PSME3
Domain
The C-terminal sequences affect heptamer stability and proteasome affinity.
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).
Post-translational modifications
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.
Sequence Similarities
Belongs to the PA28 family.
Cellular localization
- 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.
Alternative names
Proteasome activator complex subunit 3, 11S regulator complex subunit gamma, Activator of multicatalytic protease subunit 3, Ki nuclear autoantigen, Proteasome activator 28 subunit gamma, REG-gamma, PA28g, PA28gamma, PSME3