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Proteasome (prosome, macropain) subunit, alpha type, 6
Protein PSMA6 PDB 1iru.png
PDB rendering based on 1iru.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols PSMA6 ; IOTA; PROS27; p27K
External IDs OMIM602855 MGI1347006 HomoloGene2085 GeneCards: PSMA6 Gene
EC number
RNA expression pattern
PBB GE PSMA6 208805 at tn.png
More reference expression data
Species Human Mouse
Entrez 5687 26443
Ensembl ENSG00000100902 ENSMUSG00000021024
UniProt P60900 Q9QUM9
RefSeq (mRNA) NM_001282232 NM_011968
RefSeq (protein) NP_001269161 NP_036098
Location (UCSC) Chr 14:
35.59 – 35.79 Mb
Chr 12:
55.38 – 55.42 Mb
PubMed search [1] [2]

Proteasome subunit alpha type-6 is a protein that in humans is encoded by the PSMA6 gene.[1][2][3]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.


Protein Expression[edit]

The gene PMSA6 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. A pseudogene has been identified on the Y chromosome.[3] The gene has 8 exons and locates at chromosome band 14q13. The human protein Proteasome subunit alpha type-6 is also known as 20S proteasome subunit alpha-1 (based on systematic nomenclature). The protein is 27 kDa in size and composed of 246 amino acids. The calculated theoretical pI (isoelectric point) of this protein is 6.35.

Complex Assembly[edit]

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.[4][5]


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.[5] 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.[6][7] 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.[7] [8]As a component of alpha ring, Proteasome subunit alpha type-6 contributes to the formation of heptameric alpha rings and substrate entrance gate.

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.


PSMA6 has been shown to interact with PLK1[9] and PSMA3.[10][11]


  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. ^ 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/ PMID 8811196. 
  3. ^ a b "Entrez Gene: PSMA6 proteasome (prosome, macropain) subunit, alpha type, 6". 
  4. ^ 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/ PMID 8811196. 
  5. ^ a b 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. 
  6. ^ 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. 
  7. ^ a b 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. 
  8. ^ Zong, C; Gomes, AV; Drews, O; Li, X; Young, GW; Berhane, B; Qiao, X; French, SW; Bardag-Gorce, F; Ping, P (18 August 2006). "Regulation of murine cardiac 20S proteasomes: role of associating partners.". Circulation research 99 (4): 372–80. PMID 16857963. 
  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. 

Further reading[edit]