InterPro domain: IPR016652

This entry includes a group of ubiquitinyl hydrolases, also known as ubiquitin carboxyl-terminal hydrolases, including USP13 and USP5 from animals, and Ubp14 from plants and fungi.

Budding yeast Ubp14 may facilitate proteolysis by preventing unanchored ubiquitin chains from competitively inhibiting polyubiquitin-substrate binding to the 26S proteasome [ 1 , 2 ].

USP5 recognizes and recycles the unanchored polyUb chain to keep the free Ub pool stable [ 3 ]. USP13 is an ortholog of USP5. However, unlike USP5, USP13 exhibits a weak deubiquitinating activity preferring to Lys63-linked polyubiquitin (K63-polyUb) in a non-activation manner. It may function differently from USP5 in cellular deubiquitination processes [ 4 ].

1. Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol. Biol. Cell 14, 1652-63
2. In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome. EMBO J. 16, 4826-38
3. Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53. J. Biol. Chem. 284, 5030-41
4. Domain analysis reveals that a deubiquitinating enzyme USP13 performs non-activating catalysis for Lys63-linked polyubiquitin. PLoS ONE 6, e29362