Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (  ). May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin (  ). Specifically hydrolyzes 'Lys-63'-, 'Lys-48'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitins chains ( ). Essential component of TGF-beta/BMP signaling cascade . Specifically deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33 . Deubiquitinates alkylation repair enzyme ALKBH3 . OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions . Deubiquitinates mTORC2 complex component RICTOR at 'Lys-294' by removing 'Lys-63'-linked polyubiquitin chains, stabilizing RICTOR and enhancing its binding to MTOR, thus promoting mTORC2 complex assembly . Regulates chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres . Involved in axonal growth and neuronal cell migration . Regulates cellular clock function by enhancing the protein stability and transcriptional activity of the core circadian protein BMAL1 via its deubiquitinating activity . Acts as a regulator of peroxisome import by mediating deubiquitination of PEX5: specifically deubiquitinates PEX5 monoubiquitinated at 'Cys-11' following its retrotranslocation into the cytosol, resetting PEX5 for a subsequent import cycle . Deubiquitinates PEG10 (By similarity).
Subcellular locations: Cytoplasm, Cytosol, Cell projection, Growth cone, Cytoplasm, Cytoskeleton, Cilium axoneme
Widely expressed in embryonic and adult tissues.