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FLASH GENE
Symbol MC3R contributors: mct - updated : 15-05-2017
HGNC name melanocortin 3 receptor
HGNC id 6931
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven transmembrane segments (7TM) receptor
  • a DPLIY motif and helix 8, important for MC3R activation and signal transduction
  • cytoplasmic end of TM3 and the intracellular loop 2 (ICL2) were critical for MC3R function
    • conjugated GlycoP , LipoP , PhosphoP , Other
    HOMOLOGY
    interspecies ortholog to murine Mc3r
    homolog to C.elegans Y62H9A.1
    Homologene
    FAMILY
  • family A rhodopsin-like G protein-coupled receptors
    • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • acting as a receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone that is expressed in tissues other than the adrenal cortex and melanocytes
  • having a physiological effects on the cardiovascular system arising from effects on the central nervous system
  • important regulator of energy homeostasis, inflammation, and cardiovascular function
  • required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for normal regulation of cortical clock function
  • required for synchronizing metabolism during entrainment to restricted feeding during the light cycle
  • influencing body composition, natriuresis, immune function, and entrainment of circadian rhythms to nutrient intake
  • is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning
  • specific role for MC3R–containing circuits in communicating nutritional status to the hypothalamic-pituitary-adrenal (HPA) axis and in appropriately regulating nutrient partitioning from white adipose tissue (WAT) to liver in response to fasting
  • in the paraventricular nucleus (PVN), may exert a tonic excitatory effect on sympathetic activity
  • regulates several physiological functions, including feed efficiency, nutrient partitioning, fasting response, natriuresis, and immune reactions
  • is involved in the control of feeding, energy metabolism, and pituitary function
  • intact melanocortin signaling via the G protein-coupled receptors (GPCRs), MC4R and MC3R is crucial for body weight maintenance
  • neural melanocortin receptors (MCRs), MC3R and MC4R, play crucial roles in the regulation of energy homeostasis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text energy homeostasis
    PATHWAY
    metabolism
    signaling hormonal , signal transduction
    coupled to both cAMP and inositol phospholipid/Ca(2+)-mediated signaling systems
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RNF11 inhibits MC3R, MC4R signaling
    • cell & other
    REGULATION
    Other regulated by estradiol-17 beta
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension
    constitutional   deletion    
    resulted in features common to Cushing syndrome including increased adiposity, decreased lean mass, decreased immune function, and increased sensitivity to salt-induced hypertension
    Susceptibility
  • to severe obesity
  • to tuberculosis
    • Variant & Polymorphism SNP , other
  • mutation I183N completely abolishes agonist-mediated receptor activationand is associated to severe obesity
  • A293T, I335S and X361Sassociated to morbid obesity
  • SNP rs6127698 in the promoter region of MC3R showed significant association with tuberculosis susceptibility
  • C allele of rs11575886 could be a risk allele for the pulmonary TB by affecting the binding of transcription binding factor (TF)
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mc3r(-/-) mouse exhibits mild obesity without hyperphagia or hypometabolism