MC4R
entrez
4160
canonical
uniprot
P32245
canonical
ensembl
ENSG00000166603
resolver
ensp
ENSP00000299766
resolver
enst
ENST00000299766
resolver
genesymbol
MC4R
resolver
hgnc
HGNC:6932
resolver
uniprot
B2RAC3
resolver
uniprot
Q16317
resolver
uniprot
Q3MIJ6
resolver
uniprot_entry
MC4R_HUMAN
resolver
uniprot_sec
B2RAC3
resolver
uniprot_sec
Q16317
resolver
uniprot_sec
Q3MIJ6
resolver
amino_acid_sequence
MVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPLIYALRSQELRKTFKEIICCYPLGGLCDLSSRY
uniprot
proteins
disease_involvement
DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:10199800, ECO:0000269|PubMed:11443223, ECO:0000269|PubMed:11487744, ECO:0000269|PubMed:12588803, ECO:0000269|PubMed:12646665, ECO:0000269|PubMed:12970296, ECO:0000269|PubMed:14671178, ECO:0000269|PubMed:14764818, ECO:0000269|PubMed:15486053, ECO:0000269|PubMed:25163632, ECO:0000269|PubMed:29311635, ECO:0000269|PubMed:41102563}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Obesity due to MC4R deficiency is associated with reduced total cholesterol, low-density lipoprotein-cholesterol, triglycerides and hypertension, and relative protection from cardiovascular disease. {ECO:0000269|PubMed:41102563}.
uniprot
proteins
function
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, PubMed:29311635). 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). {ECO:0000269|PubMed:12588803, ECO:0000269|PubMed:12646665, ECO:0000269|PubMed:14764818, ECO:0000269|PubMed:19737927, ECO:0000269|PubMed:25163632, ECO:0000269|PubMed:29311635, ECO:0000269|PubMed:32327598, ECO:0000269|PubMed:33858992, ECO:0000269|PubMed:39562740, ECO:0000269|PubMed:39951488, ECO:0000269|PubMed:8392067, ECO:0000269|PubMed:9311920}.
uniprot
proteins
mass_dalton
36943
uniprot
proteins
mutagenesis
MUTAGEN 100; /note="E->A: Almost complete loss of alpha-MSH signaling."; /evidence="ECO:0000269|PubMed:33858992"; MUTAGEN 122; /note="D->A: Loss of high-affinity ligand binding."; /evidence="ECO:0000269|PubMed:32327598"; MUTAGEN 122; /note="D->N: About 50% loss of alpha-MSH signaling."; /evidence="ECO:0000269|PubMed:33858992"; MUTAGEN 126; /note="D->Y: Complete abolishment of receptor function."; /evidence="ECO:0000269|PubMed:33858992
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10199800
uniprot
proteins
pubmed
11443223
uniprot
proteins
pubmed
11487744
uniprot
proteins
pubmed
12588803
uniprot
proteins
pubmed
12646665
uniprot
proteins
pubmed
12970296
uniprot
proteins
pubmed
14671178
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14764818
uniprot
proteins
pubmed
15486053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19329486
uniprot
proteins
pubmed
19737927
uniprot
proteins
pubmed
23088915
uniprot
proteins
pubmed
25163632
uniprot
proteins
pubmed
29311635
uniprot
proteins
pubmed
31002796
uniprot
proteins
pubmed
32327598
uniprot
proteins
pubmed
33858992
uniprot
proteins
pubmed
39562740
uniprot
proteins
pubmed
39951488
uniprot
proteins
pubmed
41102563
uniprot
proteins
pubmed
7854347
uniprot
proteins
pubmed
8392067
uniprot
proteins
pubmed
9311920
uniprot
proteins
sequence_length
332
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25163632, ECO:0000269|PubMed:39951488}; Multi-pass membrane protein {ECO:0000255}. Cell projection, cilium membrane {ECO:0000269|PubMed:29311635}; Multi-pass membrane protein.
uniprot
proteins
transmembrane_region
TRANSMEM 48..63; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE"; TRANSMEM 84..107; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE"; TRANSMEM 119..145; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE"; TRANSMEM 167..188; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE"; TRANSMEM 192..214; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE"; TRANSMEM 244..267; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE"; TRANSMEM 280..302; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:33858992, ECO:0007744|PDB:7AUE
uniprot
proteins