C5AR1 gene

The C5AR1 gene (C5AR1 stands for: Complement C5a Receptor 1) is a protein-coding gene located on chromosome 19q13.32. An important paralog of this gene is C5AR2. Gene Ontology annotations associated with this gene include G protein-coupled receptor activity and complement component C5a binding.

The encoded protein is Complement C5a Receptor 1, a receptor for the chemotactic and pro-inflammatory peptide anaphylatoxin C5a. C5a is a strong chemoattractant for monocytes, neutrophil granulocytes and other leukocytes. Basically, the complement system is a biochemical signaling pathway involved in both innate and adaptive immune responses. The complement system has four main functions: lysis of microorganisms, promotion of phagocytosis, initiation of inflammation and immune defense.

The ligand C5a interacts with at least two sites on the receptor: a high-affinity site at the extracellular N-terminus and a second site in the transmembrane region that activates downstream signaling events (Christophe T et al. 2000; Monk PN et al. 1995; Chen Z et al. 1998). Activation of the receptor stimulates chemotaxis, the release of granule enzymes, intracellular calcium release and the production of superoxide anions (Monk PN et al. 1995; Chen Z et al. 1998)

The receptor protein is involved in several processes, including the signaling pathway of complement component C5a, mRNA transcription by RNA polymerase II and positive regulation of the ERK1 and ERK2 cascade. It is located in the apical part of the cell and in the basolateral plasma membrane. Biomarker for Alzheimer's disease, asthma, chronic obstructive pulmonary disease, rhinitis and severe acute respiratory syndrome.

Diseases associated with C5AR1 include:

• Atypical hemolytic uremic syndrome

and

• Hypersensitivity reaction type III disease.

1. Christophe T et al. (2000) Human complement 5a (C5a) anaphylatoxin receptor (CD88) phosphorylation sites and their specific role in receptor phosphorylation and attenuation of G protein-mediated responses. Desensitization of C5a receptor controls superoxide production but not receptor sequestration in HL-60 cells. J Biol Chem 275:1656-1664.
2. Monk PN et al. (1995) Mutation of glutamate 199 of the human C5a receptor defines a binding site for ligand distinct from the receptor N terminus. J Biol Chem 270:16625-16629.
3. Chen Z et al. (1998) Residues 21-30 within the extracellular N-terminal region of the C5a receptor represent a binding domain for the C5a anaphylatoxin. J Biol Chem 273:10411-10419.