MitoProteome Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins

MT000359

UniProt Annotations

Entry Information

Gene Name	ataxin 3
Protein Entry
UniProt ID
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=5; Name=1; IsoId=P54252-1; Sequence=Displayed; Name=2; IsoId=P54252-2; Sequence=VSP_002784; Name=3; IsoId=P54252-3; Sequence=VSP_002783, VSP_002784; Name=4; IsoId=P54252-4; Sequence=VSP_047086, VSP_002784; Note=Gene prediction based on EST data.; Name=5; IsoId=P54252-5; Sequence=VSP_047085, VSP_002784; Note=Gene prediction based on EST data.;
Catalytic Activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C- terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). {ECO:0000269\|PubMed:17696782}.
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. {ECO:0000269\|PubMed:7874163}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Domain	The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (By similarity). {ECO:0000250}.
Function	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. {ECO:0000269\|PubMed:12297501, ECO:0000269\|PubMed:16118278, ECO:0000269\|PubMed:17696782, ECO:0000269\|PubMed:23625928}.
Interaction	Self; NbExp=5; IntAct=EBI-946046, EBI-946046; Q9BSU1:C16orf70; NbExp=2; IntAct=EBI-946046, EBI-946080; P54257:HAP1; NbExp=6; IntAct=EBI-946046, EBI-712814; O60260:PARK2; NbExp=5; IntAct=EBI-9684323, EBI-716346; P54727:RAD23B; NbExp=2; IntAct=EBI-946046, EBI-954531; P0CG48:UBC; NbExp=2; IntAct=EBI-946046, EBI-3390054; P55072:VCP; NbExp=10; IntAct=EBI-946068, EBI-355164;
Polymorphism	The MJD1a allele carries a single nucleotide substitution in codon 349 generating a stop codon instead of a Tyr. In the Japanese population, the MJD1a allele seems to be significantly associated with Gln expansion.
Polymorphism	The poly-Gln region of ATXN3 is highly polymorphic (14 to 41 repeats) in the normal population and is expanded to about 55-82 repeats in spinocerebellar ataxia 3 (SCA3) patients.
Ptm	Monoubiquitinated N-terminally by UBE2W, possibly leading to activate the deubiquitinating enzyme activity.
Similarity	Contains 1 Josephin domain. {ECO:0000255\|PROSITE- ProRule:PRU00331}.
Similarity	Contains 3 UIM (ubiquitin-interacting motif) repeats. {ECO:0000255\|PROSITE-ProRule:PRU00213}.
Subcellular Location	Nucleus matrix {ECO:0000269\|PubMed:9580663}. Note=Predominantly nuclear, but not exclusively, inner nuclear matrix.
Subunit	Interacts with STUB1/CHIP (when monoubiquitinated) (By similarity). Interacts with DNA repair proteins RAD23A and RAD23B. {ECO:0000250}.
Tissue Specificity	Ubiquitous.
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/atxn3/";