MRAP

This gene encodes a melanocortin receptor-interacting protein. The encoded protein regulates trafficking and function of the melanocortin 2 receptor in the adrenal gland. The encoded protein can also modulate signaling of other melanocortin receptors. Mutations in this gene have been associated with familial glucocorticoid deficiency type 2. Alternatively spliced transcript variants have been described.

Full Name

MELANOCORTIN 2 RECEPTOR ACCESSORY PROTEIN

Function

Modulator of melanocortin receptors (MC1R, MC2R, MC3R, MC4R and MC5R). Acts by increasing ligand-sensitivity of melanocortin receptors and enhancing generation of cAMP by the receptors. Required both for MC2R trafficking to the cell surface of adrenal cells and for signaling in response to corticotropin (ACTH). May be involved in the intracellular trafficking pathways in adipocyte cells.

Biological Process

Negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: BHF-UCL
Negative regulation of protein localization to plasma membrane Source: BHF-UCL
Positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: BHF-UCL
Protein localization to plasma membrane Source: BHF-UCL
Regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: GO_Central

Cellular Location

Plasma membrane
Cell membrane
Endoplasmic reticulum
Endoplasmic reticulum membrane
Note: The formation of antiparallel homo- and heterodimers suggest that N- and C-terminus can both localize in the cytoplasmic and extracellular parts, depending on the context (PubMed:20371771). Upon insulin stimulation, it is redistributed into spotty structures throughout the cytoplasm.

Involvement in disease

Glucocorticoid deficiency 2 (GCCD2):
A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.

Topology

Helical: 38-58