O35815 (ATX3_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ataxin-3
EC=3.4.19.12

Alternative name(s):
Machado-Joseph disease protein 1 homolog

Gene names

Name:	Atxn3
Synonyms:	Mjd, Sca3

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	355 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Domain	Repeat
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from electronic annotation. Source: Compara cellular response to heat Inferred from electronic annotation. Source: Compara cellular response to misfolded protein Inferred from sequence or structural similarity. Source: UniProtKB exploration behavior Inferred from electronic annotation. Source: Compara histone H3 deacetylation Inferred from expression pattern PubMed 17079677. Source: RGD intermediate filament cytoskeleton organization Inferred from electronic annotation. Source: Compara microtubule cytoskeleton organization Inferred from electronic annotation. Source: Compara 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 proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell-substrate adhesion Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrial matrix Inferred from electronic annotation. Source: Compara mitochondrial membrane Inferred from electronic annotation. Source: Compara nuclear inclusion body Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 17079677. Source: RGD
Molecular_function	RNA polymerase II regulatory region DNA binding Inferred from direct assay PubMed 17079677. Source: RGD omega peptidase activity Inferred from electronic annotation. Source: InterPro 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 355	355	Ataxin-3		PRO_0000053833
Regions
	Domain	1 – 180	180	Josephin
	Repeat	224 – 243	20	UIM 1
	Repeat	244 – 263	20	UIM 2
	Repeat	329 – 348	20	UIM 3
Sites
	Active site	14	1	Nucleophile
	Active site	119	1	Proton acceptor By similarity
	Active site	134	1	By similarity
Amino acid modifications
	Modified residue	268	1	Phosphoserine By similarity
	Modified residue	273	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	14	1	C → A or S: Loss of enzyme activity. Ref.2
	Mutagenesis	119	1	H → A: Loss of enzyme activity. Ref.2
	Mutagenesis	134	1	N → A: Loss of enzyme activity. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O35815 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 87B6A6EE54FF29F5	FASTA	355	40,446
	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

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.
IPI	IPI00213014.
RefSeq	NP_067734.1. NM_021702.1.
UniGene	Rn.42932.
3D structure databases
ProteinModelPortal	O35815.
SMR	O35815. Positions 1-185.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000007505.
Protein family/group databases
MEROPS	C86.001.
PTM databases
PhosphoSite	O35815.
Proteomic databases
PaxDb	O35815.
PRIDE	O35815.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000007505; ENSRNOP00000007505; ENSRNOG00000005470.
GeneID	60331.
KEGG	rno:60331.
UCSC	RGD:621567. rat.
Organism-specific databases
CTD	4287.
RGD	621567. Atxn3.
Phylogenomic databases
eggNOG	NOG327234.
GeneTree	ENSGT00390000001830.
HOGENOM	HOG000006034.
HOVERGEN	HBG025648.
InParanoid	O35815.
KO	K11863.
OMA	LQAAMNM.
OrthoDB	EOG4SBDZS.
Gene expression databases
Genevestigator	O35815.
GermOnline	ENSRNOG00000005470. Rattus norvegicus.
Family and domain databases
InterPro	IPR006155. Josephin. IPR003903. Ubiquitin-int_motif. [Graphical view]
Pfam	PF02099. Josephin. 1 hit. PF02809. UIM. 3 hits. [Graphical view]
PRINTS	PR01233. JOSEPHIN.
SMART	SM00726. UIM. 3 hits. [Graphical view]
PROSITE	PS50957. JOSEPHIN. 1 hit. PS50330. UIM. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	611965.

Entry information

Entry name

ATX3_RAT

Accession

Primary (citable) accession number: O35815

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program