Rpn13

Rpn13, or proteasome regulatory particle non-ATPase 13, is a subunit of the 19S regulatory particle of the 26S proteasome. In humans it is encoded by the ADRM1 gene and is conserved across eukaryotes. Rpn13 functions as a ubiquitin receptor within the regulatory particle, recognizing polyubiquitin chains attached to substrates that are destined for degradation by the proteasome.

As a ubiquitin receptor, Rpn13 participates in the capture and presentation of ubiquitinated substrates to the proteolytic core. It works in concert with other ubiquitin receptors in the 19S particle, such as Rpn10, to coordinate substrate engagement, unfolding, and passage into the 20S core for degradation. Through these interactions, Rpn13 contributes to the efficiency and specificity of proteasomal degradation and can influence the extent of deubiquitination that substrates experience before degradation.

Structure and localization-wise, Rpn13 is a non-ATPase component of the 19S regulatory particle and resides in the cytoplasm as part of the assembled 26S proteasome. It contains regions capable of binding ubiquitin, which mediate its receptor function, though the precise domain architecture has been described in relation to ubiquitin-binding and proteasome interactions rather than as a single canonical motif.

Clinical and research significance: Given the central role of the ubiquitin–proteasome system in protein homeostasis, Rpn13 has drawn attention as a potential therapeutic target. Preclinical studies have explored small molecules that disrupt the Rpn13–ubiquitin interaction, aiming to impair proteasome function and selectively affect cancer cells. Ongoing research seeks to clarify the full biological roles of Rpn13 and assess the therapeutic potential of targeting this receptor.