Ataxin 3

Ataxin-3 is a protein that in humans is encoded by the ATXN3 gene.

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
Gene location (Human) Chr. Chromosome 14 (human) Band 14q32.12 Start 92,044,496 bp End 92,106,621 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 E Start 101,918,901 bp End 101,958,246 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon endothelial cell sural nerve monocyte pericardium right uterine tube Brodmann area 23 saphenous vein skin of abdomen corpus callosum Top expressed in spermatid morula superior cervical ganglion aortic valve ascending aorta interventricular septum cumulus cell spermatocyte hand pineal gland 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
Wikidata
View/Edit Human View/Edit Mouse

Clinical significance

Machado–Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by the ATXN3 gene contains 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 type I known as a 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.

Interactions

Ataxin 3 has been shown to interact with:

• RAD23A,
• RAD23B, and
• VCP.

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:10.1016/S0168-0102(97)00056-4. PMID 9274833. S2CID 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:10.1093/hmg/4.6.1001. PMID 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". American Journal of Human Genetics. 56 (1): 193–201. PMC 1801316. PMID 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:10.1038/ng1194-221. PMID 7874163. S2CID 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:10.1016/0378-1119(94)90802-8. PMID 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:10.1038/ng0696-196. PMID 8640226. S2CID 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:10.1002/ana.410410408. PMID 9124802. S2CID 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:10.1016/S0378-1119(97)00411-3. PMID 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". The Journal of Biological Chemistry. 273 (15): 9158–67. doi:10.1074/jbc.273.15.9158. PMID 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". Human Molecular Genetics. 7 (6): 991–7. CiteSeerX 10.1.1.588.3970. doi:10.1093/hmg/7.6.991. PMID 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:10.1093/hmg/9.12.1795. PMID 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". Journal of Human Genetics. 46 (7): 413–22. doi:10.1007/s100380170060. PMID 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". Proceedings of the National Academy of Sciences of the United States of America. 99 (14): 9310–5. Bibcode:2002PNAS...99.9310C. doi:10.1073/pnas.152101299. PMC 123137. PMID 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". Neurobiology of Disease. 10 (2): 88–99. doi:10.1006/nbdi.2002.0502. PMID 12127147. S2CID 25183307.
• Li F, Macfarlan T, Pittman RN, Chakravarti D (Nov 2002). "Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities". The Journal of Biological Chemistry. 277 (47): 45004–12. doi:10.1074/jbc.M205259200. PMID 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:10.1002/prot.10280. PMID 12486728. S2CID 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". The Journal of Biological Chemistry. 278 (34): 31554–63. doi:10.1074/jbc.M304205200. PMID 12766160.

External links

• GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 3
• Human ATXN3 genome location and ATXN3 gene details page in the UCSC Genome Browser.