Melanocortin-2 receptor accessory protein 2 (MRAP2)

Melanocortin-2 receptor accessory protein 2 (MRAP2) is a single-pass transmembrane protein encoded by the C6orf117 gene and acts as an accessory protein for several G protein-coupled melanocortin receptors, most critically MC2R (the ACTH receptor). It is expressed in the brain and adrenal gland, enabling correct trafficking and cell surface expression of MC2R, rendering adrenal cells responsive to ACTH. MRAP2 also interacts with MC1R, MC3R, MC4R, and MC5R, modulating their responsiveness, often acting as a negative regulator. Dimerization (antiparallel homodimers and heterodimers) and dual-topology are distinctive structural features, and N-terminal glycosylation is important for function. Mutations in MRAP2 are implicated in monogenic obesity through altered signaling of MC4R, highlighting its role in energy balance. While not a direct drug target currently, MRAP2 is essential to MC2R function and may serve as a biomarker for congenital glucocorticoid deficiency or obesity syndromes. As an accessory protein, it does not directly signal but critically modulates the physiology of the melanocortin system.

Other names

MRAP2C6orf117MC2R accessory protein 2bA51G5.2

Acts as a required accessory protein for proper cell surface trafficking and function of MC2R (ACTH receptor). Bidirectional modulation (enhancement or inhibition) of other melanocortin receptors (MC1R, MC3R, MC4R, MC5R) signaling and surface expression. Inhibits β-arrestin interaction and boosts G-protein signaling (notably for MC4R).