Proteasomal ubiquitin receptor ADRM1 (Rpn13)

Proteasomal ubiquitin receptor ADRM1 (Rpn13) is a non-ATPase subunit of the 19S regulatory particle in the 26S proteasome, essential for intracellular protein degradation. Rpn13 functions as a ubiquitin receptor, recognizing and binding ubiquitinated substrates and facilitating their recruitment and processing by the proteasome. It contains a conserved N-terminal Pru domain for ubiquitin binding and interacts with other proteasomal components, notably the deubiquitinating enzyme UCHL5/Uch37. Rpn13 is critical for protein homeostasis and targeted degradation of misfolded or regulatory proteins, and its dysfunction or inhibition is linked to diseases such as cancer. Rpn13 is a validated therapeutic target with small molecule inhibitors in development for oncology indications.

Other names

ADRM1ARM-1ARM1GP110adhesion regulating molecule 1PSMD16ADRM1 26S proteasome ubiquitin receptor26S Proteasome regulatory subunit Rpn13

Inhibition of Rpn13 prevents docking of ubiquitinated proteins for degradation Inhibitors may cause accumulation of misfolded/damaged proteins, leading to cellular stress and apoptosis, especially in cancer cells