Biology:C5AR2

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Short description: Protein-coding gene in the species Homo sapiens

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Complement component 5a receptor 2 is a protein of the complement system that in humans is encoded by the C5AR2 gene.[1][2] It is highly expressed in the blood and spleen,[3] predominantly by myeloid cells.[4][5]

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.[6] C5aR2 binds C5a, but lacks GPCR activity,[7] 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.[7] However, more recent research has uncovered independent roles for C5aR2, including modulation of the innate immune response in myeloid cells,[8][9] translocation of C5a to drive transendothelial migration of neutrophils,[10] β-arrestin recruitment and modulation of ERK signalling[11][12] and modulation of lipid metabolism in obesity through C3a-desArg binding.[13] C5aR2 has been implicated in a broad range of inflammatory and infectious diseases.[14][15]

References

  1. ↑ "A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells". Molecular Immunology 37 (8): 407–412. June 2000. doi:10.1016/S0161-5890(00)00067-5. PMID 11090875. 
  2. ↑ "HGNC:4527". https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4527. 
  3. ↑ "An Integrated Analysis of C5AR2 Related to Malignant Properties and Immune Infiltration of Breast Cancer". Frontiers in Oncology 11. 2021-09-14. doi:10.3389/fonc.2021.736725. PMID 34595119. 
  4. ↑ "The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction". The Journal of Biological Chemistry 285 (10): 7633–7644. March 2010. doi:10.1074/jbc.M109.092106. PMID 20044484. 
  5. ↑ "Monitoring C5aR2 Expression Using a Floxed tdTomato-C5aR2 Knock-In Mouse". Journal of Immunology 199 (9): 3234–3248. November 2017. doi:10.4049/jimmunol.1700710. PMID 28864475. 
  6. ↑ "The role of the anaphylatoxins in health and disease". Molecular Immunology. 12th European Meeting on Complement in Human Disease 46 (14): 2753–2766. September 2009. doi:10.1016/j.molimm.2009.04.027. PMID 19477527. 
  7. ↑ 7.0 7.1 "The human complement fragment receptor, C5L2, is a recycling decoy receptor". Molecular Immunology 46 (6): 1149–1162. March 2009. doi:10.1016/j.molimm.2008.11.001. PMID 19100624. 
  8. ↑ "C5aR2 Activation Broadly Modulates the Signaling and Function of Primary Human Macrophages". Journal of Immunology 205 (4): 1102–1112. August 2020. doi:10.4049/jimmunol.2000407. PMID 32611725. 
  9. ↑ "C5aR2 Regulates STING-Mediated Interferon Beta Production in Human Macrophages". Cells 12 (23): 2707. November 2023. doi:10.3390/cells12232707. PMID 38067135. 
  10. ↑ "Atypical complement receptor C5aR2 transports C5a to initiate neutrophil adhesion and inflammation". Science Immunology 4 (35). May 2019. doi:10.1126/sciimmunol.aav5951. PMID 31076525. 
  11. ↑ "Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling". Immunology and Cell Biology 94 (8): 787–795. September 2016. doi:10.1038/icb.2016.43. PMID 27108698. 
  12. ↑ "C5a2 can modulate ERK1/2 signaling in macrophages via heteromer formation with C5a1 and β-arrestin recruitment". Immunology and Cell Biology 92 (7): 631–639. August 2014. doi:10.1038/icb.2014.32. PMID 24777312. http://eprints.whiterose.ac.uk/99940/3/Croker%20paper%20ICB%202014%20V1%20rev.pdf. 
  13. ↑ "The ASP and C5L2 pathway: another bridge between inflammation and metabolic homeostasis" (in en). Clinical Lipidology 5 (3): 367–377. June 2010. doi:10.2217/clp.10.21. ISSN 1758-4299. https://www.tandfonline.com/doi/full/10.2217/clp.10.21. 
  14. ↑ "C5L2: a controversial receptor of complement anaphylatoxin, C5a". FASEB Journal 27 (3): 855–864. March 2013. doi:10.1096/fj.12-220509. PMID 23239822. 
  15. ↑ "The Complement Receptor C5aR2: A Powerful Modulator of Innate and Adaptive Immunity". Journal of Immunology 202 (12): 3339–3348. June 2019. doi:10.4049/jimmunol.1900371. PMID 31160390. 



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