InterPro domain: IPR044868

This entry includes Rpn13 from budding yeasts and its homologue, ADRM1 from animals.

Rpn13 is a subunit and an ubiquitin receptor of the 19S regulatory particle of the 26S proteasome lid. The 26S proteasome is a huge macromolecular protein-degradation machine consisting of a proteolytically active 20S core, in the form of four disc-like proteins, and one or two 19S regulatory particles. The regulatory particle(s) sit on the top and or bottom of the core, de-ubiquitinate the substrate peptides, unfold them and guide them into the narrow channel through the centre of the core. Rpn13 and its homologues dock onto the regulatory particle through the N-terminal region which binds Rpn2. The C-terminal part of the domain binds de-ubiquitinating enzyme Uch37/UCHL5 and enhances its isopeptidase activity. Rpn13 binds ubiquitin via a conserved amino-terminal region called the pleckstrin-like receptor for ubiquitin, termed Pru, domain [ 1 ]. The domain forms two contiguous anti-parallel beta-sheets with a configuration similar to the pleckstrin-homology domain (PHD) fold [ 2 , 3 ]. Rpn13's ability to bind ubiquitin and the proteasome subunit Rpn2/S1 simultaneously supports evidence of its role as a ubiquitin receptor. Finally, when complexed to di-ubiquitin, via the Pru, and Uch37 via the C-terminal part, it frees up the distal ubiquitin for de-ubiquitination by the Uch37 [ 4 ].

This entry represents the Pru (pleckstrin-like receptor for the Ub) domain.

1. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453, 481-8
2. Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction. Nature 453, 548-52
3. Structure of proteasome ubiquitin receptor hRpn13 and its activation by the scaffolding protein hRpn2. Mol. Cell 38, 404-15