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. Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3); also known as Machado-Joseph disease (MJD). 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 degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA 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 ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage; EC 126.96.36.199; Protease; Transcription regulation; Ubiquitin-specific protease
Molecular Function: ATPase binding; identical protein binding; protein binding; ubiquitin protein ligase binding; ubiquitin-specific protease activity
Biological Process: actin cytoskeleton organization and biogenesis; intermediate filament cytoskeleton organization and biogenesis; microtubule cytoskeleton organization and biogenesis; misfolded or incompletely synthesized protein catabolic process; nervous system development; nucleotide-excision repair; proteasomal ubiquitin-dependent protein catabolic process; protein deubiquitination; synaptic transmission; ubiquitin-dependent protein catabolic process