The proteasome (or macropain) (EC 220.127.116.11) [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
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>) .
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
- 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
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.
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