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Gene Review

PSMA5  -  proteasome (prosome, macropain) subunit,...

Homo sapiens

Synonyms: Macropain zeta chain, Multicatalytic endopeptidase complex zeta chain, PSC5, Proteasome subunit alpha type-5, Proteasome zeta chain, ...
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Disease relevance of PSMA5

  • Our animal study showed that the expression of H2Kd/scPSMA in B16F0/PSMA5, a B16F0 cell line expressing human PSMA, significantly inhibited tumor growth as demonstrated in the pulmonary metastasis assay and tumor growth study and improved overall survival [1].
  • Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome [2].
  • We confirmed (Petit F et al.: Biochem. J. 326: 93-98 (1997)) that both 20 S proteasomes and free zeta subunits possess RNase activity though the activities were very low: 4 mMoles and 0.6 mMoles of tobacco mosaic virus RNA degraded per mole of enzyme per min, respectively [3].
  • To better characterize human alpha5-subunit (PSMA5) of the 20S proteasome, we have established a high-efficiency Escherichia coli expression system [4].
  • A human immunodeficiency virus (HIV) envelope-specific UR consisting of the extracellular domain of human CD4 linked to the zeta chain of the T cell receptor (CD4 zeta) was introduced ex vivo into murine HSC by retroviral transduction [5].

Psychiatry related information on PSMA5

  • Alzheimer's disease associated presenilin 1 interacts with HC5 and ZETA, subunits of the catalytic 20S proteasome [6].
  • CJD patients showed five dominant 14-3-3 isoforms, gamma, epsilon, zeta, eta and beta, but 14-3-3 tau, which mainly originates from T lymphocytes, was not detected [7].
  • The human alpha-like globins undergo a switch from the embryonic zeta-chain to the alpha-chain early in human development, at approximately the same time as the beta-like globins switch from the embryonic epsilon-to the fetal gamma-chains [8].
  • An examination of the specific PKC isozymes in cortical homogenates revealed that cytosolic alpha- and membrane-associated gamma- and zeta PKC isozymes were elevated in cortices of bipolar affective disorder subjects, whereas cytosolic epsilon PKC was found to be reduced [9].
  • The nanocomposite particles were characterized by transmission electron spectroscopy, X-ray diffraction (XRD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), BET N(2) gas adsorption, sedimentation time studies, acid dissolution, and zeta potential (zeta) [10].

High impact information on PSMA5

  • The zeta 2-containing receptors are fully capable of transducing signals leading to IL-2 production and growth inhibition, while the presence of the zeta eta heterodimer is associated with the autolytic response of T-cell hybridomas to activation [11].
  • The zeta eta heterodimer appears to be largely responsible for coupling receptor occupancy to PI hydrolysis, the zeta 2 heterodimer may couple to tyrosine kinase activation and/or other signaling pathways [11].
  • We have recently identified a 70 kd tyrosine phosphoprotein (ZAP-70) that associates with zeta and undergoes tyrosine phosphorylation following TCR stimulation [12].
  • The compact size of the motif appears to eliminate zeta mechanisms based on enzymatic activity and suggests that one or at most a few cellular proteins interact with the zeta intracellular domain to initiate signal transduction [13].
  • We have reduced the active site of zeta to an 18 residue motif that can be appended to the intracellular domain of other transmembrane proteins to endow them with receptor-like activity [13].

Chemical compound and disease context of PSMA5

  • Here, we propose that in lupus lymphocytes, the receptor-mediated increase in protein tyrosine phosphorylation and cytoplasmic free Ca2+ responses, along with T-cell receptor zeta chain deficiency, might explain the previously described diverse and conflicting immunoregulatory defects in human lupus [14].
  • The development of gallstones depends in part on biliary cholesterol saturation and on the zeta potential of bile [15].
  • These results suggest that the increased incidence of cholelithiasis following small bowel bypass is not only due to a relative change in bile composition but is probably more significantly due to an increase in the biliary glycine/taurine ratio and a consequent decrease in the biliary zeta potential [15].
  • Furthermore, using proteins expressed in Escherichia coli, a glutathione S-transferase-Nef fusion protein coprecipitated histidine-tagged portions of the TCR zeta cytoplasmic domain which contained SNID-1 or SNID-2 [16].
  • Concomitantly the backbone torsion angles of the pyrimidine moieties have larger gamma values, larger epsilon values, and smaller zeta values than the purines [17].

Biological context of PSMA5

  • The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways [18].
  • The other is a pseudogene (psi zeta) that differs by only 3 bp in the protein coding sequence, one of which converts the codon for amino acid 6 into a chain termination codon [19].
  • Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the alpha-globin locus on the short arm of chromosome 16 (zeta = 25.85, theta = 0.05) [20].
  • This action is combined with that of DNA polymerase Pol zeta, which is essential for damage-induced mutagenesis, to complete the lesion bypass [21].
  • The Src homology region 2 (SH2) domain of Shc directly interacted with the tyrosine-phosphorylated zeta chain of the TCR [22].

Anatomical context of PSMA5

  • One of them, zeta, was found in HeLa cells at a concentration of 890 microg per g of cell protein [3].
  • Purification and refolding of human alpha5-subunit (PSMA5) of the 20S proteasome, expressed as inclusion bodies in Escherichia coli [4].
  • CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex [23].
  • Furthermore, zeta- and beta-globin synthesis is restricted to primitive and definitive erythroblasts respectively [24].
  • Following termination of the pregnancy, the diagnosis was established by the presence of only hemoglobins Barts (gamma 4) and Portland (zeta 2 gamma 2) in the fetal blood [25].

Associations of PSMA5 with chemical compounds

  • Recent studies suggest that zeta has a critical role in allowing antigen to activate the cell, whereas eta expression has been correlated with the capacity for antigen-induced phosphoinositide turnover [26].
  • Furthermore, nuclear Overhauser effects (NOEs) were observed between the zeta 3 and epsilon 3 protons of the methylleucine (MeLeu) residue at position 9 of CsA and tryptophan121 (Trp121) and phenylalanine (Phe) protons of cyclophilin, suggesting that the MeLeu9 residue of CsA interacts with cyclophilin [27].
  • Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta [28].
  • Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced zeta chain degradation, leading to the accumulation of zeta chain in large Lamp1(+) vesicles [29].
  • RESULTS: Treatment with indomethacin decreased the abundance of PKC-beta1 and increased that of PKC-beta2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and micro [30].

Other interactions of PSMA5

  • Furthermore, we were able to coimmunoprecipitate the transfected binding partners, as well as the endogenous PSEN1 and ZETA proteins from HEK 293T cells [6].

Analytical, diagnostic and therapeutic context of PSMA5

  • To produce the native PSMA5, straightforward protocols have been developed for refolding the human PSMA5 in the presence of surfactants using dilution refolding and size-exclusion chromatography matrix refolding methods [4].
  • Dissection of the TCR utilizing chimeric receptors and TCR mutants has demonstrated that the multi-subunit receptor is composed of at least two signal transducing modules, the CD3 and the zeta chain subunits [31].
  • T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-beta, CD3-epsilon, and zeta chains, as detected by FACS(R) analysis on fixed and permeabilized T-APC conjugates and by Western blot analysis on cell lysates [29].
  • Here we show that ligation of T cell receptor (TCR) by alloantigen alone, which results in anergy, activates tyrosine phosphorylation of TCR zeta and its association with fyn [32].
  • Our findings demonstrate both functional and physical association of p56lck with Fc gamma RIIIA, through direct interaction of the kinase with the zeta and/or the gamma signal transducer subunits of the receptor [33].


  1. Targeting foreign major histocompatibility complex molecules to tumors by tumor cell specific single chain antibody (scFv). Li, J., Franek, K.J., Patterson, A.L., Holmes, L.M., Burgin, K.E., Ji, J., Yu, X., Wagner, T.E., Wei, Y. Int. J. Oncol. (2003) [Pubmed]
  2. Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome. Engidawork, E., Juranville, J.F., Fountoulakis, M., Dierssen, M., Lubec, G. J. Neural Transm. Suppl. (2001) [Pubmed]
  3. Proteasome subunit zeta, a putative ribonuclease, is also found as a free monomer. Jørgensen, L., Hendil, K.B. Mol. Biol. Rep. (1999) [Pubmed]
  4. Purification and refolding of human alpha5-subunit (PSMA5) of the 20S proteasome, expressed as inclusion bodies in Escherichia coli. Han, Y.G., Liu, H.L., Zheng, H.J., Li, S.G., Bi, R.C. Protein Expr. Purif. (2004) [Pubmed]
  5. Systemic T cell-independent tumor immunity after transplantation of universal receptor-modified bone marrow into SCID mice. Hege, K.M., Cooke, K.S., Finer, M.H., Zsebo, K.M., Roberts, M.R. J. Exp. Med. (1996) [Pubmed]
  6. Alzheimer's disease associated presenilin 1 interacts with HC5 and ZETA, subunits of the catalytic 20S proteasome. Van Gassen, G., De Jonghe, C., Pype, S., Van Criekinge, W., Julliams, A., Vanderhoeven, I., Woodrow, S., Beyaert, R., Huylebroeck, D., Van Broeckhoven, C. Neurobiol. Dis. (1999) [Pubmed]
  7. 14-3-3 protein levels and isoform patterns in the cerebrospinal fluid of Creutzfeldt-Jakob disease patients in the progressive and terminal stages. Shiga, Y., Wakabayashi, H., Miyazawa, K., Kido, H., Itoyama, Y. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. (2006) [Pubmed]
  8. Chromatin structure and developmental expression of the human alpha-globin cluster. Yagi, M., Gelinas, R., Elder, J.T., Peretz, M., Papayannopoulou, T., Stamatoyannopoulos, G., Groudine, M. Mol. Cell. Biol. (1986) [Pubmed]
  9. Enhanced protein kinase C activity and translocation in bipolar affective disorder brains. Wang, H.Y., Friedman, E. Biol. Psychiatry (1996) [Pubmed]
  10. Surface modification of hydroxyapatite. Part II. Silica. Borum, L., Wilson, O.C. Biomaterials (2003) [Pubmed]
  11. Genetic and mutational analysis of the T-cell antigen receptor. Ashwell, J.D., Klusner, R.D. Annu. Rev. Immunol. (1990) [Pubmed]
  12. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Chan, A.C., Iwashima, M., Turck, C.W., Weiss, A. Cell (1992) [Pubmed]
  13. Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zeta chain. Romeo, C., Amiot, M., Seed, B. Cell (1992) [Pubmed]
  14. Immune cell signaling defects in lupus: activation, anergy and death. Tsokos, G.C., Liossis, S.N. Immunol. Today (1999) [Pubmed]
  15. The effect of jejunoileal bypass on bile composition and the formation of billiary calculi. Wise, L., Stein, T. Ann. Surg. (1978) [Pubmed]
  16. The T-cell receptor zeta chain contains two homologous domains with which simian immunodeficiency virus Nef interacts and mediates down-modulation. Schaefer, T.M., Bell, I., Fallert, B.A., Reinhart, T.A. J. Virol. (2000) [Pubmed]
  17. Solution structure of [d(GCGTATACGC)]2. Cheng, J.W., Chou, S.H., Salazar, M., Reid, B.R. J. Mol. Biol. (1992) [Pubmed]
  18. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Irving, B.A., Weiss, A. Cell (1991) [Pubmed]
  19. The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene. Proudfoot, N.J., Gil, A., Maniatis, T. Cell (1982) [Pubmed]
  20. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Reeders, S.T., Breuning, M.H., Davies, K.E., Nicholls, R.D., Jarman, A.P., Higgs, D.R., Pearson, P.L., Weatherall, D.J. Nature (1985) [Pubmed]
  21. Eukaryotic polymerases iota and zeta act sequentially to bypass DNA lesions. Johnson, R.E., Washington, M.T., Haracska, L., Prakash, S., Prakash, L. Nature (2000) [Pubmed]
  22. Interaction of Shc with the zeta chain of the T cell receptor upon T cell activation. Ravichandran, K.S., Lee, K.K., Songyang, Z., Cantley, L.C., Burn, P., Burakoff, S.J. Science (1993) [Pubmed]
  23. CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex. Anderson, P., Caligiuri, M., Ritz, J., Schlossman, S.F. Nature (1989) [Pubmed]
  24. Haemoglobin switching in human embryos: asynchrony of zeta----alpha and epsilon----gamma-globin switches in primitive and definite erythropoietic lineage. Peschle, C., Mavilio, F., Carè, A., Migliaccio, G., Migliaccio, A.R., Salvo, G., Samoggia, P., Petti, S., Guerriero, R., Marinucci, M. Nature (1985) [Pubmed]
  25. Prenatal diagnosis of homozygous alpha-thalassemia. Dozy, A.M., Forman, E.N., Abuelo, D.N., Barsel-Bowers, G., Mahoney, M.J., Forget, B.G., Kan, Y.W. JAMA (1979) [Pubmed]
  26. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors. Orloff, D.G., Ra, C.S., Frank, S.J., Klausner, R.D., Kinet, J.P. Nature (1990) [Pubmed]
  27. Isotope-edited NMR of cyclosporin A bound to cyclophilin: evidence for a trans 9,10 amide bond. Fesik, S.W., Gampe, R.T., Holzman, T.F., Egan, D.A., Edalji, R., Luly, J.R., Simmer, R., Helfrich, R., Kishore, V., Rich, D.H. Science (1990) [Pubmed]
  28. Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain. Irving, B.A., Chan, A.C., Weiss, A. J. Exp. Med. (1993) [Pubmed]
  29. Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic stimulation. Valitutti, S., Müller, S., Salio, M., Lanzavecchia, A. J. Exp. Med. (1997) [Pubmed]
  30. Overexpression of protein kinase C-beta1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells. Zhu, G.H., Wong, B.C., Slosberg, E.D., Eggo, M.C., Ching, C.K., Yuen, S.T., Lai, K.C., Soh, J.W., Weinstein, I.B., Lam, S.K. Gastroenterology (2000) [Pubmed]
  31. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Chan, A.C., Desai, D.M., Weiss, A. Annu. Rev. Immunol. (1994) [Pubmed]
  32. Differential association of protein tyrosine kinases with the T cell receptor is linked to the induction of anergy and its prevention by B7 family-mediated costimulation. Boussiotis, V.A., Barber, D.L., Lee, B.J., Gribben, J.G., Freeman, G.J., Nadler, L.M. J. Exp. Med. (1996) [Pubmed]
  33. Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. Salcedo, T.W., Kurosaki, T., Kanakaraj, P., Ravetch, J.V., Perussia, B. J. Exp. Med. (1993) [Pubmed]
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