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O35815 (ATX3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ataxin-3

EC=3.4.19.12
Alternative name(s):
Machado-Joseph disease protein 1 homolog
Gene names
Name:Atxn3
Synonyms:Mjd, Sca3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length355 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. Ref.2

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). Ref.2

Subunit structure

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

Subcellular location

Nucleus By similarity.

Tissue specificity

Ubiquitously expressed.

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.

Post-translational modification

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

Sequence similarities

Contains 1 Josephin domain.

Contains 3 UIM (ubiquitin-interacting motif) repeats.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentNucleus
   DomainRepeat
   Molecular functionHydrolase
Protease
Thiol protease
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to heat

Inferred from electronic annotation. Source: Ensembl

cellular response to misfolded protein

Inferred from sequence or structural similarity. Source: UniProtKB

exploration behavior

Inferred from electronic annotation. Source: Ensembl

histone H3 deacetylation

Inferred from expression pattern PubMed 17079677. Source: RGD

misfolded or incompletely synthesized protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

monoubiquitinated protein deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell-substrate adhesion

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentmitochondrial matrix

Inferred from electronic annotation. Source: Ensembl

mitochondrial membrane

Inferred from electronic annotation. Source: Ensembl

nuclear inclusion body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 17079677. Source: RGD

   Molecular_functionRNA polymerase II regulatory region DNA binding

Inferred from direct assay PubMed 17079677. Source: RGD

omega peptidase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 17079677. Source: RGD

ubiquitin protein ligase binding

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin thiolesterase activity

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 355355Ataxin-3
PRO_0000053833

Regions

Domain1 – 180180Josephin
Repeat224 – 24320UIM 1
Repeat244 – 26320UIM 2
Repeat329 – 34820UIM 3

Sites

Active site141Nucleophile
Active site1191Proton acceptor By similarity
Active site1341 By similarity

Amino acid modifications

Modified residue2681Phosphoserine By similarity
Modified residue2731Phosphoserine By similarity
Cross-link1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link200Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Mutagenesis141C → A or S: Loss of enzyme activity. Ref.2
Mutagenesis1191H → A: Loss of enzyme activity. Ref.2
Mutagenesis1341N → A: Loss of enzyme activity. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O35815 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 87B6A6EE54FF29F5

FASTA35540,446
        10         20         30         40         50         60 
MESIFHEKQE GSLCAQHCLN NLLQGEYFSP VELSSIAHQL DEEERLRMAE GGVTSEDYRT 

        70         80         90        100        110        120 
FLQQPSGNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ RLRIDPINER SFICNYKEHW 

       130        140        150        160        170        180 
FTVRKLGKQW FNLNSLLTGP ELISDTYLAL FLAQLQQEGY SIFVVKGDLP DCEADQLLQM 

       190        200        210        220        230        240 
IKVQQMHRPK LIGEELAHLK EQSALKADLE RVLEAADGPG MFDDDEDDLQ RALAMSRQEI 

       250        260        270        280        290        300 
DMEDEEADLR RAIQLSMQGS SRGMCEDSPQ TSSTDLSSEE LRKRREAYFE KQQHQQQEAD 

       310        320        330        340        350 
RPGYLSYPCE RPTTSSGGLR SNQAGNAMSE EDVLRATVTV SLETAKDSLK AERKK 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y12319 mRNA. Translation: CAA72986.1.
RefSeqNP_067734.1. NM_021702.1.
UniGeneRn.42932.

3D structure databases

ProteinModelPortalO35815.
SMRO35815. Positions 1-185.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248780. 2 interactions.
STRING10116.ENSRNOP00000007505.

Protein family/group databases

MEROPSC86.001.

PTM databases

PhosphoSiteO35815.

Proteomic databases

PaxDbO35815.
PRIDEO35815.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000007505; ENSRNOP00000007505; ENSRNOG00000005470.
GeneID60331.
KEGGrno:60331.
UCSCRGD:621567. rat.

Organism-specific databases

CTD4287.
RGD621567. Atxn3.

Phylogenomic databases

eggNOGNOG327234.
GeneTreeENSGT00390000001830.
HOGENOMHOG000006034.
HOVERGENHBG025648.
InParanoidO35815.
KOK11863.
OMALQAAMNM.
OrthoDBEOG779NZ3.
PhylomeDBO35815.
TreeFamTF314228.

Gene expression databases

GenevestigatorO35815.

Family and domain databases

InterProIPR006155. Josephin.
IPR003903. Ubiquitin-int_motif.
[Graphical view]
PfamPF02099. Josephin. 1 hit.
PF02809. UIM. 3 hits.
[Graphical view]
PRINTSPR01233. JOSEPHIN.
SMARTSM00726. UIM. 3 hits.
[Graphical view]
PROSITEPS50957. JOSEPHIN. 1 hit.
PS50330. UIM. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio611965.
PROO35815.

Entry information

Entry nameATX3_RAT
AccessionPrimary (citable) accession number: O35815
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: January 1, 1998
Last modified: June 11, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families