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Details for receptor: melanocortin-4 receptor

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EndoNet ID: ENR00763

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Synonyms

  • MC4
  • MC4R
  • melanocortin 4 receptor
  • melanocortin-4 receptor
  • MC4-R

General information

  • MC4R could only be detected in pituitary. [1]
  • MC4R is expressed mainly in hypothalamus. [2]
  • Is essential for the maintenance of long-term energy balance in humans. [3]
  • G protein-coupled receptor. [3]
  • Agouti-related protein (AGRP) and the melanocortin-4 receptor (MC4R) have both been identified as directly regulating food intake. [4]
  • Absence of tje melanocortin-4 receptor leads to leptin resistance downstream of POMC-containing neurons, which are a direct target of leptin. [5]
  • Its activation by alpha-MSH in the paraventricular nucleus of the hypothalamus results in the suppression of food intake. [3]

Links to other resources

UniProt P32245
Ensembl ENST00000299766

Binding hormones

  • MSH
  • AGRP
    • AgRP is an antagonist of MC3R and MC4R and may act as a inhibitor of alpha-MSH. [2]
  • alpha-MSH
    • Alpha-MSH plays an important role in the regulation of appetite and energy expenditure via central melanocortin receptor, MC4R. [2]
    • Alpha-MSH is one of the known endogenous agonists for brain melanocortin-3 and -4 receptors. [4]
    • The potency of MC4R-Ligands is alpha-MSH = ACTH > beta-MSH > gamma-MSH. [6]
  • melanotropin gamma
    • The potency of MC4R-Ligands is alpha-MSH = ACTH > beta-MSH > gamma-MSH. [6]
  • ACTH
    • The potency of MC4R-Ligands is alpha-MSH = ACTH > beta-MSH > gamma-MSH. [6]
  • melanotropin beta
    • MC4 binds beta-MSH. [7]
    • The potency of MC4R-Ligands is alpha-MSH = ACTH > beta-MSH > gamma-MSH. [6]

Anatomical structures with this receptor

  • paraventricular_nucleus_of_hypothalamus

    Induced phenotypes

    • promotion of positive energy balance
      • A component of the melanocortin system within the arcuate nucleus of hypothalamus consists of a neuronal population that produces proopiomelanocortin (POMC)-derived peptides, such as alpha-melanocyte stimulating hormone, and cocaine- and amphetamine-regulated transcript (CART) peptides, which promote positive energy balance. [8]
      • In the PVN, the peptides derived from the breakdown of POMC (mainly alpha-MSH)are endogeneous agonists of MC4R. [9]
    • negative regulation of appetite
      • A component of the melanocortin system within the arcuate nucleus of hypothalamus consists of a neuronal population that produces proopiomelanocortin (POMC)-derived peptides, such as alpha-melanocyte stimulating hormone, and cocaine- and amphetamine-regulated transcript (CART) peptides, which promote satiety. [8]
      • In the PVN, the peptides derived from the breakdown of POMC (mainly alpha-MSH)are endogeneous agonists of MC4R. [9]
    • obesity
      • Dominant mutations in the agouti peptide were known to cause an obese phenotype in mice and this has been proved to be due to the antagonism of melanocortin receptors located in the PVN [10]

  • arcuate_nucleus_of_hypothalamus

    Induced phenotypes

    • negative regulation of appetite
      • Both alpha-Melanocyte-stimulating hormone (alpha-MSH) and agouti-related protein (AGRP) exert effects on energy balance by signaling through melanocortin receptor 4 and that induced an inhibitory influence on appetite and body weight. Alpha-MSH acts as an agonist to the receptor and suppresses feeding, and AGRP conversely stimulates food intake by antagonizing the alpha-MSH signaling.g. . [11]

  • adipose_tissue

    Influences

    • negative leptin
      • Leptin secretion and gene expression of differentiated rat adipocytes is inhibited by administration of alpha-MSH (alpha-melanocyte stimulating hormone), and this effect is antagonised by antagonist of melanocortin receptor MC4R (AgRP, agouti-related protein). [12]
Reference