26S proteasome regulatory subunit, C-terminal (IPR013586)

Short name: 26S_Psome_reg_C

Overlapping homologous superfamilies


Domain relationships



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 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 [PMID: 10490625]. It occurs together with the PCI/PINT domain (IPR000717).

GO terms

Biological Process

GO:0042176 regulation of protein catabolic process

Molecular Function

GO:0030234 enzyme regulator activity

Cellular Component

GO:0000502 proteasome complex

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.