CMKLR1
Description
The CMKLR1 (chemerin chemokine-like receptor 1) is a protein-coding gene located on chromosome 12.
Chemokine like receptor 1 (CMKLR1), also known as ChemR23, is a protein encoded by the CMKLR1 gene. It acts as a G protein-coupled receptor for the chemoattractant adipokine chemerin and the omega-3 fatty acid derived specialized pro-resolving molecule, resolvin E1. CMKLR1 displays a wide RNA expression profile but is particularly abundant in plasmacytoid dendritic cells, macrophages, cardiomyocytes, adipocytes, and endothelial cells. Activation of CMKLR1 by an agonist triggers mobilization of intracellular calcium and activation of signaling cascades like ERK1 and NF-κB. Early studies suggested a role in inflammatory pathways due to the presence of chemerin in rheumatoid arthritis joint aspirate and its absence in degenerative arthritis aspirate. CMKLR1 expression by plasmacytoid dendritic cells and macrophages further supported this hypothesis. In vitro chemotaxis assays demonstrated its involvement in attracting these cells. As an adipokine receptor, CMKLR1 plays a role in adipogenesis and adipocyte maturation.
CMKLR1 acts as a receptor for the chemoattractant adipokine chemerin (RARRES2) and the omega-3 fatty acid derived molecule resolvin E1. Binding of chemerin activates G proteins G(i)/G(o) and beta-arrestin pathways, triggering cellular responses through second messenger pathways such as intracellular calcium mobilization and phosphorylation of MAP kinases (ERK1/2, TYRO3, MAPK14/P38MAPK, and PI3K). This leads to diverse effects including reduced immune responses, enhanced adipogenesis, and angiogenesis. Resolvin E1 downregulates cytokine production in macrophages by inhibiting the activation of ERK1/2 and NF-kappa-B. CMKLR1 positively regulates adipogenesis and adipocyte metabolism.
CMKLR1 is also known as CHEMERINR, ChemR23, DEZ, ERV1, RVER1.
