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FLASH GENE
Symbol MRAP2 contributors: mct/npt - updated : 07-07-2020
HGNC name melanocortin 2 receptor accessory protein 2
HGNC id 21232
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • lacks amino acids 18LDYI21 of MRAP (Sebag 2009)
    • HOMOLOGY
    intraspecies paralog to MRAP
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    basic FUNCTION
  • having ability to facilitate trafficking of the MC2R to the plasma membrane and to enable the receptor to signal in response to its unique ligand, ACTH (Chan 2009)
  • having 2 separate MC2R accessory roles: first in trafficking of the receptor, and second in enabling receptor responsiveness to ACTH (Chan 2009)
  • like MRAP(18-21A), allows MC2 receptor trafficking but not signaling (Sebag 2009)
  • transports the MC2R to the cell surface but might prevent activation
  • role for MRAP2 in regulating melanocortin receptor activity and in the development of obesity
  • regulates Ghrelin Receptor signaling and hunger sensing
  • MRAP2 regulates endometrial receptivity and function
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • can homodimerize and form heterodimers with MRAP (Chan 2009)
  • complex MC4R-MRAP2 throws light on the action of ACTH and, by extension, on the relay of stress-related information to additional biological systems
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with MRAP (interaction results in MC2R surface expression and signaling) (Chan 2009)
  • modulates MC2R activity
  • MRAP2 interaction with the melanocortin-4-receptor (MC4R) affects receptor signaling
  • MRAP2 interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PROKR1)
  • role of MRAP2 in the regulation of the orexin receptor 1 (HCRTR1)
  • is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling
  • MRAP2 altered GHSR signaling by inhibiting its constitutive activity, as well as by enhancing its G protein-dependent signaling and blocking the recruitment and signaling of ARRB in response to ghrelin
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    lower in adrenocortical carcinomas (ACC) than in other adrenal tissues
    Susceptibility to hyperphagic obesity, hyperglycemia and hypertension
    Variant & Polymorphism other
  • loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mrap2 complete knockout (KO) mice have increased body weight without detectable changes to food intake or energy expenditure