BPS/IUPHAR Guide to Pharmacology | GRAC GPCR FAMILIES

Complement peptide receptors

Formerly known as: Anaphylatoxin receptors

More information on this family may be found on the IUPHAR-DB family and introduction pages.

Complement peptide receptors (provisional nomenclature) are activated by the endogenous ~75 amino-acid anaphylatoxin polypeptides C3a (ENSG00000125730) and C5a (ENSG00000106804), generated upon stimulation of the complement cascade.

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Receptors

C3a receptor Show »« Hide

Nomenclature

C3a receptor

Other names

AZ3B, HNFAG09, C3AR, C3a anaphylatoxin chemotactic receptor, C3a-R, complement component 3a receptor 1, anaphylatoxin C3a receptor

IUPHAR-DB

C3a receptor

Genes

C3AR1 (Hs), C3ar1 (Mm), C3ar1 (Rn)

Ensembl ID

ENSG00000171860 (Hs), ENSMUSG00000040552 (Mm), ENSRNOG00000009211 (Rn)

Principal transduction

G_i/o, G_z

Rank order of potency

C3a > C5a [2]

Selective agonists
(pK_i)

E7 (pEC₅₀ 8.7) [3]

Selective antagonists
(pK_i)

SB290157 (pIC₅₀ 7.6) [1]

Radioligands
(K_d)

[¹²⁵I]C3a (human) (Agonist, Full agonist) (3.85x10^-9 M) [5]

C5a₁ receptor Show »« Hide

C5a₂ receptor Show »« Hide

Nomenclature	C5a₂ receptor
Other names	C5L2, C5A receptor beta, C5a anaphylatoxin chemotactic receptor C5L2, G protein-coupled receptor 77, G-protein coupled receptor 77, complement 5A receptor beta, E030029A11Rik, C5aR2, GPR77, C5aRL
IUPHAR-DB	C5a₂ receptor
Genes	C5AR2 (Hs), Gpr77 (Mm), Gpr77 (Rn)
Ensembl ID	ENSG00000134830 (Hs), ENSMUSG00000074361 (Mm), ENSRNOG00000049028 (Rn)
Principal transduction	-
Comment	Binds C5a complement factor, but appears to lack G protein signalling and has been termed a decoy receptor [17].

Comments Show »« Hide

Further Reading Show »« Hide

Ali, H. (2010) Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a. Immunol. Lett., 128 (1): 36-45. [PMID:19895849]

Hajishengallis, G. (2010) Complement and periodontitis. Biochem. Pharmacol., 80 (12): 1992-2001. [PMID:20599785]

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]

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]

Ward, PA. (2009) Functions of C5a receptors. J. Mol. Med., 87 (4): 375-8. [PMID:19189071]

References Show »« Hide

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. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. Huey, R; Hugli, TE. (1985) Characterization of a C5a receptor on human polymorphonuclear leukocytes (PMN). J. Immunol., 135 (3): 2063-8. [PMID:4020139]

10. 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]

11. 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]

12. Kawai, M., Quincy, D. A., Lane, B., Mollison, K. W., Or, Y. S., Luly, J. R. and Carter, G. W. (1992) Structure-function studies in a series of carboxyl-terminal octapeptide analogues of anaphylatoxin C5a. J Med Chem, 35: 220-223. [PMID:1732540]

13. Konteatis, Z. D., Siciliano, S. J., Van Riper, G., Molineaux, C. J., Pandya, S., Fischer, P., Rosen, H., Mumford, R. A. and Springer, M. S. (1994) Development of C5a receptor antagonists. Differential loss of functional responses. J Immunol, 153: 4200-4205. [PMID:7930622]

14. 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]

15. 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]

16. Postma, B; Poppelier, MJ; van Galen, JC; Prossnitz, ER; van Strijp, JA; de Haas, CJ; van Kessel, KP. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J. Immunol., 172 (11): 6994-7001. [PMID:15153520]

17. 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]

18. 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]

19. 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]

20. 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]