# Ataxin 3

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Protein-coding gene in the species Homo sapiens

ATXN3 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1YZB, 2AGA, 2DOS, 2JRI, 2KLZ, 4WTH, 4YS9 Identifiers Aliases ATXN3, AT3, ATX3, JOS, MJD, MJD1, SCA3, Ataxin 3 External IDs OMIM: 607047; MGI: 1099442; HomoloGene: 3658; GeneCards: ATXN3; OMA:ATXN3 - orthologs Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q32.12 Start 92,044,496 bp[1] End 92,106,621 bp[1] Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 E Start 101,918,901 bp[2] End 101,958,246 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon epithelium of colon tendon of biceps brachii gonad endothelial cell testicle sural nerve monocyte pericardium right uterine tube Top expressed in spermatid morula superior cervical ganglion aortic valve ascending aorta interventricular septum cumulus cell spermatocyte mesenteric lymph nodes epithelium of small intestine More reference expression data BioGPS More reference expression data Gene ontology Molecular function Lys63-specific deubiquitinase activity cysteine-type peptidase activity ATPase binding Lys48-specific deubiquitinase activity peptidase activity protein binding identical protein binding hydrolase activity thiol-dependent deubiquitinase ubiquitin protein ligase binding histone deacetylase activity Cellular component endoplasmic reticulum membrane nuclear matrix nucleoplasm nucleus nucleolus cytosol plasma membrane cytoplasm mitochondrial matrix mitochondrial membranes nuclear inclusion body Biological process nucleotide-excision repair regulation of transcription, DNA-templated protein K48-linked deubiquitination positive regulation of ERAD pathway transcription, DNA-templated nervous system development proteolysis protein K63-linked deubiquitination intermediate filament cytoskeleton organization protein localization to cytosolic proteasome complex involved in ERAD pathway microtubule cytoskeleton organization actin cytoskeleton organization chemical synaptic transmission protein deubiquitination ubiquitin-dependent protein catabolic process protein quality control for misfolded or incompletely synthesized proteins regulation of cell-substrate adhesion cellular response to heat monoubiquitinated protein deubiquitination proteasome-mediated ubiquitin-dependent protein catabolic process cellular response to misfolded protein exploration behavior histone H3 deacetylation Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 4287 110616 Ensembl ENSG00000066427 ENSMUSG00000021189 UniProt P54252 Q4VBR4 Q9CVD2 RefSeq (mRNA) NM_001024631 NM_001127696 NM_001127697 NM_001164774 NM_001164776 NM_001164777 NM_001164778 NM_001164779 NM_001164780 NM_001164781 NM_001164782 NM_004993 NM_030660 NM_001167914 NM_029705 RefSeq (protein) NP_001121168 NP_001121169 NP_001158246 NP_001158248 NP_001158249 NP_001158250 NP_001158251 NP_001158252 NP_001158253 NP_001158254 NP_004984 NP_109376 NP_001161386 NP_083981 Location (UCSC) Chr 14: 92.04 – 92.11 Mb Chr 12: 101.92 – 101.96 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**Ataxin-3** is a [protein](/source/Protein) that in humans is encoded by the *ATXN3* [gene](/source/Gene).[5][6]

## Clinical significance

[Machado–Joseph disease](/source/Machado%E2%80%93Joseph_disease), also known as spinocerebellar ataxia type 3, is an [autosomal dominant](/source/Autosomal_dominant) neurologic disorder. The protein encoded by the *ATXN3* gene contains [CAG repeats](/source/CAG_repeats) in the coding region, and the expansion of these repeats from the normal 13-36 to 68-79 is the cause of Machado–Joseph disease. This disorder is thus a [trinucleotide repeat disorder](/source/Trinucleotide_repeat_disorder) type I known as a [polyglutamine (PolyQ) disease](/source/Trinucleotide_repeat_disorder#Polyglutamine_(PolyQ)_disease). There is an inverse correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[6]

## Interactions

Ataxin 3 has been shown to [interact](/source/Protein-protein_interaction) with:

- [RAD23A](/source/RAD23A),[7]

- [RAD23B](/source/RAD23B),[7] and

- [VCP](/source/Valosin-containing_protein).[8][9]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000066427](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000066427) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000021189](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000021189) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=4287). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=110616). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid8358439_5-0)** Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, Shimazaki H, Soutome M, Endo K, Ohta S (Jul 1993). "The gene for Machado-Joseph disease maps to human chromosome 14q". *Nature Genetics*. **4** (3): 300–4. [doi](/source/Doi_(identifier)):[10.1038/ng0793-300](https://doi.org/10.1038%2Fng0793-300). [PMID](/source/PMID_(identifier)) [8358439](https://pubmed.ncbi.nlm.nih.gov/8358439). [S2CID](/source/S2CID_(identifier)) [27424416](https://api.semanticscholar.org/CorpusID:27424416).

1. ^ [***a***](#cite_ref-EntrezGene_6-0) [***b***](#cite_ref-EntrezGene_6-1) ["Entrez Gene: ATXN3 ataxin 3"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4287).

1. ^ [***a***](#cite_ref-pmid10915768_7-0) [***b***](#cite_ref-pmid10915768_7-1) Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". *Human Molecular Genetics*. **9** (12): 1795–803. [doi](/source/Doi_(identifier)):[10.1093/hmg/9.12.1795](https://doi.org/10.1093%2Fhmg%2F9.12.1795). [PMID](/source/PMID_(identifier)) [10915768](https://pubmed.ncbi.nlm.nih.gov/10915768).

1. **[^](#cite_ref-pmid12944474_8-0)** Doss-Pepe EW, Stenroos ES, Johnson WG, Madura K (Sep 2003). ["Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193705). *Molecular and Cellular Biology*. **23** (18): 6469–83. [doi](/source/Doi_(identifier)):[10.1128/MCB.23.18.6469-6483.2003](https://doi.org/10.1128%2FMCB.23.18.6469-6483.2003). [PMC](/source/PMC_(identifier)) [193705](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193705). [PMID](/source/PMID_(identifier)) [12944474](https://pubmed.ncbi.nlm.nih.gov/12944474).

1. **[^](#cite_ref-pmid18199748_9-0)** Wang Q, Li L, Ye Y (Mar 2008). ["Inhibition of p97-dependent protein degradation by Eeyarestatin I"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276333). *The Journal of Biological Chemistry*. **283** (12): 7445–54. [doi](/source/Doi_(identifier)):[10.1074/jbc.M708347200](https://doi.org/10.1074%2Fjbc.M708347200). [PMC](/source/PMC_(identifier)) [2276333](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276333). [PMID](/source/PMID_(identifier)) [18199748](https://pubmed.ncbi.nlm.nih.gov/18199748).

## Further reading

- Goto J, Watanabe M, Ichikawa Y, Yee SB, Ihara N, Endo K, Igarashi S, Takiyama Y, Gaspar C, Maciel P, Tsuji S, Rouleau GA, Kanazawa I (Aug 1997). "Machado-Joseph disease gene products carrying different carboxyl termini". *Neuroscience Research*. **28** (4): 373–7. [doi](/source/Doi_(identifier)):[10.1016/S0168-0102(97)00056-4](https://doi.org/10.1016%2FS0168-0102%2897%2900056-4). [PMID](/source/PMID_(identifier)) [9274833](https://pubmed.ncbi.nlm.nih.gov/9274833). [S2CID](/source/S2CID_(identifier)) [27241785](https://api.semanticscholar.org/CorpusID:27241785).

- Schöls L, Vieira-Saecker AM, Schöls S, Przuntek H, Epplen JT, Riess O (Jun 1995). "Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients". *Human Molecular Genetics*. **4** (6): 1001–5. [doi](/source/Doi_(identifier)):[10.1093/hmg/4.6.1001](https://doi.org/10.1093%2Fhmg%2F4.6.1001). [PMID](/source/PMID_(identifier)) [7655453](https://pubmed.ncbi.nlm.nih.gov/7655453).

- Stevanin G, Cancel G, Dürr A, Chneiweiss H, Dubourg O, Weissenbach J, Cann HM, Agid Y, Brice A (Jan 1995). ["The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801316). *American Journal of Human Genetics*. **56** (1): 193–201. [PMC](/source/PMC_(identifier)) [1801316](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801316). [PMID](/source/PMID_(identifier)) [7825578](https://pubmed.ncbi.nlm.nih.gov/7825578).

- Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I (Nov 1994). "CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1". *Nature Genetics*. **8** (3): 221–8. [doi](/source/Doi_(identifier)):[10.1038/ng1194-221](https://doi.org/10.1038%2Fng1194-221). [PMID](/source/PMID_(identifier)) [7874163](https://pubmed.ncbi.nlm.nih.gov/7874163). [S2CID](/source/S2CID_(identifier)) [29188685](https://api.semanticscholar.org/CorpusID:29188685).

- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". *Gene*. **138** (1–2): 171–4. [doi](/source/Doi_(identifier)):[10.1016/0378-1119(94)90802-8](https://doi.org/10.1016%2F0378-1119%2894%2990802-8). [PMID](/source/PMID_(identifier)) [8125298](https://pubmed.ncbi.nlm.nih.gov/8125298).

- Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A (Jun 1996). "Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo". *Nature Genetics*. **13** (2): 196–202. [doi](/source/Doi_(identifier)):[10.1038/ng0696-196](https://doi.org/10.1038%2Fng0696-196). [PMID](/source/PMID_(identifier)) [8640226](https://pubmed.ncbi.nlm.nih.gov/8640226). [S2CID](/source/S2CID_(identifier)) [21966287](https://api.semanticscholar.org/CorpusID:21966287).

- Paulson HL, Das SS, Crino PB, Perez MK, Patel SC, Gotsdiner D, Fischbeck KH, Pittman RN (Apr 1997). "Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain". *Annals of Neurology*. **41** (4): 453–62. [doi](/source/Doi_(identifier)):[10.1002/ana.410410408](https://doi.org/10.1002%2Fana.410410408). [PMID](/source/PMID_(identifier)) [9124802](https://pubmed.ncbi.nlm.nih.gov/9124802). [S2CID](/source/S2CID_(identifier)) [43460483](https://api.semanticscholar.org/CorpusID:43460483).

- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". *Gene*. **200** (1–2): 149–56. [doi](/source/Doi_(identifier)):[10.1016/S0378-1119(97)00411-3](https://doi.org/10.1016%2FS0378-1119%2897%2900411-3). [PMID](/source/PMID_(identifier)) [9373149](https://pubmed.ncbi.nlm.nih.gov/9373149).

- Wellington CL, Ellerby LM, Hackam AS, Margolis RL, Trifiro MA, Singaraja R, McCutcheon K, Salvesen GS, Propp SS, Bromm M, Rowland KJ, Zhang T, Rasper D, Roy S, Thornberry N, Pinsky L, Kakizuka A, Ross CA, Nicholson DW, Bredesen DE, Hayden MR (Apr 1998). ["Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract"](https://doi.org/10.1074%2Fjbc.273.15.9158). *The Journal of Biological Chemistry*. **273** (15): 9158–67. [doi](/source/Doi_(identifier)):[10.1074/jbc.273.15.9158](https://doi.org/10.1074%2Fjbc.273.15.9158). [PMID](/source/PMID_(identifier)) [9535906](https://pubmed.ncbi.nlm.nih.gov/9535906).

- Tait D, Riccio M, Sittler A, Scherzinger E, Santi S, Ognibene A, Maraldi NM, Lehrach H, Wanker EE (Jun 1998). ["Ataxin-3 is transported into the nucleus and associates with the nuclear matrix"](https://doi.org/10.1093%2Fhmg%2F7.6.991). *Human Molecular Genetics*. **7** (6): 991–7. [CiteSeerX](/source/CiteSeerX_(identifier)) [10.1.1.588.3970](https://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.588.3970). [doi](/source/Doi_(identifier)):[10.1093/hmg/7.6.991](https://doi.org/10.1093%2Fhmg%2F7.6.991). [PMID](/source/PMID_(identifier)) [9580663](https://pubmed.ncbi.nlm.nih.gov/9580663).

- Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". *Human Molecular Genetics*. **9** (12): 1795–803. [doi](/source/Doi_(identifier)):[10.1093/hmg/9.12.1795](https://doi.org/10.1093%2Fhmg%2F9.12.1795). [PMID](/source/PMID_(identifier)) [10915768](https://pubmed.ncbi.nlm.nih.gov/10915768).

- Ichikawa Y, Goto J, Hattori M, Toyoda A, Ishii K, Jeong SY, Hashida H, Masuda N, Ogata K, Kasai F, Hirai M, Maciel P, Rouleau GA, Sakaki Y, Kanazawa I (2001). ["The genomic structure and expression of MJD, the Machado-Joseph disease gene"](https://doi.org/10.1007%2Fs100380170060). *Journal of Human Genetics*. **46** (7): 413–22. [doi](/source/Doi_(identifier)):[10.1007/s100380170060](https://doi.org/10.1007%2Fs100380170060). [PMID](/source/PMID_(identifier)) [11450850](https://pubmed.ncbi.nlm.nih.gov/11450850).

- Chai Y, Shao J, Miller VM, Williams A, Paulson HL (Jul 2002). ["Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC123137). *Proceedings of the National Academy of Sciences of the United States of America*. **99** (14): 9310–5. [Bibcode](/source/Bibcode_(identifier)):[2002PNAS...99.9310C](https://ui.adsabs.harvard.edu/abs/2002PNAS...99.9310C). [doi](/source/Doi_(identifier)):[10.1073/pnas.152101299](https://doi.org/10.1073%2Fpnas.152101299). [PMC](/source/PMC_(identifier)) [123137](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC123137). [PMID](/source/PMID_(identifier)) [12084819](https://pubmed.ncbi.nlm.nih.gov/12084819).

- Yoshida H, Yoshizawa T, Shibasaki F, Shoji S, Kanazawa I (Jul 2002). ["Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch"](https://doi.org/10.1006%2Fnbdi.2002.0502). *Neurobiology of Disease*. **10** (2): 88–99. [doi](/source/Doi_(identifier)):[10.1006/nbdi.2002.0502](https://doi.org/10.1006%2Fnbdi.2002.0502). [PMID](/source/PMID_(identifier)) [12127147](https://pubmed.ncbi.nlm.nih.gov/12127147). [S2CID](/source/S2CID_(identifier)) [25183307](https://api.semanticscholar.org/CorpusID:25183307).

- Li F, Macfarlan T, Pittman RN, Chakravarti D (Nov 2002). ["Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities"](https://doi.org/10.1074%2Fjbc.M205259200). *The Journal of Biological Chemistry*. **277** (47): 45004–12. [doi](/source/Doi_(identifier)):[10.1074/jbc.M205259200](https://doi.org/10.1074%2Fjbc.M205259200). [PMID](/source/PMID_(identifier)) [12297501](https://pubmed.ncbi.nlm.nih.gov/12297501).

- Albrecht M, Hoffmann D, Evert BO, Schmitt I, Wüllner U, Lengauer T (Feb 2003). "Structural modeling of ataxin-3 reveals distant homology to adaptins". *Proteins*. **50** (2): 355–70. [doi](/source/Doi_(identifier)):[10.1002/prot.10280](https://doi.org/10.1002%2Fprot.10280). [PMID](/source/PMID_(identifier)) [12486728](https://pubmed.ncbi.nlm.nih.gov/12486728). [S2CID](/source/S2CID_(identifier)) [25660172](https://api.semanticscholar.org/CorpusID:25660172).

- Marchal S, Shehi E, Harricane MC, Fusi P, Heitz F, Tortora P, Lange R (Aug 2003). ["Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature"](https://doi.org/10.1074%2Fjbc.M304205200). *The Journal of Biological Chemistry*. **278** (34): 31554–63. [doi](/source/Doi_(identifier)):[10.1074/jbc.M304205200](https://doi.org/10.1074%2Fjbc.M304205200). [PMID](/source/PMID_(identifier)) [12766160](https://pubmed.ncbi.nlm.nih.gov/12766160).

## External links

- [GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 3](https://www.ncbi.nlm.nih.gov/books/NBK1196/)

- Human [*ATXN3*](https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=ATXN3) genome location and [*ATXN3*](https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=ATXN3) gene details page in the [UCSC Genome Browser](/source/UCSC_Genome_Browser).

v t e PDB gallery 1yzb: Solution structure of the Josephin domain of Ataxin-3 2aga: De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain 2dos: Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme

v t e Posttranslational modification Chaperones/ protein folding Heat shock proteins/ Chaperonins Hsp10/GroES Hsp27 Hsp47 HSP60/GroEL Hsp40/DnaJ A1 A2 A3 B1 B2 B11 B4 B6 B9 C1 C3 C5 C6 C7 C10 C11 C13 C14 C19 Hsp70 1A 1B 1L 2 4 4L 5 6 7 8 9 12A 14 Hsp90 α1 α2 β ER TRAP1 Other Alpha crystallin Clusterin Survival of motor neuron SMN1 SMN2 Protein targeting Signal peptide Mitochondrial targeting signal Ubiquitin (ubiquitylation) E1 Ubiquitin-activating enzyme UBA1 UBA2 UBA3 UBA5 UBA6 UBA7 ATG7 NAE1 SAE1 E2 Ubiquitin-conjugating enzyme A B C D1 D2 D3 E1 E2 E3 G1 G2 H I J1 J2 K L1 L2 L3 L4 L6 M N O Q1 Q2 R1 (CDC34) R2 S V1 V2 Z E3 Ubiquitin ligase VHL Cullin CBL MDM2 FANCL UBR1 Deubiquitinating enzyme: Ataxin 3 USP6 CYLD ATG3 BIRC6 UFC1 Ubiquitin-like proteins (UBL) SUMO protein (SUMOylation) E1 SUMO-activating enzyme SAE1 SAE2 E2 SUMO-conjugating enzyme UBC9 E3 SUMO ligase PIAS1 PIAS2 PIAS3 PIAS4 Other ISG15 URM1 UFM1 NEDD8 (neddylation) FAT10 ATG8 ATG12 FUB1 MUB UBL5 Prokaryotic ubiquitin-like protein Category Commons

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Adapted from the Wikipedia article [Ataxin 3](https://en.wikipedia.org/wiki/Ataxin_3) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Ataxin_3?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.