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Gene Review

C3AR1  -  complement component 3a receptor 1

Homo sapiens

Synonyms: AZ3B, C3AR, C3R1, C3a anaphylatoxin chemotactic receptor, C3a-R, ...
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Disease relevance of C3AR1


High impact information on C3AR1


Chemical compound and disease context of C3AR1

  • To determine if C3a is an essential mediator of systemic anaphylaxis, the anaphylactic response to ovalbumin (OA) was assessed in guinea pigs genetically deficient in the C3a receptor (C3aR-) compared to their control strain of animals which were C3a receptor positive (C3aR+) [7].

Biological context of C3AR1

  • Third, enhancement of chemotaxis of hemopoietic cells is also mediated by C3a-desArg, which does not bind to C3aR [8].
  • During complement activation the pro-inflammatory anaphylatoxins C3a and C5a are generated, which interact with the C3a receptor and C5a receptor (CD88), respectively [9].
  • A panel of anti-C3aR single chain Fv fragments (scFvs) was selected after four rounds of panning using the second extracellular loop of the C3aR, fused to the maltose binding protein as Ag [2].
  • When expressed in rat basophilic leukemia cells and exposed to C3a, the C3aR underwent rapid (t(1/2) approximately 15 s), dose-dependent (EC50 approximately 10 nM) and reversible phosphorylation by a kinase refractory to the effects of PKC inhibitors [10].
  • A cDNA clone encoding the human C3a anaphylatoxin receptor (C3aR) was isolated from a pcDNAI/Amp expression library prepared from U-937 cells which had been differentiated with dibutyryl cAMP to a macrophage-like phenotype [11].

Anatomical context of C3AR1


Associations of C3AR1 with chemical compounds

  • We report that normal human CD34(+) cells and lineage-differentiated hematopoietic progenitors express the complement anaphylatoxin C3a receptor (C3aR) and respond to C3a [13].
  • Second, the competitive C3aR inhibitor SB290157 does not affect C3a-mediated enhancement of CXCL12-induced chemotaxis [8].
  • Recent studies have provided evidence that C3, C3a receptor, and C5 are linked to airway hyperresponsiveness [14].
  • Sulfation of tyrosine 174 in the human C3a receptor is essential for binding of C3a anaphylatoxin [15].
  • SB 290157 was a functional antagonist, blocking C3a-induced C3aR internalization in a concentration-dependent manner and C3a-induced Ca(2+) mobilization in RBL-C3aR cells and human neutrophils with IC(50)s of 27.7 and 28 nM, respectively [16].

Physical interactions of C3AR1


Regulatory relationships of C3AR1

  • C3aR internalization is a rapid negative control mechanism and is influenced by the C5aR pathway [12].
  • Neither C5a nor FMLP stimulated any cross-internalization of the C3aR [12].
  • For U937 cells, IFN-gamma and Bt2cAMP up-regulated the C3aR to the same extent, whereas Bt2cAMP was 20-fold more effective in C5aR induction [19].

Other interactions of C3AR1

  • Chimeras were generated between the human anaphylatoxin C3a and C5a receptors (C3aR and C5aR, respectively) to define the structural requirements for ligand binding and discrimination [20].
  • On the contrary, costimulation of granulocytes with C5a, but not FMLP, drastically decreased C3aR internalization [12].
  • A novel computational method for predicting the transmembrane structure of G-protein coupled receptors: application to human C5aR and C3aR [21].
  • Unlike CD88 and C3a receptor, C5L2 transfected into RBL-2H3 cells does not support degranulation or increases in intracellular [Ca(2+)] and is not rapidly internalized in response to ligand binding [22].
  • Some of them (CTCE, C3a receptor agonist and GrobetaT) are still subject of pre-clinical development, others, such as chemokine receptor ligand AMD3100, have recently been introduced in clinical trials and already deliver promising results [23].

Analytical, diagnostic and therapeutic context of C3AR1


  1. Human plasmacytoid dendritic cells express receptors for anaphylatoxins c3a and c5a and are chemoattracted to c3a and c5a. Gutzmer, R., K??ther, B., Zwirner, J., Dijkstra, D., Purwar, R., Wittmann, M., Werfel, T. J. Invest. Dermatol. (2006) [Pubmed]
  2. Site-directed C3a receptor antibodies from phage display libraries. Hawlisch, H., Frank, R., Hennecke, M., Baensch, M., Sohns, B., Arseniev, L., Bautsch, W., Kola, A., Klos, A., Köhl, J. J. Immunol. (1998) [Pubmed]
  3. 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. Gasque, P., Singhrao, S.K., Neal, J.W., Wang, P., Sayah, S., Fontaine, M., Morgan, B.P. J. Immunol. (1998) [Pubmed]
  4. In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins. Ames, R.S., Nuthulaganti, P., Kumar, C. FEBS Lett. (1996) [Pubmed]
  5. Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Nataf, S., Stahel, P.F., Davoust, N., Barnum, S.R. Trends Neurosci. (1999) [Pubmed]
  6. The human C3a receptor is expressed on neutrophils and monocytes, but not on B or T lymphocytes. Martin, U., Bock, D., Arseniev, L., Tornetta, M.A., Ames, R.S., Bautsch, W., Köhl, J., Ganser, A., Klos, A. J. Exp. Med. (1997) [Pubmed]
  7. Minor role of the C3a receptor in systemic anaphylaxis in the guinea pig. Regal, J.F., Klos, A. Immunopharmacology (2000) [Pubmed]
  8. Complement C3a enhances CXCL12 (SDF-1)-mediated chemotaxis of bone marrow hematopoietic cells independently of C3a receptor. Honczarenko, M., Ratajczak, M.Z., Nicholson-Weller, A., Silberstein, L.E. J. Immunol. (2005) [Pubmed]
  9. Ligand Specificity of the Anaphylatoxin C5L2 Receptor and Its Regulation on Myeloid and Epithelial Cell Lines. Johswich, K., Martin, M., Thalmann, J., Rheinheimer, C., Monk, P.N., Klos, A. J. Biol. Chem. (2006) [Pubmed]
  10. Ligand-induced phosphorylation of anaphylatoxin receptors C3aR and C5aR is mediated by "G protein-coupled receptor kinases. Langkabel, P., Zwirner, J., Oppermann, M. Eur. J. Immunol. (1999) [Pubmed]
  11. Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U-937 cells. Crass, T., Raffetseder, U., Martin, U., Grove, M., Klos, A., Köhl, J., Bautsch, W. Eur. J. Immunol. (1996) [Pubmed]
  12. Modulation of C3a activity: internalization of the human C3a receptor and its inhibition by C5a. Settmacher, B., Bock, D., Saad, H., Gärtner, S., Rheinheimer, C., Köhl, J., Bautsch, W., Klos, A. J. Immunol. (1999) [Pubmed]
  13. Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1. Reca, R., Mastellos, D., Majka, M., Marquez, L., Ratajczak, J., Franchini, S., Glodek, A., Honczarenko, M., Spruce, L.A., Janowska-Wieczorek, A., Lambris, J.D., Ratajczak, M.Z. Blood (2003) [Pubmed]
  14. Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma. Hasegawa, K., Tamari, M., Shao, C., Shimizu, M., Takahashi, N., Mao, X.Q., Yamasaki, A., Kamada, F., Doi, S., Fujiwara, H., Miyatake, A., Fujita, K., Tamura, G., Matsubara, Y., Shirakawa, T., Suzuki, Y. Hum. Genet. (2004) [Pubmed]
  15. Sulfation of tyrosine 174 in the human C3a receptor is essential for binding of C3a anaphylatoxin. Gao, J., Choe, H., Bota, D., Wright, P.L., Gerard, C., Gerard, N.P. J. Biol. Chem. (2003) [Pubmed]
  16. Identification of a selective nonpeptide antagonist of the anaphylatoxin C3a receptor that demonstrates antiinflammatory activity in animal models. Ames, R.S., Lee, D., Foley, J.J., Jurewicz, A.J., Tornetta, M.A., Bautsch, W., Settmacher, B., Klos, A., Erhard, K.F., Cousins, R.D., Sulpizio, A.C., Hieble, J.P., McCafferty, G., Ward, K.W., Adams, J.L., Bondinell, W.E., Underwood, D.C., Osborn, R.R., Badger, A.M., Sarau, H.M. J. Immunol. (2001) [Pubmed]
  17. Detection of anaphylatoxin receptors on CD83+ dendritic cells derived from human skin. Kirchhoff, K., Weinmann, O., Zwirner, J., Begemann, G., Götze, O., Kapp, A., Werfel, T. Immunology (2001) [Pubmed]
  18. Identification of ligand effector binding sites in transmembrane regions of the human G protein-coupled C3a receptor. Sun, J., Ember, J.A., Chao, T.H., Fukuoka, Y., Ye, R.D., Hugli, T.E. Protein Sci. (1999) [Pubmed]
  19. Differential regulation of the C3a and C5a receptors (CD88) by IFN-gamma and PMA in U937 cells and related myeloblastic cell lines. Burg, M., Martin, U., Bock, D., Rheinheimer, C., Köhl, J., Bautsch, W., Klos, A. J. Immunol. (1996) [Pubmed]
  20. Chimeric receptors of the human C3a receptor and C5a receptor (CD88). Crass, T., Ames, R.S., Sarau, H.M., Tornetta, M.A., Foley, J.J., Köhl, J., Klos, A., Bautsch, W. J. Biol. Chem. (1999) [Pubmed]
  21. A novel computational method for predicting the transmembrane structure of G-protein coupled receptors: application to human C5aR and C3aR. Rayan, A., Siew, N., Cherno-Schwartz, S., Matzner, Y., Bautsch, W., Goldblum, A. Recept. Channels (2000) [Pubmed]
  22. The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). Cain, S.A., Monk, P.N. J. Biol. Chem. (2002) [Pubmed]
  23. Innovative strategies for PBPC mobilization. Fruehauf, S., Seeger, T., Topaly, J. Cytotherapy. (2005) [Pubmed]
  24. Molecular cloning and characterization of the human anaphylatoxin C3a receptor. Ames, R.S., Li, Y., Sarau, H.M., Nuthulaganti, P., Foley, J.J., Ellis, C., Zeng, Z., Su, K., Jurewicz, A.J., Hertzberg, R.P., Bergsma, D.J., Kumar, C. J. Biol. Chem. (1996) [Pubmed]
  25. Characterization of synthetic C3a analog peptides on human eosinophils in comparison to the native complement component C3a. Petering, H., Köhl, J., Weyergraf, A., Dulkys, Y., Kimmig, D., Smolarski, R., Kapp, A., Elsner, J. J. Immunol. (2000) [Pubmed]
  26. Renal expression of the C3a receptor and functional responses of primary human proximal tubular epithelial cells. Braun, M.C., Reins, R.Y., Li, T.B., Hollmann, T.J., Dutta, R., Rick, W.A., Teng, B.B., Ke, B. J. Immunol. (2004) [Pubmed]
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