C5a receptor

C5AR1
Identifiers
Aliases	C5AR1, C5A, C5AR, C5R1, CD88, complement component 5a receptor 1, C5a receptor, complement C5a receptor 1
External IDs	OMIM: 113995; MGI: 88232; HomoloGene: 20413; GeneCards: C5AR1; OMA:C5AR1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.32 Start 47,290,023 bp[1] End 47,322,066 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 A2|7 8.77 cM Start 15,980,668 bp[2] End 15,993,465 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood monocyte bone marrow granulocyte bone marrow cells Pituitary Gland right lung anterior pituitary periodontal fiber upper lobe of left lung Top expressed in granulocyte aortic valve stroma of bone marrow ascending aorta blood tibiofemoral joint lumbar spinal ganglion ankle choroid plexus of fourth ventricle right lung lobe More reference expression data BioGPS More reference expression data
Gene ontology Molecular function complement component C5a binding signal transducer activity complement receptor activity complement component C5a receptor activity G protein-coupled receptor activity Cellular component integral component of membrane membrane plasma membrane apical part of cell integral component of plasma membrane cell surface basolateral plasma membrane cytoplasmic vesicle secretory granule membrane Biological process negative regulation of neuron apoptotic process positive regulation of epithelial cell proliferation mRNA transcription by RNA polymerase II activation of phospholipase C activity neutrophil chemotaxis positive regulation of angiogenesis chemotaxis cellular defense response response to lipopolysaccharide animal organ regeneration immune response response to peptidoglycan positive regulation of ERK1 and ERK2 cascade positive regulation of neutrophil chemotaxis complement receptor mediated signaling pathway sensory perception of chemical stimulus positive regulation of vascular endothelial growth factor production cell proliferation in hindbrain positive regulation of macrophage chemotaxis signal transduction defense response to Gram-positive bacterium apoptotic process regulation of complement activation inflammatory response phospholipase C-activating G protein-coupled receptor signaling pathway neutrophil degranulation leukocyte migration cell chemotaxis positive regulation of cytosolic calcium ion concentration G protein-coupled receptor signaling pathway complement component C5a signaling pathway cognition regulation of astrocyte activation presynapse organization regulation of amyloid-beta clearance regulation of tau-protein kinase activity regulation of microglial cell activation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 728 12273 Ensembl ENSG00000197405 ENSMUSG00000049130 UniProt P21730 P30993 RefSeq (mRNA) NM_001736 NM_001173550 NM_007577 RefSeq (protein) NP_001727 NP_001167021 NP_031603 Location (UCSC) Chr 19: 47.29 – 47.32 Mb Chr 7: 15.98 – 15.99 Mb PubMed search [3] [4]
Wikidata
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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.^[5] C5a receptor 1 modulates inflammatory responses, obesity, development and cancers.^[6][7][8] From a signaling transduction perspective, C5a receptor 1 activation is implicated in β-arrestin2 recruitment via Rab5a,^[9] coupling of Gαi proteins,^[10] ERK1/2 phosphorylation, ^[11] calcium mobilization and Rho activation^[12] leading to downstream functions, such as secretion of cytokines, chemotaxis, and phagocytosis.

C5a receptor structure and its residues possessing role in ligand binding or signaling.

Cells

The C5a receptor 1 is expressed on:^[13]

• Granulocytes
• Macrophages
• Monocytes
• Dendritic cells
• Hepatoma-derived cell line HepG2
• Astrocytes
• Microglia

Agonist and antagonists

Potent and selective agonist and antagonists for C5a receptor 1 have been developed.^{[14][15][16][17][18][19]}

See also

• Complement component 5a for binding mechanism

References

1. GRCh38: Ensembl release 89: ENSG00000197405 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000049130 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Gerard C, Gerard NP (1994). "C5A anaphylatoxin and its seven transmembrane-segment receptor". Annual Review of Immunology. 12: 775–808. doi:10.1146/annurev.iy.12.040194.004015. PMID 8011297.
6. Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, et al. (April 2015). "The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury". The Journal of Neuroscience. 35 (16): 6517–6531. doi:10.1523/JNEUROSCI.5218-14.2015. PMC 6605214. PMID 25904802.
7. Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, et al. (February 2013). "C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling". FASEB Journal. 27 (2): 822–831. doi:10.1096/fj.12-220582. PMID 23118029. S2CID 25562647.
8. Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. (November 2008). "Modulation of the antitumor immune response by complement". Nature Immunology. 9 (11): 1225–1235. doi:10.1038/ni.1655. PMC 2678913. PMID 18820683.
9. Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J (March 2023). "Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages". Journal of Innate Immunity. 15 (1): 468–484. doi:10.1159/000530012. PMC 10105068. PMID 36882040.
10. Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, et al. (April 2023). "Mechanism of activation and biased signaling in complement receptor C5aR1". Cell Research. 33 (4): 312–324. doi:10.1038/s41422-023-00779-2. PMC 9937529. PMID 36806352.
11. Li XX, Lee JD, Massey NL, Guan C, Robertson AA, Clark RJ, et al. (October 2020). "Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function". Biochemical Pharmacology. 180: 114156. doi:10.1016/j.bcp.2020.114156. PMID 32682759. S2CID 220653568.
12. Wang X, Iyer A, Lyons AB, Körner H, Wei W (2019). "Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages". Frontiers in Immunology. 10: 2031. doi:10.3389/fimmu.2019.02031. PMC 6718513. PMID 31507616.
13. Klos A, Wende E, Wareham KJ, Monk PN (January 2013). "International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500–543. doi:10.1124/pr.111.005223. PMID 23383423.
14. Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, et al. (November 2021). "Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity". Journal of Medicinal Chemistry. 64 (22): 16598–16608. doi:10.1021/acs.jmedchem.1c01174. PMID 34762432. S2CID 244040645.
15. Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP (August 1998). "Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a". Journal of Medicinal Chemistry. 41 (18): 3417–3425. doi:10.1021/jm9800651. PMID 9719594.
16. Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, et al. (July 2008). "Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (14): 3852–3855. doi:10.1016/j.bmcl.2008.06.059. PMID 18595693.
17. Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, et al. (December 2002). "Identification of a potent and orally active non-peptide C5a receptor antagonist". The Journal of Biological Chemistry. 277 (51): 49403–49407. doi:10.1074/jbc.M209672200. PMID 12384495.
18. Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, et al. (April 2016). "Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists". Scientific Reports. 6 (1): 24575. Bibcode:2016NatSR...624575S. doi:10.1038/srep24575. PMC 4837355. PMID 27094554.
19. Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD (May 2000). "Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant". Journal of Immunology. 164 (10): 5492–5498. doi:10.4049/jimmunol.164.10.5492. PMID 10799917. S2CID 38942679.

Further reading

• Sengeløv H (1996). "Complement receptors in neutrophils". Critical Reviews in Immunology. 15 (2): 107–131. doi:10.1615/critrevimmunol.v15.i2.10. PMID 8573284.
• Beil WJ, Schulz M, Wefelmeyer U (July 2000). "Mast cell granule composition and tissue location--a close correlation". Histology and Histopathology. 15 (3): 937–946. PMID 10963136.
• Yamamoto T (January 2007). "Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes". Pathology International. 57 (1): 1–11. doi:10.1111/j.1440-1827.2007.02049.x. PMID 17199736. S2CID 22946804.
• Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (June 1992). "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". Genomics. 13 (2): 437–440. doi:10.1016/0888-7543(92)90265-T. PMID 1612600.
• Gerard NP, Gerard C (February 1991). "The chemotactic receptor for human C5a anaphylatoxin". Nature. 349 (6310): 614–617. Bibcode:1991Natur.349..614G. doi:10.1038/349614a0. PMID 1847994. S2CID 4338594.
• Boulay F, Mery L, Tardif M, Brouchon L, Vignais P (March 1991). "Expression cloning of a receptor for C5a anaphylatoxin on differentiated HL-60 cells". Biochemistry. 30 (12): 2993–2999. doi:10.1021/bi00226a002. PMID 2007135.
• Wahl SM, Allen JB, Gartner S, Orenstein JM, Popovic M, Chenoweth DE, et al. (May 1989). "HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes". Journal of Immunology. 142 (10): 3553–3559. doi:10.4049/jimmunol.142.10.3553. PMID 2541200. S2CID 44347771.
• Foreman KE, Vaporciyan AA, Bonish BK, Jones ML, Johnson KJ, Glovsky MM, et al. (September 1994). "C5a-induced expression of P-selectin in endothelial cells". The Journal of Clinical Investigation. 94 (3): 1147–1155. doi:10.1172/JCI117430. PMC 295185. PMID 7521884.
• Giannini E, Brouchon L, Boulay F (August 1995). "Identification of the major phosphorylation sites in human C5a anaphylatoxin receptor in vivo". The Journal of Biological Chemistry. 270 (32): 19166–19172. doi:10.1074/jbc.270.32.19166. PMID 7642584.
• Buhl AM, Osawa S, Johnson GL (August 1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor". The Journal of Biological Chemistry. 270 (34): 19828–19832. doi:10.1074/jbc.270.34.19828. PMID 7649993.
• Wennogle LP, Conder L, Winter C, Braunwalder A, Vlattas S, Kramer R, et al. (July 1994). "Stabilization of C5a receptor--G-protein interactions through ligand binding". Journal of Cellular Biochemistry. 55 (3): 380–388. doi:10.1002/jcb.240550316. PMID 7962171. S2CID 36216040.
• Gerard NP, Bao L, Xiao-Ping H, Eddy RL, Shows TB, Gerard C (February 1993). "Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene". Biochemistry. 32 (5): 1243–1250. doi:10.1021/bi00056a007. PMID 8383526.
• Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, et al. (August 1996). "Molecular cloning and characterization of the human anaphylatoxin C3a receptor". The Journal of Biological Chemistry. 271 (34): 20231–20234. doi:10.1074/jbc.271.34.20231. PMID 8702752.
• Werfel T, Zwirner J, Oppermann M, Sieber A, Begemann G, Drommer W, et al. (August 1996). "CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and react with a desmosomal antigen in human skin". Journal of Immunology. 157 (4): 1729–1735. doi:10.4049/jimmunol.157.4.1729. PMID 8759762. S2CID 20748991.
• Höpken UE, Lu B, Gerard NP, Gerard C (September 1996). "The C5a chemoattractant receptor mediates mucosal defence to infection". Nature. 383 (6595): 86–89. Bibcode:1996Natur.383...86H. doi:10.1038/383086a0. PMID 8779720. S2CID 4346934.
• Chen Z, Zhang X, Gonnella NC, Pellas TC, Boyar WC, Ni F (April 1998). "Residues 21-30 within the extracellular N-terminal region of the C5a receptor represent a binding domain for the C5a anaphylatoxin". The Journal of Biological Chemistry. 273 (17): 10411–10419. doi:10.1074/jbc.273.17.10411. PMID 9553099.
• Floreani AA, Heires AJ, Welniak LA, Miller-Lindholm A, Clark-Pierce L, Rennard SI, et al. (May 1998). "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 of Immunology. 160 (10): 5073–5081. doi:10.4049/jimmunol.160.10.5073. PMID 9590258.
• Ottonello L, Corcione A, Tortolina G, Airoldi I, Albesiano E, Favre A, et al. (June 1999). "rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues". Journal of Immunology. 162 (11): 6510–6517. doi:10.4049/jimmunol.162.11.6510. PMID 10352266.
• Kohleisen B, Shumay E, Sutter G, Foerster R, Brack-Werner R, Nuesse M, et al. (December 1999). "Stable expression of HIV-1 Nef induces changes in growth properties and activation state of human astrocytes". AIDS. 13 (17): 2331–2341. doi:10.1097/00002030-199912030-00004. PMID 10597774.
• Monk PN, Scola AM, Madala P, Fairlie DP (October 2007). "Function, structure and therapeutic potential of complement C5a receptors". British Journal of Pharmacology. 152 (4): 429–448. doi:10.1038/sj.bjp.0707332. PMC 2050825. PMID 17603557.

External links

• "Anaphylatoxin Receptors: C5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2014-04-07. Retrieved 2007-10-25.
• C5a+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human C5AR1 genome location and C5AR1 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P21730 (C5a anaphylatoxin chemotactic receptor 1) at the PDBe-KB.