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Gene Review

EVPL  -  envoplakin

Homo sapiens

Synonyms: 210 kDa cornified envelope precursor protein, 210 kDa paraneoplastic pemphigus antigen, EVPK, Envoplakin, p210
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Disease relevance of EVPL


High impact information on EVPL


Chemical compound and disease context of EVPL


Biological context of EVPL

  • Mutation analysis of EVPL in the three affected families failed to show tylosis-specific mutations, and haplotype analysis of three intragenic sequence polymorphisms of the EVPL gene placed it proximal to D17S1839 [3].
  • The EVPL gene has been mapped to the tylosis oesophageal cancer (TOC) locus on chromosome 17q25, where it has been demonstrated to be frequently deleted in both familial and sporadic forms of oesophageal squamous cell carcinoma (OSC) [13].
  • In this study, we examined EVPL gene mutations in 10 OSC cell lines and 20 sporadic OSCs using reverse transcription-polymerase chain reaction single-strand conformational analysis (RT-PCR SSCP) followed by direct sequencing [13].
  • The rate of EVPL gene mutation was quite low in contrast to the frequency of LOH on the TOC locus in sporadic OSCs, and the high incidence of oesophageal cancer development in tylosis families [13].
  • The exon-intron structure of the mouse envoplakin gene is common to all members of the plakin family: the N-terminal protein domain is encoded by 21 small exons, and the central rod domain and the C-terminal globular domain are coded by a single large exon [14].

Anatomical context of EVPL


Associations of EVPL with chemical compounds

  • Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin [19].
  • Together, these data indicate that involucrin, envoplakin, periplakin, and possibly other structural proteins serve as substrates for the attachment of ceramides by ester linkages to the CE for barrier function in human epidermis [20].
  • These findings raise the possibility that envoplakin and periplakin bind to the plasma membrane upon elevation of intracellular [Ca(2+)] in differentiating keratinocytes, where they serve as a scaffold for cornified cell envelope assembly [16].
  • Essentially only one lysine and two glutamine residues of involucrin and two glutamines of envoplakin were used initially [17].
  • Upon brefeldin A treatment, p210 did not redistribute in the ER as did other Golgi proteins [21].

Other interactions of EVPL


Analytical, diagnostic and therapeutic context of EVPL


  1. Chromosomal localisation of the human envoplakin gene (EVPL) to the region of the tylosis oesophageal cancer gene (TOCG) on 17q25. Ruhrberg, C., Williamson, J.A., Sheer, D., Watt, F.M. Genomics (1996) [Pubmed]
  2. Envoplakin and periplakin are the paraneoplastic pemphigus antigens. Kiyokawa, C. The Kurume medical journal. (1999) [Pubmed]
  3. Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer (TOC): the integration of genetic and physical maps of the TOC region on 17q25. Risk, J.M., Ruhrberg, C., Hennies, H., Mills, H.S., Di Colandrea, T., Evans, K.E., Ellis, A., Watt, F.M., Bishop, D.T., Spurr, N.K., Stevens, H.P., Leigh, I.M., Reis, A., Kelsell, D.P., Field, J.K. Genomics (1999) [Pubmed]
  4. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. Joly, P., Richard, C., Gilbert, D., Courville, P., Chosidow, O., Roujeau, J.C., Beylot-Barry, M., D'incan, M., Martel, P., Lauret, P., Tron, F. J. Am. Acad. Dermatol. (2000) [Pubmed]
  5. Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Korsmeyer, S.J. Annu. Rev. Immunol. (1992) [Pubmed]
  6. Expression of a translocated c-abl gene in hybrids of mouse fibroblasts and chronic myelogenous leukaemia cells. Kozbor, D., Giallongo, A., Sierzega, M.E., Konopka, J.B., Witte, O.N., Showe, L.C., Croce, C.M. Nature (1986) [Pubmed]
  7. Subcellular distribution of envoplakin and periplakin: insights into their role as precursors of the epidermal cornified envelope. DiColandrea, T., Karashima, T., Määttä, A., Watt, F.M. J. Cell Biol. (2000) [Pubmed]
  8. Paraneoplastic pemphigus sera react strongly with multiple epitopes on the various regions of envoplakin and periplakin, except for the c-terminal homologous domain of periplakin. Nagata, Y., Karashima, T., Watt, F.M., Salmhofer, W., Kanzaki, T., Hashimoto, T. J. Invest. Dermatol. (2001) [Pubmed]
  9. Phosphotyrosine antibodies identify the p210c-abl tyrosine kinase and proteins phosphorylated on tyrosine in human chronic myelogenous leukemia cells. Naldini, L., Stacchini, A., Cirillo, D.M., Aglietta, M., Gavosto, F., Comoglio, P.M. Mol. Cell. Biol. (1986) [Pubmed]
  10. CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs. Fang, G., Kim, C.N., Perkins, C.L., Ramadevi, N., Winton, E., Wittmann, S., Bhalla, K.N. Blood (2000) [Pubmed]
  11. Arginine butyrate downregulates p210 bcr-abl expression and induces apoptosis in chronic myelogenous leukemia cells. Urbano, A., Koc, Y., Foss, F.M. Leukemia (1998) [Pubmed]
  12. Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib. Agirre, X., Román-Gómez, J., Vázquez, I., Jiménez-Velasco, A., Larráyoz, M.J., Lahortiga, I., Andreu, E.J., Márquez, J., Beltrán de Heredia, J.M., Odero, M.D., Prósper, F., Calasanz, M.J. Cancer Genet. Cytogenet. (2005) [Pubmed]
  13. Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas. Iwaya, T., Maesawa, C., Kimura, T., Ogasawara, S., Ikeda, K., Kimura, Y., Noda, Y., Ishida, K., Sato, N., Saito, K., Masuda, T. Oncol. Rep. (2005) [Pubmed]
  14. Structure and regulation of the envoplakin gene. Määttä, A., Ruhrberg, C., Watt, F.M. J. Biol. Chem. (2000) [Pubmed]
  15. Unique role for the periplakin tail in intermediate filament association: specific binding to keratin 8 and vimentin. Kazerounian, S., Uitto, J., Aho, S. Exp. Dermatol. (2002) [Pubmed]
  16. Co-assembly of envoplakin and periplakin into oligomers and Ca(2+)-dependent vesicle binding: implications for cornified cell envelope formation in stratified squamous epithelia. Kalinin, A.E., Idler, W.W., Marekov, L.N., McPhie, P., Bowers, B., Steinert, P.M., Steven, A.C. J. Biol. Chem. (2004) [Pubmed]
  17. Initiation of assembly of the cell envelope barrier structure of stratified squamous epithelia. Steinert, P.M., Marekov, L.N. Mol. Biol. Cell (1999) [Pubmed]
  18. Interaction of periplakin and envoplakin with intermediate filaments. Karashima, T., Watt, F.M. J. Cell. Sci. (2002) [Pubmed]
  19. Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. Ruhrberg, C., Hajibagheri, M.A., Parry, D.A., Watt, F.M. J. Cell Biol. (1997) [Pubmed]
  20. Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope. Marekov, L.N., Steinert, P.M. J. Biol. Chem. (1998) [Pubmed]
  21. A peripheral protein associated with the cis-Golgi network redistributes in the intermediate compartment upon brefeldin A treatment. Rios, R.M., Tassin, A.M., Celati, C., Antony, C., Boissier, M.C., Homberg, J.C., Bornens, M. J. Cell Biol. (1994) [Pubmed]
  22. Identification of immature cornified envelopes in the barrier-impaired epidermis by characterization of their hydrophobicity and antigenicities of the components. Hirao, T., Denda, M., Takahashi, M. Exp. Dermatol. (2001) [Pubmed]
  23. The members of the plakin family of proteins recognized by paraneoplastic pemphigus antibodies include periplakin. Mahoney, M.G., Aho, S., Uitto, J., Stanley, J.R. J. Invest. Dermatol. (1998) [Pubmed]
  24. Exacerbation of paraneoplastic pemphigus by cyclophosphamide treatment: detection of novel autoantigens and bronchial autoantibodies. Preisz, K., Horváth, A., Sárdy, M., Somlai, B., Hársing, J., Amagai, M., Hashimoto, T., Nagata, Y., Fekete, S., Kárpáti, S. Br. J. Dermatol. (2004) [Pubmed]
  25. Epitopes in the linker subdomain region of envoplakin recognized by autoantibodies in paraneoplastic pemphigus patients. Zhang, B., Zheng, R., Wang, J., Bu, D., Zhu, X. J. Invest. Dermatol. (2006) [Pubmed]
  26. cDNA cloning of the 210-kDa paraneoplastic pemphigus antigen reveals that envoplakin is a component of the antigen complex. Kim, S.C., Kwon, Y.D., Lee, I.J., Chang, S.N., Lee, T.G. J. Invest. Dermatol. (1997) [Pubmed]
  27. Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis and bronchiolitis obliterans. Chorzelski, T., Hashimoto, T., Maciejewska, B., Amagai, M., Anhalt, G.J., Jablonska, S. J. Am. Acad. Dermatol. (1999) [Pubmed]
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