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Gene Review

EDC4  -  enhancer of mRNA decapping 4

Homo sapiens

Synonyms: Autoantigen Ge-1, Autoantigen RCD-8, Enhancer of mRNA-decapping protein 4, GE1, Ge-1, ...
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Disease relevance of EDC4


Psychiatry related information on EDC4


High impact information on EDC4

  • Because the regulatory cells generated following oral tolerization are triggered in an antigen-specific fashion but suppress in an antigen nonspecific fashion, they mediate "bystander suppression" when they encounter the fed autoantigen at the target organ [2].
  • Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen [9].
  • The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities [10].
  • The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis [11].
  • CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate [12].

Chemical compound and disease context of EDC4


Biological context of EDC4

  • The sequence was found homologous to an autoantigen recently reported named Ge-1, and contains a nuclear localization sequence (NLS), an active protein domain made by a contiguous stretch of amino acids which allows the selective entry of the protein into the nucleus [18].
  • Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3 [19].
  • B cells that had not previously encountered HEL autoantigen (naive cells) were triggered into proliferation and antibody production upon interaction with antigen and HEL-specific CD4+ T cells [20].
  • By screening a pancreatic islet cDNA library, we have identified the autoantigen recognized by highly pathogenic CD8 T cells in the non-obese diabetic mouse, one of the best animal models for human diabetes [21].
  • We infected different strains of mice with Coxsackie B4 virus to discriminate between the two possible induction mechanisms, and found that mice with susceptible MHC alleles had no viral acceleration of diabetes, but mice with a T cell receptor transgene specific for a different islet autoantigen rapidly developed diabetes [5].

Anatomical context of EDC4


Associations of EDC4 with chemical compounds


Physical interactions of EDC4


Regulatory relationships of EDC4


Other interactions of EDC4


Analytical, diagnostic and therapeutic context of EDC4


  1. The immunoreactive region in a novel autoantigen contains a nuclear localization sequence. Bloch, D.B., Rabkina, D., Quertermous, T., Bloch, K.D. Clin. Immunol. Immunopathol. (1994) [Pubmed]
  2. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Weiner, H.L., Friedman, A., Miller, A., Khoury, S.J., al-Sabbagh, A., Santos, L., Sayegh, M., Nussenblatt, R.B., Trentham, D.E., Hafler, D.A. Annu. Rev. Immunol. (1994) [Pubmed]
  3. Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris. Kljuic, A., Bazzi, H., Sundberg, J.P., Martinez-Mir, A., O'Shaughnessy, R., Mahoney, M.G., Levy, M., Montagutelli, X., Ahmad, W., Aita, V.M., Gordon, D., Uitto, J., Whiting, D., Ott, J., Fischer, S., Gilliam, T.C., Jahoda, C.A., Morris, R.J., Panteleyev, A.A., Nguyen, V.T., Christiano, A.M. Cell (2003) [Pubmed]
  4. Identification of the skin basement-membrane autoantigen in epidermolysis bullosa acquisita. Woodley, D.T., Briggaman, R.A., O'Keefe, E.J., Inman, A.O., Queen, L.L., Gammon, W.R. N. Engl. J. Med. (1984) [Pubmed]
  5. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Horwitz, M.S., Bradley, L.M., Harbertson, J., Krahl, T., Lee, J., Sarvetnick, N. Nat. Med. (1998) [Pubmed]
  6. The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Yang, Y.Y., Yin, G.L., Darnell, R.B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Structure and binding properties of a monoclonal anti-idiotypic autoantibody to anti-DNA with epibody activity. Fischel, R., Eilat, D. J. Immunol. (1992) [Pubmed]
  8. Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401-positive individuals. Reijonen, H., Elliott, J.F., van Endert, P., Nepom, G. J. Immunol. (1999) [Pubmed]
  9. Immunological aspects of demyelinating diseases. Martin, R., McFarland, H.F., McFarlin, D.E. Annu. Rev. Immunol. (1992) [Pubmed]
  10. The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Zhang, Y., LeRoy, G., Seelig, H.P., Lane, W.S., Reinberg, D. Cell (1998) [Pubmed]
  11. Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group. Bennett, S.T., Wilson, A.J., Esposito, L., Bouzekri, N., Undlien, D.E., Cucca, F., Nisticò, L., Buzzetti, R., Bosi, E., Pociot, F., Nerup, J., Cambon-Thomsen, A., Pugliese, A., Shield, J.P., McKinney, P.A., Bain, S.C., Polychronakos, C., Todd, J.A. Nat. Genet. (1997) [Pubmed]
  12. CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate. Saitoh, H., Tomkiel, J., Cooke, C.A., Ratrie, H., Maurer, M., Rothfield, N.F., Earnshaw, W.C. Cell (1992) [Pubmed]
  13. The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase. Van de Water, J., Gershwin, M.E., Leung, P., Ansari, A., Coppel, R.L. J. Exp. Med. (1988) [Pubmed]
  14. Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus. Kim, J., Namchuk, M., Bugawan, T., Fu, Q., Jaffe, M., Shi, Y., Aanstoot, H.J., Turck, C.W., Erlich, H., Lennon, V., Baekkeskov, S. J. Exp. Med. (1994) [Pubmed]
  15. Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. Odin, J.A., Huebert, R.C., Casciola-Rosen, L., LaRusso, N.F., Rosen, A. J. Clin. Invest. (2001) [Pubmed]
  16. Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis. Walsh, M.J., Murray, J.M. J. Clin. Invest. (1998) [Pubmed]
  17. Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alpha-hydroxylase. Krohn, K., Uibo, R., Aavik, E., Peterson, P., Savilahti, K. Lancet (1992) [Pubmed]
  18. Cytoplasmic detection of a novel protein containing a nuclear localization sequence by human autoantibodies. Garcia-Lozano, J.R., Gonzalez-Escribano, M.F., Wichmann, I., Nuñez-Roldan, A. Clin. Exp. Immunol. (1997) [Pubmed]
  19. Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3. Pendergraft, W.F., Preston, G.A., Shah, R.R., Tropsha, A., Carter, C.W., Jennette, J.C., Falk, R.J. Nat. Med. (2004) [Pubmed]
  20. CD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ T cells. Rathmell, J.C., Cooke, M.P., Ho, W.Y., Grein, J., Townsend, S.E., Davis, M.M., Goodnow, C.C. Nature (1995) [Pubmed]
  21. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Wong, F.S., Karttunen, J., Dumont, C., Wen, L., Visintin, I., Pilip, I.M., Shastri, N., Pamer, E.G., Janeway, C.A. Nat. Med. (1999) [Pubmed]
  22. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Zamvil, S.S., Mitchell, D.J., Moore, A.C., Kitamura, K., Steinman, L., Rothbard, J.B. Nature (1986) [Pubmed]
  23. Autoimmunity due to molecular mimicry as a cause of neurological disease. Levin, M.C., Lee, S.M., Kalume, F., Morcos, Y., Dohan, F.C., Hasty, K.A., Callaway, J.C., Zunt, J., Desiderio, D., Stuart, J.M. Nat. Med. (2002) [Pubmed]
  24. The molecular biology of thyroid peroxidase: cloning, expression and role as autoantigen in autoimmune thyroid disease. McLachlan, S.M., Rapoport, B. Endocr. Rev. (1992) [Pubmed]
  25. Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Gross, D.M., Forsthuber, T., Tary-Lehmann, M., Etling, C., Ito, K., Nagy, Z.A., Field, J.A., Steere, A.C., Huber, B.T. Science (1998) [Pubmed]
  26. Multivalent endosome targeting by homodimeric EEA1. Dumas, J.J., Merithew, E., Sudharshan, E., Rajamani, D., Hayes, S., Lawe, D., Corvera, S., Lambright, D.G. Mol. Cell (2001) [Pubmed]
  27. Cloning and characterization of the cDNA coding for a polymyositis-scleroderma overlap syndrome-related nucleolar 100-kD protein. Blüthner, M., Bautz, F.A. J. Exp. Med. (1992) [Pubmed]
  28. Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies. Richter, W., Mertens, T., Schoel, B., Muir, P., Ritzkowsky, A., Scherbaum, W.A., Boehm, B.O. J. Exp. Med. (1994) [Pubmed]
  29. Assignment of apolipoprotein H (APOH: beta-2-glycoprotein I) to human chromosome 17q23----qter; determination of the major expression site. Steinkasserer, A., Cockburn, D.J., Black, D.M., Boyd, Y., Solomon, E., Sim, R.B. Cytogenet. Cell Genet. (1992) [Pubmed]
  30. Somatostatin specifically binds p86 subunit of the autoantigen Ku. Le Romancer, M., Cherifi, Y., Reyl-Desmars, F., Lewin, M.J. C. R. Acad. Sci. III, Sci. Vie (1993) [Pubmed]
  31. Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2. Boilard, E., Bourgoin, S.G., Bernatchez, C., Surette, M.E. Blood (2003) [Pubmed]
  32. Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway. Csernok, E., Ai, M., Gross, W.L., Wicklein, D., Petersen, A., Lindner, B., Lamprecht, P., Holle, J.U., Hellmich, B. Blood (2006) [Pubmed]
  33. Calreticulin binds preferentially with B cell linear epitopes of Ro60 kD autoantigen, enhancing recognition by anti-Ro60 kD autoantibodies. Staikou, E.V., Routsias, J.G., Makri, A.A., Terzoglou, A., Sakarellos-Daitsiotis, M., Sakarellos, C., Panayotou, G., Moutsopoulos, H.M., Tzioufas, A.G. Clin. Exp. Immunol. (2003) [Pubmed]
  34. Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen. Hall, A.M., Ward, F.J., Vickers, M.A., Stott, L.M., Urbaniak, S.J., Barker, R.N. Blood (2002) [Pubmed]
  35. Suppression of heat-induced hsp70 expression by the 70-kDa subunit of the human Ku autoantigen. Li, G.C., Yang, S.H., Kim, D., Nussenzweig, A., Ouyang, H., Wei, J., Burgman, P., Li, L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  36. Nicotinamide reduces high secretion of IFN-gamma in high-risk relatives even though it does not prevent type 1 diabetes. Hedman, M., Ludvigsson, J., Faresjö, M.K. J. Interferon Cytokine Res. (2006) [Pubmed]
  37. Dendritic cells in rheumatoid arthritis. Sarkar, S., Fox, D.A. Front. Biosci. (2005) [Pubmed]
  38. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Ota, K., Matsui, M., Milford, E.L., Mackin, G.A., Weiner, H.L., Hafler, D.A. Nature (1990) [Pubmed]
  39. A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus. Khalil, I., d'Auriol, L., Gobet, M., Morin, L., Lepage, V., Deschamps, I., Park, M.S., Degos, L., Galibert, F., Hors, J. J. Clin. Invest. (1990) [Pubmed]
  40. Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle. Butler, M.H., David, C., Ochoa, G.C., Freyberg, Z., Daniell, L., Grabs, D., Cremona, O., De Camilli, P. J. Cell Biol. (1997) [Pubmed]
  41. ATM binds to beta-adaptin in cytoplasmic vesicles. Lim, D.S., Kirsch, D.G., Canman, C.E., Ahn, J.H., Ziv, Y., Newman, L.S., Darnell, R.B., Shiloh, Y., Kastan, M.B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  42. Induction of autoimmune diabetes by oral administration of autoantigen. Blanas, E., Carbone, F.R., Allison, J., Miller, J.F., Heath, W.R. Science (1996) [Pubmed]
  43. Scleroderma autoantigens are uniquely fragmented by metal-catalyzed oxidation reactions: implications for pathogenesis. Casciola-Rosen, L., Wigley, F., Rosen, A. J. Exp. Med. (1997) [Pubmed]
  44. Human organ-specific autoimmune disease. Molecular cloning and expression of an autoantibody gene repertoire for a major autoantigen reveals an antigenic immunodominant region and restricted immunoglobulin gene usage in the target organ. Chazenbalk, G.D., Portolano, S., Russo, D., Hutchison, J.S., Rapoport, B., McLachlan, S. J. Clin. Invest. (1993) [Pubmed]
  45. The 86-kD subunit of Ku autoantigen mediates homotypic and heterotypic adhesion of multiple myeloma cells. Teoh, G., Urashima, M., Greenfield, E.A., Nguyen, K.A., Lee, J.F., Chauhan, D., Ogata, A., Treon, S.P., Anderson, K.C. J. Clin. Invest. (1998) [Pubmed]
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