Complement component 5a receptor 2 is a protein of the complement system that in humans is encoded by the C5AR2 gene.[5][6] It is highly expressed in the blood and spleen,[7] predominantly by myeloid cells.[8][9]
The anaphylatoxins C3a and C5a are fragments of C3 and C5 generated via proteolytic cleavagebyC3 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.[10] C5aR2 binds C5a, but lacks GPCR activity,[11] 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.[11] However, more recent research has uncovered independent roles for C5aR2, including modulation of the innate immune response in myeloid cells,[12][13] translocation of C5a to drive transendothelial migrationofneutrophils,[14] β-arrestin recruitment and modulation of ERK signalling[15][16] and modulation of lipid metabolisminobesity through C3a-desArg binding.[17] C5aR2 has been implicated in a broad range of inflammatory and infectious diseases.[18][19]
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