PSME3

PSME3 (Proteasome Activator Subunit 3) is a protein coding gene. Among its related pathways are Cell Cycle, Mitotic and RET signaling. Gene Ontology annotations related to this gene include identical protein binding and MDM2/MDM4 family protein binding. An important paralog of the gene is PSME1.

Full Name

Proteasome Activator Subunit 3

Function

Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978).

Biological Process

Apoptotic processIEA:UniProtKB-KW
Cell cycleIEA:UniProtKB-KW
Negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of endopeptidase activityManual Assertion Based On ExperimentIBA:GO_Central
Regulation of G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Regulation of proteasomal protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Nucleus
Cytoplasm
Localizes to the cytoplasm during mitosis following nuclear envelope breakdown at this distinct stage of the cell cycle which allows its interaction with MAP3K3 kinase.

PTM

Phosphorylated by MAP3K3 (By similarity).
Phosphorylation at Ser-247 promotes its association with CCAR2.
Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1.