PROSITE documentation PDOC00326
Proteasome alpha-type subunit signature and profile


The proteasome (or macropain) (EC [1,2,3,4,5,6] is a multicatalytic proteinase complex that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. The core of this 2.5 MDa enzyme complex is formed by the 20S proteasome (core particle, CP), a barrel-shaped protease of about 700 KDa that associates with one or two 19S regulatory complexes. The 20S proteasome subunits can be classified, on the basis of sequence similarities, into two related families, α and β (see <PDOC00668>). The 20S proteasome is ubiquitous in archaea and in eukaryotes. In bacteria, the 20S has been found only in actinomycetes.

The 20S proteasome is composed of four stacked heptameric rings. Narrow substrate entry channels are created by the two outer rings, which are each formed by seven α subunits. The two inner rings create an internal chamber that houses the proteolytic active sites responsible for protein cleavage; these rings are each formed by seven β subunits (see <PDOC00668>). 20S proteasome α subunits include highly conserved N-terminal extensions that are absent from β subunits. These N-termini form a gate that controls substrate passage through the central α-ring channel. Archaeal and bacterial 20S proteasomes usually have a single type of α subunit and β subunit, each present in 14 copies in each particle. Thus, these proteasomes have 14 active sites arrayed within their central chambers. In eukaryotes, seven distinct α-subunit paralogs form each heptameric outer ring and seven distinct β-subunit paralogs form each inner ring. Only three of the seven eukaryotic β subunits (β1, β2 and β5) retain an intact active site, so each eukaryotic 20S proteasome has six proteolytic active sites [7].

Subunits that belong to the α-type group are proteins of from 210 to 290 amino acids that share a number of conserved sequence regions. The core of the α subunit is a sandwich of two five-stranded antiparallel β-sheets. The β sandwich is flanked by the α helices H3, H4, and H5 on top and by H1 and H2 at the bottom (see <PDB:1PMA>) [8].

Some subunits that are known to belong to this family are listed below:

  • Vertebrate subunits C2 (nu), C3, C8, C9, iota and zeta.
  • Drosophila PROS-25, PROS-28.1, PROS-29 and PROS-35.
  • Yeast C1 (PRS1), C5 (PRS3), C7-α (Y8) (PRS2), Y7, Y13, PRE5, PRE6 and PUP2.
  • Arabidopsis thaliana subunits α and PSM30.
  • Thermoplasma acidophilum α-subunit. In this archaebacteria the proteasome is composed of only two different subunits.
  • Rhodococcus erythropolis 20S proteasome α subunit 1 (PrcA 1) and 2 (PrcA 2).

As a signature pattern for proteasome A-type subunits we selected the best conserved region, which is located in the N-terminal part of these proteins. We also have developed a profile which covers the whole conserved region.


These proteins belong to family T1 in the classification of peptidases [9,E2].

Last update:

May 2020 / Text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

PROTEASOME_ALPHA_2, PS51475; Proteasome alpha-type subunit profile  (MATRIX)

PROTEASOME_ALPHA_1, PS00388; Proteasome alpha-type subunits signature  (PATTERN)


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TitleCrystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly.
SourceJ. Mol. Biol. 335:233-245(2004).
PubMed ID14659753

7AuthorsBudenholzer L. Cheng C.L. Li Y. Hochstrasser M.
TitleProteasome Structure and Assembly.
SourceJ. Mol. Biol. 429:3500-3524(2017).
PubMed ID28583440

8AuthorsLoewe J. Stock D. Jap B. Zwickl P. Baumeister W. Huber R.
TitleCrystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution.
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PubMed ID7725097

9AuthorsRawlings N.D. Barrett A.J.
TitleFamilies of serine peptidases.
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PubMed ID7845208


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