The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CR1  -  complement component (3b/4b) receptor 1...

Homo sapiens

Synonyms: C3BR, C3b/C4b receptor, C4BR, CD35, Complement receptor type 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CR1


Psychiatry related information on CR1

  • The results indicate that CR1 on erythrocytes, circulating immune complexes and complement cleavage products C3c and C3d in healthy subjects remain unaffected by short-term heavy physical activity and training [7].
  • Alterations in trk A, trk B and trk C receptor immunoreactivities in parietal cortex and cerebellum in Alzheimer's disease [8].

High impact information on CR1

  • The structure of the principal C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three complement control protein modules (modules 15-17) in an extended head-to-tail arrangement with flexibility at the 16-17 junction [9].
  • FDCs trap immune complexes with Fc-gamma receptors and C3d/C4b-opsonized antigens with CD21/CD35 complement receptors [10].
  • Complement receptors CR1 and CR3 are responsible for the phagocytic and adhesive properties of neutrophils, whereas the C5a receptor mediates the pro-inflammatory and chemotactic actions of the complement anaphylatoxin C5a [11].
  • In addition to stimulating chemotaxis, granule enzyme release and superoxide anion production, this receptor stimulates upregulation of expression and activity of the adhesion molecule MAC-1, and of CR1, and a decrease in cell-surface glycoprotein 100MEL-14 on neutrophils [11].
  • We report here the isolation by affinity chromatography of a macrophage glycoprotein with an apparent molecular weight (MW) of approximately 64,000 that has properties expected of the C3b receptor [12].

Chemical compound and disease context of CR1


Biological context of CR1

  • The anti-IgM-induced transient increase in the concentration of intracellular free Ca(2+) and phosphorylation of several cytoplasmic proteins are strongly reduced in the presence of the CR1 ligand [18].
  • The murine complement receptor gene family. IV. Alternative splicing of Cr2 gene transcripts predicts two distinct gene products that share homologous domains with both human CR2 and CR1 [19].
  • An identity matrix analysis suggests that human ancestral CR2 evolved before divergence of the rodent and primate branches of the evolutionary tree through a series of predictable gene duplications, possibly giving rise to the precursor of human CR1 and murine CRY [20].
  • Blocking the CR1 binding-site resulted in significant reduction of both C3-fragment deposition (22.0+/-14.5%) and MAC formation (47.4+/-13.8%) [21].
  • SCR(1-3) was able to inhibit both classical and alternative pathways of complement activation, showing that the N-terminal SCR of CR1 retain the ability to interact with C3b [3].

Anatomical context of CR1

  • In the final stage of surface marker-defined maturation, CR2 was lost from high density polymorphonuclear neutrophils and CR1 was maximally expressed [22].
  • CR1 was found on 20-40% of mouse megakaryocytes and also on a proportion of mouse platelets [23].
  • On neutrophils and mononuclear phagocytes, CR1 is the predominant C3-binding glycoprotein, but gp45-70 is present on both cell populations and on macrophage and neutrophil cell lines [1].
  • We have investigated the expression, molecular association, ligand binding properties, and ability to transduce intracellular signals of CR1 and CR2 C3 receptors on cells of the human HPB-ALL T cell line [24].
  • None of the astrocyte cells tested expressed CR3, whereas primary astrocytes and one of four astrocyte cell lines expressed CR1 (220 kDa), as assessed at the protein and mRNA level [25].

Associations of CR1 with chemical compounds

  • In the present study, we aimed to elucidate the role of human complement receptor type 1 (CR1), the other C3-receptor on B cells [18].
  • Mapping approaches employing blocking antibodies and synthetic peptides have implicated the 727-767 segment at the NH2 terminus of C3b alpha'-chain as contributing to the interactions with factor B, factor H, and CR1 [26].
  • Several previous reports concluded that the C4b fragment of human C4A (C4Ab) binds with higher affinity to CR1 than does C4Bb [27].
  • In contrast, no expression of C5, C5b-9, and CR1 was seen for any of the cell lines [28].
  • Assays for CR1-like cofactor activity for factor I using C4b-like C4 or C3b-like C3 as substrates showed that SCR(1-3) possessed such cofactor activity and that C4b-like C4 was a better substrate [3].

Physical interactions of CR1

  • C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2 [29].
  • In the simplest interpretation of these results, DAF and CR1 directly interact with C3bBb at alpha 4/5; factor H likely interacts at some other location, possibly on the C3b subunit [30].
  • The reduced level of complement receptor 1 (CR1) on erythrocytes is speculated as a key mechanism contributing to immune complex (IC) overload and exaggerated complement (C) activation in systemic lupus erythematosus (SLE) [13].
  • Selective inhibition of the two proteins on normal erythrocytes by the antisera demonstrated (i) that the factor responsible for accelerated decay of erythrocyte-bound C3 convertase is DAF and (ii) that the cofactor required for inactivation of erythrocyte-bound C3b by factor I is CR1 [31].
  • Removal of regions within CR1 eliminated binding of all species except p107 and p60cycA [32].

Enzymatic interactions of CR1


Regulatory relationships of CR1

  • Our observations have significance for the biology of normal human T cells because the majority of peripheral blood T cells that express CR1 also expressed CR2 and because a change in (Ca2+)i was induced by mAb OKB7 in purified normal T cells [24].
  • However, RA patients expressed fewer CR1 on erythrocytes within each genotype than their relatives and controls [34].
  • Paralleling this, IFN-gamma-activated MDM exhibit markedly reduced C receptor function, reflected by markedly decreased adherence and ingestion of C3b- and C3bi-coated E [35].
  • The effect of OKT1-SAP on target CD5-positive B-CLL cells was estimated using an in vitro proliferation inhibition assay in which control or OKT1-SAP-treated B-CLL cells were induced to proliferate by sequential stimulation with insolubilized anti-C3b receptor CB04 (CD35) antibody and low molecular weight B-cell growth factor [36].
  • Cofactor activity of orangutan E was partially inhibited by preclearance of CR1 and more completely inhibited by preclearance of MCP [37].

Other interactions of CR1

  • In situ hybridization studies suggest the expression of CR1 and CR2 mRNA in human epidermis [38].
  • A detailed analysis showed two distinct populations of plasma cells: (1) A population relatively smaller by forward light scattering expressed CD22, CD35, and sigE and was identified as early plasma cells (ie, lymphoplasmacytoid), and (2) a population larger by forward light scattering lacked these markers and was identified as mature plasma cells [39].
  • The data indicate that CD15 monoclonal antibodies react with a subset of the LFA-1/HMac-1/gp 150,95 glycoprotein family as well as with CR1 on human neutrophils [40].
  • Our results suggest that low levels of CR1 on erythrocytes in patients with RA are not inherited, rather they are acquired during the course of the disease [34].
  • In metastatic melanoma, 9/16 metastases were CD46+/CD59+, two were CD46-/CD59+, one CD46+/CD59-, and four CD46-/CD59-. Additionally, CD55 could be detected in two CD46+/CD59+ metastases, and CD35 in one [41].

Analytical, diagnostic and therapeutic context of CR1

  • Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM [42].
  • Independent verification of our surface plasmon resonance studies came from ELISA-based inhibition experiments in which monomers of C4Ab and C4Bb were equipotent in inhibiting the binding of soluble CR1 to plate-bound C4b [27].
  • CR1 numbers on erythrocytes were quantitated by the enzyme-linked immunosorbent assay using monoclonal anti-CR1 antibody [34].
  • This fact indicates that the new rosette-forming receptor is different from CR1 in accordance with the lack of rosette formation of Raji cells with EAC43 [43].
  • Densitometric analysis of autoradiographs obtained from Northern blots revealed that in AML patients, CR1 mRNA expression were 5.5-fold lower than controls (p=0.06), while DAF mRNA expression was significantly higher (p=0.0046) [44].


  1. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines. Cole, J.L., Housley, G.A., Dykman, T.R., MacDermott, R.P., Atkinson, J.P. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  2. CR1(CD35) and CR2(CD21) complement C3 receptors are expressed on normal human thymocytes and mediate infection of thymocytes with opsonized human immunodeficiency virus. Delibrias, C.C., Mouhoub, A., Fischer, E., Kazatchkine, M.D. Eur. J. Immunol. (1994) [Pubmed]
  3. Structure-activity relationships within the N-terminal short consensus repeats (SCR) of human CR1 (C3b/C4b receptor, CD35): SCR 3 plays a critical role in inhibition of the classical and alternative pathways of complement activation. Mossakowska, D., Dodd, I., Pindar, W., Smith, R.A. Eur. J. Immunol. (1999) [Pubmed]
  4. Ligation of CR1 (C3b receptor, CD35) on CD4+ T lymphocytes enhances viral replication in HIV-infected cells. Mouhoub, A., Delibrias, C.C., Fischer, E., Boyer, V., Kazatchkine, M.D. Clin. Exp. Immunol. (1996) [Pubmed]
  5. Levels of complement regulatory molecules in lung cancer: disappearance of the D17 epitope of CD55 in small-cell carcinoma. Sakuma, T., Kodama, K., Hara, T., Eshita, Y., Shibata, N., Matsumoto, M., Seya, T., Mori, Y. Jpn. J. Cancer Res. (1993) [Pubmed]
  6. A functional single-nucleotide polymorphism in the CR1 promoter region contributes to protection against cerebral malaria. Teeranaipong, P., Ohashi, J., Patarapotikul, J., Kimura, R., Nuchnoi, P., Hananantachai, H., Naka, I., Putaporntip, C., Jongwutiwes, S., Tokunaga, K. J. Infect. Dis. (2008) [Pubmed]
  7. Levels of complement receptor type one (CR1, CD35) on erythrocytes, circulating immune complexes and complement C3 split products C3d and C3c are not changed by short-term physical exercise or training. Thomsen, B.S., Rødgaard, A., Tvede, N., Hansen, F.R., Steensberg, J., Halkjaer Kristensen, J., Pedersen, B.K. International journal of sports medicine. (1992) [Pubmed]
  8. Alterations in trk A, trk B and trk C receptor immunoreactivities in parietal cortex and cerebellum in Alzheimer's disease. Savaskan, E., Müller-Spahn, F., Olivieri, G., Bruttel, S., Otten, U., Rosenberg, C., Hulette, C., Hock, C. Eur. Neurol. (2000) [Pubmed]
  9. Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor. Smith, B.O., Mallin, R.L., Krych-Goldberg, M., Wang, X., Hauhart, R.E., Bromek, K., Uhrin, D., Atkinson, J.P., Barlow, P.N. Cell (2002) [Pubmed]
  10. Complement facilitates early prion pathogenesis. Klein, M.A., Kaeser, P.S., Schwarz, P., Weyd, H., Xenarios, I., Zinkernagel, R.M., Carroll, M.C., Verbeek, J.S., Botto, M., Walport, M.J., Molina, H., Kalinke, U., Acha-Orbea, H., Aguzzi, A. Nat. Med. (2001) [Pubmed]
  11. The chemotactic receptor for human C5a anaphylatoxin. Gerard, N.P., Gerard, C. Nature (1991) [Pubmed]
  12. Isolation of a biologically active macrophage receptor for the third component of complement. Schneider, R.J., Kulczycki, A., Law, S.K., Atkinson, J.P. Nature (1981) [Pubmed]
  13. Association of leukocyte CR1 gene transcription with the disease severity and renal involvement in systemic lupus erythematosus. Verma, J., Arora, V., Marwaha, V., Kumar, A., Das, N. Lupus (2005) [Pubmed]
  14. Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture. Reveille, J.D., Moulds, J.M., Ahn, C., Friedman, A.W., Baethge, B., Roseman, J., Straaton, K.V., Alarcón, G.S. Arthritis Rheum. (1998) [Pubmed]
  15. Defective reticuloendothelial system C3b mediated clearance in rheumatoid arthritis and vasculitis. Cunningham, T.J., Nicholls, K.M., Chen, S.L., Mathews, J.D., Muirden, K.D. J. Rheumatol. (1985) [Pubmed]
  16. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Wassmann, B., Pfeifer, H., Goekbuget, N., Beelen, D.W., Beck, J., Stelljes, M., Bornhäuser, M., Reichle, A., Perz, J., Haas, R., Ganser, A., Schmid, M., Kanz, L., Lenz, G., Kaufmann, M., Binckebanck, A., Brück, P., Reutzel, R., Gschaidmeier, H., Schwartz, S., Hoelzer, D., Ottmann, O.G. Blood (2006) [Pubmed]
  17. Functional differentiation of normal human neutrophils. Glasser, L., Fiederlein, R.L. Blood (1987) [Pubmed]
  18. Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes. Józsi, M., Prechl, J., Bajtay, Z., Erdei, A. J. Immunol. (2002) [Pubmed]
  19. The murine complement receptor gene family. IV. Alternative splicing of Cr2 gene transcripts predicts two distinct gene products that share homologous domains with both human CR2 and CR1. Kurtz, C.B., O'Toole, E., Christensen, S.M., Weis, J.H. J. Immunol. (1990) [Pubmed]
  20. Comparative structure and evolution of murine CR2. The homolog of the human C3d/EBV receptor (CD21). Fingeroth, J.D. J. Immunol. (1990) [Pubmed]
  21. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells. Nielsen, C.H., Pedersen, M.L., Marquart, H.V., Prodinger, W.M., Leslie, R.G. Eur. J. Immunol. (2002) [Pubmed]
  22. The sequential appearance of Ia-like antigens and two different complement receptors during the maturation of human neutrophils. Ross, G.D., Jarowski, C.I., Rabellino, E.M., Winchester, R.J. J. Exp. Med. (1978) [Pubmed]
  23. Human megakaryocytes. I. Characterization of the membrane and cytoplasmic components of isolated marrow megakaryocytes. Rabellino, E.M., Nachman, R.L., Williams, N., Winchester, R.J., Ross, G.D. J. Exp. Med. (1979) [Pubmed]
  24. Expression, molecular association, and functions of C3 complement receptors CR1 (CD35) and CR2 (CD21) on the human T cell line HPB-ALL. Delibrias, C.C., Fischer, E., Bismuth, G., Kazatchkine, M.D. J. Immunol. (1992) [Pubmed]
  25. Identification and characterization of complement C3 receptors on human astrocytes. Gasque, P., Chan, P., Mauger, C., Schouft, M.T., Singhrao, S., Dierich, M.P., Morgan, B.P., Fontaine, M. J. Immunol. (1996) [Pubmed]
  26. Identification of residues within the 727-767 segment of human complement component C3 important for its interaction with factor H and with complement receptor 1 (CR1, CD35). Oran, A.E., Isenman, D.E. J. Biol. Chem. (1999) [Pubmed]
  27. The C4A and C4B isotypic forms of human complement fragment C4b have the same intrinsic affinity for complement receptor 1 (CR1/CD35). Clemenza, L., Isenman, D.E. J. Immunol. (2004) [Pubmed]
  28. Differential expression of complement proteins and regulatory decay accelerating factor in relation to differentiation of cultured human colon adenocarcinoma cell lines. Bernet-Camard, M.F., Coconnier, M.H., Hudault, S., Servin, A.L. Gut (1996) [Pubmed]
  29. Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes. Leslie, R.G., Prodinger, W.M., Nielsen, C.H. Eur. J. Immunol. (2003) [Pubmed]
  30. Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb. Hourcade, D.E., Mitchell, L., Kuttner-Kondo, L.A., Atkinson, J.P., Medof, M.E. J. Biol. Chem. (2002) [Pubmed]
  31. Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Pangburn, M.K., Schreiber, R.D., Müller-Eberhard, H.J. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  32. Quantitative analysis of regions of adenovirus E1A products involved in interactions with cellular proteins. Barbeau, D., Marcellus, R.C., Bacchetti, S., Bayley, S.T., Branton, P.E. Biochem. Cell Biol. (1992) [Pubmed]
  33. Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. Tosi, M.F., Zakem, H., Berger, M. J. Clin. Invest. (1990) [Pubmed]
  34. C3b receptor (CR1) genomic polymorphism in rheumatoid arthritis. Low receptor levels on erythrocytes are an acquired phenomenon. Kumar, A., Malaviya, A.N., Sinha, S., Khandekar, P.S., Banerjee, K., Srivastava, L.M. Immunol. Res. (1994) [Pubmed]
  35. Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-gamma activation inhibits complement receptor function and phagocytosis of this bacterium. Schlesinger, L.S., Horwitz, M.A. J. Immunol. (1991) [Pubmed]
  36. Immunotoxin-mediated inhibition of chronic lymphocytic leukemia cell proliferation in humans. Siena, S., Bregni, M., Formosa, A., Brando, B., Marenco, P., Lappi, D.A., Bonadonna, G., Gianni, A.M. Cancer Res. (1989) [Pubmed]
  37. Characterization of CR1- and membrane cofactor protein-like proteins of two primates. Nickells, M.W., Atkinson, J.P. J. Immunol. (1990) [Pubmed]
  38. Expression and localization of proteins of the complement system in human skin. Dovezenski, N., Billetta, R., Gigli, I. J. Clin. Invest. (1992) [Pubmed]
  39. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Terstappen, L.W., Johnsen, S., Segers-Nolten, I.M., Loken, M.R. Blood (1990) [Pubmed]
  40. Monoclonal antibodies that recognize lacto-N-fucopentaose III (CD15) react with the adhesion-promoting glycoprotein family (LFA-1/HMac-1/gp 150,95) and CR1 on human neutrophils. Skubitz, K.M., Snook, R.W. J. Immunol. (1987) [Pubmed]
  41. Expression of complement regulator proteins in primary and metastatic malignant melanoma. Weichenthal, M., Siemann, U., Neuber, K., Breitbart, E.W. J. Cutan. Pathol. (1999) [Pubmed]
  42. Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow. Selvaggi, K.J., Wilson, J.W., Mills, L.E., Cornwell, G.G., Hurd, D., Dodge, W., Gingrich, R., Martin, S.E., McMillan, R., Miller, W. Blood (1994) [Pubmed]
  43. Complement receptors on Raji cells. The presence of a new type of C3 receptor. Okuda, T., Tachibana, T. Immunology (1980) [Pubmed]
  44. Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. Guc, D., Canpinar, H., Kucukaksu, C., Kansu, E. Eur. J. Haematol. (2000) [Pubmed]
WikiGenes - Universities