C5a Complement Peptide Receptor 1 Antibodies

Complement C5a receptor 1 (C5aR1), also known as CD88 and encoded by C5AR1, is a class A G protein-coupled receptor activated by the anaphylatoxin C5a, which is generated during complement activation. Removal of the C-terminal arginine from C5a produces C5a-desArg, which generally has lower agonist potency at C5aR1. The receptor couples predominantly to Gi/o and activates pathways that regulate calcium mobilization, cell adhesion, and chemotaxis. C5aR1 is highly expressed on neutrophils and is also found on monocytes and macrophages. Its activation recruits myeloid cells to sites of infection or tissue injury and can trigger neutrophil degranulation and reactive oxygen species production. Agonist stimulation induces phosphorylation of the receptor’s C-terminal tail and promotes β-arrestin recruitment, desensitization, and internalization. Excessive C5aR1 signaling can amplify neutrophil-mediated vascular injury in ANCA-associated vasculitis. The oral C5aR1 antagonist avacopan (Tavneos) was approved for severe ANCA-associated vasculitis, but its EU marketing authorization was subsequently revoked following reassessment of the pivotal clinical trial data. C5a1 desensitization, β-arrestin recruitment and internalization is regulated by phosphorylation of carboxyl-terminal threonine324/serine327 (pT324/pS327-C5a1), serine332/serine334 (pS332/pS334-C5a1) threonine336 (pT336-C5a1), threonine338/threonine339 (pT338/pS339-C5a1) and threonine342 (pT342-C5a1) residues. This nomenclature refers to the human C5a1 receptor. This phosphorylation motif is conserved across species but corresponds to pS325/pS328-C5a1 and pS333/pS335-C5a1 in mice and pS325/pS328-C5a1 and pS334/pS336-C5a1 in rats. T324/S327 are also subject to phosphorylation by PKC. For more information on C5a1 receptor pharmacology please refer to the IUPHAR database. For further reading refer to:

Klos A, Wende E, Wareham KJ, Monk PN. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev. 2013 Jan;65(1):500-43. Review. Erratum in: Pharmacol Rev. 2014 Apr;66(2):466. PubMed PMID: 23383423.

Nürge B, Schulz AL, Kaemmerer D, Sänger J, Evert K, Schulz S, Lupp A. Immunohistochemical identification of complement peptide C5a receptor 1 (C5aR1) in non-neoplastic and neoplastic human tissues. PLoS One. 2021 Feb 19;16(2):e0246939. doi: 10.1371/journal.pone.0246939. PMID: 33606748; PMCID: PMC7894821.