InterPro domain: IPR039138

The ubiquitin thioesterase OTU1 is a deubiquitinating enzyme, releasing ubiquitin from tagged proteins. It hydrolyses the isopeptide bonds of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains [ 1 ]. Removal of ubiquitin does not necessarily rescue tagged proteins from degradation, because proteins are often then targeted to endoplasmic reticulum-associated degradation. Removal of the ubiquitin tag may grant access to the VCP/p97 pore, and OTU1 may be a constituent of a complex involved in macroautophagy [ 2 ]. OTU1 is also required for endo-lysosomal damage response and is recruited to damaged lysosomes to remove Lys48-linked ubiquitin conjugates to promote autophagosome formation [ 3 ]. OTU1 is a cysteine peptidase with a structural fold similar to that of papain [ 4 ]; it is a member of MEROPS peptidase family C85.

OTU2 has a preference for 'Lys-63' and 'Lys-48' -linked ubiquitin tetramers, and OTU3 for 'Lys-63' over 'Lys-48' over 'Met-1' [ 4 ].

1. OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell 154, 169-84
2. The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER. Mol. Cell 36, 28-38
3. VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. EMBO J. 36, 135-150
4. Distinct phylogenetic relationships and biochemical properties of Arabidopsis ovarian tumor-related deubiquitinases support their functional differentiation. Front Plant Sci 5, 84