Proteasome regulatory particle subunit RPN13 (RPN13)

Proteasome regulatory particle subunit RPN13 (ADRM1, hRpn13) is a non-ATPase component of the 19S regulatory particle of the eukaryotic 26S proteasome. RPN13 serves as a major receptor for ubiquitinated proteins, recognizing K48-linked diubiquitin via its N-terminal Pru domain and docking these substrates for proteasomal degradation. RPN13 also recruits and activates the deubiquitinating enzyme Uch37/UCHL5, thereby coupling substrate recognition with ubiquitin chain disassembly at the proteasome. RPN13 is targeted by specific small molecule inhibitors such as RA190, which restrict tumor growth by disrupting proteasome-mediated degradation. RPN13 dysfunction or overexpression is implicated in cancer and other proteostasis-related diseases. It is essential for cellular protein quality control, immune response regulation, and general homeostasis by ensuring timely degradation of misfolded or regulatory proteins.

Other names

ADRM1hRpn13

RA190 targets RPN13 (covalent modification) and UCHL5, leading to inhibition of ubiquitin chain removal and induction of apoptosis in cancer cells. Disruption of ubiquitin binding and protein recognition, blocking substrate degradation.