MC4R
MC4R (melanocortin 4 receptor) is a G protein-coupled receptor that binds melanocyte-stimulating hormones and corticotropin/ACTH, peptide products of the POMC precursor. It is a central component of the leptin-melanocortin pathway, which maintains energy homeostasis. Browse Assay Genie's current range of MC4R research reagents below, or read on for the biology behind the target.
MC4R is a membrane-bound receptor that binds alpha- and beta-MSH and corticotropin/ACTH, all derived from the POMC precursor. It is also activated by gamma-MSH, though with low potency. On activation it couples to G(s) protein, stimulating adenylate cyclase and the cAMP-dependent signalling pathway. In the hypothalamus this promotes anorexigenic signalling and contributes to a negative energy balance.
The receptor regulates food intake. Agonists suppress appetite, whereas the antagonist Agouti-related protein (AGRP) precludes agonist-induced signalling and so stimulates appetite. In the paraventricular nucleus (PVN) of the hypothalamus, alpha-MSH and AGRP also modulate neuronal firing through closure of the inwardly rectifying potassium channel KCNJ13, independently of G(s) signalling. Also in the PVN, MC4R interacts with opsin 3 (OPN3), which couples to G(i/o) proteins to inhibit MC4R-mediated cAMP signalling and thereby promotes food intake. Interaction with MGRN1 displaces the G(s) protein and further decreases signalling activity.
Beyond the hypothalamus, MC4R in intestinal epithelial cells contributes to inhibition of hepatic glucose production via nesfatin-1/NUCB2, raising cAMP levels and glucagon-like peptide 1 (GLP-1) secretion. The MC4R gene is intronless and belongs to the melanocortin receptor gene group and the G protein-coupled receptor 1 family. The protein localises to the cell membrane and to the cilium membrane. Defects in this gene are a cause of autosomal dominant obesity. Mouse and rat orthologs are both designated Mc4r.
MC4R is central to the leptin-melanocortin pathway, and defects in the gene cause autosomal dominant obesity.
Agonists suppress appetite while AGRP blocks agonist-induced signalling, making MC4R a focal point for studying food intake regulation.
MC4R couples to G(s) to stimulate adenylate cyclase, and is modulated by OPN3 and MGRN1, offering a model for receptor regulation.
In intestinal epithelial cells MC4R acts with nesfatin-1/NUCB2 to raise cAMP and GLP-1 secretion, inhibiting hepatic glucose production.
MC4R is a G protein-coupled receptor that binds alpha- and beta-MSH and ACTH. Through G(s) coupling it raises cAMP, promoting anorexigenic signalling in the hypothalamus and a negative energy balance. AGRP antagonises it, stimulating appetite. It is a core part of the leptin-melanocortin pathway.
The HGNC name is melanocortin 4 receptor, and UniProt lists it as melanocortin receptor 4; no other aliases are recorded. It belongs to the melanocortin receptor gene group, alongside receptors such as MC1R and MC5R, and to the G protein-coupled receptor 1 family.
Mouse and rat both carry an ortholog named Mc4r. Defects in the human MC4R gene are a cause of autosomal dominant obesity, consistent with the receptor's role in energy homeostasis. Check the datasheet of any product for its validated reactivity.
Other melanocortin receptors and related G protein-coupled receptors with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P32245; product specifications from Assay Genie datasheets.