InterPro domain: IPR013586

Intracellular proteins, including short-lived proteins such as cyclin, Mos, Myc, p53, NF-kappaB, and IkappaB, are degraded by the ubiquitin-proteasome system. The 26S proteasome is a self-compartmentalising protease responsible for the regulated degradation of intracellular proteins in eukaryotes [ 1 , 2 ]. This giant intracellular protease is formed by several subunits arranged into two 19S polar caps, where protein recognition and ATP-dependent unfolding occur, flanking a 20S central barrel-shaped structure with an inner proteolytic chamber. This overall structure is highly conserved among eukaryotes and is essential for cell viability. Proteins targeted to the 26S proteasome are conjugated with a polyubiquitin chain by an enzymatic cascade before delivery to the 26S proteasome for degradation into oligopeptides.

The 26S proteasome can be divided into two subcomplexes: the 19S regulatory particle (RP) and the 20S core particle (CP) [ 3 ]. The 19S component is divided into a "base" subunit containing six ATPases (Rpt proteins) and two non-ATPases (Rpn1, Rpn2), and a "lid" subunit composed of eight stoichiometric proteins (Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, Rpn12) [ 4 ]. Additional non-essential and species specific proteins may also be present. The 19S unit performs several essential functions including binding the specific protein substrates, unfolding them, cleaving the attached ubiquitin chains, opening the 20S subunit, and driving the unfolded polypeptide into the proteolytic chamber for degradation. The 26s proteasome and 19S regulator are of medical interest due to their involvement in burn rehabilitation [ 5 ].

This eukaryotic domain is found at the C terminus of 26S proteasome regulatory subunits such as the non-ATPase Rpn3 subunit which is essential for proteasomal function [ 6 ]. It occurs together with the PCI/PINT domain ( IPR000717 ).

1. The proteasome: a proteolytic nanomachine of cell regulation and waste disposal. Biochim. Biophys. Acta 1695, 19-31
2. Proteasome plasticity. FEBS Lett. 579, 3214-23
3. Proteasome Structure and Assembly. null
4. A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3. Cell 94, 615-23
5. Effects of tumor necrosis factor-alpha on the 26S proteasome and 19S regulator in skeletal muscle of severely scalded mice. J. Mol. Biol. 27, 226-33
6. Functional characterization of rpn3 uncovers a distinct 19S proteasomal subunit requirement for ubiquitin-dependent proteolysis of cell cycle regulatory proteins in budding yeast. Mol. Cell. Biol. 19, 6872-90