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{{Infobox_gene}}
{{Infobox_gene}}
'''Ataxin-2''' is a [[protein]] that in humans is encoded by the ''ATXN2'' [[gene]].<ref name="pmid8358438">{{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 = Nat Genet | volume = 4 | issue = 3 | pages = 295–9 |date=Sep 1993 | pmid = 8358438 | pmc =  | doi = 10.1038/ng0793-295 |display-authors=etal}}</ref><ref name="pmid9225980">{{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 = Hum Genet | volume = 100 | issue = 1 | pages = 114–22 |date=Jul 1997 | pmid = 9225980 | pmc =  | doi =10.1007/s004390050476 }}</ref>
'''Ataxin-2''' is a [[protein]] that in humans is encoded by the ''ATXN2'' [[gene]].<ref name="pmid8358438">{{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 }}</ref><ref name="pmid9225980">{{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 }}</ref> Mutations in ATXN2 cause [[spinocerebellar ataxia]] type 2 (SCA2).


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Protein structure ==
{{PBB Summary
Ataxin-2 contains the following protein domains:<ref>{{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 }}</ref>
| section_title =  
* Two [[LSm]] domains, which likely allow it to bind RNA
| summary_text = Mutations in ATXN2 cause [[spinocerebellar ataxia]] type 2 (SCA2). The [[autosomal dominant]] cerebellar ataxias (ADCA) are a heterogeneous group of [[neurodegenerative disorder]]s characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. SCA2 is caused by the expansion of a CAG repeat in the coding region of the ATXN2 gene producing an elongated [[polyglutamine tract]] in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 12, and it has been determined that the disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100. Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.<ref name="entrez">{{cite web | title = Entrez Gene: ATXN2 ataxin 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6311| accessdate = }}</ref>
* A PAM2 motif, predicted to associate with the [[poly(A)-binding protein]]
}}
* A [[polyglutamine tract]] in some species (located near the amino terminal in primates and between the LSm domains in insects)<ref name=":0">{{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 }}</ref>
A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.<ref name="entrez">{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6311|title=Entrez Gene: ATXN2 ataxin 2|accessdate=}}</ref>


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).<ref name="pmid20740007">{{cite journal | vauthors = Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM | title = Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS | journal = Nature | volume = 466 | issue = 7310 | pages = 1069–1075 |date=Aug 2010 | pmid = 20740007 | pmc = 2965417  | doi = 10.1038/nature09320|display-authors=etal}}</ref>
== Species, tissue, and subcellular distribution ==
''ATXN2'' is conserved across [[eukaryote]]s. Most vertebrates have two [[Homology (biology)|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.<ref name=":0" />


==References==
''ATXN2'' is ubiquitously expressed in different tissues. Within individual cells, it localizes to the [[Golgi apparatus]] and [[stress granule]]s.<ref name=":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 }}</ref>
 
== 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 granule]]s and [[P-bodies]], which also play roles in RNA regulation.<ref name=":1" />
 
== 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 [[Neurodegeneration|degenerate]] in the [[cerebellum]], [[Inferior olivary nucleus|inferior olive]], [[pons]], and other areas. Symptoms of SCA2 include [[ataxia]] (a loss of coordinated movements), [[parkinsonism]], and dementia in some cases.<ref>{{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}}</ref> 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).<ref name="pmid20740007">{{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 }}</ref>
 
== References ==
{{reflist}}
{{reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_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 }}
| citations =
* {{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=Stevanin G, Dürr A, Brice A |title=Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology. |journal=Eur. J. Hum. Genet. |volume=8 |issue= 1 |pages= 4–18 |year= 2000 |pmid= 10713882 |doi= 10.1038/sj.ejhg.5200403 }}
* {{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=Pulst SM, Nechiporuk A, Nechiporuk T |title=Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. |journal=Nat. Genet. |volume=14 |issue= 3 |pages= 269–76 |year= 1996 |pmid= 8896555 |doi= 10.1038/ng1196-269 |display-authors=etal}}
* {{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=Sanpei K, Takano H, Igarashi S |title=Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. |journal=Nat. Genet. |volume=14 |issue= 3 |pages= 277–84 |year= 1996 |pmid= 8896556 |doi= 10.1038/ng1196-277 |display-authors=etal}}
* {{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=Imbert G, Saudou F, Yvert G |title=Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. |journal=Nat. Genet. |volume=14 |issue= 3 |pages= 285–91 |year= 1996 |pmid= 8896557 |doi= 10.1038/ng1196-285 |display-authors=etal}}
* {{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=Sahba S, Nechiporuk A, Figueroa KP |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 |year= 1998 |pmid= 9480749 |doi= 10.1006/geno.1997.5131 |display-authors=etal}}
* {{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=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=Ann. Neurol. |volume=45 |issue= 2 |pages= 232–41 |year= 1999 |pmid= 9989626 |doi=10.1002/1531-8249(199902)45:2<232::AID-ANA14>3.0.CO;2-7 }}
* {{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=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=Nat. Genet. |volume=26 |issue= 1 |pages= 44–50 |year= 2000 |pmid= 10973246 |doi= 10.1038/79162 }}
* {{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=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 |year= 2001 |pmid= 11311558 |doi=10.1016/S0378-1119(01)00402-4 }}
* {{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=Kiehl TR, Shibata H, Vo T |title=Identification and expression of a mouse ortholog of A2BP1. |journal=Mamm. Genome |volume=12 |issue= 8 |pages= 595–601 |year= 2002 |pmid= 11471052 |doi=10.1007/s00335-001-2056-4 |display-authors=etal}}
* {{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=Choudhry S, Mukerji M, Srivastava AK |title=CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms. |journal=Hum. Mol. Genet. |volume=10 |issue= 21 |pages= 2437–46 |year= 2002 |pmid= 11689490 |doi=10.1093/hmg/10.21.2437 |display-authors=etal}}
* {{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=Pang JT, Giunti P, Chamberlain S |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 |year= 2002 |pmid= 11872620 |doi=10.1093/brain/awf060 |display-authors=etal}}
* {{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=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
* {{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=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 |year= 2003 |pmid= 12524342 |doi= | pmc=1462369 }}
* {{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=Wiedemeyer R, Westermann F, Wittke I |title=Ataxin-2 promotes apoptosis of human neuroblastoma cells |journal=Oncogene |volume=22 |issue= 3 |pages= 401–11 |year= 2003 |pmid= 12545161 |doi= 10.1038/sj.onc.1206150 |display-authors=etal}}
* {{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}}
*{{cite journal | vauthors=Payami H, Nutt J, Gancher S |title=SCA2 may present as levodopa-responsive parkinsonism |journal=Mov. Disord. |volume=18 |issue= 4 |pages= 425–9 |year= 2003 |pmid= 12671950 |doi= 10.1002/mds.10375 |display-authors=etal}}
*{{cite journal | vauthors=Svetel M, Djarmati A, Dragasević N |title=SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism |journal=Eur. J. Neurol. |volume=10 |issue= 5 |pages= 597 |year= 2003 |pmid= 12940846 |doi=10.1046/j.1468-1331.2003.00671.x |display-authors=etal}}
*{{cite journal | vauthors=Brenneis C, Bösch SM, Schocke M |title=Atrophy pattern in SCA2 determined by voxel-based morphometry |journal=NeuroReport |volume=14 |issue= 14 |pages= 1799–802 |year= 2003 |pmid= 14534423 |doi= 10.1097/01.wnr.0000094105.16607.18 |display-authors=etal}}
}}
{{refend}}
{{refend}}


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
== External links ==
 
==External links==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sca2  GeneReviews/NIH/NCBI/UW entry on Spinocerebellar Ataxia Type 2]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sca2  GeneReviews/NIH/NCBI/UW entry on Spinocerebellar Ataxia Type 2]
* {{UCSC gene info|ATXN2}}
* {{UCSC gene info|ATXN2}}
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Latest revision as of 05:10, 9 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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PubMed searchn/an/a
Wikidata
View/Edit Human

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

Ataxin-2 contains the following protein domains:[3]

  • Two LSm domains, which likely allow it to bind RNA
  • A PAM2 motif, predicted to associate with the poly(A)-binding protein
  • A polyglutamine tract in some species (located near the amino terminal in primates and between the LSm domains in insects)[4]

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

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.[4]

ATXN2 is ubiquitously expressed in different tissues. Within individual cells, it localizes to the Golgi apparatus and stress granules.[6]

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. ↑ 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. PMID 8358438.
  2. ↑ 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. PMID 9225980.
  3. ↑ Albrecht M, Golatta M, Wüllner U, Lengauer T (August 2004). "Structural and functional analysis of ataxin-2 and ataxin-3". European Journal of Biochemistry. 271 (15): 3155–70. doi:10.1111/j.1432-1033.2004.04245.x. PMID 15265035.
  4. ↑ 4.0 4.1 Jiménez-López D, Guzmán P (July 2014). "Insights into the evolution and domain structure of Ataxin-2 proteins across eukaryotes". BMC Research Notes. 7: 453. doi:10.1186/1756-0500-7-453. PMC 4105795. PMID 25027299.
  5. ↑ "Entrez Gene: ATXN2 ataxin 2".
  6. ↑ 6.0 6.1 Orr HT (April 2012). "Cell biology of spinocerebellar ataxia". The Journal of Cell Biology. 197 (2): 167–77. doi:10.1083/jcb.201105092. PMC 3328388. PMID 22508507.
  7. ↑ Reference, Genetics Home. "SCA2". Genetics Home Reference. Retrieved 2018-01-11.
  8. ↑ 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 (August 2010). "Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS". Nature. 466 (7310): 1069–75. doi:10.1038/nature09320. PMC 2965417. PMID 20740007.

Further reading

  • 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. PMID 10713882.
  • 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. PMID 8896555.
  • 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. PMID 8896556.
  • 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. PMID 8896557.
  • 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. PMID 9480749.
  • Huynh DP, Del Bigio MR, Ho DH, Pulst SM (February 1999). "Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2". Annals of Neurology. 45 (2): 232–41. doi:10.1002/1531-8249(199902)45:2<232::AID-ANA14>3.0.CO;2-7. PMID 9989626.
  • 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. PMID 10973246.
  • Affaitati A, de Cristofaro T, Feliciello A, Varrone S (April 2001). "Identification of alternative splicing of spinocerebellar ataxia type 2 gene". Gene. 267 (1): 89–93. doi:10.1016/S0378-1119(01)00402-4. PMID 11311558.
  • 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. PMID 11471052.
  • 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. PMID 11689490.
  • 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. PMID 11872620.
  • Satterfield TF, Jackson SM, Pallanck LJ (December 2002). "A Drosophila homolog of the polyglutamine disease gene SCA2 is a dosage-sensitive regulator of actin filament formation". Genetics. 162 (4): 1687–702. PMC 1462369. PMID 12524342.
  • Wiedemeyer R, Westermann F, Wittke I, Nowock J, Schwab M (January 2003). "Ataxin-2 promotes apoptosis of human neuroblastoma cells". Oncogene. 22 (3): 401–11. doi:10.1038/sj.onc.1206150. PMID 12545161.
  • 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 (April 2003). "SCA2 may present as levodopa-responsive parkinsonism". Movement Disorders. 18 (4): 425–9. doi:10.1002/mds.10375. PMID 12671950.
  • 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. PMID 12940846.
  • Brenneis C, Bösch SM, Schocke M, Wenning GK, Poewe W (October 2003). "Atrophy pattern in SCA2 determined by voxel-based morphometry". NeuroReport. 14 (14): 1799–802. doi:10.1097/00001756-200310060-00008. PMID 14534423.

External links

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