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P54252 Proteins UIM domain Repeats
Uniprot ID:P54252
Protein name: Ataxin-3
Gene : ATXN3 ATX3 MJD MJD1 SCA3
Protein Family:
Squence Length : 361
Sequnce
>P54252 362 MESIFHEKQEGSLCAQHCLNNLLQGEYFSPVELSSIAHQLDEEERMRMAEGGVTSEDYRTFLQQPSGNMDDSGFFSIQVISNALKVWGLELILFNSPEYQRLRIDPINERSFICNYKEHWFTVRKLGKQWFNLNSLLTGPELISDTYLALFLAQLQQEGYSIFVVKGDLPDCEADQLLQMIRVQQMHRPKLIGEELAQLKEQRVHKTDLERVLEANDGSGMLDEDEEDLQRALALSRQEIDMEDEEADLRRAIQLSMQGSSRNISQDMTQTSGTNLTSEELRKRREAYFEKQQQKQQQQQQQQQQGDLSGQSSHPCERPATSSGALGSDLGDAMSEEDMLQAAVTMSLETVRNDLKTEGKK
Domains
DOMAIN 1 180 Josephin DOMAIN 224 243 UIM 1 DOMAIN 244 263 UIM 2 DOMAIN 331 349 UIM 3
UIM sequence regions
224 - 243 EEDLQRALALSRQEIDMEDE 244 - 263 EADLRRAIQLSMQGSSRNIS 331 - 349 AMSEEDMLQAAVTMSLETV
Function
"Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:16118278). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (PubMed:17696782). 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 (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (PubMed:12297501). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460)"
Active Site
ACT_SITE 14 14 Nucleophile. ACT_SITE 119 119 Proton acceptor. ACT_SITE 134 134
Mutation
14 14 C->A: Loss of deubiquitination activity 236 236 S->A: Inhibits substrate trapping 256 256 S->A: Inhibits substrate trapping 335 335 S->A: No effect on ubiquitination
Disease
"DISEASE: Spinocerebellar ataxia 3 (SCA3) [MIM:109150]: 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 (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 ATX3 coding region Longer expansions result in earlier onset and more severe clinical manifestations of the disease Note=The disease is caused by mutations affecting the gene represented in this entry"