From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Available structures
PDBOrtholog search: PDBe RCSB
AliasesAPTX, AOA, AOA1, AXA1, EAOH, EOAHA, FHA-HIT, aprataxin
External IDsMGI: 1913658 HomoloGene: 41634 GeneCards: APTX
Gene location (Human)
Chromosome 9 (human)
Chr.Chromosome 9 (human)[1]
Chromosome 9 (human)
Genomic location for APTX
Genomic location for APTX
Band9p21.1Start32,972,606 bp[1]
End33,025,168 bp[1]
RNA expression pattern
PBB GE APTX 218527 at fs.png
More reference expression data
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 9: 32.97 – 33.03 MbChr 4: 40.68 – 40.7 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Aprataxin is a protein that in humans is encoded by the APTX gene.[5][6][7]

This gene encodes a member of the histidine triad (HIT) superfamily, some of which have nucleotide-binding and diadenosine polyphosphate hydrolase activities. The encoded protein may play a role in single-stranded DNA repair. Mutations in this gene have been associated with ataxia–ocular apraxia. Multiple transcript variants encoding distinct isoforms have been identified for this gene, however, the full length nature of some variants has not been determined.[7]


Aprataxin removes AMP from DNA ends following abortive ligation attempts by DNA Ligase IV during non-homologous end joining, thereby permitting subsequent attempts at ligation.[8][9]

DNA strand breaks[edit]

Ataxia oculomotor apraxia-1 is a neurological disorder caused by mutations in the APTX gene that encodes aprataxin.[10] The neurological disorder appears to be caused by the gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA ligation events.[10]

Premature aging[edit]

Aptx−/− mutant mice have been generated, but they lack an obvious phenotype.[10] Another mouse model was generated in which a mutation of superoxide dismutase I (SOD1) is expressed in an Aptx−/− mouse.[11] The SOD1 mutation causes a reduction in transcription recovery following oxidative stress. These mice showed accelerated cellular senescence. This study also demonstrated a protective role of Aptx in vivo and suggested that the loss of Aptx function results in progressive accumulation of DNA breaks in the nervous system, triggering hallmarks of systemic premature aging [11] (see DNA damage theory of aging).


Aprataxin has been shown to interact with:


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000137074 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028411 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, Koike R, Hiroi T, Yuasa T, Awaya Y, Sakai T, Takahashi T, Nagatomo H, Sekijima Y, Kawachi I, Takiyama Y, Nishizawa M, Fukuhara N, Saito K, Sugano S, Tsuji S (Oct 2001). "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene". Nat Genet. 29 (2): 184–8. doi:10.1038/ng1001-184. PMID 11586299.
  6. ^ Moreira MC, Barbot C, Tachi N, Kozuka N, Uchida E, Gibson T, Mendonca P, Costa M, Barros J, Yanagisawa T, Watanabe M, Ikeda Y, Aoki M, Nagata T, Coutinho P, Sequeiros J, Koenig M (Oct 2001). "The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin". Nat Genet. 29 (2): 189–93. doi:10.1038/ng1001-189. PMID 11586300.
  7. ^ a b "Entrez Gene: APTX aprataxin".
  8. ^ Rass U, Ahel I, West SC (December 2008). "Molecular mechanism of DNA deadenylation by the neurological disease protein aprataxin". J. Biol. Chem. 283 (49): 33994–4001. doi:10.1074/jbc.M807124200. PMC 2662222. PMID 18836178.
  9. ^ Reynolds JJ, El-Khamisy SF, Katyal S, Clements P, McKinnon PJ, Caldecott KW (March 2009). "Defective DNA ligation during short-patch single-strand break repair in ataxia oculomotor apraxia 1". Mol. Cell. Biol. 29 (5): 1354–62. doi:10.1128/MCB.01471-08. PMC 2643831. PMID 19103743.
  10. ^ a b c Ahel I, Rass U, El-Khamisy SF, Katyal S, Clements PM, McKinnon PJ, Caldecott KW, West SC (2006). "The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates". Nature. 443 (7112): 713–6. doi:10.1038/nature05164. PMID 16964241.
  11. ^ a b Carroll J, Page TK, Chiang SC, Kalmar B, Bode D, Greensmith L, Mckinnon PJ, Thorpe JR, Hafezparast M, El-Khamisy SF (2015). "Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing". Hum. Mol. Genet. 24 (3): 828–40. doi:10.1093/hmg/ddu500. PMC 4291253. PMID 25274775.
  12. ^ a b Date H, Igarashi S, Sano Y, Takahashi T, Takahashi T, Takano H, Tsuji S, Nishizawa M, Onodera O (December 2004). "The FHA domain of aprataxin interacts with the C-terminal region of XRCC1". Biochem. Biophys. Res. Commun. 325 (4): 1279–85. doi:10.1016/j.bbrc.2004.10.162. PMID 15555565.
  13. ^ a b c Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF (May 2004). "Aprataxin, a novel protein that protects against genotoxic stress". Hum. Mol. Genet. 13 (10): 1081–93. doi:10.1093/hmg/ddh122. PMID 15044383.
  14. ^ Clements PM, Breslin C, Deeks ED, Byrd PJ, Ju L, Bieganowski P, Brenner C, Moreira MC, Taylor AM, Caldecott KW (November 2004). "The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4". DNA Repair (Amst.). 3 (11): 1493–502. doi:10.1016/j.dnarep.2004.06.017. PMID 15380105.

Further reading[edit]

External links[edit]