PSMA3

Proteasome (prosome, macropain) subunit, alpha type, 3

PDB rendering based on 1iru.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPSMA3 ; HC8; PSC3
External IDsOMIM: 176843 MGI: 104883 HomoloGene: 2082 GeneCards: PSMA3 Gene
EC number3.4.25.1
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez568419167
EnsemblENSG00000100567ENSMUSG00000060073
UniProtP25788O70435
RefSeq (mRNA)NM_002788NM_011184
RefSeq (protein)NP_002779NP_035314
Location (UCSC)Chr 14:
58.71 – 58.74 Mb		Chr 12:
70.97 – 71 Mb
PubMed search

Proteasome subunit alpha type-3 also known as macropain subunit C8 and proteasome component C8 is a protein that in humans is encoded by the PSMA3 gene.[1][2] This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex.

Function

The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological precesses. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. As a component of alpha ring, proteasome subunit alpha type-3 contributes to the formation of heptameric alpha rings and substrate entrance gate.

Structure

The human protein proteasome subunit alpha type-3 is 28 kDa in size and composed of 254 amino acids. The calculated theoretical pI of this protein is 5.19.

Complex assembly

The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.[3][4]

Mechanism

Crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.[4] Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit.[5][6] The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.[6][7]

Interactions

PSMA3 has been shown to interact with

References

  1. ↑ Tamura T, Lee DH, Osaka F, Fujiwara T, Shin S, Chung CH et al. (Jun 1991). "Molecular cloning and sequence analysis of cDNAs for five major subunits of human proteasomes (multi-catalytic proteinase complexes)". Biochim Biophys Acta 1089 (1): 95–102. doi:10.1016/0167-4781(91)90090-9. PMID 2025653.
  2. ↑ Coux O, Tanaka K, Goldberg AL (Nov 1996). "Structure and functions of the 20S and 26S proteasomes". Annu Rev Biochem 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
  3. ↑ Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
  4. ↑ 4.0 4.1 Tomko RJ, Hochstrasser M (2013). "Molecular architecture and assembly of the eukaryotic proteasome". Annual Review of Biochemistry 82: 415–45. doi:10.1146/annurev-biochem-060410-150257. PMID 23495936.
  5. ↑ Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD et al. (Apr 1997). "Structure of 20S proteasome from yeast at 2.4 A resolution". Nature 386 (6624): 463–71. doi:10.1038/386463a0. PMID 9087403.
  6. ↑ 6.0 6.1 Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R et al. (Nov 2000). "A gated channel into the proteasome core particle". Nature Structural Biology 7 (11): 1062–7. doi:10.1038/80992. PMID 11062564.
  7. ↑ Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B et al. (Aug 2006). "Regulation of murine cardiac 20S proteasomes: role of associating partners". Circulation Research 99 (4): 372–80. doi:10.1161/01.RES.0000237389.40000.02. PMID 16857963.
  8. ↑ Boelens WC, Croes Y, de Jong WW (Jan 2001). "Interaction between alphaB-crystallin and the human 20S proteasomal subunit C8/alpha7". Biochim. Biophys. Acta 1544 (1–2): 311–9. doi:10.1016/S0167-4838(00)00243-0. PMID 11341940.
  9. ↑ Feng Y, Longo DL, Ferris DK (Jan 2001). "Polo-like kinase interacts with proteasomes and regulates their activity". Cell Growth Differ. 12 (1): 29–37. PMID 11205743.
  10. ↑ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H et al. (Sep 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
  11. ↑ Gerards WL, de Jong WW, Bloemendal H, Boelens W (Jan 1998). "The human proteasomal subunit HsC8 induces ring formation of other alpha-type subunits". J. Mol. Biol. 275 (1): 113–21. doi:10.1006/jmbi.1997.1429. PMID 9451443.
  12. ↑ Bae MH, Jeong CH, Kim SH, Bae MK, Jeong JW, Ahn MY et al. (Oct 2002). "Regulation of Egr-1 by association with the proteasome component C8". Biochim. Biophys. Acta 1592 (2): 163–7. doi:10.1016/S0167-4889(02)00310-5. PMID 12379479.

Further reading

  • Goff SP (2003). "Death by deamination: a novel host restriction system for HIV-1". Cell 114 (3): 281–3. doi:10.1016/S0092-8674(03)00602-0. PMID 12914693.
  • Kristensen P, Johnsen AH, Uerkvitz W, Tanaka K, Hendil KB (1995). "Human proteasome subunits from 2-dimensional gels identified by partial sequencing". Biochem. Biophys. Res. Commun. 205 (3): 1785–9. doi:10.1006/bbrc.1994.2876. PMID 7811265.
  • Akioka H, Forsberg NE, Ishida N, Okumura K, Nogami M, Taguchi H et al. (1995). "Isolation and characterization of the HC8 subunit gene of the human proteasome". Biochem. Biophys. Res. Commun. 207 (1): 318–23. doi:10.1006/bbrc.1995.1190. PMID 7857283.
  • Castaño JG, Mahillo E, Arizti P, Arribas J (1996). "Phosphorylation of C8 and C9 subunits of the multicatalytic proteinase by casein kinase II and identification of the C8 phosphorylation sites by direct mutagenesis". Biochemistry 35 (12): 3782–9. doi:10.1021/bi952540s. PMID 8619999.
  • Seeger M, Ferrell K, Frank R, Dubiel W (1997). "HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation". J. Biol. Chem. 272 (13): 8145–8. doi:10.1074/jbc.272.13.8145. PMID 9079628.
  • Gerards WL, de Jong WW, Bloemendal H, Boelens W (1998). "The human proteasomal subunit HsC8 induces ring formation of other alpha-type subunits". J. Mol. Biol. 275 (1): 113–21. doi:10.1006/jmbi.1997.1429. PMID 9451443.
  • Madani N, Kabat D (1998). "An Endogenous Inhibitor of Human Immunodeficiency Virus in Human Lymphocytes Is Overcome by the Viral Vif Protein". J. Virol. 72 (12): 10251–5. PMC 110608. PMID 9811770.
  • Simon JH, Gaddis NC, Fouchier RA, Malim MH (1998). "Evidence for a newly discovered cellular anti-HIV-1 phenotype". Nat. Med. 4 (12): 1397–400. doi:10.1038/3987. PMID 9846577.
  • Mulder LC, Muesing MA (2000). "Degradation of HIV-1 integrase by the N-end rule pathway". J. Biol. Chem. 275 (38): 29749–53. doi:10.1074/jbc.M004670200. PMID 10893419.
  • Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Höhfeld J et al. (2001). "The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins". Nat. Cell Biol. 3 (1): 93–6. doi:10.1038/35050618. PMID 11146632.
  • Feng Y, Longo DL, Ferris DK (2001). "Polo-like kinase interacts with proteasomes and regulates their activity". Cell Growth Differ. 12 (1): 29–37. PMID 11205743.
  • Boelens WC, Croes Y, de Jong WW (2001). "Interaction between alphaB-crystallin and the human 20S proteasomal subunit C8/alpha7". Biochim. Biophys. Acta 1544 (1–2): 311–9. doi:10.1016/S0167-4838(00)00243-0. PMID 11341940.
  • Touitou R, Richardson J, Bose S, Nakanishi M, Rivett J, Allday MJ (2001). "A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8 α-subunit of the 20S proteasome". EMBO J. 20 (10): 2367–75. doi:10.1093/emboj/20.10.2367. PMC 125454. PMID 11350925.
  • Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002). "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein". Nature 418 (6898): 646–50. doi:10.1038/nature00939. PMID 12167863.
  • Claverol S, Burlet-Schiltz O, Girbal-Neuhauser E, Gairin JE, Monsarrat B (2003). "Mapping and structural dissection of human 20 S proteasome using proteomic approaches". Mol. Cell Proteomics 1 (8): 567–78. doi:10.1074/mcp.M200030-MCP200. PMID 12376572.
  • Bae MH, Jeong CH, Kim SH, Bae MK, Jeong JW, Ahn MY et al. (2003). "Regulation of Egr-1 by association with the proteasome component C8". Biochim. Biophys. Acta 1592 (2): 163–7. doi:10.1016/S0167-4889(02)00310-5. PMID 12379479.
  • Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W et al. (2002). "The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processing". J. Mol. Biol. 323 (4): 771–82. doi:10.1016/S0022-2836(02)00998-1. PMID 12419264.