Ataxin-2

From WikiProjectMed
(Redirected from ATXN2)
Jump to navigation Jump to search
ATXN2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesATXN2, ASL13, ATX2, SCA2, TNRC13, ataxin 2
External IDsOMIM: 601517 MGI: 1277223 HomoloGene: 2234 GeneCards: ATXN2
Orthologs
SpeciesHumanMouse
Entrez

6311

20239

Ensembl

ENSG00000204842

ENSMUSG00000042605

UniProt

Q99700

O70305

RefSeq (mRNA)

NM_001310121
NM_001310123
NM_002973
NM_001372574

NM_009125
NM_001359153

RefSeq (protein)

NP_001297050
NP_001297052
NP_002964
NP_001359503

NP_033151
NP_001346082

Location (UCSC)Chr 12: 111.44 – 111.6 MbChr 5: 121.71 – 121.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ataxin-2 is a protein that in humans is encoded by the ATXN2 gene.[5][6] Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2).

Protein structure

Ataxin-2 contains the following protein domains:[7]

  • 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)[8]

A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.[9]

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.[8]

ATXN2 is ubiquitously expressed in different tissues. Within individual cells, it localizes to the Golgi apparatus and stress granules.[10]

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.[10]

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.[11] 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).[12]

Primary open-angle glaucoma (POAG) and intraocular pressure (IOP)

Genome-wide association studies have revealed a significant association of ATXN2 variants with POAG and IOP. Further investigation of the genetic and biological mechanisms underlying the association between ATXN2 and POAG could provide valuable insights into the pathogenesis and potential therapeutic targets for glaucoma.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000204842 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042605 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. S2CID 7387082.
  6. ^ 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. S2CID 25999127.
  7. ^ 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.
  8. ^ a b 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.
  9. ^ "Entrez Gene: ATXN2 ataxin 2".
  10. ^ a b 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.
  11. ^ Reference, Genetics Home. "SCA2". Genetics Home Reference. Retrieved 2018-01-11.
  12. ^ 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. Bibcode:2010Natur.466.1069E. doi:10.1038/nature09320. PMC 2965417. PMID 20740007.
  13. ^ Zukerman R, Harris A, Vercellin AV, Siesky B, Pasquale LR, Ciulla TA (December 2020). "Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations". Genes. 12 (1): 55. doi:10.3390/genes12010055. PMC 7823611. PMID 33396423.

Further reading

External links

Retrieved from "https://mdwiki.org/wiki/Ataxin-2"