Melanocortin receptor 3 (MC3R) (MC3R)

Melanocortin receptor 3 (MC3R) is a member of the G protein-coupled receptor (GPCR) family, specifically the rhodopsin-like (Class A) subfamily [1.2.1, 1.3.3]. It is primarily expressed in the central nervous system, particularly within the arcuate nucleus of the hypothalamus, and in peripheral tissues such as the heart, kidney, and immune cells [1.1.1, 1.4.1]. MC3R plays a pivotal role in energy homeostasis, nutrient partitioning, and the regulation of circadian rhythms and sexual maturation [1.4.2, 1.5.2]. Unlike the closely related MC4R, which primarily regulates satiety, MC3R acts as an inhibitory autoreceptor on proopiomelanocortin (POMC) neurons, providing a feedback mechanism for the melanocortin system [1.1.1, 1.4.1]. Mutations in the MC3R gene are associated with monogenic obesity, reduced lean mass, and delayed puberty in humans [1.3.2, 1.5.1]. Pharmacologically, MC3R is targeted by non-selective melanocortin agonists like setmelanotide for the treatment of genetic obesity, although its specific therapeutic potential is complicated by its role in feedback inhibition and its interaction with other metabolic pathways like GLP-1 signaling [1.1.4, 1.5.2].

Other names

Melanocortin-3 receptorMC3-RMC3 receptorBMIQ9OB20OQTL

MC3R is a Gs-coupled receptor that activates the adenylate cyclase/cAMP signaling pathway upon agonist binding [1.2.1, 1.5.4]. It acts as an inhibitory autoreceptor on POMC neurons in the hypothalamus, regulating the release of melanocortin peptides and maintaining energy balance [1.1.1, 1.4.1]. In the periphery, it modulates inflammatory responses and cardiovascular functions [1.1.2, 1.5.2].