Page last updated: 2024-10-24

proteasome regulatory particle

Definition

Target type: cellularcomponent

A multisubunit complex, which caps one or both ends of the proteasome core complex. This complex recognizes and unfolds ubiquitinated proteins, and translocates them to the proteasome core complex. [GOC:mtg_sensu, GOC:rb]

The proteasome regulatory particle (RP), also known as the 19S regulatory particle, is a multi-protein complex that recognizes, unfolds, and delivers proteins to the proteasome core particle (CP) for degradation. It is a highly dynamic structure, and its composition can vary depending on the cell type and cellular conditions. However, in general, it consists of two subcomplexes: the lid and the base.

The **lid** is responsible for recognizing ubiquitinated substrates, which are proteins tagged for degradation. It contains a number of ATPase-associated factors (AAA+ ATPases) that bind to ubiquitin chains and unfold the substrate protein. The lid also contains several deubiquitinating enzymes (DUBs) that remove ubiquitin chains from substrates, allowing for the precise regulation of protein degradation.

The **base** interacts directly with the CP and is responsible for translocating the unfolded substrate into the CP's catalytic chamber. The base contains six AAA+ ATPases that form a ring-like structure. These ATPases use the energy from ATP hydrolysis to unfold the substrate and drive it through a narrow pore into the CP.

The **structure** of the RP is highly complex and dynamic. It undergoes conformational changes during the substrate recognition, unfolding, and translocation processes. These changes are crucial for ensuring that only the correct substrates are degraded and that the degradation process is efficient and regulated.

The **function** of the RP is essential for maintaining cellular homeostasis. It degrades misfolded, damaged, and short-lived proteins, thus preventing the accumulation of toxic or dysfunctional proteins. It also regulates cellular processes such as signal transduction, cell cycle control, and immune response by degrading specific proteins involved in these pathways.'
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Proteins (7)

ProteinDefinitionTaxonomy
26S proteasome non-ATPase regulatory subunit 6A 26S proteasome non-ATPase regulatory subunit 6 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q15008]Homo sapiens (human)
26S proteasome non-ATPase regulatory subunit 13A 26S proteasome non-ATPase regulatory subunit 13 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
26S proteasome non-ATPase regulatory subunit 1A 26S proteasome non-ATPase regulatory subunit 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q99460]Homo sapiens (human)
26S proteasome non-ATPase regulatory subunit 2A 26S proteasome non-ATPase regulatory subunit 2 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
26S proteasome non-ATPase regulatory subunit 7A 26S proteasome non-ATPase regulatory subunit 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P51665]Homo sapiens (human)
26S proteasome non-ATPase regulatory subunit 8A 26S proteasome non-ATPase regulatory subunit 8 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
26S proteasome non-ATPase regulatory subunit 12A 26S proteasome non-ATPase regulatory subunit 12 that is encoded in the genome of human. [PRO:WCB, UniProtKB:O00232]Homo sapiens (human)

Compounds (3)

CompoundDefinitionClassesRoles
bortezomibamino acid amide;
L-phenylalanine derivative;
pyrazines
antineoplastic agent;
antiprotozoal drug;
protease inhibitor;
proteasome inhibitor
carfilzomibepoxide;
morpholines;
tetrapeptide
antineoplastic agent;
proteasome inhibitor
belactosin abelactosin A: isolated from Streptomyces; structure in first source