458–61. doi:10.1172/JCI116853. PMC 288430. PMID 8227361. 

Further reading[edit]

  • Cone RD, Mountjoy KG, Robbins LS, Nadeau JH, Johnson KR, Roselli-Rehfuss L et al. (May 1993). "Cloning and functional characterization of a family of receptors for the melanotropic peptides". Annals of the New York Academy of Sciences 680: 342–63. doi:10.1111/j.1749-6632.1993.tb19694.x. PMID 8390157. 
  • Allolio B, Reincke M (1997). "Adrenocorticotropin receptor and adrenal disorders". Hormone Research 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 (Aug 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 (Feb 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 (Nov 1993). "Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene". The Journal of Clinical Investigation 92 (5): 2458–61. doi:10.1172/JCI116853. PMC 288430. PMID 8227361. 
  • Gantz I, Tashiro T, Barcroft C, Konda Y, Shimoto Y, Miwa H et al. (Oct 1993). "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, Shimoto Y, Miwa H, Munzert G et al. (Apr 1993). "Molecular cloning of a novel melanocortin receptor". The Journal of Biological Chemistry 268 (11): 8246–50. PMID 8463333. 
  • Naville D, Barjhoux L, Jaillard C, Faury D, Despert F, Esteva B et al. (Apr 1996). "Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency". The Journal of Clinical Endocrinology and Metabolism 81 (4): 1442–8. doi:10.1210/jc.81.4.1442. PMID 8636348. 
  • Naville D, Jaillard C, Barjhoux L, Durand P, Bégeot M (Jan 1997). "Genomic structure and promoter characterization of the human ACTH receptor gene". Biochemical and Biophysical Research Communications 230 (1): 7–12. doi:10.1006/bbrc.1996.5911. PMID 9020063. 
  • Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS et al. (Mar 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Molecular Endocrinology 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374. 
  • Naville D, Barjhoux L, Jaillard C, Saez JM, Durand P, Bégeot M (Apr 1997). "Stable expression of normal and mutant human ACTH receptor: study of ACTH binding and coupling to adenylate cyclase". Molecular and Cellular Endocrinology 129 (1): 83–90. doi:10.1016/S0303-7207(97)04043-4. PMID 9175632. 
  • Penhoat A, Naville D, Jaillard C, Durand P, Bégeot M (May 1997). "Presence of multiple functional polyadenylation signals in the 3'-untranslated region of human corticotropin receptor cDNA". Biochimica Et Biophysica Acta 1356 (3): 249–52. doi:10.1016/S0167-4889(97)00031-1. PMID 9194567. 
  • Ishii T, Ogata T, Sasaki G, Sato S, Kinoshita EI, Matsuo N (Sep 2000). "Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH". Clinical Endocrinology 53 (3): 389–92. doi:10.1046/j.1365-2265.2000.01040.x. PMID 10971458. 
  • Flück CE, Martens JW, Conte FA, Miller WL (Sep 2002). "Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay". The Journal of Clinical Endocrinology and Metabolism 87 (9): 4318–23. doi:10.1210/jc.2002-020501. PMID 12213892. 
  • Swords FM, Baig A, Malchoff DM, Malchoff CD, Thorner MO, King PJ et al. (Dec 2002). "Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity". Molecular Endocrinology 16 (12): 2746–53. doi:10.1210/me.2002-0099. PMID 12456795. 
  • Roy S, Rached M, Gallo-Payet N (Jul 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". Molecular Endocrinology 21 (7): 1656–69. doi:10.1210/me.2007-0041. PMID 17456795. 

External links[edit]