View source for Biology:C5a receptor

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox_gene}}

The '''C5a receptor''' also known as '''complement component 5a receptor 1''' ('''C5AR1''') or '''CD88''' ('''C'''luster of '''D'''ifferentiation '''88''') is a [[Biology:G protein-coupled receptor|G protein-coupled receptor]]  for [[Biology:Complement component 5a|C5a]]. It functions as a [[Biology:Complement receptor|complement receptor]].<ref name="pmid8011297">{{cite journal | vauthors = Gerard C, Gerard NP | title = C5A anaphylatoxin and its seven transmembrane-segment receptor | journal = Annual Review of Immunology | volume = 12 | pages = 775–808 | year = 1994 | pmid = 8011297 | doi = 10.1146/annurev.iy.12.040194.004015 }}</ref> C5a receptor modulates inflammatory responses, obesity, development and cancers.<ref>{{cite journal | vauthors = Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ | title = The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury | journal = The Journal of Neuroscience | volume = 35 | issue = 16 | pages = 6517–31 | date = April 2015 | pmid = 25904802 | pmc = 6605214 | doi = 10.1523/JNEUROSCI.5218-14.2015}}</ref><ref>{{cite journal | vauthors = Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP | title = C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling | journal = FASEB Journal | volume = 27 | issue = 2 | pages = 822–31 | date = February 2013 | pmid = 23118029 | doi = 10.1096/fj.12-220582 | s2cid = 25562647 }}</ref><ref>{{cite journal | vauthors = Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, Coukos G, Lambris JD | title = Modulation of the antitumor immune response by complement | journal = Nature Immunology | volume = 9 | issue = 11 | pages = 1225–35 | date = November 2008 | pmid = 18820683 | pmc = 2678913 | doi = 10.1038/ni.1655 }}</ref>

[[Image:C5a-receptor.png|450px|center|thumb|C5a receptor structure and its residues possessing role in ligand binding or signaling.]]

==Cells==
The C5a receptor is expressed on:<ref name="pmid= 23383423">{{cite journal | vauthors = Klos A, Wende E, Wareham KJ, Monk PN | title = International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors | journal = Pharmacological Reviews | volume = 65 | issue = 1 | pages = 500–43 | date = January 2013 | pmid = 23383423 | doi = 10.1124/pr.111.005223 | doi-access = free }}</ref>
*Granulocytes
*Monocytes
*Dendritic cells
*Hepatoma-derived cell line HepG2
*Astrocytes
*[[Biology:Microglia|Microglia]]

== Agonist and antagonists ==
Potent and selective [[Biology:Agonist|agonist]] and [[Biology:Receptor antagonist|antagonists]] for C5aR have been developed.<ref>{{Cite journal |last1=Gorman |first1=Declan M. |last2=Li |first2=Xaria X. |last3=Lee |first3=John D. |last4=Fung |first4=Jenny N. |last5=Cui |first5=Cedric S. |last6=Lee |first6=Han Siean |last7=Rolfe |first7=Barbara E. |last8=Woodruff |first8=Trent M. |last9=Clark |first9=Richard J. |date=2021-11-25 |title=Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity |url=https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01174 |journal=Journal of Medicinal Chemistry |language=en |volume=64 |issue=22 |pages=16598–16608 |doi=10.1021/acs.jmedchem.1c01174 |pmid=34762432 |s2cid=244040645 |issn=0022-2623}}</ref><ref>{{cite journal | vauthors = Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP | title = Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 18 | pages = 3417–25 | date = August 1998 | pmid = 9719594 | doi =  10.1021/jm9800651}}</ref><ref>{{cite journal | vauthors = Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, Lommen GV, Hornby PJ, He W | title = Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 18 | issue = 14 | pages = 3852–5 | date = July 2008 | pmid = 18595693 | doi = 10.1016/j.bmcl.2008.06.059 }}</ref><ref>{{cite journal | vauthors = Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, Kamahori T, Ehara S, Itoh K, Ohtsuka T, Ohbora T, Mishina T, Komatsu H, Naka Y | title = Identification of a potent and orally active non-peptide C5a receptor antagonist | journal = The Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 49403–7 | date = December 2002 | pmid = 12384495 | doi = 10.1074/jbc.M209672200 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, Kok WM, Stoermer MJ, Sweet MJ, Reid RC, Suen JY, Fairlie DP | title = Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 24575 | date = April 2016 | pmid = 27094554 | pmc = 4837355 | doi = 10.1038/srep24575 | bibcode = 2016NatSR...624575S }}</ref><ref>{{cite journal|pmid=10799917|year=2000 |last1=Ulrich |first1=J. T. |last2=Cieplak |first2=W. |last3=Paczkowski |first3=N. J. |last4=Taylor |first4=S. M. |last5=Sanderson |first5=S. D. |title=Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant |journal=Journal of Immunology (Baltimore, Md. : 1950) |volume=164 |issue=10 |pages=5492–5498 |doi=10.4049/jimmunol.164.10.5492 |s2cid=38942679 }}</ref>

== See also ==
*[[Biology:Complement component 5a|Complement component 5a]] for binding mechanism

== References ==
{{Reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Sengeløv H | title = Complement receptors in neutrophils | journal = Critical Reviews in Immunology | volume = 15 | issue = 2 | pages = 107–31 | year = 1996 | pmid = 8573284 | doi = 10.1615/critrevimmunol.v15.i2.10 }}
* {{cite journal | vauthors = Beil WJ, Schulz M, Wefelmeyer U | title = Mast cell granule composition and tissue location--a close correlation | journal = Histology and Histopathology | volume = 15 | issue = 3 | pages = 937–46 | date = July 2000 | pmid = 10963136 }}
* {{cite journal | vauthors = Yamamoto T | title = Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes | journal = Pathology International | volume = 57 | issue = 1 | pages = 1–11 | date = January 2007 | pmid = 17199736 | doi = 10.1111/j.1440-1827.2007.02049.x | s2cid = 22946804 }}
* {{cite journal | vauthors = Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C | title = Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19 | journal = Genomics | volume = 13 | issue = 2 | pages = 437–40 | date = June 1992 | pmid = 1612600 | doi = 10.1016/0888-7543(92)90265-T }}
* {{cite journal | vauthors = Gerard NP, Gerard C | title = The chemotactic receptor for human C5a anaphylatoxin | journal = Nature | volume = 349 | issue = 6310 | pages = 614–7 | date = February 1991 | pmid = 1847994 | doi = 10.1038/349614a0 | bibcode = 1991Natur.349..614G | s2cid = 4338594 }}
* {{cite journal | vauthors = Boulay F, Mery L, Tardif M, Brouchon L, Vignais P | title = Expression cloning of a receptor for C5a anaphylatoxin on differentiated HL-60 cells | journal = Biochemistry | volume = 30 | issue = 12 | pages = 2993–9 | date = March 1991 | pmid = 2007135 | doi = 10.1021/bi00226a002 }}
* {{cite journal | vauthors = Wahl SM, Allen JB, Gartner S, Orenstein JM, Popovic M, Chenoweth DE, Arthur LO, Farrar WL, Wahl LM | title = HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes | journal = Journal of Immunology | volume = 142 | issue = 10 | pages = 3553–9 | date = May 1989 | pmid = 2541200 }}
* {{cite journal | vauthors = Foreman KE, Vaporciyan AA, Bonish BK, Jones ML, Johnson KJ, Glovsky MM, Eddy SM, Ward PA | title = C5a-induced expression of P-selectin in endothelial cells | journal = The Journal of Clinical Investigation | volume = 94 | issue = 3 | pages = 1147–55 | date = September 1994 | pmid = 7521884 | pmc = 295185 | doi = 10.1172/JCI117430 }}
* {{cite journal | vauthors = Giannini E, Brouchon L, Boulay F | title = Identification of the major phosphorylation sites in human C5a anaphylatoxin receptor in vivo | journal = The Journal of Biological Chemistry | volume = 270 | issue = 32 | pages = 19166–72 | date = August 1995 | pmid = 7642584 | doi = 10.1074/jbc.270.32.19166 | doi-access = free }}
* {{cite journal | vauthors = Buhl AM, Osawa S, Johnson GL | title = Mitogen-activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor | journal = The Journal of Biological Chemistry | volume = 270 | issue = 34 | pages = 19828–32 | date = August 1995 | pmid = 7649993 | doi = 10.1074/jbc.270.34.19828 | doi-access = free }}
* {{cite journal | vauthors = Wennogle LP, Conder L, Winter C, Braunwalder A, Vlattas S, Kramer R, Cioffi C, Hu SI | title = Stabilization of C5a receptor--G-protein interactions through ligand binding | journal = Journal of Cellular Biochemistry | volume = 55 | issue = 3 | pages = 380–8 | date = July 1994 | pmid = 7962171 | doi = 10.1002/jcb.240550316 | s2cid = 36216040 }}
* {{cite journal | vauthors = Gerard NP, Bao L, Xiao-Ping H, Eddy RL, Shows TB, Gerard C | title = Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene | journal = Biochemistry | volume = 32 | issue = 5 | pages = 1243–50 | date = February 1993 | pmid = 8383526 | doi = 10.1021/bi00056a007 }}
* {{cite journal | vauthors = Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C | title = Molecular cloning and characterization of the human anaphylatoxin C3a receptor | journal = The Journal of Biological Chemistry | volume = 271 | issue = 34 | pages = 20231–4 | date = August 1996 | pmid = 8702752 | doi = 10.1074/jbc.271.34.20231 | doi-access = free }}
* {{cite journal | vauthors = Werfel T, Zwirner J, Oppermann M, Sieber A, Begemann G, Drommer W, Kapp A, Götze O | title = CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and react with a desmosomal antigen in human skin | journal = Journal of Immunology | volume = 157 | issue = 4 | pages = 1729–35 | date = August 1996 | pmid = 8759762 }}
* {{cite journal | vauthors = Höpken UE, Lu B, Gerard NP, Gerard C | title = The C5a chemoattractant receptor mediates mucosal defence to infection | journal = Nature | volume = 383 | issue = 6595 | pages = 86–9 | date = September 1996 | pmid = 8779720 | doi = 10.1038/383086a0 | bibcode = 1996Natur.383...86H | s2cid = 4346934 }}
* {{cite journal | vauthors = Chen Z, Zhang X, Gonnella NC, Pellas TC, Boyar WC, Ni F | title = Residues 21-30 within the extracellular N-terminal region of the C5a receptor represent a binding domain for the C5a anaphylatoxin | journal = The Journal of Biological Chemistry | volume = 273 | issue = 17 | pages = 10411–9 | date = April 1998 | pmid = 9553099 | doi = 10.1074/jbc.273.17.10411 | doi-access = free }}
* {{cite journal | vauthors = Floreani AA, Heires AJ, Welniak LA, Miller-Lindholm A, Clark-Pierce L, Rennard SI, Morgan EL, Sanderson SD | title = Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke | journal = Journal of Immunology | volume = 160 | issue = 10 | pages = 5073–81 | date = May 1998 | pmid = 9590258 }}
* {{cite journal | vauthors = Ottonello L, Corcione A, Tortolina G, Airoldi I, Albesiano E, Favre A, D'Agostino R, Malavasi F, Pistoia V, Dallegri F | title = rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues | journal = Journal of Immunology | volume = 162 | issue = 11 | pages = 6510–7 | date = June 1999 | pmid = 10352266 }}
* {{cite journal | vauthors = Kohleisen B, Shumay E, Sutter G, Foerster R, Brack-Werner R, Nuesse M, Erfle V | title = Stable expression of HIV-1 Nef induces changes in growth properties and activation state of human astrocytes | journal = AIDS | volume = 13 | issue = 17 | pages = 2331–41 | date = December 1999 | pmid = 10597774 | doi = 10.1097/00002030-199912030-00004 }}
* {{cite journal | vauthors = Monk PN, Scola AM, Madala P, Fairlie DP | title = Function, structure and therapeutic potential of complement C5a receptors | journal = British Journal of Pharmacology | volume = 152 | issue = 4 | pages = 429–48 | date = October 2007 | pmid = 17603557 | pmc = 2050825 | doi = 10.1038/sj.bjp.0707332 }}
{{refend}}

== External links ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2972 | title = Anaphylatoxin Receptors: C5a  | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
* {{MeshName|C5a+receptors}}
* {{UCSC gene info|C5AR1}}
* {{PDBe-KB2|P21730|C5a anaphylatoxin chemotactic receptor 1}}

{{Clusters of differentiation}}
{{G protein-coupled receptors}}

{{Sourceattribution|C5a receptor|1}}