“Ataxin-2”的意思、由来-开放百科全书

Ataxin-2 is a protein that in humans is encoded by the ATXN2 gene.^[1]^[2] Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2).

Protein structure

A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.^[5]

Species, tissue, and subcellular distribution

Function

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.^[6]

Clinical significance

Spinocerebellar ataxia type 2 (SCA2)

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.^[7] 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.

Amyotrophic lateral sclerosis (ALS)

In 2010, work from Aaron Gitler and Nancy Bonini at the University of Pennsylvania discovered that intermediate-size CAG repeat expansions are significantly associated with risk for developing amyotrophic lateral sclerosis (Lou Gehrig's disease).^[8]

References

1. ^{{cite journal | vauthors = Gispert S, Twells R, Orozco G, Brice A, Weber J, Heredero L, Scheufler K, Riley B, Allotey R, Nothers C | title = Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1 | journal = Nature Genetics | volume = 4 | issue = 3 | pages = 295–9 | date = July 1993 | pmid = 8358438 | pmc = | doi = 10.1038/ng0793-295 }}
2. ^{{cite journal | vauthors = Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA | title = cDNAs with long CAG trinucleotide repeats from human brain | journal = Human Genetics | volume = 100 | issue = 1 | pages = 114–22 | date = July 1997 | pmid = 9225980 | pmc = | doi = 10.1007/s004390050476 }}
3. ^{{cite journal | vauthors = Albrecht M, Golatta M, Wüllner U, Lengauer T | title = Structural and functional analysis of ataxin-2 and ataxin-3 | language = en | journal = European Journal of Biochemistry | volume = 271 | issue = 15 | pages = 3155–70 | date = August 2004 | pmid = 15265035 | doi = 10.1111/j.1432-1033.2004.04245.x }}
4. ^¹{{cite journal | vauthors = Jiménez-López D, Guzmán P | title = Insights into the evolution and domain structure of Ataxin-2 proteins across eukaryotes | journal = BMC Research Notes | volume = 7 | pages = 453 | date = July 2014 | pmid = 25027299 | pmc = 4105795 | doi = 10.1186/1756-0500-7-453 }}
5. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6311|title=Entrez Gene: ATXN2 ataxin 2|accessdate=}}
6. ^¹{{cite journal | vauthors = Orr HT | title = Cell biology of spinocerebellar ataxia | language = en | journal = The Journal of Cell Biology | volume = 197 | issue = 2 | pages = 167–77 | date = April 2012 | pmid = 22508507 | doi = 10.1083/jcb.201105092 | url = http://jcb.rupress.org/content/197/2/167 | pmc = 3328388 }}
7. ^{{Cite web|url=https://ghr.nlm.nih.gov/condition/spinocerebellar-ataxia-type-2|title=SCA2|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2018-01-11}}
8. ^{{cite journal | vauthors = Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rüb U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD | title = Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS | journal = Nature | volume = 466 | issue = 7310 | pages = 1069–75 | date = August 2010 | pmid = 20740007 | pmc = 2965417 | doi = 10.1038/nature09320 }}

Further reading

{{cite journal | vauthors = Stevanin G, Dürr A, Brice A | title = Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology | journal = European Journal of Human Genetics | volume = 8 | issue = 1 | pages = 4–18 | date = January 2000 | pmid = 10713882 | doi = 10.1038/sj.ejhg.5200403 }}

{{cite journal | vauthors = 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 | title = Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2 | journal = Nature Genetics | volume = 14 | issue = 3 | pages = 269–76 | date = November 1996 | pmid = 8896555 | doi = 10.1038/ng1196-269 }}

{{cite journal | vauthors = 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 | title = Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT | journal = Nature Genetics | volume = 14 | issue = 3 | pages = 277–84 | date = November 1996 | pmid = 8896556 | doi = 10.1038/ng1196-277 }}

{{cite journal | vauthors = 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 | title = Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats | journal = Nature Genetics | volume = 14 | issue = 3 | pages = 285–91 | date = November 1996 | pmid = 8896557 | doi = 10.1038/ng1196-285 }}

{{cite journal | vauthors = Sahba S, Nechiporuk A, Figueroa KP, Nechiporuk T, Pulst SM | title = Genomic structure of the human gene for spinocerebellar ataxia type 2 (SCA2) on chromosome 12q24.1 | journal = Genomics | volume = 47 | issue = 3 | pages = 359–64 | date = February 1998 | pmid = 9480749 | doi = 10.1006/geno.1997.5131 }}

{{cite journal | vauthors = Huynh DP, Del Bigio MR, Ho DH, Pulst SM | title = Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2 | journal = Annals of Neurology | volume = 45 | issue = 2 | pages = 232–41 | date = February 1999 | pmid = 9989626 | doi = 10.1002/1531-8249(199902)45:2<232::AID-ANA14>3.0.CO;2-7 }}

{{cite journal | vauthors = Huynh DP, Figueroa K, Hoang N, Pulst SM | title = Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human | journal = Nature Genetics | volume = 26 | issue = 1 | pages = 44–50 | date = September 2000 | pmid = 10973246 | doi = 10.1038/79162 }}

{{cite journal | vauthors = Affaitati A, de Cristofaro T, Feliciello A, Varrone S | title = Identification of alternative splicing of spinocerebellar ataxia type 2 gene | journal = Gene | volume = 267 | issue = 1 | pages = 89–93 | date = April 2001 | pmid = 11311558 | doi = 10.1016/S0378-1119(01)00402-4 }}

{{cite journal | vauthors = Kiehl TR, Shibata H, Vo T, Huynh DP, Pulst SM | title = Identification and expression of a mouse ortholog of A2BP1 | journal = Mammalian Genome | volume = 12 | issue = 8 | pages = 595–601 | date = August 2001 | pmid = 11471052 | doi = 10.1007/s00335-001-2056-4 }}

{{cite journal | vauthors = Choudhry S, Mukerji M, Srivastava AK, Jain S, Brahmachari SK | title = CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms | journal = Human Molecular Genetics | volume = 10 | issue = 21 | pages = 2437–46 | date = October 2001 | pmid = 11689490 | doi = 10.1093/hmg/10.21.2437 }}

{{cite journal | vauthors = Pang JT, Giunti P, Chamberlain S, An SF, Vitaliani R, Scaravilli T, Martinian L, Wood NW, Scaravilli F, Ansorge O | title = Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases | journal = Brain | volume = 125 | issue = Pt 3 | pages = 656–63 | date = March 2002 | pmid = 11872620 | doi = 10.1093/brain/awf060 }}

{{cite journal | vauthors = Satterfield TF, Jackson SM, Pallanck LJ | title = A Drosophila homolog of the polyglutamine disease gene SCA2 is a dosage-sensitive regulator of actin filament formation | journal = Genetics | volume = 162 | issue = 4 | pages = 1687–702 | date = December 2002 | pmid = 12524342 | pmc = 1462369 | doi = }}

{{cite journal | vauthors = Wiedemeyer R, Westermann F, Wittke I, Nowock J, Schwab M | title = Ataxin-2 promotes apoptosis of human neuroblastoma cells | journal = Oncogene | volume = 22 | issue = 3 | pages = 401–11 | date = January 2003 | pmid = 12545161 | doi = 10.1038/sj.onc.1206150 }}

{{cite journal | vauthors = Payami H, Nutt J, Gancher S, Bird T, McNeal MG, Seltzer WK, Hussey J, Lockhart P, Gwinn-Hardy K, Singleton AA, Singleton AB, Hardy J, Farrer M | title = SCA2 may present as levodopa-responsive parkinsonism | journal = Movement Disorders | volume = 18 | issue = 4 | pages = 425–9 | date = April 2003 | pmid = 12671950 | doi = 10.1002/mds.10375 }}

{{cite journal | vauthors = Svetel M, Djarmati A, Dragasević N, Savić D, Culjković B, Romac S, Kostić VS | title = SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism | journal = European Journal of Neurology | volume = 10 | issue = 5 | pages = 597 | date = September 2003 | pmid = 12940846 | doi = 10.1046/j.1468-1331.2003.00671.x }}

{{cite journal | vauthors = Brenneis C, Bösch SM, Schocke M, Wenning GK, Poewe W | title = Atrophy pattern in SCA2 determined by voxel-based morphometry | journal = NeuroReport | volume = 14 | issue = 14 | pages = 1799–802 | date = October 2003 | pmid = 14534423 | doi = 10.1097/00001756-200310060-00008}}