Proteasome 26S subunit ubiquitin receptor non-ATPase 4 (PSMD4)

Proteasome 26S subunit ubiquitin receptor non-ATPase 4 (PSMD4, also known as Rpn10 or S5A) is a key regulatory subunit of the 19S regulatory particle of the 26S proteasome, the major proteolytic machinery in eukaryotic cells. PSMD4 acts as an intrinsic ubiquitin receptor, directly recognizing and binding polyubiquitinated protein substrates and facilitating their delivery to the proteolytic core for degradation. This functional role places PSMD4 at the center of the regulated proteolysis that controls protein turnover, cell cycle progression, apoptosis, and response to cellular stress. Dysregulation of this subunit or the proteasome complex broadly has been implicated in cancer, neurodegenerative diseases, infections, and immune disorders. The human PSMD4 protein is encoded by the *PSMD4* gene and consists of 377 amino acids with a molecular weight of approximately 41 kDa. PSMD4 contains a ubiquitin-interacting motif (UIM) and mediates interactions with shuttle factors such as RAD23A/B. It is widely expressed in human tissues, reflecting its essential role in proteostasis. Because proteasome inhibition is cytotoxic to rapidly dividing cells and modulates immune pathways, the proteasome (including PSMD4) is a therapeutic target, primarily in cancers (e.g., multiple myeloma).

Other names

PSMD4Rpn10S5AProteasome regulatory subunit Rpn10

Inhibition of proteasomal protein degradation leading to accumulation of ubiquitinated proteins, disruption of cell cycle progression, and induction of apoptosis. Some drugs may modulate immune response or stress pathways indirectly by altering proteasome function