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Gene Review

Cr1l  -  complement component (3b/4b) receptor 1-like

Rattus norvegicus

Synonyms: Antigen 5I2, Complement component receptor 1-like protein, Complement regulatory protein Crry, Cr1, Crry
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Disease relevance of Crry

  • In addition, anti-Crry F(ab)(2) enhanced the susceptibility of 13762 rat mammary adenocarcinoma cells (that endogenously express Crry) to ADCC mediated by allogeneic rat NK cells in the absence of added complement [1].
  • Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli [2].
  • Tumor-specific inhibition of membrane-bound complement regulatory protein Crry with bispecific monoclonal antibodies prevents tumor outgrowth in a rat colorectal cancer lung metastases model [3].
  • Thus, our results suggest that various ocular tissues up-regulate the expression of Crry and CD59 to avoid self-injury during autoimmune uveitis and that these CRPs play an active role in the resolution of EAAU by down-regulating complement activation in vivo [4].
  • Severe anterior uveitis developed in Lewis rats injected with a neutralizing mAb against Crry, with increased formation of C3 split products [5].

High impact information on Crry

  • Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG [2].
  • Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface [2].
  • We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry [2].
  • Furthermore, inhibition of Crry expressed by proximal tubular epithelial cells in vitro resulted in alternative pathway-mediated injury to the cells [6].
  • We found that loss of polarity of complement receptor 1-related protein y (Crry) in the tubular epithelium preceded activation of the alternative pathway along the basolateral aspect of the tubular cells [6].

Biological context of Crry


Anatomical context of Crry

  • The expression of rat Crry on the surface of different human tumor cell lines inhibited ADCC mediated by rat natural killer (NK) cells [1].
  • Our results support a multifunctional role for Crry/p65 in T cells and suggest new links between the natural and adaptive immune responses [8].
  • The murine decay-accelerating factor and membrane cofactor protein analogue Crry was present in rat platelets, neutrophils, E, and splenocytes as two distinct proteins of 65 to 70 kDa and 75 to 85 kDa [9].
  • When both Crry and CD59 were blocked, deposits of membrane attack complex were found in the synovium [10].
  • When Crry and CD59 were functionally blocked at 2 weeks after the induction of CIA, swelling of the knee joints was markedly increased [10].

Associations of Crry with chemical compounds

  • C3 opsonization is known to enhance NK cell-mediated cytolysis, and a potential mechanism for Crry-mediated inhibition of NK cell lysis is through Crry modulation of C3 deposition on target cells [1].
  • Crry is a membrane-associated complement regulatory protein expressed on glomerular mesangial, endothelial, and epithelial cells, which reduces C3/C5 convertase activity [11].
  • Secreted soluble Crry was produced by induction of the AOX1 promoter with methanol [12].
  • These solution studies have been applied to several SCR-containing proteins in the complement system, most notably Factor H with 20 SCR domains, a complement receptor type 2 fragment with two SCR domains, and rat complement receptor-related protein (Crry) which contains five SCR domains [13].

Other interactions of Crry

  • A Crry expression vector was constructed and was tagged with a c-myc epitope that allowed transfected Crry to be distinguished from the constitutively expressed protein [11].
  • Steady state levels of FcRIII (1.4 kb) and Crry (1.9 and 2.1 kb) mRNAs were higher in adult rat nerves than in 6 day and 21 day postnatal rat nerves, indicating that the expression of these receptors is developmentally regulated [14].
  • In the present study, we demonstrated, by the reverse transcription-polymerase chain reaction method, the mRNA expression of complement components (C3, C4, and C5) and membrane regulators (decay-accelerating factor, membrane cofactor protein, Crry, and CD59) in cultured SMCs derived from the rat carotid artery [15].

Analytical, diagnostic and therapeutic context of Crry

  • In additional northern blots, a nucleotide probe for mouse Crry hybridized to mRNA of 2.1 to 2.4 kb from rat GEC, slightly larger than the 1.9- to 2.1-kb mouse Crry mRNA [16].
  • The extended multidomain solution structures of the complement protein Crry and its chimeric conjugate Crry-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy [17].
  • These results demonstrate that Crry inhibits complement-mediated tumor cell eradication by immunotherapeutic mAbs and show that tumor-specific inhibition of complement regulatory proteins using bi-mAbs can significantly improve mAb-mediated immunotherapy [3].
  • METHODS: Immunohistochemistry was used to examine the distribution of the MCRs Crry, DAF, and CD59 in the synovium of knee joints before and 2, 4, and 10 weeks after induction of CIA by immunization with type II collagen [10].
  • The overexpression of Crry was also confirmed by Western blotting and immunoprecipitation [11].


  1. Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell-mediated cytotoxicity. Caragine, T.A., Imai, M., Frey, A.B., Tomlinson, S. Blood (2002) [Pubmed]
  2. Inhibition of complement regulation is key to the pathogenesis of active Heymann nephritis. Schiller, B., He, C., Salant, D.J., Lim, A., Alexander, J.J., Quigg, R.J. J. Exp. Med. (1998) [Pubmed]
  3. Tumor-specific inhibition of membrane-bound complement regulatory protein Crry with bispecific monoclonal antibodies prevents tumor outgrowth in a rat colorectal cancer lung metastases model. Gelderman, K.A., Kuppen, P.J., Okada, N., Fleuren, G.J., Gorter, A. Cancer Res. (2004) [Pubmed]
  4. Suppression of complement regulatory proteins (CRPs) exacerbates experimental autoimmune anterior uveitis (EAAU). Jha, P., Sohn, J.H., Xu, Q., Wang, Y., Kaplan, H.J., Bora, P.S., Bora, N.S. J. Immunol. (2006) [Pubmed]
  5. Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins. Sohn, J.H., Kaplan, H.J., Suk, H.J., Bora, P.S., Bora, N.S. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  6. Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. Thurman, J.M., Ljubanović, D., Royer, P.A., Kraus, D.M., Molina, H., Barry, N.P., Proctor, G., Levi, M., Holers, V.M. J. Clin. Invest. (2006) [Pubmed]
  7. Molecular characterization of rat Crry: widespread distribution of two alternative forms of Crry mRNA. Quigg, R.J., Lo, C.F., Alexander, J.J., Sneed, A.E., Moxley, G. Immunogenetics (1995) [Pubmed]
  8. Crry/p65, a membrane complement regulatory protein, has costimulatory properties on mouse T cells. Fernández-Centeno, E., de Ojeda, G., Rojo, J.M., Portolés, P. J. Immunol. (2000) [Pubmed]
  9. Characterization of rat complement receptors and regulatory proteins. CR2 and Crry are conserved, and the C3b receptor of neutrophils and platelets is distinct from CR1. Quigg, R.J., Holers, V.M. J. Immunol. (1995) [Pubmed]
  10. Membrane complement regulators protect against the development of type II collagen-induced arthritis in rats. Mizuno, M., Nishikawa, K., Spiller, O.B., Morgan, B.P., Okada, N., Okada, H., Matsuo, S. Arthritis Rheum. (2001) [Pubmed]
  11. Overexpression of Crry protects mesangial cells from complement-mediated injury. Nangaku, M., Quigg, R.J., Shankland, S.J., Okada, N., Johnson, R.J., Couser, W.G. J. Am. Soc. Nephrol. (1997) [Pubmed]
  12. Production of the rat complement regulator, Crry, as an active soluble protein in Pichia pastoris. He, C., Alexander, J.J., Lim, A., Quigg, R.J. Arch. Biochem. Biophys. (1997) [Pubmed]
  13. Solution structures of complement components by X-ray and neutron scattering and analytical ultracentrifugation. Perkins, S.J., Gilbert, H.E., Aslam, M., Hannan, J., Holers, V.M., Goodship, T.H. Biochem. Soc. Trans. (2002) [Pubmed]
  14. Expression of genes encoding receptors for IgG (FcRIII) and for C3b/C4b (Crry) in rat sciatic nerve during development and Wallerian degeneration. Vedeler, C.A., Conti, G., Bannerman, P., Pleasure, D. J. Neurosci. Res. (1992) [Pubmed]
  15. mRNA expression of complement components and regulators in rat arterial smooth muscle cells. Li, W., Tada, T., Miwa, T., Okada, N., Ito, J., Okada, H., Tateyama, H., Eimoto, T. Microbiol. Immunol. (1999) [Pubmed]
  16. Molecular characterization of rat glomerular epithelial cell complement receptors. Quigg, R.J., Sneed, A.E. J. Am. Soc. Nephrol. (1994) [Pubmed]
  17. The extended multidomain solution structures of the complement protein Crry and its chimeric conjugate Crry-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy. Aslam, M., Guthridge, J.M., Hack, B.K., Quigg, R.J., Holers, V.M., Perkins, S.J. J. Mol. Biol. (2003) [Pubmed]
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