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Gene Review

CD59  -  CD59 molecule, complement regulatory protein

Homo sapiens

Synonyms: 16.3A5, 1F5, 1F5 antigen, 20 kDa homologous restriction factor, CD59 glycoprotein, ...
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Disease relevance of CD59

  • Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria [1].
  • Survival of Helicobacter pylori From complement lysis by binding of GPI-anchored protectin (CD59) [2].
  • Although many of the clinical manifestations (e.g., hemolytic anemia) of the disease can be explained by a deficiency of GPI-anchored complement regulatory proteins such as CD59 and CD55, it is unclear why the PNH clone dominates hematopoiesis and why it is prone to evolve into acute leukemia [3].
  • Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia [4].
  • Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis [5].
  • We propose that up-regulation of CD59 via ERK5/KLF2 activation leads to endothelial resistance to complement-mediated injury and protects from atherogenesis in regions of laminar shear stress [6].

Psychiatry related information on CD59


High impact information on CD59

  • The cell content of CD55 and CD59 was assessed by fluorescence-activated flow cytometry [8].
  • To test this concept, transgenic swine expressing the human CRP decay accelerating factor and CD59 were developed using a novel expression system involving transfer of the proteins from erythrocytes to endothelial cells [9].
  • Fractionally mobile integral proteins, such as band 3, and highly mobile receptors, such as CD59 as well as glycophorin C in protein 4.1-deficient cells, appeared to be squeezed out of areas dense in the underlying network and enriched in areas of network dilation [10].
  • Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59 [11].
  • Antibodies to CD59 inhibit CD2-dependent T cell activation in murine T cell hybridomas expressing human CD2 [11].

Chemical compound and disease context of CD59

  • We have found that human immunodeficiency virus type 1 (HIV-1) particles produced by infected T-cell lines acquire the GPI-linked proteins Thy-1 and CD59, as well as the ganglioside GM1, which is known to partition preferentially into lipid rafts [12].
  • The former group includes the sucrose hemolysis test for screening and Ham's acid hemolysis test for confirmation; the latter group includes FCM analyses of CD55 and CD59, which have recently replaced Ham's test, and FCM quantification of specific GPI-anchor binding using fluorescent-labeled inactive toxin aerolysin (FLAER) [13].
  • Protectin (CD59), a glycosylphosphatidylinositol-anchored cell membrane glycoprotein, is differentially expressed on melanocytic cells and represents the main restriction factor of C-mediated lysis of melanoma cells [14].
  • No correlation of CD59 excretion was observed with duration of the disease level of proteinuria, serum albumin concentration or serum creatinine level [15].
  • However, the identification of several genes not previously known to exhibit increased expression in cardiac hypertrophy (e.g., prostaglandin D synthases; CD59 antigen) also suggests a number of new avenues for further investigation [16].

Biological context of CD59

  • Additional experiments showed that the expression and function of CD59 are both glycosylation independent [17].
  • CD59 antigen was purified from human urine and erythrocyte stroma by affinity chromatography using the mAb YTH 53.1 immobilized on Sepharose, and, following transient expression of a human T cell cDNA library in COS cells, the corresponding cDNA also identified using the antibody [18].
  • Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation [19].
  • From 4 of these patients we were able to produce Epstein-Barr virus-immortalized lymphoblastoid cell lines (LCLs) that have a PNH phenotype (absent CD59, DAF, and CD48) [20].
  • Expression of GPI-anchored CD59 either via transfection or incorporation rendered U937 targets more susceptible to NK cytotoxicity, whereas incorporation of CD59 via a BiMP anchor to similar levels did not alter susceptibility to NK cytotoxicity [21].

Anatomical context of CD59

  • These observations suggest that direct interactions between CD2 and both CD58 and CD59 contribute to T cell activation and adhesion [11].
  • CD59 antigen was released from the surface of transfected COS cells by phosphatidylinositol-specific phospholipase C, demonstrating that it is attached to the cell membrane by means of a glycolipid anchor; it is therefore likely to be absent from the surface of affected erythrocytes in the disease paroxysmal nocturnal hemoglobinuria [18].
  • CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells [18].
  • No detectable binding was observed to CD59-transfected CHO cells despite a report suggesting that CD59 may bind to the human CD2 adhesion domain [22].
  • We demonstrated previously that anchor-intact SP CD59 is present on the membranes of vesicles (prostasomes) and that cells acquire this protein during incubation with SP [23].

Associations of CD59 with chemical compounds


Physical interactions of CD59

  • Although its mechanism of action is not well understood, CD59 is thought to prevent assembly of the MAC by binding to the C8 and/or C9 proteins of the nascent complex [17].
  • The CD2 molecule plays an important role in T cell adhesion by interacting with the ligands CD58 (LFA-3) and CD59 [26].
  • Here we have examined the roles of these putative p53-binding sequences within the CD59 gene in regulation of CD59 expression [27].
  • The hearts from mice transgenic for human CD59 had substantially less and in some cases no membrane attack complex (MAC) and hearts from CD59/DAF transgenic mice had substantially less or no C5b and MAC [28].

Co-localisations of CD59


Regulatory relationships of CD59

  • Finally, the ability of CD59 to enhance CD58-dependent T cell responses was shown to be dependent on N-glycosylation of CD59 at amino acid Asn18 [30].
  • Since CD46 was consistently expressed in colorectal carcinomas the low expression or even lack of CD59 in a subset of tumours might not lead to critical complement-mediated attack of CD59-negative tumour cells [31].
  • Affinity-purified antibody against C9 residues 320-411 inhibited CD59 binding to C9 by > 50% and completely inhibited its binding to the isolated C9b domain [32].
  • We have also shown that acetylation status of p53 regulates CD59 expression on cells exposed to inflammatory cytokines to model inflammation [27].
  • Compared with controls, less MAC was deposited in many CD59-expressing hearts and less C5b and MAC in DAF-expressing hearts [28].

Other interactions of CD59


Analytical, diagnostic and therapeutic context of CD59

  • It was found that the CD59 antigen is a small protein (approximately 20 kD as judged by SDS-PAGE, 11.5 kD predicted from the isolated cDNA) sometimes associated with larger components (45 and 80 kD) in urine [18].
  • In an enzyme-linked immunosorbent assay, the binding of CD59 correlated inversely with the appearance of the C5b-9 neoantigen [2].
  • GTP binding assays performed with immunoprecipitations of CD59 indicated that there was GTP-binding activity associated with this molecule [36].
  • To determine whether neoplasms also express these proteins, we examined the distribution of the complement inhibitors decay-accelerating factor (DAF), CD59 (protectin), and membrane cofactor protein in frozen samples of human breast, colon, kidney, and lung carcinomas and in adjacent non-neoplastic tissues, using immunohistochemistry [37].
  • Northern blot analysis using six different probes located in the 3'-region of the gene shows that more than four different CD59 mRNA molecules are generated by alternative polyadenylation [38].


  1. Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. Yamashina, M., Ueda, E., Kinoshita, T., Takami, T., Ojima, A., Ono, H., Tanaka, H., Kondo, N., Orii, T., Okada, N. N. Engl. J. Med. (1990) [Pubmed]
  2. Survival of Helicobacter pylori From complement lysis by binding of GPI-anchored protectin (CD59). Rautemaa, R., Rautelin, H., Puolakkainen, P., Kokkola, A., Kärkkäinen, P., Meri, S. Gastroenterology (2001) [Pubmed]
  3. Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria. Brodsky, R.A., Vala, M.S., Barber, J.P., Medof, M.E., Jones, R.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Sugimori, C., Chuhjo, T., Feng, X., Yamazaki, H., Takami, A., Teramura, M., Mizoguchi, H., Omine, M., Nakao, S. Blood (2006) [Pubmed]
  5. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Golay, J., Zaffaroni, L., Vaccari, T., Lazzari, M., Borleri, G.M., Bernasconi, S., Tedesco, F., Rambaldi, A., Introna, M. Blood (2000) [Pubmed]
  6. KLF2-dependent, shear stress-induced expression of CD59: a novel cytoprotective mechanism against complement-mediated injury in the vasculature. Kinderlerer, A.R., Ali, F., Johns, M., Lidington, E.A., Leung, V., Boyle, J.J., Hamdulay, S.S., Evans, P.C., Haskard, D.O., Mason, J.C. J. Biol. Chem. (2008) [Pubmed]
  7. Expression of decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 in the human astroglioma cell line, D54-MG, and primary rat astrocytes. Yang, C., Jones, J.L., Barnum, S.R. J. Neuroimmunol. (1993) [Pubmed]
  8. Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria. Miyata, T., Yamada, N., Iida, Y., Nishimura, J., Takeda, J., Kitani, T., Kinoshita, T. N. Engl. J. Med. (1994) [Pubmed]
  9. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. McCurry, K.R., Kooyman, D.L., Alvarado, C.G., Cotterell, A.H., Martin, M.J., Logan, J.S., Platt, J.L. Nat. Med. (1995) [Pubmed]
  10. Molecular maps of red cell deformation: hidden elasticity and in situ connectivity. Discher, D.E., Mohandas, N., Evans, E.A. Science (1994) [Pubmed]
  11. Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Hahn, W.C., Menu, E., Bothwell, A.L., Sims, P.J., Bierer, B.E. Science (1992) [Pubmed]
  12. Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. Nguyen, D.H., Hildreth, J.E. J. Virol. (2000) [Pubmed]
  13. Laboratory diagnosis of paroxysmal nocturnal hemoglobinuria. Krauss, J.S. Ann. Clin. Lab. Sci. (2003) [Pubmed]
  14. Melanoma cells constitutively release an anchor-positive soluble form of protectin (sCD59) that retains functional activities in homologous complement-mediated cytotoxicity. Brasoveanu, L.I., Fonsatti, E., Visintin, A., Pavlovic, M., Cattarossi, I., Colizzi, F., Gasparollo, A., Coral, S., Horejsi, V., Altomonte, M., Maio, M. J. Clin. Invest. (1997) [Pubmed]
  15. Urinary excretion of protectin (CD59), complement SC5b-9 and cytokines in membranous glomerulonephritis. Lehto, T., Honkanen, E., Teppo, A.M., Meri, S. Kidney Int. (1995) [Pubmed]
  16. Identification of differentially expressed genes in cardiac hypertrophy by analysis of expressed sequence tags. Hwang, D.M., Dempsey, A.A., Lee, C.Y., Liew, C.C. Genomics (2000) [Pubmed]
  17. Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59. Bodian, D.L., Davis, S.J., Morgan, B.P., Rushmere, N.K. J. Exp. Med. (1997) [Pubmed]
  18. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. Davies, A., Simmons, D.L., Hale, G., Harrison, R.A., Tighe, H., Lachmann, P.J., Waldmann, H. J. Exp. Med. (1989) [Pubmed]
  19. Molecular basis for a link between complement and the vascular complications of diabetes. Acosta, J., Hettinga, J., Flückiger, R., Krumrei, N., Goldfine, A., Angarita, L., Halperin, J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  20. Production and characterization of lymphoblastoid cell lines with the paroxysmal nocturnal hemoglobinuria phenotype. Hillmen, P., Bessler, M., Crawford, D.H., Luzzatto, L. Blood (1993) [Pubmed]
  21. Expression of glycosylphosphatidylinositol-anchored CD59 on target cells enhances human NK cell-mediated cytotoxicity. Omidvar, N., Wang, E.C., Brennan, P., Longhi, M.P., Smith, R.A., Morgan, B.P. J. Immunol. (2006) [Pubmed]
  22. A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2: divergence of CD2 ligands during the evolution of humans and mice. Arulanandam, A.R., Moingeon, P., Concino, M.F., Recny, M.A., Kato, K., Yagita, H., Koyasu, S., Reinherz, E.L. J. Exp. Med. (1993) [Pubmed]
  23. GPI-anchored complement regulatory proteins in seminal plasma. An analysis of their physical condition and the mechanisms of their binding to exogenous cells. Rooney, I.A., Heuser, J.E., Atkinson, J.P. J. Clin. Invest. (1996) [Pubmed]
  24. The glycosylphosphatidylinositol-anchored CD59 protein stimulates both T cell receptor zeta/ZAP-70-dependent and -independent signaling pathways in T cells. Deckert, M., Ticchioni, M., Mari, B., Mary, D., Bernard, A. Eur. J. Immunol. (1995) [Pubmed]
  25. Lipopolysaccharide signal transduction in oral keratinocytes--involvement of CD59 but not CD14. Yamamoto, T., Nakane, T., Doi, S., Osaki, T. Cell. Signal. (2003) [Pubmed]
  26. Detection of a glycosylation-dependent ligand for the T lymphocyte cell adhesion molecule CD2 using a novel multimeric recombinant CD2-binding assay. Parish, C.R., Recny, M.A., Knoppers, M.H., Waldron, J.C., Warren, H.S. J. Immunol. (1993) [Pubmed]
  27. p53 regulates cellular resistance to complement lysis through enhanced expression of CD59. Donev, R.M., Cole, D.S., Sivasankar, B., Hughes, T.R., Morgan, B.P. Cancer Res. (2006) [Pubmed]
  28. Transgenic expression of human complement regulatory proteins in mice results in diminished complement deposition during organ xenoperfusion. McCurry, K.R., Kooyman, D.L., Diamond, L.E., Byrne, G.W., Logan, J.S., Platt, J.L. Transplantation (1995) [Pubmed]
  29. Calreticulin is at the surface of circulating neutrophils and uses CD59 as an adaptor molecule. Ghiran, I., Klickstein, L.B., Nicholson-Weller, A. J. Biol. Chem. (2003) [Pubmed]
  30. CD59 costimulation of T cell activation. CD58 dependence and requirement for glycosylation. Menu, E., Tsai, B.C., Bothwell, A.L., Sims, P.J., Bierer, B.E. J. Immunol. (1994) [Pubmed]
  31. Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium. Koretz, K., Brüderlein, S., Henne, C., Möller, P. Br. J. Cancer (1993) [Pubmed]
  32. Identity of a peptide domain of human C9 that is bound by the cell-surface complement inhibitor, CD59. Chang, C.P., Hüsler, T., Zhao, J., Wiedmer, T., Sims, P.J. J. Biol. Chem. (1994) [Pubmed]
  33. MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells. de Marco, M.C., Martín-Belmonte, F., Kremer, L., Albar, J.P., Correas, I., Vaerman, J.P., Marazuela, M., Byrne, J.A., Alonso, M.A. J. Cell Biol. (2002) [Pubmed]
  34. Expression of complement inhibitors CD46, CD55, and CD59 on tumor cells does not predict clinical outcome after rituximab treatment in follicular non-Hodgkin lymphoma. Weng, W.K., Levy, R. Blood (2001) [Pubmed]
  35. Correction of delF508-CFTR activity with benzo(c)quinolizinium compounds through facilitation of its processing in cystic fibrosis airway cells. Dormer, R.L., Dérand, R., McNeilly, C.M., Mettey, Y., Bulteau-Pignoux, L., Métayé, T., Vierfond, J.M., Gray, M.A., Galietta, L.J., Morris, M.R., Pereira, M.M., Doull, I.J., Becq, F., McPherson, M.A. J. Cell. Sci. (2001) [Pubmed]
  36. The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes. Solomon, K.R., Rudd, C.E., Finberg, R.W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  37. Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin). Niehans, G.A., Cherwitz, D.L., Staley, N.A., Knapp, D.J., Dalmasso, A.P. Am. J. Pathol. (1996) [Pubmed]
  38. Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation. Tone, M., Walsh, L.A., Waldmann, H. J. Mol. Biol. (1992) [Pubmed]
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