GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.
- Home
- Targets
- G protein-coupled receptors
- Complement peptide receptors
Complement peptide receptors C
Formerly known as: Anaphylatoxin receptors
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
Show »« Hide
More detailed introduction 
Complement peptide receptors (nomenclature as agreed by the NC-IUPHAR subcommittee on Complement peptide receptors [35]) are activated by the endogenous ~75 amino-acid anaphylatoxin polypeptides C3a (C3, P01024) and C5a (C5, P01031), generated upon stimulation of the complement cascade. C3a and C5a exert their functions through binding to their receptors (C3a receptor, C5a receptor 1 and C5a receptor 2), causing cell recruitment and triggering cellular degranulation that contributes to local inflammation.
Receptors
|
C3a receptor
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||||||||||||
|
C5a1 receptor
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||||||||||||
|
C5a2 receptor
C
Show summary »« Hide summary
More detailed page
|
Further reading
* Key recommended reading is highlighted with an asterisk
* Arbore G, Kemper C. (2016) A novel "complement-metabolism-inflammasome axis" as a key regulator of immune cell effector function. Eur J Immunol, 46 (7): 1563-73. [PMID:27184294]
Coulthard LG, Hawksworth OA, Conroy J, Lee JD, Woodruff TM. (2018) Complement C3a receptor modulates embryonic neural progenitor cell proliferation and cognitive performance. Mol Immunol, 101: 176-181. [PMID:30449309]
* Coulthard LG, Woodruff TM. (2015) Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. J Immunol, 194 (8): 3542-8. [PMID:25848071]
Klos A, Wende E, Wareham KJ, Monk PN. (2013) International Union of Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev, 65 (1): 500-43. [PMID:23383423]
* Laumonnier Y, Karsten CM, Köhl J. (2017) Novel insights into the expression pattern of anaphylatoxin receptors in mice and men. Mol Immunol, 89: 44-58. [PMID:28600003]
Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM. (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB J, 27 (3): 855-64. [PMID:23239822]
Li XX, Lee JD, Kemper C, Woodruff TM. (2019) The Complement Receptor C5aR2: A Powerful Modulator of Innate and Adaptive Immunity. J Immunol, 202 (12): 3339-3348. [PMID:31160390]
Manthey HD, Woodruff TM, Taylor SM, Monk PN. (2009) Complement component 5a (C5a). Int J Biochem Cell Biol, 41 (11): 2114-7. [PMID:19464229]
Monk PN, Scola AM, Madala P, Fairlie DP. (2007) Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol, 152 (4): 429-48. [PMID:17603557]
Pandey S, Maharana J, Li XX, Woodruff TM, Shukla AK. (2020) Emerging Insights into the Structure and Function of Complement C5a Receptors. Trends Biochem Sci, 45 (8): 693-705. [PMID:32402749]
Reichhardt MP, Meri S. (2018) Intracellular complement activation-An alarm raising mechanism?. Semin Immunol, 38: 54-62. [PMID:29631809]
Sacks SH. (2010) Complement fragments C3a and C5a: the salt and pepper of the immune response. Eur J Immunol, 40 (3): 668-70. [PMID:20186746]
* West EE, Woodruff T, Fremeaux-Bacchi V, Kemper C. (2024) Complement in human disease: approved and up-and-coming therapeutics. Lancet, 403 (10424): 392-405. [PMID:37979593]
References
1. 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]
2. 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]
3. 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]
4. Arbore G, West EE, Spolski R, Robertson AA, Klos A, Rheinheimer C, Dutow P, Woodruff TM, Yu ZX, O'Neill LA et al.. (2016) T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells. Science, 352 (6292): aad1210. [PMID:27313051]
5. Bamberg CE, Mackay CR, Lee H, Zahra D, Jackson J, Lim YS, Whitfeld PL, Craig S, Corsini E, Lu B et al.. (2010) The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. J Biol Chem, 285 (10): 7633-44. [PMID:20044484]
6. Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L, Baumgart T, Shugarts S, Lohr L, Dang T et al.. (2016) Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS ONE, 11 (10): e0164646. [PMID:27768695]
7. Brandolini L, Grannonico M, Bianchini G, Colanardi A, Sebastiani P, Paladini A, Piroli A, Allegretti M, Varrassi G, Di Loreto S. (2019) Correction to: The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury. Neurotox Res, 36 (2): 439. [PMID:31062231]
8. Brennan FH, Jogia T, Gillespie ER, Blomster LV, Li XX, Nowlan B, Williams GM, Jacobson E, Osborne GW, Meunier FA et al.. (2019) Complement receptor C3aR1 controls neutrophil mobilization following spinal cord injury through physiological antagonism of CXCR2. JCI Insight, 4 (9): e98254. [PMID:31045582]
9. Brodbeck RM, Cortright DN, Kieltyka AP, Yu J, Baltazar CO, Buck ME, Meade R, Maynard GD, Thurkauf A, Chien DS et al.. (2008) Identification and characterization of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a novel, orally bioavailable C5a receptor inverse agonist. J Pharmacol Exp Ther, 327 (3): 898-909. [PMID:18753409]
10. Buhl AM, Eisfelder BJ, Worthen GS, Johnson GL, Russell M. (1993) Selective coupling of the human anaphylatoxin C5a receptor and alpha 16 in human kidney 293 cells. FEBS Lett, 323 (1-2): 132-4. [PMID:8388335]
11. Cain SA, Monk PN. (2002) The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem, 277 (9): 7165-9. [PMID:11773063]
12. Carvelli J, Demaria O, Vély F, Batista L, Chouaki Benmansour N, Fares J, Carpentier S, Thibult ML, Morel A, Remark R et al.. (2020) Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis. Nature, 588 (7836): 146-150. [PMID:32726800]
13. Chao TH, Ember JA, Wang M, Bayon Y, Hugli TE, Ye RD. (1999) Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function. J Biol Chem, 274 (14): 9721-8. [PMID:10092660]
14. Chen T, Lennon VA, Liu YU, Bosco DB, Li Y, Yi MH, Zhu J, Wei S, Wu LJ. (2020) Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion. J Clin Invest, 130 (8): 4025-4038. [PMID:32568214]
15. Coulthard LG, Woodruff TM. (2015) Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. J Immunol, 194 (8): 3542-8. [PMID:25848071]
16. Croker DE, Halai R, Fairlie DP, Cooper MA. (2013) C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2. Immunol Cell Biol, 91 (10): 625-33. [PMID:24060963]
17. Croker DE, Halai R, Kaeslin G, Wende E, Fehlhaber B, Klos A, Monk PN, Cooper MA. (2014) C5a2 can modulate ERK1/2 signaling in macrophages via heteromer formation with C5a1 and β-arrestin recruitment. Immunol Cell Biol, 92 (7): 631-9. [PMID:24777312]
18. Croker DE, Monk PN, Halai R, Kaeslin G, Schofield Z, Wu MC, Clark RJ, Blaskovich MA, Morikis D, Floudas CA et al.. (2016) Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling. Immunol Cell Biol, 94 (8): 787-95. [PMID:27108698]
19. 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]
20. Ember JA, Johansen NL, Hugli TE. (1991) Designing synthetic superagonists of C3a anaphylatoxin. Biochemistry, 30 (15): 3603-12. [PMID:2015217]
21. Gao H, Neff TA, Guo RF, Speyer CL, Sarma JV, Tomlins S, Man Y, Riedemann NC, Hoesel LM, Younkin E et al.. (2005) Evidence for a functional role of the second C5a receptor C5L2. FASEB J, 19 (8): 1003-5. [PMID:15784721]
22. Gavrilyuk V, Kalinin S, Hilbush BS, Middlecamp A, McGuire S, Pelligrino D, Weinberg G, Feinstein DL. (2005) Identification of complement 5a-like receptor (C5L2) from astrocytes: characterization of anti-inflammatory properties. J Neurochem, 92 (5): 1140-9. [PMID:15715664]
23. Gorlov IP, Kamat A, Bogatcheva NV, Jones E, Lamb DJ, Truong A, Bishop CE, McElreavey K, Agoulnik AI. (2002) Mutations of the GREAT gene cause cryptorchidism. Hum Mol Genet, 11 (19): 2309-18. [PMID:12217959]
24. Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, Rolfe BE, Woodruff TM, Clark RJ. (2021) Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity. J Med Chem, 64 (22): 16598-16608. [PMID:34762432]
25. Gorman DM, Li XX, Payne CD, Cui CS, Lee JD, Rosengren KJ, Woodruff TM, Clark RJ. (2021) Development of Synthetic Human and Mouse C5a: Application to Binding and Functional Assays In Vitro and In Vivo. ACS Pharmacol Transl Sci, 4 (6): 1808-1817. [PMID:34927012]
26. Hammann-Hänni A, Kaufmann P, Klein G, Schmid K, Dingemanse J. (2023) Effect of Severe Renal Impairment on Pharmacokinetics, Safety, and Tolerability of ACT-1014-6470, a Novel Oral Complement Factor 5a Receptor 1 Antagonist. Clin Pharmacol Drug Dev, 12 (2): 152-158. [PMID:36285509]
27. Hawksworth OA, Li XX, Coulthard LG, Wolvetang EJ, Woodruff TM. (2017) New concepts on the therapeutic control of complement anaphylatoxin receptors. Mol Immunol, 89: 36-43. [PMID:28576324]
28. Honczarenko M, Lu B, Nicholson-Weller A, Gerard NP, Silberstein LE, Gerard C. (2005) C5L2 receptor is not involved in C3a / C3a-desArg-mediated enhancement of bone marrow hematopoietic cell migration to CXCL12. Leukemia, 19 (9): 1682-3; author reply 1684-5. [PMID:15990859]
29. Huey R, Hugli TE. (1985) Characterization of a C5a receptor on human polymorphonuclear leukocytes (PMN). J Immunol, 135 (3): 2063-8. [PMID:4020139]
30. 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]
31. Kalant D, Cain SA, Maslowska M, Sniderman AD, Cianflone K, Monk PN. (2003) The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein. J Biol Chem, 278 (13): 11123-9. [PMID:12540846]
32. Kalant D, MacLaren R, Cui W, Samanta R, Monk PN, Laporte SA, Cianflone K. (2005) C5L2 is a functional receptor for acylation-stimulating protein. J Biol Chem, 280 (25): 23936-44. [PMID:15833747]
33. Kawai M, Quincy DA, Lane B, Mollison KW, Or YS, Luly JR, Carter GW. (1992) Structure-function studies in a series of carboxyl-terminal octapeptide analogues of anaphylatoxin C5a. J Med Chem, 35: 220-223. [PMID:1732540]
34. 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]
35. Klos A, Wende E, Wareham KJ, Monk PN. (2013) International Union of Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev, 65 (1): 500-43. [PMID:23383423]
36. Konteatis ZD, Siciliano SJ, Van Riper G, Molineaux CJ, Pandya S, Fischer P, Rosen H, Mumford RA, Springer MS. (1994) Development of C5a receptor antagonists. Differential loss of functional responses. J Immunol, 153 (9): 4200-5. [PMID:7930622]
37. Lee A. (2022) Avacopan: First Approval. Drugs, 82 (1): 79-85. [PMID:34826105]
38. Li R, Coulthard LG, Wu MC, Taylor SM, Woodruff TM. (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB J, 27 (3): 855-64. [PMID:23239822]
39. Li XX, Clark RJ, Woodruff TM. (2020) C5aR2 Activation Broadly Modulates the Signaling and Function of Primary Human Macrophages. J Immunol, 205 (4): 1102-1112. [PMID:32611725]
40. 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]
41. Li XX, Lee JD, Kemper C, Woodruff TM. (2019) The Complement Receptor C5aR2: A Powerful Modulator of Innate and Adaptive Immunity. J Immunol, 202 (12): 3339-3348. [PMID:31160390]
42. Li XX, Lee JD, Massey NL, Guan C, Robertson AAB, Clark RJ, Woodruff TM. (2020) Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function. Biochem Pharmacol, 180: 114156. [PMID:32682759]
43. March DR, Proctor LM, Stoermer MJ, Sbaglia R, Abbenante G, Reid RC, Woodruff TM, Wadi K, Paczkowski N, Tyndall JD et al.. (2004) Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activity. Mol Pharmacol, 65 (4): 868-79. [PMID:15044616]
44. 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]
45. Miyabe Y, Miyabe C, Mani V, Mempel TR, Luster AD. (2019) Atypical complement receptor C5aR2 transports C5a to initiate neutrophil adhesion and inflammation. Sci Immunol, 4 (35). DOI: 10.1126/sciimmunol.aav5951 [PMID:31076525]
46. Monk PN, Scola AM, Madala P, Fairlie DP. (2007) Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol, 152 (4): 429-48. [PMID:17603557]
47. Moriconi A, Cunha TM, Souza GR, Lopes AH, Cunha FQ, Carneiro VL, Pinto LG, Brandolini L, Aramini A, Bizzarri C et al.. (2014) Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief. Proc Natl Acad Sci USA, 111 (47): 16937-42. [PMID:25385614]
48. Nabizadeh JA, Manthey HD, Steyn FJ, Chen W, Widiapradja A, Md Akhir FN, Boyle GM, Taylor SM, Woodruff TM, Rolfe BE. (2016) The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses. J Immunol, 196 (11): 4783-92. [PMID:27183625]
49. Nandagopal S, Li CG, Xu Y, Sodji QH, Graves EE, Giaccia AJ. (2022) C3aR Signaling Inhibits NK-cell Infiltration into the Tumor Microenvironment in Mouse Models. Cancer Immunol Res, 10 (2): 245-258. [PMID:34819308]
50. 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]
51. Okinaga S, Slattery D, Humbles A, Zsengeller Z, Morteau O, Kinrade MB, Brodbeck RM, Krause JE, Choe HR, Gerard NP et al.. (2003) C5L2, a nonsignaling C5A binding protein. Biochemistry, 42 (31): 9406-15. [PMID:12899627]
52. Otto M, Hawlisch H, Monk PN, Müller M, Klos A, Karp CL, Köhl J. (2004) C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism. J Biol Chem, 279 (1): 142-51. [PMID:14570896]
53. Pandey S, Kumari P, Baidya M, Kise R, Cao Y, Dwivedi-Agnihotri H, Banerjee R, Li XX, Cui CS, Lee JD et al.. (2021) Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors. Mol Cell, 81 (22): 4605-4621.e11. [PMID:34582793]
54. Pandey S, Li XX, Srivastava A, Baidya M, Kumari P, Dwivedi H, Chaturvedi M, Ghosh E, Woodruff TM, Shukla AK. (2019) Partial ligand-receptor engagement yields functional bias at the human complement receptor, C5aR1. J Biol Chem, 294 (24): 9416-9429. [PMID:31036565]
55. Pandey S, Maharana J, Li XX, Woodruff TM, Shukla AK. (2020) Emerging Insights into the Structure and Function of Complement C5a Receptors. Trends Biochem Sci, 45 (8): 693-705. [PMID:32402749]
56. 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]
57. 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]
58. 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]
59. Scola AM, Johswich KO, Morgan BP, Klos A, Monk PN. (2009) The human complement fragment receptor, C5L2, is a recycling decoy receptor. Mol Immunol, 46 (6): 1149-62. [PMID:19100624]
60. 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]
61. Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, Kamahori T, Ehara S, Itoh K, Ohtsuka T et al.. (2002) Identification of a potent and orally active non-peptide C5a receptor antagonist. J Biol Chem, 277 (51): 49403-7. [PMID:12384495]
62. Sünderhauf A, Skibbe K, Preisker S, Ebbert K, Verschoor A, Karsten CM, Kemper C, Huber-Lang M, Basic M, Bleich A et al.. (2017) Regulation of epithelial cell expressed C3 in the intestine - Relevance for the pathophysiology of inflammatory bowel disease?. Mol Immunol, 90: 227-238. [PMID:28843904]
63. Takahashi M, Moriguchi S, Suganuma H, Shiota A, Tani F, Usui H, Kurahashi K, Sasaki R, Yoshikawa M. (1997) Identification of casoxin C, an ileum-contracting peptide derived from bovine kappa-casein, as an agonist for C3a receptors. Peptides, 18 (3): 329-36. [PMID:9145417]
64. Takahashi M, Moriguchi S, Yoshikawa M, Sasaki R. (1994) Isolation and characterization of oryzatensin: a novel bioactive peptide with ileum-contracting and immunomodulating activities derived from rice albumin. Biochem Mol Biol Int, 33 (6): 1151-8. [PMID:7804141]
65. Van Lith LH, Oosterom J, Van Elsas A, Zaman GJ. (2009) C5a-stimulated recruitment of beta-arrestin2 to the nonsignaling 7-transmembrane decoy receptor C5L2. J Biomol Screen, 14 (9): 1067-75. [PMID:19641221]
66. Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG et al.. (2020) Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol, 2 (12): e764-e773. DOI: 10.1016/S2665-9913(20)30341-6 [PMID:33015643]
67. Wende E, Laudeley R, Bleich A, Bleich E, Wetsel RA, Glage S, Klos A. (2013) The complement anaphylatoxin C3a receptor (C3aR) contributes to the inflammatory response in dextran sulfate sodium (DSS)-induced colitis in mice. PLoS ONE, 8 (4): e62257. [PMID:23638016]
68. Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP. (1998) Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a. J Med Chem, 41 (18): 3417-25. [PMID:9719594]
69. Yamamoto T. (2000) Molecular mechanism of monocyte predominant infiltration in chronic inflammation: mediation by a novel monocyte chemotactic factor, S19 ribosomal protein dimer. Pathol Int, 50 (11): 863-71. [PMID:11107061]
70. Yoshikawa M. (2015) Bioactive peptides derived from natural proteins with respect to diversity of their receptors and physiological effects. Peptides, 72: 208-25. [PMID:26297549]
71. Zhang T, Wu KY, Ma N, Wei LL, Garstka M, Zhou W, Li K. (2020) The C5a/C5aR2 axis promotes renal inflammation and tissue damage. JCI Insight, 5 (7). [PMID:32191644]
72. Zhao SJ, Wu KY, Min XY, Wang CX, Cao B, Ma N, Yang XL, Zhu ZR, Fu RG, Zhou W et al.. (2022) Protective role for C3aR in experimental chronic pyelonephritis. FASEB J, 36 (11): e22599. [PMID:36250902]
NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Trent M. Woodruff (Chairperson) |
Other contributors:
Antonia Cianciulli
Liam Coulthard
Owen Hawksworth
John D. Lee
Xaria X. Li
Vincenzo Mitolo (Past contributor)
Maria A. Panaro |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
SB290157 has also been reported to have agonist properties at the C3a receptor [40,44]. The chemoattractant receptor C5a2 (also known as GPR77, C5L2) binds C5a and has putative roles in either opposing or promoting inflammatory responses [11,21-22,41,55]. Binding to this site may be displaced with the rank order C5a des-Arg (C5) > C5a (C5, P01031) [11,51] while there is controversy over the ability of C3a (C3, P01024) and C3a des Arg (C3, P01024) to compete [28,31-32,51]. C5a2 appears to lack G protein signalling and has been termed a decoy receptor [59]. However, C5a2 does recruit β-arrestin 2 after ligand binding, which might provide a signalling pathway for this receptor [5,65], and forms heteromers with C5a1. A recent study has identified p90RSK (90 kDa ribosomal s6 kinase) phosphorylation as a potential signalling pathway for C5a2 [53]. C5a, but not C5a-des Arg, induces upregulation of heterodimer formation between complement C5a receptors C5a1 and C5a2 [16]. There are also reports of pro-inflammatory activity of C5a2, mediated by HMGB1, likely through AKT and MAPK signalling pathways (reviewed in [38,71]). In T cells it has been shown that C5a1 and C5a2 act in opposition to each other and that altering the equilibrium between the two receptors, by differential expression or production of C5a-des Arg (which favours C5a2), can affect the final cellular response [4]. In human macrophages, C5a2 was observed to modulate multiple complement and chemokine receptor-mediated signalling and pattern recognition-induced cytokine responses, independent of C5a1 [39]. In addition, C5a2 is reported to act as a C5a transporter on endothelial cells, and is required for the transport of C5a into the vessel lumen and the subsequent neutrophil arrest in arthritis [45].