Rpn2

Rpn2, short for Regulatory Particle Non-ATPase 2, is a core component of the 19S regulatory particle of the 26S proteasome, a major protease complex responsible for ubiquitin-dependent protein turnover in eukaryotic cells. As a non-ATPase subunit, Rpn2 resides in the base alongside Rpn1 and helps shape the entrance to the proteasome core and coordinate substrate processing in conjunction with the ATPase rings.

Rpn2 participates in recognizing polyubiquitin chains on substrates and contributes to the docking of the 19S particle to the 20S core particle. It interacts with other base subunits to form a platform that supports unfolding and translocation of substrates into the proteolytic chamber. The protein is largely cytosolic but can be found in both the cytoplasm and nucleus, consistent with proteasome localization throughout the cell.

Genetically, RPN2 is conserved across eukaryotes. In yeast, RPN2 is essential for viability; loss-of-function mutants exhibit severe defects in proteasome function and protein homeostasis. In higher eukaryotes, the gene is part of the conserved PSMD family; the human orthologs contribute to the integrity of the 19S regulatory particle.

Clinical and research interest in RPN2 has grown due to its role in proteasome biology and its altered expression in several cancers. Changes in RPN2 levels can affect proteasome activity and cellular sensitivity to proteasome inhibitors, making it relevant to studies of cancer biology and potential therapeutic strategies.