|SwissProt ID Link
||Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.
||Nucleus matrix. Predominantly nuclear, but not exclusively, inner nuclear matrix.
|Involvement in Disease
||Spinocerebellar ataxia 3: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I
which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATX3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. The disease is caused by mutations affecting the gene represented in this entry.
||Monoubiquitinated N-terminally by UBE2W, possibly leading to activate the deubiquitinating enzyme activity.
||Interacts with STUB1/CHIP (when monoubiquitinated). Interacts with DNA repair proteins RAD23A and RAD23B.
||Contains 1 Josephin domain.
Contains 3 UIM (ubiquitin-interacting motif) domains.