26S proteasome regulatory subunit P45-like (IPR005937)
Short name: 26S_Psome_P45-like
Overlapping homologous superfamilies
- 26S proteasome regulatory subunit P45-like (IPR005937)
- 26S Proteasome regulatory subunit 4 (IPR035244)
- 26S Proteasome regulatory subunit 6A (IPR035254)
- 26S Proteasome regulatory subunit 6B (IPR035256)
- 26S Proteasome regulatory subunit 7 (IPR035245)
- 26S proteasome regulatory subunit 10B (IPR035263)
- 26S proteasome regulatory subunit 8 (IPR035261)
- Proteasome-activating nucleotidase PAN (IPR023501)
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 [PMID: 15571806, PMID: 15890341]. 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) [PMID: 28583440]. 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) [PMID: 9741626]. 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 [PMID: 16566573].
This family includes the six paralogous AAA-ATPases, termed Rpt1-Rpt6, of the 19S component base [PMID: 28583440]. Members of this family may be phosphorylated within the proteasome. This phosphorylation event may play a key role in ATP-dependent proteolysis because a good correlation exists between the inhibition pattern of protein kinase inhibitors against the phosphorylation of p45 (Rpt6) and that against the ATP-dependent proteolytic activity [PMID: 11148024, PMID: 16250896].
- TIGR01242 (26Sp45)