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Details on Person UniProt:P32245 MC4R
| Class:Id | ReferenceGeneProduct:59045 |
|---|---|
| _chainChangeLog | chain:1-332 added on Fri February 6 2015 |
| _displayName | UniProt:P32245 MC4R |
| _timestamp | 2026-02-20 21:41:19 |
| chain | chain:1-332 |
| checksum | E80010BAADBED2B4 |
| comment | 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 (PubMed:12646665, PubMed:14764818, PubMed:25163632, PubMed:32327598, PubMed:33858992, PubMed:8392067). Functions as a central component of the leptin-melanocortin pathway, which is essential for maintaining energy homeostasis (PubMed:32327598, PubMed:33858992). 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 (PubMed:12588803, PubMed:14764818, PubMed:25163632, PubMed:33858992). Regulates food intake: activation by agonists suppresses appetite, whereas the antagonist Agouti-related protein/AGRP precludes agonist-induced signaling, thereby stimulating appetite (PubMed:9311920). 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 (PubMed:32327598). 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 (PubMed:39951488). 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 (PubMed:39562740). Interaction with MGRN1 displaces the G(s) protein, further decreasing MC4R signaling activity (PubMed:19737927). Also activated by gamma-MSH, though with low potency (PubMed:8392067).COFACTOR Homodimer; disulfide-linked, also forms higher order oligomers. Interacts with GNAS (PubMed:33858992). Interacts with ATRNL1 (By similarity). Interacts with MGRN1; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production. Interacts with MRAP and MRAP2; these associated factors increase ligand-sensitivity and generation of cAMP. Forms a complex with OPN3 and KCNJ13; interaction with OPN3 inhibits MC4R-mediated signaling (PubMed:39951488).INTERACTION Brain, placental, and gut tissues.POLYMORPHISM Genetic variations in MC4R define the body mass index quantitative trait locus 20 (BMIQ20) [MIM:618406]. MC4R loss-of-function variants are associated with higher body mass index, obesity, type 2 diabetes, and coronary artery disease. Gain-of-function variants have been reported to be associated with lower body mass index and resistance to obesity.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the G-protein coupled receptor 1 family.ONLINE INFORMATION Melanocortin receptor entry |
| description | recommendedName: Melanocortin receptor 4 shortName: MC4-R |
| geneName | MC4R |
| identifier | P32245 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Calcium Cell membrane Disease variant Disulfide bond G-protein coupled receptor Glycoprotein Lipoprotein Membrane Obesity Palmitate Receptor Reference proteome Transducer Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | MC4R |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8997265] ENSEMBL:ENSG00000166603 MC4R [Homo sapiens] |
| secondaryIdentifier | MC4R_HUMAN B2RAC3 Q16317 Q3MIJ6 |
| sequenceLength | 332 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:388606] MC4R [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P32245 MC4R (59045)
