PSMA5

Proteasome (prosome, macropain) subunit, alpha type, 5

PDB rendering based on 1iru.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPSMA5 ; PSC5; ZETA
External IDsOMIM: 176844 MGI: 1347009 HomoloGene: 2084 GeneCards: PSMA5 Gene
EC number3.4.25.1
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez568626442
EnsemblENSG00000143106ENSMUSG00000068749
UniProtP28066Q9Z2U1
RefSeq (mRNA)NM_001199772NM_011967
RefSeq (protein)NP_001186701NP_036097
Location (UCSC)Chr 1:
109.94 – 109.97 Mb		Chr 3:
108.26 – 108.28 Mb
PubMed search

Proteasome subunit alpha type-5 also known as 20S proteasome subunit alpha-5 is a protein that in humans is encoded by the PSMA5 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-5 contributes to the formation of heptameric alpha rings and substrate entrance gate.

Expression

The gene PSMA5 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit.[2] The gene has 9 exons and locates at chromosome band 1p13. The human protein proteasome subunit alpha type-5 is 26.5 kDa in size and composed of 241 amino acids. The calculated theoretical pI (isoelectric point) of this protein is 4.69.

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

PSMA5 has been shown to interact with PLK1.[8]

References

  1. ↑ DeMartino GN, Orth K, McCullough ML, Lee LW, Munn TZ, Moomaw CR et al. (Oct 1991). "The primary structures of four subunits of the human, high-molecular-weight proteinase, macropain (proteasome), are distinct but homologous". Biochim Biophys Acta 1079 (1): 29–38. doi:10.1016/0167-4838(91)90020-Z. PMID 1888762.
  2. ↑ 2.0 2.1 "Entrez Gene: PSMA5 proteasome (prosome, macropain) subunit, alpha type, 5".
  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. ↑ 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.

Further reading