A polyglutamine tract in some species (located near the amino terminal in primates and between the LSm domains in insects)
A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.
Species, tissue, and subcellular distribution
ATXN2 is conserved across eukaryotes. Most vertebrates have two orthologs of the gene (called ATXN2 and ATXN2L in humans), with the exception of birds which only have one. Plant species have two to six ATXN2 orthologs.
Ataxin-2 is involved in regulating mRNA translation through its interactions with the poly(A)-binding protein. It is also involved in the formation of stress granules and P-bodies, which also play roles in RNA regulation.
The polyglutamine tract in human ataxin-2 is unstable and can expand as it is transmitted across generations. Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. Longer expansions can cause spinocerebellar ataxia type 2 (SCA2), a fatal progressive genetic disorder in which neurons degenerate in the cerebellum, inferior olive, pons, and other areas. Symptoms of SCA2 include ataxia (a loss of coordinated movements), parkinsonism, and dementia in some cases. The disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100, and can expand in size when transmitted to successive generations. How the polyglutamine expansion in ataxin-2 leads to these symptoms is unknown.
^Gispert S, Twells R, Orozco G, Brice A, Weber J, Heredero L, Scheufler K, Riley B, Allotey R, Nothers C (July 1993). "Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1". Nature Genetics. 4 (3): 295–9. doi:10.1038/ng0793-295. PMID8358438.
^Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (July 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics. 100 (1): 114–22. doi:10.1007/s004390050476. PMID9225980.
Stevanin G, Dürr A, Brice A (January 2000). "Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology". European Journal of Human Genetics. 8 (1): 4–18. doi:10.1038/sj.ejhg.5200403. PMID10713882.
Pulst SM, Nechiporuk A, Nechiporuk T, Gispert S, Chen XN, Lopes-Cendes I, Pearlman S, Starkman S, Orozco-Diaz G, Lunkes A, DeJong P, Rouleau GA, Auburger G, Korenberg JR, Figueroa C, Sahba S (November 1996). "Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2". Nature Genetics. 14 (3): 269–76. doi:10.1038/ng1196-269. PMID8896555.
Sanpei K, Takano H, Igarashi S, Sato T, Oyake M, Sasaki H, Wakisaka A, Tashiro K, Ishida Y, Ikeuchi T, Koide R, Saito M, Sato A, Tanaka T, Hanyu S, Takiyama Y, Nishizawa M, Shimizu N, Nomura Y, Segawa M, Iwabuchi K, Eguchi I, Tanaka H, Takahashi H, Tsuji S (November 1996). "Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT". Nature Genetics. 14 (3): 277–84. doi:10.1038/ng1196-277. PMID8896556.
Imbert G, Saudou F, Yvert G, Devys D, Trottier Y, Garnier JM, Weber C, Mandel JL, Cancel G, Abbas N, Dürr A, Didierjean O, Stevanin G, Agid Y, Brice A (November 1996). "Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats". Nature Genetics. 14 (3): 285–91. doi:10.1038/ng1196-285. PMID8896557.
Sahba S, Nechiporuk A, Figueroa KP, Nechiporuk T, Pulst SM (February 1998). "Genomic structure of the human gene for spinocerebellar ataxia type 2 (SCA2) on chromosome 12q24.1". Genomics. 47 (3): 359–64. doi:10.1006/geno.1997.5131. PMID9480749.
Huynh DP, Figueroa K, Hoang N, Pulst SM (September 2000). "Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human". Nature Genetics. 26 (1): 44–50. doi:10.1038/79162. PMID10973246.
Kiehl TR, Shibata H, Vo T, Huynh DP, Pulst SM (August 2001). "Identification and expression of a mouse ortholog of A2BP1". Mammalian Genome. 12 (8): 595–601. doi:10.1007/s00335-001-2056-4. PMID11471052.
Choudhry S, Mukerji M, Srivastava AK, Jain S, Brahmachari SK (October 2001). "CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms". Human Molecular Genetics. 10 (21): 2437–46. doi:10.1093/hmg/10.21.2437. PMID11689490.
Pang JT, Giunti P, Chamberlain S, An SF, Vitaliani R, Scaravilli T, Martinian L, Wood NW, Scaravilli F, Ansorge O (March 2002). "Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases". Brain. 125 (Pt 3): 656–63. doi:10.1093/brain/awf060. PMID11872620.
Svetel M, Djarmati A, Dragasević N, Savić D, Culjković B, Romac S, Kostić VS (September 2003). "SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism". European Journal of Neurology. 10 (5): 597. doi:10.1046/j.1468-1331.2003.00671.x. PMID12940846.