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Gene Review

Psma5  -  proteasome (prosome, macropain) subunit,...

Mus musculus

Synonyms: Macropain zeta chain, Multicatalytic endopeptidase complex zeta chain, Proteasome subunit alpha type-5, Proteasome zeta chain
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Disease relevance of Psma5

  • Actin is transformed sarcoma 180 cells is composed of the nonmuscle beta and gamma species and of a third, more acidic stable variant termed zeta [1].
  • T cell antigen receptor zeta chain down-regulation and impaired in vitro T cell function have been described in cancer and autoimmune and infectious diseases [2].
  • Regulation of human embryonic globin genes zeta 2 and epsilon in stably transformed mouse erythroleukemia cells [3].
  • We have previously described HIV glycoprotein 120 (gp120)-specific chimeric immune receptors (CIRs) in which the extracellular domain of CD4 is linked to the signaling domain of zeta (CD4zeta) or gamma (CD4gamma) [4].
  • FLIP also inhibited the expression and activation of protein kinase C (PKC) (alpha, zeta) during hypoxia/reoxygenation and promoted an association of inactive forms of PKC with Bax [5].

Psychiatry related information on Psma5


High impact information on Psma5

  • Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy [7].
  • Protein kinase C zeta isoform is critical for mitogenic signal transduction [8].
  • The duplicated human embryonic alpha-like globin genes encode a 5' functional zeta (xi 2) gene and a highly homologous pseudogene (psi xi 1) [9].
  • Determination of the ratio of gamma plus beta to zeta actin in different cytoskeletal preparations of intact and enucleated sarcoma 180 cells indicated that this actin species is not localized specifically to any of the major actin-containing structures preserved in the cytoskeletons [1].
  • Expression from cloned cDNAs of the epsilon 1 subunit together with the zeta 1 subunit in Xenopus oocytes yields functional GluR channels with high activity and characteristics of the NMDA receptor channel [10].

Chemical compound and disease context of Psma5


Biological context of Psma5

  • Intrathymic signalling in immature CD4+CD8+ thymocytes results in tyrosine phosphorylation of the T-cell receptor zeta chain [16].
  • Recent studies have revealed the molecular and functional diversity of the NMDA receptor channel subunits, which are classified into the epsilon and zeta families according to the amino-acid sequence homology [17].
  • Since activated thymocytes also undergo programmed cell death, these results may have important implications for the role of the zeta eta.TCR in negative selection [18].
  • In most cases the hydrolysis of phosphoinositides was also impaired after stimulation with antibody to CD3, although one zeta eta- cell produced normal concentrations of IP [18].
  • Thus zeta allows the binding of antigen/major histocompatibility complex (MHC) to alpha beta to effect TCR signaling [19].

Anatomical context of Psma5

  • Included in the murine T cell antigen receptor complex are two glycoproteins of 25 kd (gamma) and 21 kd (delta) and two nonglycosylated polypeptides of 26 kd (epsilon) and 16 kd (zeta) [20].
  • In contrast to the wide distribution of the epsilon 1 and zeta 1 subunit messenger RNAs in the brain, the epsilon 2 subunit mRNA is expressed only in the forebrain and the epsilon 3 subunit mRNA is found predominantly in the cerebellum [21].
  • Hybridomas without zeta and eta were reconstituted with mutated zeta chains [19].
  • However, as previously described, murine thymocytes and lymph node T cells express a constitutively tyrosine-phosphorylated zeta subunit in the basal state [22].
  • The microfilament poison, cytochalasin D, disrupts this association and enhances the coprecipitation of actin with TCR zeta after receptor ligation [23].

Associations of Psma5 with chemical compounds

  • Here we report that replacement by glutamine of asparagine 598 in putative transmembrane segment M2 of the zeta 1 subunit, strongly reduces the sensitivity of the heteromeric epsilon 2/zeta 1 NMDA receptor channel to Mg2+ block [17].
  • With sequence-specific phosphotyrosine antibodies, it was found that zeta undergoes a series of ordered phosphorylation events upon TCR engagement [24].
  • Yeast DNA polymerase zeta (zeta) is essential for error-free replication past thymine glycol [25].
  • We demonstrate in this work that dexamethasone, a synthetic GC, inhibits the early signaling events initiated upon TCR ligation, such as tyrosine phosphorylation of several TCR-associated substrates including the zeta chain, the ZAP70 kinase, and the transmembrane adapter molecule linker for activation of T cells [26].
  • Treatment of T cells with cytochalasin B, an actin-depolymerizing agent, leads to the complete dissociation of zeta chain from the Triton-insoluble fraction, suggesting a linkage between zeta chain and the cytoskeletal matrix [27].

Analytical, diagnostic and therapeutic context of Psma5

  • Molecular cloning of the zeta chain of the T cell antigen receptor [28].
  • To examine the significance of the zeta subunit in T cell development, mice deficient for zeta expression were generated by gene targeting [29].
  • S1 nuclease and primary transcript in situ hybridization analyses demonstrate that all seven murine globin genes (zeta, alpha1, alpha2, epsilony, betaH1, betamaj, and betamin) are transcribed during primitive erythropoiesis, however transcription of the zeta, epsilony, and betaH1 genes is restricted to the primitive erythroid lineage [30].
  • We show here that TCR ligation induces association of tyrosine-phosphorylated TCR zeta with the detergent-insoluble cell fraction [23].
  • Although differences in tissue distribution and DNA binding capacity of Oct-1 between wild-type and eta-deficient mice were not evident from in situ hybridization and gel shift analysis, the high mortality in the eta-deficient strain may well be due to the disturbance of Oct-1 transcription by the mutation in the zeta/eta locus [31].


  1. Coexistence of three major isoactins in a single sarcoma 180 cell. Bravo, R., Fey, S.J., Small, J.V., Larsen, P.M., Celis, J.E. Cell (1981) [Pubmed]
  2. Sustained exposure to bacterial antigen induces interferon-gamma-dependent T cell receptor zeta down-regulation and impaired T cell function. Bronstein-Sitton, N., Cohen-Daniel, L., Vaknin, I., Ezernitchi, A.V., Leshem, B., Halabi, A., Houri-Hadad, Y., Greenbaum, E., Zakay-Rones, Z., Shapira, L., Baniyash, M. Nat. Immunol. (2003) [Pubmed]
  3. Regulation of human embryonic globin genes zeta 2 and epsilon in stably transformed mouse erythroleukemia cells. Vyas, P., Sharpe, J.A., Watt, P., Higgs, D.R., Wood, W.G. Blood (1992) [Pubmed]
  4. Developmental dissociation of T cells from B, NK, and myeloid cells revealed by MHC class II-specific chimeric immune receptors bearing TCR-zeta or FcR-gamma chain signaling domains. Lin, W.Y., Roberts, M.R. Blood (2002) [Pubmed]
  5. FLIP protects against hypoxia/reoxygenation-induced endothelial cell apoptosis by inhibiting Bax activation. Wang, X., Wang, Y., Zhang, J., Kim, H.P., Ryter, S.W., Choi, A.M. Mol. Cell. Biol. (2005) [Pubmed]
  6. Alterations of protein kinase C isozyme and substrate proteins in mouse brain after electroconvulsive seizures. Chen, C.C. Brain Res. (1994) [Pubmed]
  7. Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Sloan-Lancaster, J., Shaw, A.S., Rothbard, J.B., Allen, P.M. Cell (1994) [Pubmed]
  8. Protein kinase C zeta isoform is critical for mitogenic signal transduction. Berra, E., Diaz-Meco, M.T., Dominguez, I., Municio, M.M., Sanz, L., Lozano, J., Chapkin, R.S., Moscat, J. Cell (1993) [Pubmed]
  9. Recombination within the human embryonic xi-globin locus: a common xi-xi chromosome produced by gene conversion of the psi xi gene. Hill, A.V., Nicholls, R.D., Thein, S.L., Higgs, D.R. Cell (1985) [Pubmed]
  10. Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Meguro, H., Mori, H., Araki, K., Kushiya, E., Kutsuwada, T., Yamazaki, M., Kumanishi, T., Arakawa, M., Sakimura, K., Mishina, M. Nature (1992) [Pubmed]
  11. Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. Finke, J.H., Zea, A.H., Stanley, J., Longo, D.L., Mizoguchi, H., Tubbs, R.R., Wiltrout, R.H., O'Shea, J.J., Kudoh, S., Klein, E. Cancer Res. (1993) [Pubmed]
  12. Phosphatidylinositol-3-kinase activation and atypical protein kinase C zeta phosphorylation characterize the DMSO signalling in erythroleukemia cells. Cataldi, A., Di Pietro, R., Centurione, L., Grilli, A., Cutroneo, G., Miscia, S. Cell. Signal. (2000) [Pubmed]
  13. Expression and characterization of the zeta 1 subunit of the N-methyl-D-aspartate (NMDA) receptor channel in a baculovirus system. Kawamoto, S., Uchino, S., Hattori, S., Hamajima, K., Mishina, M., Nakajima-Iijima, S., Okuda, K. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  14. Barium sulphate with a negative zeta potential accelerates skin permeability barrier recovery and prevents epidermal hyperplasia induced by barrier disruption. Fuziwara, S., Ogawa, K., Aso, D., Yoshizawa, D., Takata, S., Denda, M. Br. J. Dermatol. (2004) [Pubmed]
  15. Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Kralisch, S., Klein, J., Lossner, U., Bluher, M., Paschke, R., Stumvoll, M., Fasshauer, M. Mol. Cell. Endocrinol. (2005) [Pubmed]
  16. Intrathymic signalling in immature CD4+CD8+ thymocytes results in tyrosine phosphorylation of the T-cell receptor zeta chain. Nakayama, T., Singer, A., Hsi, E.D., Samelson, L.E. Nature (1989) [Pubmed]
  17. Identification by mutagenesis of a Mg(2+)-block site of the NMDA receptor channel. Mori, H., Masaki, H., Yamakura, T., Mishina, M. Nature (1992) [Pubmed]
  18. Activation-driven programmed cell death and T cell receptor zeta eta expression. Merćep, M., Weissman, A.M., Frank, S.J., Klausner, R.D., Ashwell, J.D. Science (1989) [Pubmed]
  19. Structural mutations of the T cell receptor zeta chain and its role in T cell activation. Frank, S.J., Niklinska, B.B., Orloff, D.G., Merćep, M., Ashwell, J.D., Klausner, R.D. Science (1990) [Pubmed]
  20. Identification of the components of the murine T cell antigen receptor complex. Samelson, L.E., Harford, J.B., Klausner, R.D. Cell (1985) [Pubmed]
  21. Molecular diversity of the NMDA receptor channel. Kutsuwada, T., Kashiwabuchi, N., Mori, H., Sakimura, K., Kushiya, E., Araki, K., Meguro, H., Masaki, H., Kumanishi, T., Arakawa, M. Nature (1992) [Pubmed]
  22. ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells. van Oers, N.S., Killeen, N., Weiss, A. Immunity (1994) [Pubmed]
  23. Tyrosine-phosphorylated T cell receptor zeta chain associates with the actin cytoskeleton upon activation of mature T lymphocytes. Rozdzial, M.M., Malissen, B., Finkel, T.H. Immunity (1995) [Pubmed]
  24. Fidelity of T cell activation through multistep T cell receptor zeta phosphorylation. Kersh, E.N., Shaw, A.S., Allen, P.M. Science (1998) [Pubmed]
  25. Yeast DNA polymerase zeta (zeta) is essential for error-free replication past thymine glycol. Johnson, R.E., Yu, S.L., Prakash, S., Prakash, L. Genes Dev. (2003) [Pubmed]
  26. Glucocorticoids attenuate T cell receptor signaling. Van Laethem, F., Baus, E., Smyth, L.A., Andris, F., Bex, F., Urbain, J., Kioussis, D., Leo, O. J. Exp. Med. (2001) [Pubmed]
  27. Cell-surface-expressed T-cell antigen-receptor zeta chain is associated with the cytoskeleton. Caplan, S., Zeliger, S., Wang, L., Baniyash, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  28. Molecular cloning of the zeta chain of the T cell antigen receptor. Weissman, A.M., Baniyash, M., Hou, D., Samelson, L.E., Burgess, W.H., Klausner, R.D. Science (1988) [Pubmed]
  29. T cell development in mice that lack the zeta chain of the T cell antigen receptor complex. Love, P.E., Shores, E.W., Johnson, M.D., Tremblay, M.L., Lee, E.J., Grinberg, A., Huang, S.P., Singer, A., Westphal, H. Science (1993) [Pubmed]
  30. Mechanisms of developmental control of transcription in the murine alpha- and beta-globin loci. Trimborn, T., Gribnau, J., Grosveld, F., Fraser, P. Genes Dev. (1999) [Pubmed]
  31. Targeted disruption of the CD3 eta locus causes high lethality in mice: modulation of Oct-1 transcription on the opposite strand. Ohno, H., Goto, S., Taki, S., Shirasawa, T., Nakano, H., Miyatake, S., Aoe, T., Ishida, Y., Maeda, H., Shirai, T. EMBO J. (1994) [Pubmed]
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