Property Summary

NCBI Gene PubMed Count 79
PubMed Score 165.33
PubTator Score 244.42

Knowledge Summary

Patent (8,967)

Gene RIF (64)

PMID Text
26223677 melanocortin receptors MC2R, MC3R and MC5R are most abundantly expressed in glandular epithelium of the endometrium
26115626 the MC2R gene may contribute to the development of intracerebral hemorrhage.
25860801 MC2R and MC1R signals are consecutively required for the regulation of EPO signal transduction in erythroblast differentiation, and MC5R signal transduction is required to induce enucleation.
25605722 results suggest that Phe(7) in ACTH plays an important role in ligand selectivity and that the third transmembrane domain of MC2R is crucial for ACTH selectivity and potency
25055195 The A allele at rs1941088 in the MC2R gene, which encodes the adrenocorticotropic hormone (corticotropin, ACTH) receptor, is associated with a low cortisol response in critically ill children.
24884994 MC2R overexpression is associated with myelolipomas.
24224542 The patient with familial glucocorticoid deficiency was found to be homozygous for a novel mutation in the melanocortin-2 receptor gene (635insC, I154H).
23231661 The ACTHR gene -2T>C variant may be one important factor that influences stress perception of patients with alopecia areata.
23023242 Significant differences in the gene expression of aldosterone synthase and adrenocorticotropic hormone receptor distinguishes adrenal neoplasms from primary aldosteronism.
22842514 Our observations suggest that MC2R is involved in prostate carcinogenesis and that targeting MC2R signaling may provide a novel avenue in prostate carcinoma treatment.
22487832 No significant difference was found between plasma lipid and glucose levels and various GR and ACTHR genotypes.
22357529 GRA5556G, GRA5556G, GAGG4534/4536AAAG polymorphisms and ACTHR promoter T-2C variants might be associated with quantitative trait of stress.
21920850 Intracellular Ser and Thr (S/T) residues of MC2R were found to play important roles not only in plasma membrane targeting and function but also in promoting receptor internalization.
21778684 Familial glucocorticoid deficiency in five Arab kindreds with homozygous point mutations of the ACTH receptor (MC2R).
21367968 The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex.
21211532 C-terminal tail of the MC(4) receptor with the corresponding regions from the MC(2) receptor resulted in MRAP-dependent signaling
21195128 ACTH binding to MC2R stimulates PKA-dependent p44/p42(mapk) phosphorylation.
20962024 Loss of the C terminus of MC2R impairs cell surface expression and ACTH sensitivity but does not disrupt interaction of MC2R with melanocortin receptor accessory protein.
20734064 Observational study of gene-disease association. (HuGE Navigator)
20634197 Meta-analysis of gene-disease association. (HuGE Navigator)
20590821 MC2R expression is aberrant in alopecia areata (AA). A deficit in ACTH/MC2R activity may play an important role in the pathophysiology of AA.
20403506 Observational study of gene-disease association. (HuGE Navigator)
20042918 The results showed that the haplotype TCCT in MC2R promoter significantly led to increased MC2R expression and strong responses to adrenocorticotropin hormone.
20022931 Absence of MC2R N-glycosylation abrogates to a large extent MC2R cell surface expression in the absence of accessory proteins, whereas when MC2R is N-glycosylated, it can be expressed at the plasma membrane without assistance.
19903795 No mutations in MC2R, MRAP or STAR were identified in any patient with Addison's disease
19903795 Observational study of gene-disease association. (HuGE Navigator)
19723618 Observational study of gene-disease association. (HuGE Navigator)
19574343 Observational study of gene-disease association. (HuGE Navigator)
19558534 Data show that tall stature is associated with mutations in MC2R but not in MRAP.
19558534 Observational study of gene-disease association. (HuGE Navigator)
19453261 Observational study of gene-disease association. (HuGE Navigator)
19372376 Includes the study of a polymorphic upstream ORF in this gene, and shows that it functions to reduce protein levels by ~37%.
19095219 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19024088 The polymorphisms of the MC2R promoter might be one important factor that influences the efficacy of ACTH therapy on infantile spasms.
19024088 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18981183 MRAP not only facilitates MC2 receptor trafficking but also allows properly localized receptor to bind ACTH and consequently signal.
18840636 The majority of MC2R mutations found in familial glucocorticoid deficiency type 1 fail to function because they fail to traffic to the cell surface
18838498 Observational study of gene-disease association. (HuGE Navigator)
18818285 The transmembrane domain of MRAP is the MC2R interaction domain and a conserved N-terminal tyrosine-rich domain of MRAP is required for trafficking MC2R to the cell surface.
18551113 Observational study of gene-disease association. (HuGE Navigator)
18505908 In cortices attached to adrenocortical adenomas, MC2R mRNA was expressed faintly in zona fasciculata and zona reticularis.
18492762 two mutations of the ACTH receptor (MC2R) gene are reported in this familial glucocorticoid deficiency clinical case.
18359160 Significant differences in genotype frequency among ethnic groups studied were found for each of the six variants analyzed. the allele -184A with a protective effect from heroin addiction in Hispanics.
18359160 Observational study of gene-disease association. (HuGE Navigator)
18356748 The MC2R promoter polymorphism modulates the hypothalamo-pituitary-adrenal axis in children and may play a role in altered regulation of adrenarche.
18356748 Observational study of gene-disease association. (HuGE Navigator)
18197087 results do not support an involvement of the -2 CTC to CCC ACTH receptor promoter polymorphism in somatoform disorders
17959886 Corticotrophin-releasing hormone induces ACTHR receptor as potently as ACTH during late gestation.
17877367 Results indicate that ACTH1-16 is the minimal peptide required for hMC2R binding and signaling.
17712720 Transcription factors of the CREB/CREM/ATF family have a moderate effect on human MC2-R promoter activity, but seem to play a minor role in transmitting stimulation of the cAMP pathway to increased MC2-R expression.
17595257 Testicular adrenal rest tumors produce adrenal-specific steroids and express adrenal-specific enzymes and ACTH and AII receptors, confirming the strong resemblance with adrenal tissue.
17456795 MC2R-green fluorescent protein fusion transfected with either MRAPalpha or MRAPbeta was impaired both in cell membrane localization and signaling.
17223989 MC2R mutations were found in patients diagnosed with salt-losing forms of adrenal hypoplasia; these changes represent severely disruptive loss-of-function mutations including the first reported homozygous frameshift mutation
16497811 PKA and protein kinase C act synergistically to induce hMC2R desensitization, but only PKA is essential for receptor internalization
16260430 Genetic variations within ACTH receptor promoter result in decreased DHEA secretion. We might have identified one of the genetic factors responsible for variation in ACTH-dependent DHEA secretion.
15982783 Specific factors, missing in cells which do not express any melanocortin receptor, are involved in the correct addressing of human MC2R to the cell membrane.
15879363 DAX-1 is a major repressor of ACTH-R gene expression in vitro and in vivo.
15240582 Observational study of gene-disease association. (HuGE Navigator)
15240582 We describe an ACTH receptor promoter polymorphism that results in lower promoter activity in vitro and is associated with lower cortisol secretion to prolonged ACTH stimulation in vivo. Might influence cortisol homeostasis under stress conditions.
15171714 Data show that an E-box is involved in the repression of melanocortin 2 receptor gene expression in granulosa cells through interactions with several factors.
15062562 Study of two mutations in the same allele of MC2R associated with clinical hypersensitivity to ACTH shows that each alone produces an inactive receptor, but together lead to a receptor with a highly significant elevation in constitutive activity
14671214 ACTH feedback loop in pituitary. Loss of expression of ACTH-R in corticotroph adenomas in Cushing's disease may play role in resistance to feedback of pituitary-adrenal axis.
12530626 Cyclic AMP-induced regulation of transcriptional activity of gene achieved through two SF1 binding elements in proximal promoter. Regulation by angiotensin II by two AP1 binding sites. Region in promoter responsible for tissue-specific gene expression.
12456795 findings suggest a novel mechanism is involved in the constitutive activation of the melanocortin 2 receptor in which failure of desensitization appears to be associated with enhanced basal receptor activity

AA Sequence

MKHIINSYENINNTARNNSDCPRVVLPEEIFFTISIVGVLENLIVLLAVFKNKNLQAPMYFFICSLAISD      1 - 70
MLGSLYKILENILIILRNMGYLKPRGSFETTADDIIDSLFVLSLLGSIFSLSVIAADRYITIFHALRYHS     71 - 140
IVTMRRTVVVLTVIWTFCTGTGITMVIFSHHVPTVITFTSLFPLMLVFILCLYVHMFLLARSHTRKISTL    141 - 210
PRANMKGAITLTILLGVFIFCWAPFVLHVLLMTFCPSNPYCACYMSLFQVNGMLIMCNAVIDPFIYAFRS    211 - 280
PELRDAFKKMIFCSRYW                                                         281 - 297
//

Text Mined References (82)

PMID Year Title
26223677 2015 Expression of melanocortin receptors in human endometrium.
26115626 2015 Association between two promoter polymorphisms (rs1893219 and rs1893220) of MC2R gene and intracerebral hemorrhage in Korean population.
25860801 2015 Melanocortins contribute to sequential differentiation and enucleation of human erythroblasts via melanocortin receptors 1, 2 and 5.
25605722 2015 Third transmembrane domain of the adrenocorticotropic receptor is critical for ligand selectivity and potency.
25055195 2014 A single nucleotide polymorphism in the corticotropin receptor gene is associated with a blunted cortisol response during pediatric critical illness.
24884994 2014 Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia.
24224542 Neonatal hyperpigmentation: diagnosis of familial glucocorticoid deficiency with a novel mutation in the melanocortin-2 receptor gene.
23231661 2013 The -2T/C polymorphism in the adrenocorticotropin receptor gene affects stress perception of patients with alopecia areata.
23023242 2012 Expression of aldosterone synthase and adrenocorticotropic hormone receptor in adrenal incidentalomas from normotensive and hypertensive patients: Distinguishing subclinical or atypical primary aldosteronism from adrenal incidentaloma.
22842514 2012 Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation.
22487832 2012 [Association between plasma lipid, glucose, cortisol and adrenocorticotropic hormone levels and GR and ACTHR gene polymorphisms].
22357529 2011 [Associations of GR and ACTHR gene polymorphisms with quantitative trait of strain].
21920850 2011 Mechanisms of melanocortin-2 receptor (MC2R) internalization and recycling in human embryonic kidney (hek) cells: identification of Key Ser/Thr (S/T) amino acids.
21778684 2011 Familial glucocorticoid deficiency in five Arab kindreds with homozygous point mutations of the ACTH receptor (MC2R): genotype and phenotype correlations.
21367968 2011 Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland.
21211532 2011 Use of chimeric melanocortin-2 and -4 receptors to identify regions responsible for ligand specificity and dependence on melanocortin 2 receptor accessory protein.
21195128 2011 Adrenocorticotropin hormone (ACTH) effects on MAPK phosphorylation in human fasciculata cells and in embryonic kidney 293 cells expressing human melanocortin 2 receptor (MC2R) and MC2R accessory protein (MRAP)?.
20962024 2011 Loss of the C terminus of melanocortin receptor 2 (MC2R) results in impaired cell surface expression and ACTH insensitivity.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20634197 2010 Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.
20590821 2010 Melanocortin receptor type 2 (MC2R, ACTH receptor) expression in patients with alopecia areata.
20403506 2010 Genetic variation in neuroendocrine genes associates with somatic symptoms in the general population: results from the EPIFUND study.
20371771 2010 Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2.
20108423 2010 Novel human pathological mutations. Gene symbol: MC2R. Disease: Glucocorticoid deficiency.
20042918 2010 ACTH receptor (MC2R) promoter variants associated with infantile spasms modulate MC2R expression and responsiveness to ACTH.
20022931 2010 Role of asparagine-linked glycosylation in cell surface expression and function of the human adrenocorticotropin receptor (melanocortin 2 receptor) in 293/FRT cells.
19903795 2010 Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency.
19723618 2010 Genetic variation in the hypothalamic-pituitary-adrenal stress axis influences susceptibility to musculoskeletal pain: results from the EPIFUND study.
19574343 2009 Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).
19558534 2010 Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2.
19453261 2009 High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.
19372376 2009 Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans.
19329486 2009 MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family.
19095219 2009 Variation in catechol-O-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder.
19024088 2008 Genetic polymorphisms of MC2R gene associated with responsiveness to adrenocorticotropic hormone therapy in infantile spasms.
18981183 2009 Regions of melanocortin 2 (MC2) receptor accessory protein necessary for dual topology and MC2 receptor trafficking and signaling.
18840636 2008 The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface.
18838498 2010 Association of HPA axis genes with suicidal behaviour in schizophrenia.
18818285 2009 Distinct melanocortin 2 receptor accessory protein domains are required for melanocortin 2 receptor interaction and promotion of receptor trafficking.
18551113 2008 Further evidence for the role of ENPP1 in obesity: association with morbid obesity in Finns.
18505908 2008 Analysis of mRNA expression for steroidogenic enzymes in the remaining adrenal cortices attached to adrenocortical adenomas.
18492762 2008 A novel adrenocorticotropin receptor mutation alters its structure and function, causing familial glucocorticoid deficiency.
18359160 2008 Association of polymorphisms in the melanocortin receptor type 2 (MC2R, ACTH receptor) gene with heroin addiction.
18356748 2008 ACTH receptor promoter polymorphism associates with severity of premature adrenarche and modulates hypothalamo-pituitary-adrenal axis in children.
18197087 2008 No evidence of association between adrenocorticotropic hormone receptor promoter polymorphism and somatoform disorders.
17959886 2007 The regulation of adrenocorticotrophic hormone receptor by corticotropin-releasing hormone in human fetal adrenal definitive/transitional zone cells.
17877367 2007 Molecular identification of the human melanocortin-2 receptor responsible for ligand binding and signaling.
17712720 2007 Regulation of human MC2-R gene expression by CREB, CREM, and ICER in the adrenocortical cell line Y1.
17595257 2007 Testicular tumors in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency show functional features of adrenocortical tissue.
17456795 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.
17223989 2007 Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia.
16497811 2006 Human melanocortin receptor 2 expression and functionality: effects of protein kinase A and protein kinase C on desensitization and internalization.
16260430 2005 Genetic influence of an ACTH receptor promoter polymorphism on adrenal androgen secretion.
15982783 2005 Expression of the human melanocortin-2 receptor in different eukaryotic cells.
15879363 2005 Clinical and molecular evidence for DAX-1 inhibition of steroidogenic factor-1-dependent ACTH receptor gene expression.
15654338 2005 Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15240582 2004 Characterization of an adrenocorticotropin (ACTH) receptor promoter polymorphism leading to decreased adrenal responsiveness to ACTH.
15171714 2004 An E-box-containing region is involved in the tissue-specific expression of the human MC2R gene.
15062562 2004 Constitutive activation of the human ACTH receptor resulting from a synergistic interaction between two naturally occurring missense mutations in the MC2R gene.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14671214 2003 Identification of adrenocorticotropin receptor messenger ribonucleic acid in the human pituitary and its loss of expression in pituitary adenomas.
12620396 2003 The structure and evolution of the melanocortin and MCH receptors in fish and mammals.
12530626 2002 The human MC2-R gene expression: different aspects of its control.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12456795 2002 Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity.
12213892 2002 Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.
12036966 2002 Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus.
10971458 2000 Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH.
9218248 Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides.
9194567 1997 Presence of multiple functional polyadenylation signals in the 3'-untranslated region of human corticotropin receptor cDNA.
9175632 1997 Stable expression of normal and mutant human ACTH receptor: study of ACTH binding and coupling to adenylate cyclase.
9167964 1997 Adrenocorticotropin receptor and adrenal disorders.
9058374 1997 Effects of recombinant agouti-signaling protein on melanocortin action.
9020063 1997 Genomic structure and promoter characterization of the human ACTH receptor gene.
8636348 1996 Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency.
8463333 1993 Molecular cloning of a novel melanocortin receptor.
8390157 1993 Cloning and functional characterization of a family of receptors for the melanotropic peptides.
8276410 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.
8227361 1993 Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene.
8094489 1993 Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor.
1325670 1992 The cloning of a family of genes that encode the melanocortin receptors.