PolyQ Ataxin-2 , ATXN2 (12q24.12)

https://www.ncbi.nlm.nih.gov/pubmed/27103069/

ATXN2provided by HGNC

Official Full Name

ataxin 2provided by HGNC

Also known as

ATX2; SCA2; TNRC13

Summary

This gene belongs to a group of genes that is associated with microsatellite-expansion diseases, a class of neurological and neuromuscular disorders caused by expansion of short stretches of repetitive DNA. The protein encoded by this gene has two globular domains near the N-terminus, one of which contains a clathrin-mediated trans-Golgi signal and an endoplasmic reticulum (ER) exit signal. The encoded cytoplasmic protein localizes to the endoplasmic reticulum (ER) and plasma membrane (PM), is involved in endocytosis, and modulates mTOR signals, modifying ribosomal translation and mitochondrial function. The N-terminal region of the protein contains a polyglutamine (polyQ)  tract of 14-31 residues that can be expanded in the pathogenic state to 32-200 residues. Intermediate length expansions of this tract increase susceptibility to amyotrophic lateral sclerosis, while long expansions of this tract result in spinocerebellar ataxia-2, an autosomal-dominantly inherited, neurodegenerative disorder. Genome-wide association studies indicate that loss-of-function mutations in this gene may be associated with susceptibility to type I diabetes, obesity and hypertension. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

Expression

Ubiquitous expression in testis (RPKM 11.3), brain (RPKM 9.4) and 25 other tissues See more

Orthologs

Preferred Names

ataxin-2

Names

spinocerebellar ataxia type 2 protein

trinucleotide repeat-containing gene 13 protein

 https://www.ncbi.nlm.nih.gov/protein/NP_001297052.1

 

ORIGIN      
        1 mrmvhiltsv vcdlvldaah ekstesssgp kreeimesil fkcsdfvvvq fkdmdssyak
       61 rdaftdsais akvngehkek dlepwdagel taneeleale ndvsngwdpn dmfryneeny
      121 gvvstydssl ssytvplerd nseeflkrea ranqlaeeie ssaqykarva lenddrseee
      181 kytavqrnss ereghsintr enkyippgqr nreviswgsg rqnsprmgqp gsgsmpsrst
      241 shtsdfnpns gsdqrvvngg vpwpspcpsp ssrppsryqs gpnslppraa tptrppsrpp
      301 srpsrppshp sahgspapvs tmpkrmsseg pprmspkaqr hprnhrvsag rgsissglef
      361 vshnppseaa tppvartsps ggtwssvvsg vprlspkthr prsprqnsig ntpsgpvlas
      421 pqagiiptea vampipaasp tpaspasnra vtpsseakds rlqdqrqnsp agnkenikpn
      481 etspsfskae nkgispvvse hrkqiddlkk fkndfrlqps stsesmdqll nknregeksr
      541 dlikdkieps akdsfienss snctsgsskp nspsispsil sntehkrgpe vtsqgvqtss
      601 packqekddk eekkdaaeqv rkstlnpnak efnprsfsqp kpsttptspr pqaqpspsmv
      661 ghqqptpvyt qpvcfapnmm ypvpvspgvq plypipmtpm pvnqaktyra vpnmpqqrqd
      721 qhhqsammhp asaagppiaa tppaystqyv ayspqqfpnq plvqhvphyq sqhphvyspv
      781 iqgnarmmap pthaqpglvs ssatqygahe qthamyvstg slaqqyahpn atlhphtphp
      841 qpsatptgqq qsqhggshpa pspvqhhqhq aaqalhlasp qqqsaiyhag laptppsmtp
      901 asntqspqns fpaaqqtvft ihpshvqpay tnpphmahvp qahvqsgmvp shptahapmm
      961 lmttqppggp qaalaqsalq pipvsttahf pymthpsvqa hhqqql

 Conserved Domains (4) summary

pfam06741
Location:144 → 205

LsmAD; LsmAD domain

pfam14438
Location:3 → 76

SM-ATX; Ataxin 2 SM domain

cl26386
Location:303 → 494

DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III

cl26464
Location:664 → 988

Atrophin-1 family

Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

? cl26464 Atrophin-1 Superfamily (this model, PSSM-Id:331285 is obsolete)

Related articles in PubMed

1. Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients. Tavares de Andrade HM, et al. Neurobiol Aging, 2018 Sep. PMID 29934271
2. Analysis of ATXN2 trinucleotide repeats in Korean patients with amyotrophic lateral sclerosis. Kim YE, et al. Neurobiol Aging, 2018 Jul. PMID 29665996
3. Neurological phenotypes in spinocerebellar ataxia type 2: Role of mitochondrial polymorphism A10398G and other risk factors. Monte TL, et al. Parkinsonism Relat Disord, 2017 Sep. PMID 28648514
4. Normal ATXN2 alleles influences on the age at onset in spinocerebellar ataxia type 2. Almaguer-Mederos LE, et al. Mov Disord, 2017 Sep. PMID 28620961
5. Simulation Based Investigation of Deleterious nsSNPs in ATXN2 Gene and Its Structural Consequence Toward Spinocerebellar Ataxia. Sinha S, et al. J Cell Biochem, 2018 Jan. PMID 28612427

See all (192) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. Study found that ATXN2 intermediate-length expansions (larger than 26 repeats) were associated with an increased risk for amyotrophic lateral sclerosis.
2. This study showed that Normal ATXN2 alleles influences on the age at onset in spinocerebellar ataxia type 2.
3. STAU1 is recruited to mutant ATXN2 aggregates in spinocerebellar ataxia type 2 fibroblasts.
4. Intermediate-length ATXN2 repeat expansions might be a risk factor in Korean patients with ALS.
5. A novel variant in ATXN2 was identified in a Chinese population that was linked to age of onset in Machado-Joseph disease.(MJD deubiquitinase) 
6. Among correlations found, such as that between dystonia and CAG expansion. Of note was the association between cognitive decline and the variant G at mitochondrial polymorphism A10398G, a variant formerly related to earlier ages at onset in SCA2.
7. SCA2 should be considered as a cause of typical Parkinson's disease phenotype even in the absence of cerebellar ataxia
8. Este es el primer estudio que permite sugerir la asociacion del polimorfismo (CAG)n del gen ATXN2 con el desarrollo de DM tipo 2 pura en poblacion de escasos recursos. Los alelos normales largos del VNTR son factores que aumentan el riesgo para DM tipo 2 pura en la poblacion mexicana analizada.
9. Deleterious non synonymous single nucleotide polymorphisms in ATXN2 Gene is associated with protein instability and conformational changes resulting in spinocerebellar ataxia.
10. Intermediate expansions of the CAG repeat in ATXN2 are associated with amyotrophic lateral sclerosis. They are mostly associated with TDP-43 proteinopathy, but not with 1C2-positive polyglutamine inclusions.

Submit: New GeneRIF Correction See all GeneRIFs (108)