S5a (Rpn10) is a component of the regulatory complex (19S) of the 26S proteasome. By binding to and recognizing poly-ubiquitinated proteins, it functions as a receptor for proteins destined for proteolytic degradation. S5a has a low affinity for mono-, di- and tri-Ub but binds efficiently to tetrameric ubiquitin and has a preference for longer polymers. The protein recognizes ubiquitin conjugates via two UIM (ubiquitin-interacting motif) domains at located at residues 211-230 (I) and 282-301 (II). Although both UIMs bind to poly-ubiquitin in vitro, UIM II has a 10-fold higher affinity for ubiquitin than UIM I. This affinity resin can be used for the enrichment, isolation and identification of ubiquitinated proteins, proteins that contain ubiquitin-like domains and/or 26S substrates.