Proteasome subunit alpha type-3 (PSMA3)

Proteasome subunit alpha type-3 (PSMA3) is a protein encoded by the PSMA3 gene in humans, functioning as a critical component of the 20S core proteasome complex[1][2]. The 20S proteasome core is a multicatalytic protease fundamental for the degradation of most intracellular proteins, including misfolded, damaged, or regulatory proteins involved in cell cycle, apoptosis, and immune response[2][3]. PSMA3 is one of seven alpha subunits that form the outer rings of the core particle, controlling substrate entry into the proteolytic chamber[1][3]. Through assembly with beta subunits, the proteasome exerts threonine-type endopeptidase activity in an ATP- and ubiquitin-dependent manner[2][3]. PSMA3 also participates in specialized immunoproteasome complexes essential for generating peptides presented by MHC class I molecules, linking it to immune surveillance and disease processes, including cancer and neurodegeneration[1][2][3]. The core proteasome can be pharmacologically targeted, most notably in multiple myeloma and other malignancies, by drugs that inhibit its catalytic function, with clinical consequences for protein homeostasis and cell viability[2].

Other names

Proteasome 20S subunit alpha 3PSMA3Macropain subunit C8Proteasome component C8Proteasome subunit alpha-7HC8PSC8PSC3Multicatalytic endopeptidase complex subunit C8Proteasome subunit C8Testicular secretory protein Li 43

Proteasome inhibitors block the proteolytic (protease) activity of the 20S proteasome core complex, leading to accumulation of ubiquitinated proteins, induction of cell cycle arrest, and apoptosis, particularly in rapidly growing cells such as cancer cells[2].