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Gene Review

PSMB9  -  proteasome (prosome, macropain) subunit,...

Homo sapiens

Synonyms: LMP2, Low molecular mass protein 2, Macropain chain 7, Multicatalytic endopeptidase complex chain 7, PSMB6i, ...
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Disease relevance of PSMB9


Psychiatry related information on PSMB9


High impact information on PSMB9

  • Two beta-subunits of the proteasome, LMP2 and LMP7, are inducible by interferon-gamma and alter the catalytic activities of this particle, enhancing the presentation of at least some antigens [7].
  • This ubiquitin-dependent proteolytic pathway is implicated in MHC class I presentation. gamma-Interferon (gamma-IFN), a stimulator of antigen presentation, induces a subclass of proteasomes that contain two MHC-encoded subunits, LMP2 and 7 (refs 5-10) [8].
  • The LMP-2 gene is tightly linked to HAM1, a gene thought to be required for translocating peptide fragments of endogenous antigens into the endoplasmic reticulum for association with MHC class I molecules [9].
  • In contrast, cross-linking slg on cells transformed by LMP2 null mutant EBV recombinants triggers the same protein tyrosine kinase cascade as in noninfected B lymphocytes [10].
  • In wild-type EBV-transformed cells, LMP2 is constitutively tyrosine phosphorylated and is associated with Lyn and Syk protein-tyrosine kinases (PTKs) [10].

Chemical compound and disease context of PSMB9

  • The predominant (P) and minor (M) forms of HHV8 ORF-K15 are structurally related integral membrane proteins that have only 33% overall amino acid identity to one another but retain conserved likely tyrosine kinase signaling motifs and may be distant evolutionary relatives of the LMP2 latency protein of Epstein-Barr virus [11].
  • Despite their general inhibitory effect on HLA class I expression, all proteasome inhibitors tested enhanced the presentation of 2 subdominant HLA-A2 epitopes from EBV LMP1 and LMP2, while the presentation of the immunodominant HLA-A11-restricted epitope from EBNA4 was inhibited by MG132 and lactacystin and increased by ZL(3)VS [12].

Biological context of PSMB9


Anatomical context of PSMB9


Associations of PSMB9 with chemical compounds

  • When processed from their precursors, three pairs of the 10 homologous, but distinct, beta-type subunits of eukaryotic proteasomes, that is, X/LMP7, Y/LMP2, and Z/MECL1, have an NH2-terminal threonine residue, assumed to be part of a catalytic center [21].
  • Generation of the HLA-A0201 (A2) influenza Matrix 58-66 epitope contained within the full-length Matrix protein is impaired in cells lacking the proteasome subunits low molecular protein 2 (LMP2) and LMP7 [22].
  • Ribavirin-enhanced TAP-1-LMP2 expression was a transcriptional event where site mutations of the IFN-stimulated response element (ISRE) blocked RSV and ribavirin-inducible promoter activity [23].
  • In contrast, proteasome subunit C2, which is present in all proteasomes, was found to be evenly distributed throughout the cytoplasm and in the nucleus, as was the delta subunit, which is replaced by LMP2 in immunoproteasomes. gamma-Interferon increased the level of immunoproteasomes, but had no effect on their distribution [24].
  • The LMP2 and LMP7 mRNAs were mainly expressed in the luminal and glandular epithelium on Day 12 of pregnancy [25].

Regulatory relationships of PSMB9

  • Conversely, the uptake of LMP2 is strongly enhanced by MECL-1 expression [26].

Other interactions of PSMB9

  • At the transcript level, the interferon-gamma-responsive subunits LMP2 (beta1i), MECL1 (beta2i), and the proteasome activator subunit PA28alpha were markedly up regulated [1].
  • Interferon (IFN) gamma induces replacements of the proteasomal subunits X and Y by LMP7 and LMP2, respectively, resulting in an alteration of the proteolytic specificity [21].
  • In addition to homologues of the human genes PSMB5 through PSMB9, two new genes, PSMB11 and PSMB12, have been found for which there are no known corresponding genes in humans [27].
  • In this study, we report on the effect of polymorphism and matching of HLA-DMA, -DMB, and LMP2 genes on kidney graft outcome [28].
  • An adjacent GC box was required for basal expression of both genes as well as augmenting the TNF-alpha induction of the distal LMP2 gene [29].

Analytical, diagnostic and therapeutic context of PSMB9

  • Coexpression of Lmp2 and Lmp7 with the constitutively expressed subunits delta and MB1 was demonstrated in the BL lines by immunoprecipitation and two-dimensional gel fractionation of the 20S proteasomes [30].
  • We observed similar changes in reactivity with the Ye-2 or the B27.M2 antibody of lymphoblastoid cells upon gamma interferon treatment, which significantly correlated with the increased RT-PCR values for the LMP2 gene [31].
  • LMP, MECL, and PA28 expression was analyzed by reverse transcription-PCR (RT-PCR) of mRNA and by Western blot analysis for LMP2 [31].
  • Molecular cloning of complementary DNAs encoding X and Y showed that their proteins are proteasomal subunits with high amino acid similarity to LMP7 and LMP2, respectively [32].
  • TAP1 and TAP2 alleles were assigned by ARMS PCR, and LMP2 alleles were assigned by restriction enzyme digestion of a PCR product [33].


  1. Immunoproteasome subunit LMP2 expression is deregulated in Sjogren's syndrome but not in other autoimmune disorders. Krause, S., Kuckelkorn, U., Dörner, T., Burmester, G.R., Feist, E., Kloetzel, P.M. Ann. Rheum. Dis. (2006) [Pubmed]
  2. Association of the large multifunctional proteasome (LMP2) gene with Graves' disease is a result of linkage disequilibrium with the HLA haplotype DRB1*0304-DQB1*02-DQA1*0501. Heward, J.M., Allahabadia, A., Sheppard, M.C., Barnett, A.H., Franklyn, J.A., Gough, S.C. Clin. Endocrinol. (Oxf) (1999) [Pubmed]
  3. Inhibition of apoptosis in acute promyelocytic leukemia cells leads to increases in levels of oxidized protein and LMP2 immunoproteasome. Khan, M.A., Oubrahim, H., Stadtman, E.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Loss of interferon-gamma inducibility of TAP1 and LMP2 in a renal cell carcinoma cell line. Dovhey, S.E., Ghosh, N.S., Wright, K.L. Cancer Res. (2000) [Pubmed]
  5. Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Kageshita, T., Hirai, S., Ono, T., Hicklin, D.J., Ferrone, S. Am. J. Pathol. (1999) [Pubmed]
  6. Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains. Mishto, M., Bellavista, E., Santoro, A., Stolzing, A., Ligorio, C., Nacmias, B., Spazzafumo, L., Chiappelli, M., Licastro, F., Sorbi, S., Pession, A., Ohm, T., Grune, T., Franceschi, C. Neurobiol. Aging (2006) [Pubmed]
  7. Antigen processing and presentation by the class I major histocompatibility complex. York, I.A., Rock, K.L. Annu. Rev. Immunol. (1996) [Pubmed]
  8. Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Gaczynska, M., Rock, K.L., Goldberg, A.L. Nature (1993) [Pubmed]
  9. Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene. Martinez, C.K., Monaco, J.J. Nature (1991) [Pubmed]
  10. Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Miller, C.L., Burkhardt, A.L., Lee, J.H., Stealey, B., Longnecker, R., Bolen, J.B., Kieff, E. Immunity (1995) [Pubmed]
  11. Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi's sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. Poole, L.J., Zong, J.C., Ciufo, D.M., Alcendor, D.J., Cannon, J.S., Ambinder, R., Orenstein, J.M., Reitz, M.S., Hayward, G.S. J. Virol. (1999) [Pubmed]
  12. Proteasome inhibitors reconstitute the presentation of cytotoxic T-cell epitopes in Epstein-Barr virus-associated tumors. Gavioli, R., Vertuani, S., Masucci, M.G. Int. J. Cancer (2002) [Pubmed]
  13. Polymorphisms of transporter associated with antigen processing type 1 (TAP1), proteasome subunit beta type 9 (PSMB9) and their common promoter in African children with different manifestations of malaria. Niesporek, S., Meyer, C.G., Kremsner, P.G., May, J. International journal of immunogenetics. (2005) [Pubmed]
  14. Delineation of the subunit composition of human proteasomes using antisera against the major histocompatibility complex-encoded LMP2 and LMP7 subunits. Patel, S.D., Monaco, J.J., McDevitt, H.O. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. Sequence information within proteasomal prosequences mediates efficient integration of beta-subunits into the 20 S proteasome complex. Schmidt, M., Zantopf, D., Kraft, R., Kostka, S., Preissner, R., Kloetzel, P.M. J. Mol. Biol. (1999) [Pubmed]
  16. Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules. Arnold, D., Driscoll, J., Androlewicz, M., Hughes, E., Cresswell, P., Spies, T. Nature (1992) [Pubmed]
  17. Major histocompatibility-encoded human proteasome LMP2. Genomic organization and a new form of mRNA. Singal, D.P., Ye, M., Quadri, S.A. J. Biol. Chem. (1995) [Pubmed]
  18. IFN-gamma-mediated coordinated transcriptional regulation of the human TAP-1 and LMP-2 genes in human renal cell carcinoma. Seliger, B., Hammers, S., Höhne, A., Zeidler, R., Knuth, A., Gerharz, C.D., Huber, C. Clin. Cancer Res. (1997) [Pubmed]
  19. Variations in proteasome subunit composition and enzymatic activity in B-lymphoma lines and normal B cells. Frisan, T., Levitsky, V., Masucci, M.G. Int. J. Cancer (2000) [Pubmed]
  20. Proteasome subunit LMP2 is required for matrix metalloproteinase-2 and -9 expression and activities in human invasive extravillous trophoblast cell line. Wang, H.X., Wang, H.M., Lin, H.Y., Yang, Q., Zhang, H., Tsang, B.K., Zhu, C. J. Cell. Physiol. (2006) [Pubmed]
  21. Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma. Hisamatsu, H., Shimbara, N., Saito, Y., Kristensen, P., Hendil, K.B., Fujiwara, T., Takahashi, E., Tanahashi, N., Tamura, T., Ichihara, A., Tanaka, K. J. Exp. Med. (1996) [Pubmed]
  22. Generation of an immunodominant CTL epitope is affected by proteasome subunit composition and stability of the antigenic protein. Gileadi, U., Moins-Teisserenc, H.T., Correa, I., Booth, B.L., Dunbar, P.R., Sewell, A.K., Trowsdale, J., Phillips, R.E., Cerundolo, V. J. Immunol. (1999) [Pubmed]
  23. Ribavirin treatment up-regulates antiviral gene expression via the interferon-stimulated response element in respiratory syncytial virus-infected epithelial cells. Zhang, Y., Jamaluddin, M., Wang, S., Tian, B., Garofalo, R.P., Casola, A., Brasier, A.R. J. Virol. (2003) [Pubmed]
  24. Association of immunoproteasomes with the endoplasmic reticulum. Brooks, P., Murray, R.Z., Mason, G.G., Hendil, K.B., Rivett, A.J. Biochem. J. (2000) [Pubmed]
  25. Expression of proteasome subunits low molecular mass polypeptide (LMP) 2 and LMP7 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy. Wang, H.X., Wang, H.M., Li, Q.L., Lin, H.Y., Qian, D., Zhu, C. Biol. Reprod. (2004) [Pubmed]
  26. The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome. Groettrup, M., Standera, S., Stohwasser, R., Kloetzel, P.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  27. Analysis of a 26-kb region linked to the Mhc in zebrafish: genomic organization of the proteasome component beta/transporter associated with antigen processing-2 gene cluster and identification of five new proteasome beta subunit genes. Murray, B.W., Sültmann, H., Klein, J. J. Immunol. (1999) [Pubmed]
  28. Impact of the MHC-encoded HLA-DMA, DMB, and LMP2 gene polymorphisms on kidney graft outcome. Chevrier, D., Giral, M., Muller, J.Y., Bignon, J.D., Soulillou, J.P. Hum. Immunol. (1998) [Pubmed]
  29. Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. Wright, K.L., White, L.C., Kelly, A., Beck, S., Trowsdale, J., Ting, J.P. J. Exp. Med. (1995) [Pubmed]
  30. Phenotype-dependent differences in proteasome subunit composition and cleavage specificity in B cell lines. Frisan, T., Levitsky, V., Polack, A., Masucci, M.G. J. Immunol. (1998) [Pubmed]
  31. Invasion by Salmonella typhimurium induces increased expression of the LMP, MECL, and PA28 proteasome genes and changes in the peptide repertoire of HLA-B27. Maksymowych, W.P., Ikawa, T., Yamaguchi, A., Ikeda, M., McDonald, D., Laouar, L., Lahesmaa, R., Tamura, N., Khuong, A., Yu, D.T., Kane, K.P. Infect. Immun. (1998) [Pubmed]
  32. cDNA cloning and interferon gamma down-regulation of proteasomal subunits X and Y. Akiyama, K., Yokota, K., Kagawa, S., Shimbara, N., Tamura, T., Akioka, H., Nothwang, H.G., Noda, C., Tanaka, K., Ichihara, A. Science (1994) [Pubmed]
  33. Analysis of the MHC class II encoded components of the HLA class I antigen processing pathway in ankylosing spondylitis. Burney, R.O., Pile, K.D., Gibson, K., Calin, A., Kennedy, L.G., Sinnott, P.J., Powis, S.H., Wordsworth, B.P. Ann. Rheum. Dis. (1994) [Pubmed]
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