Ataxin 1

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Protein ATXN1 PDB 1oa8.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases ATXN1, ATX1, D6S504E, SCA1, ataxin 1
External IDs OMIM: 601556 MGI: 104783 HomoloGene: 281 GeneCards: ATXN1
Gene location (Human)
Chromosome 6 (human)
Chr. Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for ATXN1
Genomic location for ATXN1
Band 6p22.3 Start 16,299,112 bp[1]
End 16,761,491 bp[1]
RNA expression pattern
PBB GE ATXN1 203231 s at fs.png

PBB GE ATXN1 203232 s at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 6: 16.3 – 16.76 Mb Chr 6: 45.55 – 45.97 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Ataxin-1 is a DNA-binding protein which in humans is encoded by the ATXN1 gene.[5][6]

Mutations in ataxin-1 cause spinocerebellar ataxia type 1, an inherited neurodegenerative disease characterized by a progressive loss of cerebellar neurons, particularly Purkinje neurons.


ATXN1 is conserved across multiple species, including humans, mice, and Drosophila.[7]

In humans, ATXN1 is located on the short arm of chromosome 6. The gene contains 9 exons, two of which are protein-coding. There is a CAG repeat in the coding sequence which is longer in humans than other species (6-38 uninterrupted CAG repeats in healthy humans versus 2 in the mouse gene). This repeat is prone to errors in DNA replication and can vary widely in length between individuals.[8]


Notable features of the Ataxin-1 protein structure[9] include:


The function of Ataxin-1 is not completely understood. It appears to be involved in regulating gene expression based on its location in the nucleus of the cell, its association with promoter regions of several genes, and its interactions with transcriptional regulators[10] and parts of the RNA splicing machinery.[11]


Ataxin 1 has been shown to interact with:

Role in disease[edit]

ATXN1 is the gene mutated in spinocerebellar ataxia type 1 (SCA1), a dominantly-inherited, fatal genetic disease in which neurons in the cerebellum and brain stem degenerate over the course of years or decades.[8] SCA1 is a trinucleotide repeat disorder caused by expansion of the CAG repeat in ATXN1; this leads to an expanded polyglutamine tract in the protein. This elongation is variable in length, with as few as 6 and as many as 81 repeats reported in humans.[17][8] Repeats of 39 or more uninterrupted CAG triplets cause disease, and longer repeat tracts are correlated with earlier age of onset and faster progression.[18]

How polyglutamine expansion in Ataxin-1 causes neuronal dysfunction and degeneration is still unclear. Disease likely occurs through the combination of several processes.


Mutant Ataxin-1 protein spontaneously misfolds and forms aggregates in cells,[19] much like other disease-associated proteins such as tau, , and huntingtin. This led to the hypothesis that the aggregates are toxic to neurons, but it has been shown in mice that aggregation is not required for pathogenesis.[20] Other neuronal proteins can modulate the formation of Ataxin-1 aggregates and this in turn may affect aggregate-induced toxicity.[21]

[22] [23] [24] [25] [26] [27]

Altered protein-protein interactions[edit]

Soluble Ataxin-1 interacts with many other proteins. Polyglutamine expansion in Ataxin-1 can affect these interactions, sometimes causing loss of function (where the protein fails to perform one of its normal functions) and sometimes causing toxic gain of function (where the protein binds too strongly or to an inappropriate target).[28] This, in turn, could alter the expression of the genes ataxin-1 regulates, leading to disease.


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000124788 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046876 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Volz A, Fonatsch C, Ziegler A (Jun 1992). "Regional mapping of the gene for autosomal dominant spinocerebellar ataxia (SCA1) by localizing the closely linked D6S89 locus to 6p24.2----p23.05". Cytogenetics and Cell Genetics. 60 (1): 37–9. doi:10.1159/000133291. PMID 1582256. 
  6. ^ "Entrez Gene: ATXN1 ataxin 1". 
  7. ^ "Atx-1 - Ataxin 1 - Drosophila melanogaster (Fruit fly) - Atx-1 gene & protein". Retrieved 2018-01-11. 
  8. ^ a b c Orr HT, Chung MY, Banfi S, Kwiatkowski TJ, Servadio A, Beaudet AL, McCall AE, Duvick LA, Ranum LP, Zoghbi HY (July 1993). "Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1". Nature Genetics. 4 (3): 221–6. doi:10.1038/ng0793-221. PMID 8358429. 
  9. ^ Zoghbi HY, Orr HT (March 2009). "Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1". The Journal of Biological Chemistry. 284 (12): 7425–9. doi:10.1074/jbc.r800041200. PMID 18957430. 
  10. ^ Lam YC, Bowman AB, Jafar-Nejad P, Lim J, Richman R, Fryer JD, Hyun ED, Duvick LA, Orr HT, Botas J, Zoghbi HY (December 2006). "ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology". Cell. 127 (7): 1335–47. doi:10.1016/j.cell.2006.11.038. PMID 17190598. 
  11. ^ Kim E, Lee Y, Choi S, Song JJ (July 2014). "Structural basis of the phosphorylation dependent complex formation of neurodegenerative disease protein Ataxin-1 and RBM17". Biochemical and Biophysical Research Communications. 449 (4): 399–404. doi:10.1016/j.bbrc.2014.05.063. PMID 24858692. 
  12. ^ Suter B, Fontaine JF, Yildirimman R, Raskó T, Schaefer MH, Rasche A, Porras P, Vázquez-Álvarez BM, Russ J, Rau K, Foulle R, Zenkner M, Saar K, Herwig R, Andrade-Navarro MA, Wanker EE (2013). "Development and application of a DNA microarray-based yeast two-hybrid system". Nucleic Acids Research. 41 (3): 1496–507. doi:10.1093/nar/gks1329. PMC 3561971Freely accessible. PMID 23275563. 
  13. ^ Hong S, Ka S, Kim S, Park Y, Kang S (May 2003). "p80 coilin, a coiled body-specific protein, interacts with ataxin-1, the SCA1 gene product". Biochimica et Biophysica Acta. 1638 (1): 35–42. doi:10.1016/s0925-4439(03)00038-3. PMID 12757932. 
  14. ^ a b Hong S, Lee S, Cho SG, Kang S (June 2008). "UbcH6 interacts with and ubiquitinates the SCA1 gene product ataxin-1". Biochemical and Biophysical Research Communications. 371 (2): 256–60. doi:10.1016/j.bbrc.2008.04.066. PMID 18439907. 
  15. ^ Koshy B, Matilla T, Burright EN, Merry DE, Fischbeck KH, Orr HT, Zoghbi HY (September 1996). "Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products interact with glyceraldehyde-3-phosphate dehydrogenase". Human Molecular Genetics. 5 (9): 1311–8. doi:10.1093/hmg/5.9.1311. PMID 8872471. 
  16. ^ Hong S, Kim SJ, Ka S, Choi I, Kang S (June 2002). "USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product". Molecular and Cellular Neurosciences. 20 (2): 298–306. doi:10.1006/mcne.2002.1103. PMID 12093161. 
  17. ^ Matilla T, Volpini V, Genís D, Rosell J, Corral J, Dávalos A, Molins A, Estivill X (December 1993). "Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias". Human Molecular Genetics. 2 (12): 2123–8. PMID 8111382. 
  18. ^ Donato SD, Mariotti C, Taroni F (2012-01-01). Dürr SH, ed. Handbook of Clinical Neurology. Ataxic Disorders. 103. Elsevier. pp. 399–421. 
  19. ^ Shastry BS (July 2003). "Neurodegenerative disorders of protein aggregation". Neurochemistry International. 43 (1): 1–7. doi:10.1016/s0197-0186(02)00196-1. PMID 12605877. 
  20. ^ Klement IA, Skinner PJ, Kaytor MD, Yi H, Hersch SM, Clark HB, Zoghbi HY, Orr HT (1998). "Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice". Cell. 95 (1): 41–53. doi:10.1016/s0092-8674(00)81781-x. PMID 9778246. 
  21. ^ Petrakis S, Raskó T, Russ J, Friedrich RP, Stroedicke M, Riechers SP, et al. (Aug 2012). "Identification of human proteins that modify misfolding and proteotoxicity of pathogenic ataxin-1". PLoS Genetics. 8 (8): e1002897. doi:10.1371/journal.pgen.1002897. PMC 3420947Freely accessible. PMID 22916034. 
  22. ^ Al-Ramahi I, Lam YC, Chen HK, de Gouyon B, Zhang M, Pérez AM, Branco J, de Haro M, Patterson C, Zoghbi HY, Botas J (September 2006). "CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation". The Journal of Biological Chemistry. 281 (36): 26714–24. doi:10.1074/jbc.M601603200. PMID 16831871. 
  23. ^ de Chiara C, Menon RP, Dal Piaz F, Calder L, Pastore A (December 2005). "Polyglutamine is not all: the functional role of the AXH domain in the ataxin-1 protein". Journal of Molecular Biology. 354 (4): 883–93. doi:10.1016/j.jmb.2005.09.083. PMID 16277991. 
  24. ^ Tsuda H, Jafar-Nejad H, Patel AJ, Sun Y, Chen HK, Rose MF, Venken KJ, Botas J, Orr HT, Bellen HJ, Zoghbi HY (August 2005). "The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins". Cell. 122 (4): 633–44. doi:10.1016/j.cell.2005.06.012. PMID 16122429. 
  25. ^ Mizutani A, Wang L, Rajan H, Vig PJ, Alaynick WA, Thaler JP, Tsai CC (September 2005). "Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1". The EMBO Journal. 24 (18): 3339–51. doi:10.1038/sj.emboj.7600785. PMC 1224676Freely accessible. PMID 16121196. 
  26. ^ Park Y, Hong S, Kim SJ, Kang S (February 2005). "Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product". Molecules and Cells. 19 (1): 23–30. PMID 15750336. 
  27. ^ Irwin S, Vandelft M, Pinchev D, Howell JL, Graczyk J, Orr HT, Truant R (January 2005). "RNA association and nucleocytoplasmic shuttling by ataxin-1". Journal of Cell Science. 118 (Pt 1): 233–42. doi:10.1242/jcs.01611. PMID 15615787. 
  28. ^ Lim J, Crespo-Barreto J, Jafar-Nejad P, Bowman AB, Richman R, Hill DE, Orr HT, Zoghbi HY (April 2008). "Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1". Nature. 452 (7188): 713–8. doi:10.1038/nature06731. PMC 2377396Freely accessible. PMID 18337722. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.