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Protein

Ataxin-3

Gene

Atxn3

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

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).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei14 – 141Nucleophile
Active sitei119 – 1191Proton acceptorPROSITE-ProRule annotation
Active sitei134 – 1341PROSITE-ProRule annotation

GO - Molecular functioni

  1. ATPase binding Source: ParkinsonsUK-UCL
  2. identical protein binding Source: ParkinsonsUK-UCL
  3. Lys48-specific deubiquitinase activity Source: ParkinsonsUK-UCL
  4. Lys63-specific deubiquitinase activity Source: ParkinsonsUK-UCL
  5. omega peptidase activity Source: InterPro
  6. RNA polymerase II regulatory region DNA binding Source: RGD
  7. ubiquitin protein ligase binding Source: UniProtKB
  8. ubiquitin-specific protease activity Source: UniProtKB
  9. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. actin cytoskeleton organization Source: ParkinsonsUK-UCL
  2. cellular response to heat Source: Ensembl
  3. cellular response to misfolded protein Source: UniProtKB
  4. exploration behavior Source: Ensembl
  5. histone H3 deacetylation Source: RGD
  6. intermediate filament cytoskeleton organization Source: ParkinsonsUK-UCL
  7. microtubule cytoskeleton organization Source: ParkinsonsUK-UCL
  8. misfolded or incompletely synthesized protein catabolic process Source: UniProtKB
  9. monoubiquitinated protein deubiquitination Source: UniProtKB
  10. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  11. protein K48-linked deubiquitination Source: ParkinsonsUK-UCL
  12. protein K63-linked deubiquitination Source: ParkinsonsUK-UCL
  13. regulation of cell-substrate adhesion Source: ParkinsonsUK-UCL
  14. regulation of transcription, DNA-templated Source: UniProtKB-KW
  15. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

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, Sca3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 6

Organism-specific databases

RGDi621567. Atxn3.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. cytosol Source: ParkinsonsUK-UCL
  2. mitochondrial matrix Source: Ensembl
  3. mitochondrial membrane Source: Ensembl
  4. nuclear inclusion body Source: Ensembl
  5. nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi14 – 141C → A or S: Loss of enzyme activity. 1 Publication
Mutagenesisi119 – 1191H → A: Loss of enzyme activity. 1 Publication
Mutagenesisi134 – 1341N → A: Loss of enzyme activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 355355Ataxin-3PRO_0000053833Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki1 – 1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki200 – 200Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei268 – 2681PhosphoserineBy similarity
Modified residuei273 – 2731PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO35815.
PRIDEiO35815.

PTM databases

PhosphoSiteiO35815.

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

GenevestigatoriO35815.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi248780. 2 interactions.
STRINGi10116.ENSRNOP00000007505.

Structurei

3D structure databases

ProteinModelPortaliO35815.
SMRiO35815. Positions 1-185.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 180180JosephinPROSITE-ProRule annotationAdd
BLAST
Domaini224 – 24320UIM 1PROSITE-ProRule annotationAdd
BLAST
Domaini244 – 26320UIM 2PROSITE-ProRule annotationAdd
BLAST
Domaini329 – 34820UIM 3PROSITE-ProRule annotationAdd
BLAST

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 (By similarity).By similarity

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG327234.
GeneTreeiENSGT00390000001830.
HOGENOMiHOG000006034.
HOVERGENiHBG025648.
InParanoidiO35815.
KOiK11863.
OMAiEDEENFQ.
OrthoDBiEOG779NZ3.
PhylomeDBiO35815.
TreeFamiTF314228.

Family and domain databases

InterProiIPR006155. Josephin.
IPR003903. Ubiquitin-int_motif.
[Graphical view]
PfamiPF02099. Josephin. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
PRINTSiPR01233. JOSEPHIN.
SMARTiSM00726. UIM. 3 hits.
[Graphical view]
PROSITEiPS50957. JOSEPHIN. 1 hit.
PS50330. UIM. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35815-1 [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 RVLEAADGPG MFDDDEDDLQ RALAMSRQEI DMEDEEADLR
260 270 280 290 300
RAIQLSMQGS SRGMCEDSPQ TSSTDLSSEE LRKRREAYFE KQQHQQQEAD
310 320 330 340 350
RPGYLSYPCE RPTTSSGGLR SNQAGNAMSE EDVLRATVTV SLETAKDSLK

AERKK
Length:355
Mass (Da):40,446
Last modified:January 1, 1998 - v1
Checksum:i87B6A6EE54FF29F5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y12319 mRNA. Translation: CAA72986.1.
RefSeqiNP_067734.1. NM_021702.1.
UniGeneiRn.42932.

Genome annotation databases

EnsembliENSRNOT00000007505; ENSRNOP00000007505; ENSRNOG00000005470.
GeneIDi60331.
KEGGirno:60331.
UCSCiRGD:621567. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y12319 mRNA. Translation: CAA72986.1.
RefSeqiNP_067734.1. NM_021702.1.
UniGeneiRn.42932.

3D structure databases

ProteinModelPortaliO35815.
SMRiO35815. Positions 1-185.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248780. 2 interactions.
STRINGi10116.ENSRNOP00000007505.

Protein family/group databases

MEROPSiC86.001.

PTM databases

PhosphoSiteiO35815.

Proteomic databases

PaxDbiO35815.
PRIDEiO35815.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000007505; ENSRNOP00000007505; ENSRNOG00000005470.
GeneIDi60331.
KEGGirno:60331.
UCSCiRGD:621567. rat.

Organism-specific databases

CTDi4287.
RGDi621567. Atxn3.

Phylogenomic databases

eggNOGiNOG327234.
GeneTreeiENSGT00390000001830.
HOGENOMiHOG000006034.
HOVERGENiHBG025648.
InParanoidiO35815.
KOiK11863.
OMAiEDEENFQ.
OrthoDBiEOG779NZ3.
PhylomeDBiO35815.
TreeFamiTF314228.

Miscellaneous databases

NextBioi611965.
PROiO35815.

Gene expression databases

GenevestigatoriO35815.

Family and domain databases

InterProiIPR006155. Josephin.
IPR003903. Ubiquitin-int_motif.
[Graphical view]
PfamiPF02099. Josephin. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
PRINTSiPR01233. JOSEPHIN.
SMARTiSM00726. UIM. 3 hits.
[Graphical view]
PROSITEiPS50957. JOSEPHIN. 1 hit.
PS50330. UIM. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Characterization of the rat spinocerebellar ataxia type 3 gene."
    Schmitt I., Brattig T., Gossen M., Riess O.
    Neurogenetics 1:103-112(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain and Testis.
  2. "Josephin domain-containing proteins from a variety of species are active de-ubiquitination enzymes."
    Tzvetkov N., Breuer P.
    Biol. Chem. 388:973-978(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-14; HIS-119 AND ASN-134, FUNCTION.
  3. "Structural modeling of ataxin-3 reveals distant homology to adaptins."
    Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U., Lengauer T.
    Proteins 50:355-370(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.

Entry informationi

Entry nameiATX3_RAT
AccessioniPrimary (citable) accession number: O35815
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: January 1, 1998
Last modified: January 7, 2015
This is version 103 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.