Anaphylatoxin Receptors

Complement Component GPCRs / Anaphylatoxin Receptors List

Gene Name  Approved Name  Aliases Chromosome
C3AR1 complement C3a receptor 1 AZ3B, C3AR, HNFAG09 12p13.31
C5AR1 complement C5a receptor 1 C5A, C5AR, C5R1, CD88 19q13.32
C5AR2 complement component 5a receptor 2 C5L2, GPF77, GPR77 19q13.32

Anaphylatoxin Receptors Background

The activation of the complement cascade produces a number of small fragments that are bioactive: potent chemoattractants and secretagogues that act on immune and non-immune cells. Similar peptides can also be released by the actions of non-complement proteases, for instance during clotting. Initially these were termed anaphylatoxins because of their effect on mast cell histamine release, but were reclassified as complement component peptides. They include C3a and C5a, which are involved immune response, neural development and organ regeneration. A third peptide, C4a, has a similar structure, but it is inactive in humans. Since the primary function of complement component peptides is in inflammation, they are important targets for the development of anti-inflammatory therapies.

The anaphylatoxin chemotactic receptors (also known as complement peptide receptors) are a group of rhodopsin-like G-protein coupled receptors (GPCRs). There are three subtypes: C3a receptor (C3AR1), C5a receptor (C5AR1) and C5a anaphylatoxin receptor C5L2 (C5AR2). Both C3AR1 and C5AR1 receptors are classical GPCRs. However, C5AR2 appears to be permanently uncoupled from G proteins but can associate with beta-arrestin. Nevertheless, it has been shown that activation of both C5AR1 and C5AR2 is required for a full pro-inflammatory response, particularly in mice. Several receptor antagonists have been reported, although none, so far, have been show to be effective in humans.

Anaphylatoxin Receptors References

1. Monk P N, et al. (2007). Function, structure and therapeutic potential of complement C5a receptors. British journal of pharmacology, 152(4), 429-448.
2. Banda N K, et al. (2012). Role of C3a receptors, C5a receptors, and complement protein C6 deficiency in collagen antibody-induced arthritis in mice. The Journal of Immunology, 188(3), 1469-1478.
3. Ames R S, et al. (1996). Molecular cloning and characterization of the human anaphylatoxin C3a receptor. Journal of Biological Chemistry, 271(34), 20231-20234.
4. Schraufstatter I U, et al. (2009). C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. The Journal of Immunology, 182(6), 3827-3836.
5. Gerard C, et al. (1994). C5A anaphylatoxin and its seven transmembrane-segment receptor. Annual review of immunology, 12(1), 775-808.