Adrenocorticotropic hormone receptor

Function

G protein-coupled receptor for corticotropin/ACTH, primarily expressed in adrenal cortex where it plays a key role in the regulation of adrenocortical function. Upon activation, couples to G(s) protein, stimulating adenylate cyclase and activating the cAMP-dependent signaling pathway, the MAPK cascade as well as the PKA pathway, leading to steroidogenic factor 1/NR5A1-mediated transcriptional activation. Activation by ACTH facilitates the release of adrenal glucocorticoids, including cortisol and corticosterone. In addition, MC2R is required for fetal and neonatal adrenal gland development (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

ACTH_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Melcrt_ACTH_rcpt

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 2

• 8GY7 EM 3.30A
• 9K3L EM 3.01A

A predicted model is available from AlphaFold.

Gene Ontology · 10

• GO:0005737 cytoplasm
• GO:0005886 plasma membrane
• GO:0004978 corticotropin receptor activity
• GO:0004930 G protein-coupled receptor activity
• GO:0004977 melanocortin receptor activity
• GO:0046872 metal ion binding
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0031948 positive regulation of glucocorticoid biosynthetic process

Disease associations

• glucocorticoid deficiency 1 MONDO:0024536

Drugs targeting this protein · 1

• COSYNTROPIN agonist

Related proteins · sequence + function similarity

• Adrenocorticotropic hormone receptor 0.99
• Adrenocorticotropic hormone receptor 0.99
• Adrenocorticotropic hormone receptor 0.98
• Adrenocorticotropic hormone receptor 0.98
• Adrenocorticotropic hormone receptor 0.98
• Adrenocorticotropic hormone receptor 0.98
• Melanocortin receptor 5 0.96
• Melanocortin receptor 5 0.96
• Melanocortin receptor 4 0.96
• Melanocortin receptor 3 0.96
• Melanocortin receptor 5 0.96
• Melanocortin receptor 4 0.96

Co-cited proteins · studied together in the literature

• Melanocortin-2 receptor accessory protein 3 shared papers
• Pro-opiomelanocortin 2 shared papers
• Melanocortin-2 receptor accessory protein 2 2 shared papers
• Melanocyte-stimulating hormone receptor 1 shared papers
• Melanocyte-stimulating hormone receptor 1 shared papers
• Melanocortin-2 receptor accessory protein 2 1 shared papers
• Melanocyte-stimulating hormone receptor 2 shared papers
• Melanocortin receptor 3 1 shared papers
• Melanocortin receptor 4 1 shared papers

Literature · 17 cited papers

• Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1. Cell Res. · 2023
• The E3 ubiquitin ligase Mahogunin ubiquitinates the melanocortin 2 receptor. Endocrinology · 2011
• Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2. Sci. Signal. · 2010
• Novel human pathological mutations. Gene symbol: MC2R. Disease: Glucocorticoid deficiency. Hum. Genet. · 2010
• Opposite effects of the melanocortin-2 (MC2) receptor accessory protein MRAP on MC2 and MC5 receptor dimerization and trafficking. J. Biol. Chem. · 2009
• MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Structural insights into the role of the ACTH receptor cysteine residues on receptor function. Am. J. Physiol. · 2007
• Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nat. Genet. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay. J. Clin. Endocrinol. Metab. · 2002
• Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH. Clin. Endocrinol. (Oxf.) · 2000
• … and 5 more in the literature graph