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    MRAP2 melanocortin 2 receptor accessory protein 2 [ Homo sapiens (human) ]

    Gene ID: 112609, updated on 5-Mar-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.

    Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.
    da Fonseca ACP, Abreu GM, Zembrzuski VM, Campos Junior M, Carneiro JRI, Nogueira Neto JF, Magno FCCM, Rosado EL, Bozza PT, de Cabello GMK, Cabello PH.

    06/26/2021
    Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.

    Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.
    Chen V, Bruno AE, Britt LL, Hernandez CC, Gimenez LE, Peisley A, Cone RD, Millhauser GL., Free PMC Article

    03/13/2021
    The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.

    The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.
    Rouault AAJ, Rosselli-Murai LK, Hernandez CC, Gimenez LE, Tall GG, Sebag JA., Free PMC Article

    12/12/2020
    The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets.

    Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension.
    Baron M, Maillet J, Huyvaert M, Dechaume A, Boutry R, Loiselle H, Durand E, Toussaint B, Vaillant E, Philippe J, Thomas J, Ghulam A, Franc S, Charpentier G, Borys JM, Lévy-Marchal C, Tauber M, Scharfmann R, Weill J, Aubert C, Kerr-Conte J, Pattou F, Roussel R, Balkau B, Marre M, Boissel M, Derhourhi M, Gaget S, Canouil M, Froguel P, Bonnefond A., Free PMC Article

    01/25/2020
    Data found that MRAP2 was significantly up-regulated in women with unexplained infertility. The epithelium of the uterine glands showed hypertrophy in women with unexplained infertility. MRAP2 expression alteration in the endometrium on infertile women suggestes a potential role in regulating endometrial stability.

    MRAP2 regulates endometrial receptivity and function.
    D'Aurora M, Romani F, Franchi S, Diomede F, Merciaro I, Impicciatore GG, Trubiani O, Stuppia L, Tiboni GM, Gatta V.

    05/18/2019
    The accepted idea that melanocortin Receptor Accessory Proteins (MRAPs) are specific regulators of melanocortin receptors was recently challenged by the discovery that MRAP2 inhibits the activity of prokineticin receptors. Recent studies are starting to explain the role of the unusual structure of MRAPs and to illustrate the importance of MRAP2 for the maintenance of both energy and glucose homeostasis. [review]

    Melanocortin Receptor Accessory Proteins (MRAPs): Functions in the melanocortin system and beyond.
    Rouault AAJ, Srinivasan DK, Yin TC, Lee AA, Sebag JA.

    12/1/2018
    In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1. Importantly, like MC4R and PKRs, OX1R is predominately expressed in the brain where it regulates food intake

    Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling.
    Rouault AAJ, Lee AA, Sebag JA.

    02/10/2018
    This was the first study describing an effect of a MRAP2 mutation on mediated by regulation of the melanocortin-4 receptor FUNCTION IN HUMAN.

    Decreased melanocortin-4 receptor function conferred by an infrequent variant at the human melanocortin receptor accessory protein 2 gene.
    Schonnop L, Kleinau G, Herrfurth N, Volckmar AL, Cetindag C, Müller A, Peters T, Herpertz S, Antel J, Hebebrand J, Biebermann H, Hinney A.

    06/24/2017
    no gene harboring deletions were identified in the SIM1 and MRAP2 regions in the Prader Willi like (PWL) cohort; further functional analysis of p.P352S found in SIM1 and p.A40S found in MRAP2 is useful; this would provide further support for possible role of SIM1 and MRAP2 in the pathogenesis of the PWL phenotype in a limited number of patients

    Copy number variation (CNV) analysis and mutation analysis of the 6q14.1-6q16.3 genes SIM1 and MRAP2 in Prader Willi like patients.
    Geets E, Zegers D, Beckers S, Verrijken A, Massa G, Van Hoorenbeeck K, Verhulst S, Van Gaal L, Van Hul W.

    12/17/2016
    Data show that co-expression with MRAPalpha, but not MRAP2, enhances MC4R constitutive activity. MRAPalpha-enhanced MC4R constitutive activity is not dependent on MC4R complex glycosylation but may result from MRAPalpha-induced changes in MC4R conformational states.

    hMRAPα, but Not hMRAP2, Enhances hMC4R Constitutive Activity in HEK293 Cells and This Is Not Dependent on hMRAPα Induced Changes in hMC4R Complex N-linked Glycosylation.
    Kay EI, Botha R, Montgomery JM, Mountjoy KG., Free PMC Article

    06/11/2016
    MC3R is a 2-exon gene that requires a 5' UTR for translation, localization, and potential interaction with MRAP2

    Melanocortin 3 receptor has a 5' exon that directs translation of apically localized protein from the second in-frame ATG.
    Park J, Sharma N, Cutting GR., Free PMC Article

    05/23/2015
    In a study of humans with severe, early-onset obesity, they found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.

    Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity.
    Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, Ramanathan V, Strochlic DE, Ferket P, Linhart K, Ho C, Novoselova TV, Garg S, Ridderstråle M, Marcus C, Hirschhorn JN, Keogh JM, O'Rahilly S, Chan LF, Clark AJ, Farooqi IS, Majzoub JA., Free PMC Article

    08/10/2013
    Data suggest that MRAP2 regulates expression of melanocortin receptors (MC1R-MC5R); MRAP2 is highly expressed in fetal adrenal glands; MRAP2 is also expressed in hypothalamus, a site that expresses high levels of MC3R and MC4R. [REVIEW]

    Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.
    Novoselova TV, Jackson D, Campbell DC, Clark AJ, Chan LF.

    05/11/2013
    MRAP2 is positively regulated by ACTH and AngII in human adrenocortical tissues.

    Melanocortin 2 receptor-associated protein (MRAP) and MRAP2 in human adrenocortical tissues: regulation of expression and association with ACTH responsiveness.
    Hofland J, Delhanty PJ, Steenbergen J, Hofland LJ, van Koetsveld PM, van Nederveen FH, de Herder WW, Feelders RA, de Jong FH.

    07/28/2012
    The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex.

    Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland.
    Gorrigan RJ, Guasti L, King P, Clark AJ, Chan LF., Free PMC Article

    10/8/2011
    MRAP2 is an endogenous inhibitor that competes with MRAP for binding to MC2R and decreases the potency of adrenocorticotropic hormone (ACTH).

    Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2.
    Sebag JA, Hinkle PM., Free PMC Article

    08/30/2010
    identify MRAP and MRAP2 as unique bidirectional regulators of the melanocortin receptor family

    MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family.
    Chan LF, Webb TR, Chung TT, Meimaridou E, Cooray SN, Guasti L, Chapple JP, Egertová M, Elphick MR, Cheetham ME, Metherell LA, Clark AJ., Free PMC Article

    01/21/2010
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