Biology:Ataxin 3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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

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

• "Machado-Joseph disease gene products carrying different carboxyl termini". Neuroscience Research 28 (4): 373–7. Aug 1997. doi:10.1016/S0168-0102(97)00056-4. PMID 9274833. 
• "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. Jun 1995. doi:10.1093/hmg/4.6.1001. PMID 7655453. 
• "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. Jan 1995. PMID 7825578. 
• "CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1". Nature Genetics 8 (3): 221–8. Nov 1994. doi:10.1038/ng1194-221. PMID 7874163. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. Jan 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo". Nature Genetics 13 (2): 196–202. Jun 1996. doi:10.1038/ng0696-196. PMID 8640226. 
• "Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain". Annals of Neurology 41 (4): 453–62. Apr 1997. doi:10.1002/ana.410410408. PMID 9124802. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. Oct 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "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. Apr 1998. doi:10.1074/jbc.273.15.9158. PMID 9535906. 
• "Ataxin-3 is transported into the nucleus and associates with the nuclear matrix". Human Molecular Genetics 7 (6): 991–7. Jun 1998. doi:10.1093/hmg/7.6.991. PMID 9580663. 
• "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. Jul 2000. doi:10.1093/hmg/9.12.1795. PMID 10915768. 
• "The genomic structure and expression of MJD, the Machado-Joseph disease gene". Journal of Human Genetics 46 (7): 413–22. 2001. doi:10.1007/s100380170060. PMID 11450850. 
• "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. Jul 2002. doi:10.1073/pnas.152101299. PMID 12084819. Bibcode: 2002PNAS...99.9310C. 
• "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. Jul 2002. doi:10.1006/nbdi.2002.0502. PMID 12127147. 
• "Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities". The Journal of Biological Chemistry 277 (47): 45004–12. Nov 2002. doi:10.1074/jbc.M205259200. PMID 12297501. 
• "Structural modeling of ataxin-3 reveals distant homology to adaptins". Proteins 50 (2): 355–70. Feb 2003. doi:10.1002/prot.10280. PMID 12486728. 
• "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. Aug 2003. 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.