Q9CVD2 (ATX3_MOUSE) 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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. Ref.5
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).
Subunit structure	Interacts with DNA repair proteins RAD23A and RAD23B By similarity. Interacts with STUB1/CHIP (when monoubiquitinated). Ref.5
Subcellular location	Nucleus By similarity.
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 (Ref.5).
Post-translational modification	Monoubiquitinated by UBE2W, possibly leading to activate the deubiquitinating enzyme activity.
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 mutant phenotype PubMed 19843543. Source: MGI cellular response to misfolded protein Inferred from mutant phenotype Ref.5. Source: UniProtKB exploration behavior Inferred from mutant phenotype PubMed 17764659. Source: MGI histone H3 deacetylation Inferred from electronic annotation. Source: Compara 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 mutant phenotype Ref.5. Source: UniProtKB monoubiquitinated protein deubiquitination Inferred from direct assay Ref.5. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.5. Source: UniProtKB regulation of cell-substrate adhesion Inferred from mutant phenotype PubMed 20637808. Source: MGI 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 direct assay PubMed 18353661. Source: MGI mitochondrial membrane Inferred from direct assay PubMed 18353661. Source: MGI nuclear inclusion body Inferred from direct assay PubMed 17626202. Source: MGI
Molecular_function	RNA polymerase II regulatory region DNA binding Inferred from electronic annotation. Source: Compara omega peptidase activity Inferred from electronic annotation. Source: InterPro ubiquitin thiolesterase activity Inferred from direct assay Ref.5. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.5. 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_0000053832
Regions
	Domain	1 – 180	180	Josephin
	Repeat	224 – 243	20	UIM 1
	Repeat	244 – 263	20	UIM 2
	Repeat	329 – 348	20	UIM 3
	Compositional bias	282 – 285	4	Poly-Arg
	Compositional bias	292 – 297	6	Poly-Gln
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	219	1	Phosphoserine Ref.2
	Modified residue	268	1	Phosphoserine Ref.3
	Modified residue	273	1	Phosphoserine Ref.3
Experimental info
	Mutagenesis	14	1	C → A: Abolishes deubiquitinating activity. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9CVD2 [UniParc]. Last modified February 28, 2003. Version 2. Checksum: D148DD10EA481D5B	FASTA	355	40,533
	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 RVLEAADGSG IFDEDEDDLQ RALAISRQEI 250 260 270 280 290 300 DMEDEEADLR RAIQLSMQGS SRSMCENSPQ TSSPDLSSEE LRRRREAYFE KQQQQQQEVD 310 320 330 340 350 RPGPLSYPRE RPTTSSGGRR SDQGGDAVSE EDMLRAAVTM SLETAKDNLK AERKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: NOD. Tissue: Stomach and Thymus.
[2]	"Phosphoproteomic analysis of the developing mouse brain." Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P. Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, MASS SPECTROMETRY. Tissue: Embryonic brain.
[3]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268 AND SER-273, MASS SPECTROMETRY. Tissue: Liver.
[4]	"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.
[5]	"Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP." Scaglione K.M., Zavodszky E., Todi S.V., Patury S., Xu P., Rodriguez-Lebron E., Fischer S., Konen J., Djarmati A., Peng J., Gestwicki J.E., Paulson H.L. Mol. Cell 43:599-612(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STUB1, UBIQUITINATION, MUTAGENESIS OF CYS-14.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK008675 mRNA. Translation: BAB25825.3. AK030842 mRNA. Translation: BAC27155.1.
IPI	IPI00138394.
RefSeq	NP_083981.2. NM_029705.3.
UniGene	Mm.485508.
3D structure databases
ProteinModelPortal	Q9CVD2.
SMR	Q9CVD2. Positions 1-171, 220-264.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9CVD2. 1 interaction.
MINT	MINT-2837817.
Protein family/group databases
MEROPS	C86.001.
PTM databases
PhosphoSite	Q9CVD2.
Proteomic databases
PaxDb	Q9CVD2.
PRIDE	Q9CVD2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021606; ENSMUSP00000021606; ENSMUSG00000021189.
GeneID	110616.
KEGG	mmu:110616.
Organism-specific databases
CTD	4287.
MGI	MGI:1099442. Atxn3.
Phylogenomic databases
eggNOG	NOG327234.
GeneTree	ENSGT00390000001830.
HOGENOM	HOG000006034.
HOVERGEN	HBG025648.
InParanoid	Q9CVD2.
KO	K11863.
OMA	LQAAMNM.
OrthoDB	EOG4SBDZS.
Gene expression databases
ArrayExpress	Q9CVD2.
Bgee	Q9CVD2.
CleanEx	MM_ATXN3.
Genevestigator	Q9CVD2.
GermOnline	ENSMUSG00000021189. Mus musculus.
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
ChiTaRS	ATXN3. mouse.
NextBio	364339.
SOURCE	Search...

Entry information

Entry name

ATX3_MOUSE

Accession

Primary (citable) accession number: Q9CVD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	February 28, 2003
Last modified:	April 3, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program