InterPro domain: IPR030298

OTUB1 (also known as otubain-1) is a deubiquitinating enzyme that belongs to the OTU family of cysteine proteases [ 1 ]. OTUB1 can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation [ 2 ]. It also plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites [ 3 , 4 ]. Mutations in OTUB1 cause tumour predisposition syndrome (TPDS), characterised by predisposition to develop a variety of tumours [ 5 ].

1. E2 ubiquitin-conjugating enzymes regulate the deubiquitinating activity of OTUB1. Nat. Struct. Mol. Biol. 20, 1033-9
2. Otubains: a new family of cysteine proteases in the ubiquitin pathway. EMBO Rep. 4, 517-22
3. Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1. Nature 466, 941-6
4. DNA repair: Blocking ubiquitin transfer. Nature 466, 929-30
5. Germline BAP1 mutations predispose to malignant mesothelioma. Nat. Genet. 43, 1022-5