UniProt functional annotation for P32245



	UniProt functional annotation for P32245

UniProt code: P32245.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP). {ECO:0000269|PubMed:12646665, ECO:0000269|PubMed:25163632}.

Subunit: Interacts with ATRNL1 (By similarity). Homodimer; disulfide- linked, also forms higher order oligomers. Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; 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. {ECO:0000250, ECO:0000269|PubMed:19329486, ECO:0000269|PubMed:19737927, ECO:0000269|PubMed:23088915}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:25163632}; Multi-pass membrane protein {ECO:0000255}.

Tissue specificity: 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. {ECO:0000269|PubMed:31002796}.

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:14671178, ECO:0000269|PubMed:14764818, ECO:0000269|PubMed:15486053, ECO:0000269|PubMed:25163632}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP). {ECO:0000269\|PubMed:12646665, ECO:0000269\|PubMed:25163632}.


Subunit:		Interacts with ATRNL1 (By similarity). Homodimer; disulfide- linked, also forms higher order oligomers. Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; 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. {ECO:0000250, ECO:0000269\|PubMed:19329486, ECO:0000269\|PubMed:19737927, ECO:0000269\|PubMed:23088915}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:25163632}; Multi-pass membrane protein {ECO:0000255}.
Tissue specificity:		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. {ECO:0000269\|PubMed:31002796}.
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:14671178, ECO:0000269\|PubMed:14764818, ECO:0000269\|PubMed:15486053, ECO:0000269\|PubMed:25163632}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the G-protein coupled receptor 1 family. {ECO:0000255\|PROSITE-ProRule:PRU00521}.