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

LMP-2A  -  K15

Human herpesvirus 4

This record was discontinued.
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 LMP-2A

  • We have previously shown that the EBV latent genes LMP-1 and LMP-2A (for latent membrane proteins 1 and 2A), transactivate a human endogenous retrovirus (HERV), HERV-K18, in infected B lymphocytes [1].
  • When the new assays were used to screen a collection of endemic Burkitt's lymphoma tumours, abundant Qp-driven EBNA1 expression was found, whereas the other latent transcripts (with the exception of LMP2A) were either absent or detectable only at trace levels [2].
  • To determine whether these two virus-encoded cytoplasmic domains are endowed with signalling functions, we constructed chimeric proteins by replacing the cytoplasmic tail of CD8-alpha with that of either BLV gp30 or EBV LMP2A [3].
  • One of the few viral transcripts expressed in EBV-positive Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma is latent membrane protein 2A (LMP2A) [4].
  • These antibodies were applied to the immunohistochemical detection of LMP2A in Hodgkin's disease (HD) [5].

High impact information on LMP-2A

  • Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples [6].
  • Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals [7].
  • Furthermore, spontaneous germinal centers developed in gut-associated lymphoid tissue of LMP2A mice, indicating that microbial antigens can promote germinal centers independently of BCR-mediated antigen recognition [8].
  • Using a novel mouse model we have identified the intracellular adaptor protein Src homology 2 (SH2) domain-containing leukocyte protein (SLP)-65 as a critical downstream effector of LMP2A in vivo [9].
  • This modulation of STAT activity correlated with the ability of LMP2A to inhibit the autocrine secretion of IL-6 from carcinoma cell lines [10].

Chemical compound and disease context of LMP-2A


Biological context of LMP-2A


Anatomical context of LMP-2A


Associations of LMP-2A with chemical compounds

  • To assess the function of LMP-2A, we have utilized a colony formation assay for the progenitor B cells that uses the B-cell proliferation factor IL-7 [15].
  • LMP2A has important roles in modulating B-cell receptor (BCR) signal transduction by associating with the cellular tyrosine kinases Lyn and Syk via specific phosphotyrosine motifs found within the LMP2A N-terminal tail domain [16].
  • Interestingly, the LMP2A(222-230) epitope could be efficiently generated from incomplete EBV-LMP2A fragments that were produced by puromycin treatment or gene-engineered shortened EBV-LMP2A lacking some of its hydrophobic domains [21].
  • We also show that the juxtamembrane cysteine repeats in the LMP2A C terminus are the major targets for palmitoylation but that this acylation is not required for targeting of LMP2A to detergent-insoluble glycolipid-enriched membrane microdomains [22].
  • Deletion and site-specific mutation of LMP2A indicates that LMP2A is ubiquitinated at its amino-terminus and is not ubiquitinated on lysine residues [13].
  • Utilization by Shb of the LMP2A ITAM motif regulates stability of the Syk tyrosine kinase in LMP2A-expressing cells [23].

Physical interactions of LMP-2A

  • Their substitution with six membrane-spanning domains from the LMP-2A protein of EBV yields a derivative which neither coimmunoprecipitates with LMP-1 nor signals to increase the activity of NF-kappaB as does wild-type LMP-1 [24].

Co-localisations of LMP-2A


Regulatory relationships of LMP-2A

  • Interestingly, when LMP2B was expressed in conjunction with LMP2A, there was a restoration of normal BCR signal transduction upon BCR cross-linking [16].
  • Tyrosine phosphorylation, calcium mobilization, and induction of BZLF1 expression were no longer blocked in the LMP2A ITAM mutant LCLs following BCR cross-linking [26].
  • We report that LMP2A protein controls the expression of TRAF2 mRNA, which in turn is necessary for signaling by LMP1 [27].

Other interactions of LMP-2A

  • Since these mRNAs are readily detected in largely latently infected cells and do not increase in abundance with EBV replication, these putative latent-infection membrane proteins are tentatively designated LMP-2A and LMP-2B, respectively [28].
  • In addition, we also detected other latent EBV transcripts (ie., BARF0-, LMP2A-, and Q/K-driven EBNA1 transcripts in these carcinomas using reverse transcription-PCR analysis [29].
  • In long-term virus carriers, the mononuclear cells were again positive for latent (EBER1) and negative for lytic (BZLF1) markers; Cp/Wp-initiated RNAs were not detected in these samples, but in several individuals it was possible to amplify both Fp-initiated EBNA1 mRNA and LMP2A mRNA signals [30].
  • EBNA1 and BamHI-A rightward transcripts (BART) were detected in 7 of 7 and LMP2A transcripts in 5 of 7 tumors with well-preserved RNA [31].

Analytical, diagnostic and therapeutic context of LMP-2A


  1. Cutting edge: Epstein-Barr virus transactivates the HERV-K18 superantigen by docking to the human complement receptor 2 (CD21) on primary B cells. Hsiao, F.C., Lin, M., Tai, A., Chen, G., Huber, B.T. J. Immunol. (2006) [Pubmed]
  2. Analysis of Epstein-Barr virus latent gene expression in endemic Burkitt's lymphoma and nasopharyngeal carcinoma tumour cells by using quantitative real-time PCR assays. Bell, A.I., Groves, K., Kelly, G.L., Croom-Carter, D., Hui, E., Chan, A.T., Rickinson, A.B. J. Gen. Virol. (2006) [Pubmed]
  3. The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events. Beaufils, P., Choquet, D., Mamoun, R.Z., Malissen, B. EMBO J. (1993) [Pubmed]
  4. Epstein-Barr Virus (EBV) LMP2A induces alterations in gene transcription similar to those observed in Reed-Sternberg cells of Hodgkin lymphoma. Portis, T., Dyck, P., Longnecker, R. Blood (2003) [Pubmed]
  5. Immunohistochemical detection of the Epstein-Barr virus-encoded latent membrane protein 2A in Hodgkin's disease and infectious mononucleosis. Niedobitek, G., Kremmer, E., Herbst, H., Whitehead, L., Dawson, C.W., Niedobitek, E., von Ostau, C., Rooney, N., Grässer, F.A., Young, L.S. Blood (1997) [Pubmed]
  6. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. Pathmanathan, R., Prasad, U., Sadler, R., Flynn, K., Raab-Traub, N. N. Engl. J. Med. (1995) [Pubmed]
  7. Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Caldwell, R.G., Wilson, J.B., Anderson, S.J., Longnecker, R. Immunity (1998) [Pubmed]
  8. B cell receptor signal strength determines B cell fate. Casola, S., Otipoby, K.L., Alimzhanov, M., Humme, S., Uyttersprot, N., Kutok, J.L., Carroll, M.C., Rajewsky, K. Nat. Immunol. (2004) [Pubmed]
  9. Epstein-Barr virus latent membrane protein 2A (LMP2A) employs the SLP-65 signaling module. Engels, N., Merchant, M., Pappu, R., Chan, A.C., Longnecker, R., Wienands, J. J. Exp. Med. (2001) [Pubmed]
  10. Epstein-Barr virus-encoded LMP2A regulates viral and cellular gene expression by modulation of the NF-kappaB transcription factor pathway. Stewart, S., Dawson, C.W., Takada, K., Curnow, J., Moody, C.A., Sixbey, J.W., Young, L.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not induce switching from latent to lytic Epstein-Barr virus infection in Burkitt's lymphoma Akata cells. Rao, S.P., Rechsteiner, M.P., Berger, C., Sigrist, J.A., Nadal, D., Bernasconi, M. Mol. Cancer (2007) [Pubmed]
  12. Signal transduction through the B cell antigen receptor is normal in ataxia-telangiectasia B lymphocytes. Speck, P., Ikeda, M., Ikeda, A., Lederman, H.M., Longnecker, R. J. Biol. Chem. (2002) [Pubmed]
  13. Lysine-independent ubiquitination of Epstein-Barr virus LMP2A. Ikeda, M., Ikeda, A., Longnecker, R. Virology (2002) [Pubmed]
  14. Sequence polymorphism in the Epstein-Barr virus latent membrane protein (LMP)-2 gene. Busson, P., Edwards, R.H., Tursz, T., Raab-Traub, N. J. Gen. Virol. (1995) [Pubmed]
  15. Pre-B-cell colony formation assay. Ikeda, M., Longnecker, R. Methods Mol. Biol. (2005) [Pubmed]
  16. Epstein-barr virus latent membrane protein 2B (LMP2B) modulates LMP2A activity. Rovedo, M., Longnecker, R. J. Virol. (2007) [Pubmed]
  17. Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling. Shaknovich, R., Basso, K., Bhagat, G., Mansukhani, M., Hatzivassiliou, G., Murty, V.V., Buettner, M., Niedobitek, G., Alobeid, B., Cattoretti, G. Haematologica (2006) [Pubmed]
  18. Sporadic EBV-associated lymphoepithelial salivary gland carcinoma with EBV-positive low-grade myoepithelial component. Herbst, H., Niedobitek, G. Virchows Arch. (2006) [Pubmed]
  19. Epstein-Barr virus latent-infection membrane proteins are palmitoylated and raft-associated: protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic factors. Higuchi, M., Izumi, K.M., Kieff, E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  20. Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. Lu, J., Lin, W.H., Chen, S.Y., Longnecker, R., Tsai, S.C., Chen, C.L., Tsai, C.H. J. Biol. Chem. (2006) [Pubmed]
  21. Three immunoproteasome-associated subunits cooperatively generate a cytotoxic T-lymphocyte epitope of Epstein-Barr virus LMP2A by overcoming specific structures resistant to epitope liberation. Ito, Y., Kondo, E., Demachi-Okamura, A., Akatsuka, Y., Tsujimura, K., Tanimoto, M., Morishima, Y., Takahashi, T., Kuzushima, K. J. Virol. (2006) [Pubmed]
  22. C-terminal domain of the Epstein-Barr virus LMP2A membrane protein contains a clustering signal. Matskova, L., Ernberg, I., Pawson, T., Winberg, G. J. Virol. (2001) [Pubmed]
  23. The Shb signalling scaffold binds to and regulates constitutive signals from the Epstein-Barr virus LMP2A membrane protein. Matskova, L.V., Helmstetter, C., Ingham, R.J., Gish, G., Lindholm, C.K., Ernberg, I., Pawson, T., Winberg, G. Oncogene (2007) [Pubmed]
  24. LMP-1's transmembrane domains encode multiple functions required for LMP-1's efficient signaling. Kaykas, A., Worringer, K., Sugden, B. J. Virol. (2002) [Pubmed]
  25. Epstein-Barr virus latent membrane protein 2B (LMP2B) co-localizes with LMP2A in perinuclear regions in transiently transfected cells. Lynch, D.T., Zimmerman, J.S., Rowe, D.T. J. Gen. Virol. (2002) [Pubmed]
  26. The immunoreceptor tyrosine-based activation motif of Epstein-Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Fruehling, S., Longnecker, R. Virology (1997) [Pubmed]
  27. EBV LMP2A affects LMP1-mediated NF-kappaB signaling and survival of lymphoma cells by regulating TRAF2 expression. Guasparri, I., Bubman, D., Cesarman, E. Blood (2008) [Pubmed]
  28. Two related Epstein-Barr virus membrane proteins are encoded by separate genes. Sample, J., Liebowitz, D., Kieff, E. J. Virol. (1989) [Pubmed]
  29. Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. zur Hausen, A., Brink, A.A., Craanen, M.E., Middeldorp, J.M., Meijer, C.J., van den Brule, A.J. Cancer Res. (2000) [Pubmed]
  30. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. Tierney, R.J., Steven, N., Young, L.S., Rickinson, A.B. J. Virol. (1994) [Pubmed]
  31. Epstein-Barr virus (EBV) in endemic Burkitt's lymphoma: molecular analysis of primary tumor tissue. Tao, Q., Robertson, K.D., Manns, A., Hildesheim, A., Ambinder, R.F. Blood (1998) [Pubmed]
  32. Identification of latent membrane protein 2A (LMP2A) domains essential for the LMP2A dominant-negative effect on B-lymphocyte surface immunoglobulin signal transduction. Fruehling, S., Lee, S.K., Herrold, R., Frech, B., Laux, G., Kremmer, E., Grässer, F.A., Longnecker, R. J. Virol. (1996) [Pubmed]
  33. Consistent transcription of the Epstein-Barr virus LMP2 gene in nasopharyngeal carcinoma. Busson, P., McCoy, R., Sadler, R., Gilligan, K., Tursz, T., Raab-Traub, N. J. Virol. (1992) [Pubmed]
WikiGenes - Universities