Rpn10

Rpn10 is a non-ATPase subunit of the 19S regulatory particle of the eukaryotic 26S proteasome. It is involved in recognizing and delivering ubiquitinated substrates to the proteasome core for degradation. In budding yeast, the protein is encoded by the RPN10 gene, and in humans the ortholog is encoded by PSMD4 (also referred to as S5a). The conservation of Rpn10 across eukaryotes reflects its fundamental role in protein quality control.

Function and mechanism

Rpn10 acts as a ubiquitin receptor within the 19S regulatory particle, binding polyubiquitin chains on substrate proteins via a ubiquitin-interacting motif. This recognition helps recruit substrates to the proteasome and coordinates their processing, in concert with other ubiquitin receptors such as Rpn13. Through these interactions, Rpn10 contributes to efficient substrate engagement, deubiquitination, and translocation into the 20S core particle where proteolysis occurs.

Structure and interactions

As a component of the 19S regulatory particle, Rpn10 participates in assembling or stabilizing the receptor module that mediates substrate capture. The ubiquitin-interacting motif enables direct binding to ubiquitin to facilitate substrate targeting, while its position within the regulatory particle supports integration with other subunits involved in substrate processing.

Genetics and relevance

Loss or impairment of RPN10 in yeast leads to defects in proteasome function, accumulation of ubiquitinated proteins, and slower degradation of certain substrates. In humans, disruption of the Rpn10 homolog can affect proteasome activity and has been studied in contexts such as cancer biology and immune signaling, underscoring the essential role of the ubiquitin-proteasome system in cellular homeostasis.

See also

Ubiquitin-proteasome system; 26S proteasome; ubiquitin receptors.