lmmol · Proteins

Melanocortin receptor 4

UniProt P32245 Organism Homo sapiens Gene MC4R

Also known as: MC4R

Function

G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha- and beta-MSH) and corticotropin/ACTH, which are peptide products of the POMC precursor. Functions as a central component of the leptin-melanocortin pathway, which is essential for maintaining energy homeostasis. Upon activation, couples to G(s) protein, stimulating adenylate cyclase and the cAMP-dependent signaling pathway, which promotes anorexogenic signaling in the hypothalamus and contributes to a negative energy balance. Regulates food intake: activation by agonists suppresses appetite, whereas the antagonist Agouti-related protein/AGRP precludes agonist-induced signaling, thereby stimulating appetite. Modulates the firing activity of neurons in paraventricular nucleus (PVN) of the hypothalamus via alpha-MSH and AGRP regulation of inwardly rectifying potassium channel KCNJ13 closure, independently of G(s) signaling. In the PVN, also interacts with opsin 3/OPN3, which couples to G(i/o) proteins to inhibit MC4R-mediated cAMP signaling, thereby promoting food intake. In intestinal epithelial cells, contributes to inhibition of hepatic glucose production via nesfatin-1/NUCB2, leading to increased cAMP levels and glucagon-like peptide 1 (GLP-1) secretion. Interaction with MGRN1 displaces the G(s) protein, further decreasing MC4R signaling activity. Also activated by gamma-MSH, though with low potency.

Classification

Family (Pfam)
PF00001 7tm_1
InterPro
GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, MC3-5R, Mcort_rcpt_4, Melcrt_ACTH_rcpt
Functional cluster
G Protein-Coupled Receptors

Experimental structures · PDB · 12

A predicted model is available from AlphaFold.

Gene Ontology · 18

Disease associations

Drugs targeting this protein · 5

Neighborhood · nearest proteins

MC4RMC4RMC4RMC4RNEFAADCY3POMC
Nearest neighbours of Melanocortin receptor 4: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 25 cited papers

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