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Protein

Ataxin-3

Gene

Atxn3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei14NucleophileBy similarity1
Active sitei119Proton acceptorPROSITE-ProRule annotation1
Active sitei134PROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: ParkinsonsUK-UCL
  • cellular response to heat Source: MGI
  • cellular response to misfolded protein Source: UniProtKB
  • exploration behavior Source: MGI
  • histone H3 deacetylation Source: Ensembl
  • intermediate filament cytoskeleton organization Source: ParkinsonsUK-UCL
  • microtubule cytoskeleton organization Source: ParkinsonsUK-UCL
  • misfolded or incompletely synthesized protein catabolic process Source: UniProtKB
  • monoubiquitinated protein deubiquitination Source: UniProtKB
  • positive regulation of ERAD pathway Source: MGI
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein deubiquitination Source: MGI
  • protein K48-linked deubiquitination Source: ParkinsonsUK-UCL
  • protein K63-linked deubiquitination Source: ParkinsonsUK-UCL
  • protein localization to cytosolic proteasome complex involved in ERAD pathway Source: MGI
  • regulation of cell-substrate adhesion Source: ParkinsonsUK-UCL
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
  • ubiquitin-dependent protein catabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.
ReactomeiR-MMU-5689877. Josephin domain DUBs.

Protein family/group databases

MEROPSiC86.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Ataxin-3 (EC:3.4.19.12)
Alternative name(s):
Machado-Joseph disease protein 1 homolog
Gene namesi
Name:Atxn3
Synonyms:Mjd
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1099442. Atxn3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: ParkinsonsUK-UCL
  • mitochondrial matrix Source: MGI
  • mitochondrial membrane Source: MGI
  • nuclear inclusion body Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14C → A: Abolishes deubiquitinating activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000538321 – 355Ataxin-3Add BLAST355

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki200Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei219PhosphoserineCombined sources1
Modified residuei268PhosphoserineCombined sources1
Modified residuei272PhosphoserineCombined sources1
Modified residuei273PhosphoserineCombined sources1
Modified residuei321PhosphoserineCombined sources1

Post-translational modificationi

Monoubiquitinated by UBE2W, possibly leading to activate the deubiquitinating enzyme activity.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9CVD2.
MaxQBiQ9CVD2.
PaxDbiQ9CVD2.
PRIDEiQ9CVD2.

PTM databases

iPTMnetiQ9CVD2.
PhosphoSitePlusiQ9CVD2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000021189.
CleanExiMM_ATXN3.
ExpressionAtlasiQ9CVD2. baseline and differential.
GenevisibleiQ9CVD2. MM.

Interactioni

Subunit structurei

Interacts with DNA repair proteins RAD23A and RAD23B (By similarity). Interacts with STUB1/CHIP (when monoubiquitinated).By similarity1 Publication

GO - Molecular functioni

  • ATPase binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi225755. 16 interactors.
IntActiQ9CVD2. 2 interactors.
MINTiMINT-2837817.
STRINGi10090.ENSMUSP00000021606.

Structurei

3D structure databases

ProteinModelPortaliQ9CVD2.
SMRiQ9CVD2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 180JosephinPROSITE-ProRule annotationAdd BLAST180
Domaini224 – 243UIM 1PROSITE-ProRule annotationAdd BLAST20
Domaini244 – 263UIM 2PROSITE-ProRule annotationAdd BLAST20
Domaini329 – 348UIM 3PROSITE-ProRule annotationAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi282 – 285Poly-Arg4
Compositional biasi292 – 297Poly-Gln6

Domaini

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 (PubMed:21855799).1 Publication

Sequence similaritiesi

Contains 1 Josephin domain.PROSITE-ProRule annotation
Contains 3 UIM (ubiquitin-interacting motif) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2935. Eukaryota.
ENOG4111G4B. LUCA.
GeneTreeiENSGT00390000001830.
HOGENOMiHOG000006034.
HOVERGENiHBG025648.
InParanoidiQ9CVD2.
KOiK11863.
OMAiMLQAAMN.
OrthoDBiEOG091G0OC6.
PhylomeDBiQ9CVD2.
TreeFamiTF314228.

Family and domain databases

InterProiIPR033865. Ataxin-3.
IPR006155. Josephin.
IPR003903. UIM_dom.
[Graphical view]
PANTHERiPTHR14159. PTHR14159. 1 hit.
PfamiPF02099. Josephin. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
SMARTiSM01246. Josephin. 1 hit.
SM00726. UIM. 3 hits.
[Graphical view]
PROSITEiPS50957. JOSEPHIN. 1 hit.
PS50330. UIM. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9CVD2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESIFHEKQE GSLCAQHCLN NLLQGEYFSP VELSSIAHQL DEEERLRMAE
60 70 80 90 100
GGVTSEDYRT FLQQPSGNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ
110 120 130 140 150
RLRIDPINER SFICNYKEHW FTVRKLGKQW FNLNSLLTGP ELISDTYLAL
160 170 180 190 200
FLAQLQQEGY SIFVVKGDLP DCEADQLLQM IKVQQMHRPK LIGEELAHLK
210 220 230 240 250
EQSALKADLE RVLEAADGSG IFDEDEDDLQ RALAISRQEI DMEDEEADLR
260 270 280 290 300
RAIQLSMQGS SRSMCENSPQ TSSPDLSSEE LRRRREAYFE KQQQQQQEVD
310 320 330 340 350
RPGPLSYPRE RPTTSSGGRR SDQGGDAVSE EDMLRAAVTM SLETAKDNLK

AERKK
Length:355
Mass (Da):40,533
Last modified:February 28, 2003 - v2
Checksum:iD148DD10EA481D5B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK008675 mRNA. Translation: BAB25825.3.
AK030842 mRNA. Translation: BAC27155.1.
CCDSiCCDS26115.1.
RefSeqiNP_083981.2. NM_029705.3.
UniGeneiMm.271914.

Genome annotation databases

EnsembliENSMUST00000021606; ENSMUSP00000021606; ENSMUSG00000021189.
GeneIDi110616.
KEGGimmu:110616.
UCSCiuc007otv.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK008675 mRNA. Translation: BAB25825.3.
AK030842 mRNA. Translation: BAC27155.1.
CCDSiCCDS26115.1.
RefSeqiNP_083981.2. NM_029705.3.
UniGeneiMm.271914.

3D structure databases

ProteinModelPortaliQ9CVD2.
SMRiQ9CVD2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi225755. 16 interactors.
IntActiQ9CVD2. 2 interactors.
MINTiMINT-2837817.
STRINGi10090.ENSMUSP00000021606.

Protein family/group databases

MEROPSiC86.001.

PTM databases

iPTMnetiQ9CVD2.
PhosphoSitePlusiQ9CVD2.

Proteomic databases

EPDiQ9CVD2.
MaxQBiQ9CVD2.
PaxDbiQ9CVD2.
PRIDEiQ9CVD2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021606; ENSMUSP00000021606; ENSMUSG00000021189.
GeneIDi110616.
KEGGimmu:110616.
UCSCiuc007otv.2. mouse.

Organism-specific databases

CTDi4287.
MGIiMGI:1099442. Atxn3.

Phylogenomic databases

eggNOGiKOG2935. Eukaryota.
ENOG4111G4B. LUCA.
GeneTreeiENSGT00390000001830.
HOGENOMiHOG000006034.
HOVERGENiHBG025648.
InParanoidiQ9CVD2.
KOiK11863.
OMAiMLQAAMN.
OrthoDBiEOG091G0OC6.
PhylomeDBiQ9CVD2.
TreeFamiTF314228.

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.
ReactomeiR-MMU-5689877. Josephin domain DUBs.

Miscellaneous databases

ChiTaRSiAtxn3. mouse.
PROiQ9CVD2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021189.
CleanExiMM_ATXN3.
ExpressionAtlasiQ9CVD2. baseline and differential.
GenevisibleiQ9CVD2. MM.

Family and domain databases

InterProiIPR033865. Ataxin-3.
IPR006155. Josephin.
IPR003903. UIM_dom.
[Graphical view]
PANTHERiPTHR14159. PTHR14159. 1 hit.
PfamiPF02099. Josephin. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
SMARTiSM01246. Josephin. 1 hit.
SM00726. UIM. 3 hits.
[Graphical view]
PROSITEiPS50957. JOSEPHIN. 1 hit.
PS50330. UIM. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATX3_MOUSE
AccessioniPrimary (citable) accession number: Q9CVD2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: February 28, 2003
Last modified: November 30, 2016
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.