C5AR2

Complement component 5a receptor 2 is a protein of the complement system that in humans is encoded by the C5AR2 gene. It is highly expressed in the blood and spleen, predominantly by myeloid cells.

Function

The anaphylatoxins C3a and C5a are fragments of C3 and C5 generated via proteolytic cleavage by C3 convertases and C5 convertases during the complement cascade. They are pro-inflammatory mediators which bind to the anaphylatoxin receptors, C3aR, C5aR1 and C5aR2. The anaphylatoxin receptors are a family of three proteins which beloing to the G protein-coupled receptor superfamily. C3aR and C5aR1 bind C3a and C5a, respectively, which mediate a broad range of effects in host defense, including chemoattraction, vasodilation and immune cell activation. C5aR2 binds C5a, but lacks GPCR activity, and its function is less well understood.

C5aR2 was initially thought be a decoy receptor, acting as a sink for C5a to negatively regulate C5aR1 function. However, more recent research has uncovered independent roles for C5aR2, including modulation of the innate immune response in myeloid cells, translocation of C5a to drive transendothelial migration of neutrophils, β-arrestin recruitment and modulation of ERK signalling and modulation of lipid metabolism in obesity through C3a-desArg binding. C5aR2 has been implicated in a broad range of inflammatory and infectious diseases.