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C5a receptor

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

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{{Infobox_gene}}

The C5a receptor also known as complement component 5a receptor 1 (C5AR1) or CD88 (Cluster of Differentiation 88) is a G protein-coupled receptor for C5a. It functions as a complement receptor.{{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 }} C5a receptor 1 modulates inflammatory responses, obesity, development and cancers.{{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 = 6517–6531 | date = April 2015 | pmid = 25904802 | pmc = 6605214 | doi = 10.1523/JNEUROSCI.5218-14.2015 }}{{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 = 822–831 | date = February 2013 | pmid = 23118029 | doi = 10.1096/fj.12-220582 | doi-access = free | s2cid = 25562647 }}{{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 = 1225–1235 | date = November 2008 | pmid = 18820683 | pmc = 2678913 | doi = 10.1038/ni.1655 }} From a signaling transduction perspective, C5a receptor 1 activation is implicated in β-arrestin2 recruitment via Rab5a,{{cite journal | vauthors = Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J | title = Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages | journal = Journal of Innate Immunity | volume = 15 | issue = 1 | pages = 468–484 | date = March 2023 | pmid = 36882040 | doi = 10.1159/000530012 | pmc = 10105068 }} coupling of Gαi proteins,{{cite journal | vauthors = Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, Tian X, Wang B, Bin Y, Chen P, Yan W, Fu P, Shao Z | title = Mechanism of activation and biased signaling in complement receptor C5aR1 | journal = Cell Research | volume = 33 | issue = 4 | pages = 312–324 | date = April 2023 | pmid = 36806352 | doi = 10.1038/s41422-023-00779-2 | pmc = 9937529 }} ERK1/2 phosphorylation, {{cite journal | vauthors = Li XX, Lee JD, Massey NL, Guan C, Robertson AA, Clark RJ, Woodruff TM | title = Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function | journal = Biochemical Pharmacology | volume = 180 | pages = 114156 | date = October 2020 | pmid = 32682759 | doi = 10.1016/j.bcp.2020.114156 | s2cid = 220653568 }} calcium mobilization and Rho activation{{cite journal | vauthors = Wang X, Iyer A, Lyons AB, Körner H, Wei W | title = Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages | journal = Frontiers in Immunology | volume = 10 | pages = 2031 | date = 2019 | pmid = 31507616 | pmc = 6718513 | doi = 10.3389/fimmu.2019.02031 | doi-access = free }} leading to downstream functions, such as secretion of cytokines, chemotaxis, and phagocytosis.

Image:C5a-receptor.png

Cells

The C5a receptor 1 is expressed on:{{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 = 500–543 | date = January 2013 | pmid = 23383423 | doi = 10.1124/pr.111.005223 | doi-access = free }}

Agonist and antagonists

Potent and selective agonist and antagonists for C5a receptor 1 have been developed.{{cite journal | vauthors = Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, Rolfe BE, Woodruff TM, Clark RJ | title = Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity | journal = Journal of Medicinal Chemistry | volume = 64 | issue = 22 | pages = 16598–16608 | date = November 2021 | pmid = 34762432 | doi = 10.1021/acs.jmedchem.1c01174 | s2cid = 244040645 }}{{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 = 3417–3425 | date = August 1998 | pmid = 9719594 | doi = 10.1021/jm9800651 }}{{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 = 3852–3855 | date = July 2008 | pmid = 18595693 | doi = 10.1016/j.bmcl.2008.06.059 }}{{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 = 49403–49407 | date = December 2002 | pmid = 12384495 | doi = 10.1074/jbc.M209672200 | doi-access = free }}{{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 }}{{cite journal | vauthors = Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD | 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 | volume = 164 | issue = 10 | pages = 5492–5498 | date = May 2000 | pmid = 10799917 | doi = 10.4049/jimmunol.164.10.5492 | s2cid = 38942679 | doi-access = free }}

See also

References

{{Reflist|33em}}

Further reading

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  • {{cite journal | vauthors = Sengeløv H | title = Complement receptors in neutrophils | journal = Critical Reviews in Immunology | volume = 15 | issue = 2 | pages = 107–131 | 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 = 937–946 | 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 = 437–440 | 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 = 614–617 | date = February 1991 | pmid = 1847994 | doi = 10.1038/349614a0 | s2cid = 4338594 | bibcode = 1991Natur.349..614G }}
  • {{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 = 2993–2999 | 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 = 3553–3559 | date = May 1989 | pmid = 2541200 | doi = 10.4049/jimmunol.142.10.3553 | s2cid = 44347771 | doi-access = free }}
  • {{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 = 1147–1155 | 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 = 19166–19172 | 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 = 19828–19832 | 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 = 380–388 | 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 = 1243–1250 | 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 = 20231–20234 | 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 = 1729–1735 | date = August 1996 | pmid = 8759762 | doi = 10.4049/jimmunol.157.4.1729 | s2cid = 20748991 | doi-access = free }}
  • {{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 = 86–89 | date = September 1996 | pmid = 8779720 | doi = 10.1038/383086a0 | s2cid = 4346934 | bibcode = 1996Natur.383...86H }}
  • {{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 = 10411–10419 | 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 = 5073–5081 | date = May 1998 | pmid = 9590258 | doi = 10.4049/jimmunol.160.10.5073 | doi-access = free }}
  • {{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 = 6510–6517 | date = June 1999 | pmid = 10352266 | doi = 10.4049/jimmunol.162.11.6510 | doi-access = free }}
  • {{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 = 2331–2341 | 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 = 429–448 | date = October 2007 | pmid = 17603557 | pmc = 2050825 | doi = 10.1038/sj.bjp.0707332 }}

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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 | access-date = 2007-10-25 | archive-date = 2014-04-07 | archive-url = https://web.archive.org/web/20140407074942/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2972 | url-status = dead }}
  • {{MeshName|C5a+receptors}}
  • {{UCSC gene info|C5AR1}}
  • {{PDBe-KB2|P21730|C5a anaphylatoxin chemotactic receptor 1}}

{{Clusters of differentiation}}

{{G protein-coupled receptors}}

{{Complement system}}