View source for C5AR2

{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
'''Complement component 5a receptor 2''' is a [[protein]] of the [[complement system]] that in humans is encoded by the ''C5AR2'' [[gene]].<ref name="pmid11165367">{{cite journal | vauthors = Ohno M, Hirata T, Enomoto M, Araki T, Ishimaru H, Takahashi TA | title = A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells | journal = Molecular Immunology | volume = 37 | issue = 8 | pages = 407–412 | date = June 2000 | pmid = 11090875 | doi = 10.1016/S0161-5890(00)00067-5 }}</ref><ref name="HGNC GPR77">{{cite web |title=HGNC:4527 |url=https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/4527 |access-date=2019-08-30}}</ref> It is highly expressed in the blood and spleen,<ref>{{cite journal | vauthors = Zhu Y, Wang X, Xu Y, Chen L, Ding P, Chen J, Hu W | title = An Integrated Analysis of C5AR2 Related to Malignant Properties and Immune Infiltration of Breast Cancer | journal = Frontiers in Oncology | volume = 11 | pages = 736725 | date = 2021-09-14 | pmid = 34595119 | pmc = 8476960 | doi = 10.3389/fonc.2021.736725 | doi-access = free }}</ref> predominantly by [[Myeloid tissue|myeloid]] cells.<ref>{{cite journal | vauthors = Bamberg CE, Mackay CR, Lee H, Zahra D, Jackson J, Lim YS, Whitfeld PL, Craig S, Corsini E, Lu B, Gerard C, Gerard NP  | title = The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction | journal = The Journal of Biological Chemistry | volume = 285 | issue = 10 | pages = 7633–7644 | date = March 2010 | pmid = 20044484 | pmc = 2844210 | doi = 10.1074/jbc.M109.092106 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Karsten CM, Wiese AV, Mey F, Figge J, Woodruff TM, Reuter T, Scurtu O, Kordowski A, Almeida LN, Briukhovetska D, Quell KM, Sun J, Ender F, Schmudde I, Vollbrandt T, Laumonnier Y, Köhl J  | title = Monitoring C5aR2 Expression Using a Floxed tdTomato-C5aR2 Knock-In Mouse | journal = Journal of Immunology | volume = 199 | issue = 9 | pages = 3234–3248 | date = November 2017 | pmid = 28864475 | doi = 10.4049/jimmunol.1700710 }}</ref>
== Function ==
The [[anaphylatoxin]]s [[C3a (complement)|C3a]] and [[Complement component 5a|C5a]] are fragments of [[Complement component 3|C3]] and [[Complement component 5|C5]] generated via [[Proteolysis|proteolytic cleavage]] by [[C3-convertase|C3 convertases]] and [[C5-convertase|C5 convertases]] during the complement cascade. They are pro-inflammatory mediators which bind to the [[anaphylatoxin receptors]], [[C3a receptor|C3aR]], [[C5a receptor|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 [[Chemotaxis|chemoattraction]], [[vasodilation]] and immune cell activation.<ref>{{cite journal | vauthors = Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Köhl J | title = The role of the anaphylatoxins in health and disease | journal = Molecular Immunology | volume = 46 | issue = 14 | pages = 2753–2766 | date = September 2009 | pmid = 19477527 | pmc = 2725201 | doi = 10.1016/j.molimm.2009.04.027 | series = 12th European Meeting on Complement in Human Disease }}</ref> C5aR2 binds C5a, but lacks GPCR activity,<ref name=":0">{{cite journal | vauthors = Scola AM, Johswich KO, Morgan BP, Klos A, Monk PN | title = The human complement fragment receptor, C5L2, is a recycling decoy receptor | journal = Molecular Immunology | volume = 46 | issue = 6 | pages = 1149–1162 | date = March 2009 | pmid = 19100624 | pmc = 2697321 | doi = 10.1016/j.molimm.2008.11.001 }}</ref> and its function is less well understood.
C5aR2 was initially thought be a [[Decoy receptors|decoy receptor]], acting as a sink for C5a to negatively regulate C5aR1 function.<ref name=":0" /> However, more recent research has uncovered independent roles for C5aR2, including modulation of the innate immune response in myeloid cells,<ref>{{cite journal | vauthors = Li XX, Clark RJ, Woodruff TM | title = C5aR2 Activation Broadly Modulates the Signaling and Function of Primary Human Macrophages | journal = Journal of Immunology | volume = 205 | issue = 4 | pages = 1102–1112 | date = August 2020 | pmid = 32611725 | doi = 10.4049/jimmunol.2000407 }}</ref><ref>{{cite journal | vauthors = Wright O, Harris A, Nguyen VD, Zhou Y, Durand M, Jayyaratnam A, Gormley D, O'Neill LA, Triantafilou K, Nichols EM, Booty LM  | title = C5aR2 Regulates STING-Mediated Interferon Beta Production in Human Macrophages | journal = Cells | volume = 12 | issue = 23 | pages = 2707 | date = November 2023 | pmid = 38067135 | pmc = 10706378 | doi = 10.3390/cells12232707 | doi-access = free }}</ref> translocation of C5a to drive [[Chemotaxis|transendothelial migration]] of [[neutrophil]]s,<ref>{{cite journal | vauthors = Miyabe Y, Miyabe C, Mani V, Mempel TR, Luster AD | title = Atypical complement receptor C5aR2 transports C5a to initiate neutrophil adhesion and inflammation | journal = Science Immunology | volume = 4 | issue = 35 | date = May 2019 | pmid = 31076525 | doi = 10.1126/sciimmunol.aav5951 }}</ref> [[Arrestin beta 2|β-arrestin]] recruitment and modulation of [[MAPK/ERK pathway|ERK signalling]]<ref>{{cite journal | vauthors = Croker DE, Monk PN, Halai R, Kaeslin G, Schofield Z, Wu MC, Clark RJ, Blaskovich MA, Morikis D, Floudas CA, Cooper MA, Woodruff TM  | title = Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling | journal = Immunology and Cell Biology | volume = 94 | issue = 8 | pages = 787–795 | date = September 2016 | pmid = 27108698 | doi = 10.1038/icb.2016.43 }}</ref><ref>{{cite journal | vauthors = Croker DE, Halai R, Kaeslin G, Wende E, Fehlhaber B, Klos A, Monk PN, Cooper MA  | title = C5a2 can modulate ERK1/2 signaling in macrophages via heteromer formation with C5a1 and β-arrestin recruitment | journal = Immunology and Cell Biology | volume = 92 | issue = 7 | pages = 631–639 | date = August 2014 | pmid = 24777312 | doi = 10.1038/icb.2014.32 | s2cid = 24704330 | url = http://eprints.whiterose.ac.uk/99940/3/Croker%20paper%20ICB%202014%20V1%20rev.pdf }}</ref> and modulation of [[lipid metabolism]] in [[obesity]] through [[Acylation stimulating protein|C3a-desArg]] binding.<ref>{{Cite journal | vauthors = Fisette A, Cianflone K |date= June 2010 |title=The ASP and C5L2 pathway: another bridge between inflammation and metabolic homeostasis |url=https://www.tandfonline.com/doi/full/10.2217/clp.10.21 |journal=Clinical Lipidology |language=en |volume=5 |issue=3 |pages=367–377 |doi=10.2217/clp.10.21 |s2cid=85816536 |issn=1758-4299}}</ref> C5aR2 has been implicated in a broad range of inflammatory and infectious diseases.<ref>{{cite journal | vauthors = Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM | title = C5L2: a controversial receptor of complement anaphylatoxin, C5a | journal = FASEB Journal | volume = 27 | issue = 3 | pages = 855–864 | date = March 2013 | pmid = 23239822 | doi = 10.1096/fj.12-220509 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Li XX, Lee JD, Kemper C, Woodruff TM | title = The Complement Receptor C5aR2: A Powerful Modulator of Innate and Adaptive Immunity | journal = Journal of Immunology | volume = 202 | issue = 12 | pages = 3339–3348 | date = June 2019 | pmid = 31160390 | doi = 10.4049/jimmunol.1900371 }}</ref>
== References ==
{{reflist}}
{{G protein-coupled receptors}}
[[Category:G protein-coupled receptors]]