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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 482 | 12p13.31 | C3AR1 | complement C3a receptor 1 | 24 |
| Mouse | 7 | 477 | 6 F2 | C3ar1 | complement component 3a receptor 1 | 24 |
| Rat | 7 | 473 | 4q42 | C3ar1 | complement C3a receptor 1 | |
| Previous and Unofficial Names |
| C3AR | C3a anaphylatoxin chemotactic receptor | C3a-R | anaphylatoxin C3a receptor | complement component 3a receptor 1 |
| Database Links |
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| Specialist databases | |
| GPCRdb | c3ar_human (Hs), c3ar_mouse (Mm), c3ar_rat (Rn) |
| Other databases | |
| Alphafold | Q16581 (Hs), O09047 (Mm), O55197 (Rn) |
| ChEMBL Target | CHEMBL4761 (Hs) |
| Ensembl Gene | ENSG00000171860 (Hs), ENSMUSG00000040552 (Mm), ENSRNOG00000009211 (Rn) |
| Entrez Gene | 719 (Hs), 12267 (Mm), 84007 (Rn) |
| Human Protein Atlas | ENSG00000171860 (Hs) |
| KEGG Gene | hsa:719 (Hs), mmu:12267 (Mm), rno:84007 (Rn) |
| OMIM | 605246 (Hs) |
| Pharos | Q16581 (Hs) |
| RefSeq Nucleotide | NM_004054 (Hs), NM_009779 (Mm), NM_032060 (Rn) |
| RefSeq Protein | NP_004045 (Hs), NP_033909 (Mm), NP_114449 (Rn) |
| UniProtKB | Q16581 (Hs), O09047 (Mm), O55197 (Rn) |
| Wikipedia | C3AR1 (Hs) |
| Natural/Endogenous Ligands |
| C5a {Sp: Human} |
| C3a {Sp: Human} |
| C5a {Sp: Mouse} |
| C3a {Sp: Mouse} |
| C5a {Sp: Rat} |
| C3a {Sp: Rat} |
| Comments: C3a anaphylatoxin has a higher potency than C5a anaphylatoxin |
| Potency order of endogenous ligands (Human) |
| C3a (C3, P01024) > C5a (C5, P01031) [3] |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The receptor affinity of pEC50 5.9 for WWGKKYRASKLGLAR was detected by a binding assay. C3a receptor has no detectable affinity for the metabolite C3a des Arg. The rodent receptor was recently suggested to interact with vgf gene product TLQP-21, however the binding affinity was found to be relatively low [21]. SB290157 has also been reported to have agonist properties at the C3a receptor [32]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The pIC50 value for FLTChaAR affinity value was obtained from a binding assay. SB290157 has also been reported to have agonist properties at the C3a receptor [32]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a. The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [48,55]. C3aR is also reported to provide protection from tissue damage in an intestinal ischemia-reperfusion model, an effect that is mediated by inhibition of neutrophil mobilisation [57]. The biological action of C3aR agonists and antagonists can be monitored by measuring receptor-mediated cytokine release from human macrophages [40], and C3aR biology further examined by assessing granulocyte/neutrophil mobilisation in response to injury or G-CSF [57]. |
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| G protein (identity unknown) | Other - See Comments |
| Comments: β-arrestin is required for mast cell degranulation in response to C3a | |
| References: 19,54 | |
| Secondary Transduction Mechanisms |
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| Comments: C3aR exhibits a cell-type specific use of secondary signalling cascades. For example, in astrocytes, C3aR causes a transient increase in intracellular calcium mediated by PKC activity, a decrease in cAMP concentrations and an increase in MAPK pathway constituent phosphorylation [43]. In mast cells and human umbilical vein endothelial cells, C3aR activation has also been shown to cause sustained MAPK phosphorylation, leading to the production of cytokines, however in neural precursors C3aR is an inhibitor of this pathway [33,46,53]. | |
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| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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2. Ames RS, Lee D, Foley JJ, Jurewicz AJ, Tornetta MA, Bautsch W, Settmacher B, Klos A, Erhard KF, Cousins RD et al.. (2001) Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models. J Immunol, 166 (10): 6341-8. [PMID:11342658]
3. Ames RS, Nuthulaganti P, Kumar C. (1996) In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins. FEBS Lett, 395 (2-3): 157-9. [PMID:8898085]
4. Ames RS, Tornetta MA, Foley JJ, Hugli TE, Sarau HM. (1997) Evidence that the receptor for C4a is distinct from the C3a receptor. Immunopharmacology, 38 (1-2): 87-92. [PMID:9476119]
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7. Bellows-Peterson ML, Fung HK, Floudas CA, Kieslich CA, Zhang L, Morikis D, Wareham KJ, Monk PN, Hawksworth OA, Woodruff TM. (2012) De novo peptide design with C3a receptor agonist and antagonist activities: theoretical predictions and experimental validation. J Med Chem, 55 (9): 4159-68. [PMID:22500977]
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9. Busch C, Girke G, Kohl B, Stoll C, Lemke M, Krasnici S, Ertel W, Silawal S, John T, Schulze-Tanzil G. (2013) Complement gene expression is regulated by pro-inflammatory cytokines and the anaphylatoxin C3a in human tenocytes. Mol Immunol, 53 (4): 363-73. [PMID:23070120]
10. Bénard M, Raoult E, Vaudry D, Leprince J, Falluel-Morel A, Gonzalez BJ, Galas L, Vaudry H, Fontaine M. (2008) Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Mol Immunol, 45 (14): 3767-74. [PMID:18635264]
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13. Dantas de Araujo A, Wu C, Wu KC, Reid RC, Durek T, Lim J, Fairlie DP. (2017) Europium-Labeled Synthetic C3a Protein as a Novel Fluorescent Probe for Human Complement C3a Receptor. Bioconjug Chem, 28 (6): 1669-1676. [PMID:28562031]
14. Denonne F, Binet S, Burton M, Collart P, Defays S, Dipesa A, Eckert M, Giannaras A, Kumar S, Levine B et al.. (2007) Discovery of new C3aR ligands. Part 2: amino-piperidine derivatives. Bioorg Med Chem Lett, 17 (12): 3262-5. [PMID:17459702]
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16. Fischer WH, Hugli TE. (1997) Regulation of B cell functions by C3a and C3a(desArg): suppression of TNF-alpha, IL-6, and the polyclonal immune response. J Immunol, 159 (9): 4279-86. [PMID:9379023]
17. Gasque P, Singhrao SK, Neal JW, Götze O, Morgan BP. (1997) Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. Am J Pathol, 150 (1): 31-41. [PMID:9006319]
18. Gasque P, Singhrao SK, Neal JW, Wang P, Sayah S, Fontaine M, Morgan BP. (1998) The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis. J Immunol, 160 (7): 3543-54. [PMID:9531317]
19. Guo Q, Subramanian H, Gupta K, Ali H. (2011) Regulation of C3a receptor signaling in human mast cells by G protein coupled receptor kinases. PLoS ONE, 6 (7): e22559. [PMID:21799898]
20. Halai R, Bellows-Peterson ML, Branchett W, Smadbeck J, Kieslich CA, Croker DE, Cooper MA, Morikis D, Woodruff TM, Floudas CA et al.. (2014) Derivation of ligands for the complement C3a receptor from the C-terminus of C5a. Eur J Pharmacol, 745: 176-81. [PMID:25446428]
21. Hannedouche S, Beck V, Leighton-Davies J, Beibel M, Roma G, Oakeley EJ, Lannoy V, Bernard J, Hamon J, Barbieri S et al.. (2013) Identification of the C3a receptor (C3AR1) as the target of the VGF-derived peptide TLQP-21 in rodent cells. J Biol Chem, 288 (38): 27434-43. [PMID:23940034]
22. Hartmann K, Henz BM, Krüger-Krasagakes S, Köhl J, Burger R, Guhl S, Haase I, Lippert U, Zuberbier T. (1997) C3a and C5a stimulate chemotaxis of human mast cells. Blood, 89 (8): 2863-70. [PMID:9108406]
23. Helske S, Oksjoki R, Lindstedt KA, Lommi J, Turto H, Werkkala K, Kupari M, Kovanen PT. (2008) Complement system is activated in stenotic aortic valves. Atherosclerosis, 196 (1): 190-200. [PMID:17498719]
24. Hollmann TJ, Haviland DL, Kildsgaard J, Watts K, Wetsel RA. (1998) Cloning, expression, sequence determination, and chromosome localization of the mouse complement C3a anaphylatoxin receptor gene. Mol Immunol, 35 (3): 137-48. [PMID:9694514]
25. Ignatius A, Schoengraf P, Kreja L, Liedert A, Recknagel S, Kandert S, Brenner RE, Schneider M, Lambris JD, Huber-Lang M. (2011) Complement C3a and C5a modulate osteoclast formation and inflammatory response of osteoblasts in synergism with IL-1β. J Cell Biochem, 112 (9): 2594-605. [PMID:21598302]
26. Jinsmaa Y, Takenaka Y, Yoshikawa M. (2001) Designing of an orally active complement C3a agonist peptide with anti-analgesic and anti-amnesic activity. Peptides, 22 (1): 25-32. [PMID:11179594]
27. Kildsgaard J, Hollmann TJ, Matthews KW, Bian K, Murad F, Wetsel RA. (2000) Cutting edge: targeted disruption of the C3a receptor gene demonstrates a novel protective anti-inflammatory role for C3a in endotoxin-shock. J Immunol, 165 (10): 5406-9. [PMID:11067891]
28. Kwan WH, Hashimoto D, Paz-Artal E, Ostrow K, Greter M, Raedler H, Medof ME, Merad M, Heeger PS. (2012) Antigen-presenting cell-derived complement modulates graft-versus-host disease. J Clin Invest, 122 (6): 2234-8. [PMID:22585573]
29. Lajoie S, Lewkowich IP, Suzuki Y, Clark JR, Sproles AA, Dienger K, Budelsky AL, Wills-Karp M. (2010) Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol, 11 (10): 928-35. [PMID:20802484]
30. Li XX, Kumar V, Clark RJ, Lee JD, Woodruff TM. (2020) The "C3aR Antagonist" SB290157 is a Partial C5aR2 Agonist. Front Pharmacol, 11: 591398. [PMID:33551801]
31. Lim R, Lappas M. (2012) Decreased expression of complement 3a receptor (C3aR) in human placentas from severe preeclamptic pregnancies. Eur J Obstet Gynecol Reprod Biol, 165 (2): 194-8. [PMID:22901903]
32. Mathieu MC, Sawyer N, Greig GM, Hamel M, Kargman S, Ducharme Y, Lau CK, Friesen RW, O'Neill GP, Gervais FG et al.. (2005) The C3a receptor antagonist SB 290157 has agonist activity. Immunol Lett, 100 (2): 139-45. [PMID:16154494]
33. Monsinjon T, Gasque P, Chan P, Ischenko A, Brady JJ, Fontaine MC. (2003) Regulation by complement C3a and C5a anaphylatoxins of cytokine production in human umbilical vein endothelial cells. FASEB J, 17 (9): 1003-14. [PMID:12773483]
34. Niebuhr M, Bäumer W, Kietzmann M, Wichmann K, Heratizadeh A, Werfel T. (2012) Participation of complement 3a receptor (C3aR) in the sensitization phase of Th2 mediated allergic contact dermatitis. Exp Dermatol, 21 (1): 52-6. [PMID:22151392]
35. Ohinata K, Inui A, Asakawa A, Wada K, Wada E, Yoshikawa M. (2002) Albutensin A and complement C3a decrease food intake in mice. Peptides, 23 (1): 127-33. [PMID:11814627]
36. Peng Q, Li K, Anderson K, Farrar CA, Lu B, Smith RA, Sacks SH, Zhou W. (2008) Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood, 111 (4): 2452-61. [PMID:18056835]
37. Purwar R, Wittmann M, Zwirner J, Oppermann M, Kracht M, Dittrich-Breiholz O, Gutzmer R, Werfel T. (2006) Induction of C3 and CCL2 by C3a in keratinocytes: a novel autocrine amplification loop of inflammatory skin reactions. J Immunol, 177 (7): 4444-50. [PMID:16982879]
38. Quell KM, Karsten CM, Kordowski A, Almeida LN, Briukhovetska D, Wiese AV, Sun J, Ender F, Antoniou K, Schröder T et al.. (2017) Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse. J Immunol, 199 (2): 688-706. [PMID:28626064]
39. Rahpeymai Y, Hietala MA, Wilhelmsson U, Fotheringham A, Davies I, Nilsson AK, Zwirner J, Wetsel RA, Gerard C, Pekny M et al.. (2006) Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J, 25 (6): 1364-74. [PMID:16498410]
40. Reid RC, Yau MK, Singh R, Hamidon JK, Lim J, Stoermer MJ, Fairlie DP. (2014) Potent heterocyclic ligands for human complement c3a receptor. J Med Chem, 57 (20): 8459-70. [PMID:25259874]
41. Reid RC, Yau MK, Singh R, Hamidon JK, Reed AN, Chu P, Suen JY, Stoermer MJ, Blakeney JS, Lim J et al.. (2013) Downsizing a human inflammatory protein to a small molecule with equal potency and functionality. Nat Commun, 4: 2802. [PMID:24257095]
42. Rowley JA, Reid RC, Poon EKY, Wu KC, Lim J, Lohman RJ, Hamidon JK, Yau MK, Halili MA, Durek T et al.. (2020) Potent Thiophene Antagonists of Human Complement C3a Receptor with Anti-Inflammatory Activity. J Med Chem, 63 (2): 529-541. [PMID:31910011]
43. Sayah S, Jauneau AC, Patte C, Tonon MC, Vaudry H, Fontaine M. (2003) Two different transduction pathways are activated by C3a and C5a anaphylatoxins on astrocytes. Brain Res Mol Brain Res, 112 (1-2): 53-60. [PMID:12670702]
44. Schraufstatter IU, Discipio RG, Zhao M, Khaldoyanidi SK. (2009) C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. J Immunol, 182 (6): 3827-36. [PMID:19265162]
45. Scully CC, Blakeney JS, Singh R, Hoang HN, Abbenante G, Reid RC, Fairlie DP. (2010) Selective hexapeptide agonists and antagonists for human complement C3a receptor. J Med Chem, 53 (13): 4938-48. [PMID:20527893]
46. Shinjyo N, Ståhlberg A, Dragunow M, Pekny M, Pekna M. (2009) Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells. Stem Cells, 27 (11): 2824-32. [PMID:19785034]
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target has curated data in GtoImmuPdb
