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Gene Review

PSMC1  -  proteasome (prosome, macropain) 26S...

Homo sapiens

Synonyms: 26S protease regulatory subunit 4, 26S proteasome AAA-ATPase subunit RPT2, P26S4, P26s4, Proteasome 26S subunit ATPase 1, ...
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Disease relevance of PSMC1

  • Comparison of the proteins of DpCPV with those of other members in the family Reoviridae lead us to suggest that S1, S3, S4 and S6 encode the viral structural protein VP1, VP2, VP3 and VP4, respectively [1].
  • These mature cellular antiviral mRNAs are not produced after infection with influenza A virus, but IFN regulatory factor-3 is activated and the transcription of the ISRE-controlled p56 gene is induced [2].
  • Antibodies reactive with human T-cell leukemia virus type I (HTLV-I) proteins p19, p24, gp46, p56, and gp68 were detected in four of 27 patients with mycosis fungoides/Sézary syndrome (MF/SS) and one patient with Kaposi's sarcoma using radioimmunoprecipitation and Western blot analysis [3].
  • In this paper, the effect of heat stress on the rate of synthesis of p56 is determined [4].
  • We screened a human placenta cDNA library by yeast two-hybrid assay using HPV 16 E7 as a bait and identified the subunit 4 (S4) ATPase of the 26 S proteasome as a novel E7-binding protein [5].

High impact information on PSMC1

  • In addition, we provide genetic evidence for a physical interaction between the S4 and the related S7 subunit in the 26S multiprotein protease [6].
  • Comparison of tryptic peptide maps of the bcl-3 protein synthesized in vitro, and p56 and p38 from HeLa cells, shows that they are all structurally related [7].
  • Specifically, in vitro and in vivo co-precipitation studies have revealed that the 19S regulatory components of the proteasome, Sug1 (S8) and S4, bind through amino acids (aa) 4-25 of Ad5 E1A [8].
  • In mature sperm, p56 is located at the tip and base of the nucleus from where it is removed by egg cytosol in vitro [9].
  • In the egg, p56 is present in a subset of cytoplasmic membranes (MV2 beta) which contributes the bulk of the nuclear envelope during male pronuclear formation. p56-containing vesicles are required for nuclear envelope assembly and have a chromatin-binding capacity that is mediated by p56 [9].

Chemical compound and disease context of PSMC1


Biological context of PSMC1

  • The phosphorylation of S4 was confirmed by double immunoprecipitation experiments in which 26S proteasomes were immunoprecipitated as above and dissociated and then S4 was immunoprecipitated with subunit-specific antibodies [12].
  • Antiserum to recombinant yeast subunit mts2 (mitosis temperature sensitive gene 2; S4) did not react with any protein of the expected size but detected a 30-kDa peptide that was not associated with the 26S proteasome; this was found only in muscle from the layer strain [13].
  • For this study we determined the nucleotide sequences of the T2W S1, S2, S3 and S4 genome segments to allow molecular comparison with other reoviruses [14].
  • The data suggest that p56 is a translational product of the c-ets proto-oncogene and imply that p56 may be involved in regulating the growth of lymphoid cells [15].
  • APC was chemically modified to create the FRET donor species, Fl-FPR-APC, with a fluorescein dye (Fl) covalently attached to the active site via a D-Phe-Pro-Arg (FPR) tether and located in the active site near S4 [16].

Anatomical context of PSMC1

  • Immunochemical accessibility of ribosomal protein S4 in the 30 S ribosome. The interaction of S4 with S5 and S12 [17].
  • We suggest that p56 is a sea urchin LBR homologue that targets membranes to chromatin and later anchors the membrane to the lamina [9].
  • Several housekeeping genes including U6 small nuclear RNA (snRNA), ribosomal proteins S4 and S13, a core protein of the spliceosome [small nuclear ribonucleoprotein (snRNP) E], and a cip-like protease (clpP) were identified [18].
  • The absorbed anti-bp90 serum retained the ability to immunoprecipitate P135gag-mybE-ets from E26-transformed cells and specifically reacted with a 56-kilodalton polypeptide (p56) detected in chicken lymphoid organs and in T and B lymphocytes of both avian and human origin [15].
  • CD2-mediated interleukin-2 production occurs via activation of Jun kinase in cell lines lacking p56 [19].

Associations of PSMC1 with chemical compounds

  • Since S4-like ATPases contain putative coiled-coils within the first 150 NH2-terminal amino acids, we propose that coiled-coil interactions are responsible for the specificity of the observed subunit associations and that these associations are important for self-assembly of the regulatory complex [20].
  • Compared with other trypsin-like serine proteases, the S2 and S3/S4 pockets of uPA are reduced in size because of the 99-insertion loop [21].
  • Nuclear signaling induced by ionizing radiation involves colocalization of the activated p56/p53lyn tyrosine kinase with p34cdc2 [22].
  • It is proposed that p56 is a steroid receptor-associated heat shock protein which can now be termed hsp56 [4].
  • Induction of p56 also occurs in IM-9 cells subjected to chemical stress (sodium arsenite) [4].

Physical interactions of PSMC1

  • Progressive COOH-terminal deletions that removed as much as 300 amino acids from S4 had no effect on the binding of S4 to S7 [20].

Other interactions of PSMC1

  • These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7 [23].
  • In striking contrast, truncation of 85 NH2-terminal amino acids from S4 abrogated binding, clearly implicating the NH2 terminus of S4 in its specific interaction with S7 [20].
  • Here we demonstrate that PSMC1, an ATPase-like subunit of the 19 S proteasome component, also interacts with HBX and PSMA7 [24].
  • S4, S6, S10b, and S6' displayed specific binding to components of the regulatory complex separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) or two-dimensional PAGE [20].
  • The effect of S5 and S12 on S4 accessibility is consistent with data from a variety of other approaches, suggesting that these proteins form a structural and functional domain in the small ribosomal subunit [17].

Analytical, diagnostic and therapeutic context of PSMC1


  1. Genomic sequence analyses of segments 1 to 6 of Dendrolimus punctatus cytoplasmic polyhedrosis virus. Zhao, S.L., Liang, C.Y., Hong, J.J., Peng, H.Y. Arch. Virol. (2003) [Pubmed]
  2. Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: outcome with influenza A virus is unique. Kim, M.J., Latham, A.G., Krug, R.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Human T-cell leukemia virus type I or a related retrovirus in patients with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma. Srivastava, B.I., Banki, K., Perl, A. Cancer Res. (1992) [Pubmed]
  4. Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. Sanchez, E.R. J. Biol. Chem. (1990) [Pubmed]
  5. The human papillomavirus E7 oncoprotein functionally interacts with the S4 subunit of the 26 S proteasome. Berezutskaya, E., Bagchi, S. J. Biol. Chem. (1997) [Pubmed]
  6. Defective mitosis due to a mutation in the gene for a fission yeast 26S protease subunit. Gordon, C., McGurk, G., Dillon, P., Rosen, C., Hastie, N.D. Nature (1993) [Pubmed]
  7. The proto-oncogene bcl-3 encodes an I kappa B protein. Kerr, L.D., Duckett, C.S., Wamsley, P., Zhang, Q., Chiao, P., Nabel, G., McKeithan, T.W., Baeuerle, P.A., Verma, I.M. Genes Dev. (1992) [Pubmed]
  8. Regulation of the 26S proteasome by adenovirus E1A. Turnell, A.S., Grand, R.J., Gorbea, C., Zhang, X., Wang, W., Mymryk, J.S., Gallimore, P.H. EMBO J. (2000) [Pubmed]
  9. Targeting of membranes to sea urchin sperm chromatin is mediated by a lamin B receptor-like integral membrane protein. Collas, P., Courvalin, J.C., Poccia, D. J. Cell Biol. (1996) [Pubmed]
  10. Kinetic and modeling studies of subsites S4-S3' of Moloney murine leukemia virus protease. Menéndez-Arias, L., Weber, I.T., Soss, J., Harrison, R.W., Gotte, D., Oroszlan, S. J. Biol. Chem. (1994) [Pubmed]
  11. 1-beta-D-arabinofuranosylcytosine activates tyrosine phosphorylation of p34cdc2 and its association with the Src-like p56/p53lyn kinase in human myeloid leukemia cells. Yuan, Z.M., Kharbanda, S., Kufe, D. Biochemistry (1995) [Pubmed]
  12. Phosphorylation of ATPase subunits of the 26S proteasome. Mason, G.G., Murray, R.Z., Pappin, D., Rivett, A.J. FEBS Lett. (1998) [Pubmed]
  13. Ubiquitin gene expression and ubiquitin conjugation in chicken muscle do not reflect differences in growth rate between broiler and layer birds. Harper, J.M., Mee, M.P., Arnold, J.E., Boorman, K.N., Mayer, R.J., Buttery, P.J. J. Anim. Sci. (1999) [Pubmed]
  14. Genetic characterization of a new mammalian reovirus, type 2 Winnipeg (T2W). Jiang, J., Hermann, L., Coombs, K.M. Virus Genes (2006) [Pubmed]
  15. The proto-oncogene c-ets is preferentially expressed in lymphoid cells. Chen, J.H. Mol. Cell. Biol. (1985) [Pubmed]
  16. Protein S alters the active site location of activated protein C above the membrane surface. A fluorescence resonance energy transfer study of topography. Yegneswaran, S., Wood, G.M., Esmon, C.T., Johnson, A.E. J. Biol. Chem. (1997) [Pubmed]
  17. Immunochemical accessibility of ribosomal protein S4 in the 30 S ribosome. The interaction of S4 with S5 and S12. Winkelmann, D.A., Kahan, L. J. Mol. Biol. (1983) [Pubmed]
  18. The miniaturized nuclear genome of eukaryotic endosymbiont contains genes that overlap, genes that are cotranscribed, and the smallest known spliceosomal introns. Gilson, P.R., McFadden, G.I. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  19. A p56lck-independent pathway of CD2 signaling involves Jun kinase. Sunder-Plassmann, R., Reinherz, E.L. J. Biol. Chem. (1998) [Pubmed]
  20. Specific interactions between ATPase subunits of the 26 S protease. Richmond, C., Gorbea, C., Rechsteiner, M. J. Biol. Chem. (1997) [Pubmed]
  21. (4-aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase. Sperl, S., Jacob, U., Arroyo de Prada, N., Stürzebecher, J., Wilhelm, O.G., Bode, W., Magdolen, V., Huber, R., Moroder, L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  22. Nuclear signaling induced by ionizing radiation involves colocalization of the activated p56/p53lyn tyrosine kinase with p34cdc2. Kharbanda, S., Saleem, A., Yuan, Z.M., Kraeft, S., Weichselbaum, R., Chen, L.B., Kufe, D. Cancer Res. (1996) [Pubmed]
  23. Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex. Matilla, A., Gorbea, C., Einum, D.D., Townsend, J., Michalik, A., van Broeckhoven, C., Jensen, C.C., Murphy, K.J., Ptácek, L.J., Fu, Y.H. Hum. Mol. Genet. (2001) [Pubmed]
  24. Structural and functional characterization of interaction between hepatitis B virus X protein and the proteasome complex. Zhang, Z., Torii, N., Furusaka, A., Malayaman, N., Hu, Z., Liang, T.J. J. Biol. Chem. (2000) [Pubmed]
  25. Identification of a phylogenetically conserved Sug1 CAD family member that is differentially expressed in the mouse nervous system. Sun, D., Swaffield, J.C., Johnston, S.A., Milligan, C.E., Zoeller, R.T., Schwartz, L.M. J. Neurobiol. (1997) [Pubmed]
  26. A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins. Katiyar, S., Li, G., Lennarz, W.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  27. SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activity. Cuevas, B., Lu, Y., Watt, S., Kumar, R., Zhang, J., Siminovitch, K.A., Mills, G.B. J. Biol. Chem. (1999) [Pubmed]
  28. A uracil-DNA glycosylase inhibitor encoded by a non-uracil containing viral DNA. Serrano-Heras, G., Salas, M., Bravo, A. J. Biol. Chem. (2006) [Pubmed]
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