Aprataxin

Aprataxin
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3KT9​, 4NDF​, 4NDG​, 4NDH​, 4NDI​
Identifiers
Symbols	APTX ; AOA; AOA1; AXA1; EAOH; EOAHA; FHA-HIT
External IDs	OMIM: 606350 MGI: 1913658 HomoloGene: 41634 GeneCards: APTX Gene
Gene ontology Molecular function • chromatin binding • damaged DNA binding • double-stranded DNA binding • double-stranded RNA binding • protein binding • phosphoglycolate phosphatase activity • DNA 5'-adenosine monophosphate hydrolase activity • polynucleotide 3'-phosphatase activity • metal ion binding • protein N-terminus binding • phosphoprotein binding Cellular component • chromatin • nuclear chromatin • nucleus • nucleoplasm • nucleolus • cytoplasm Biological process • single strand break repair • DNA ligation • double-strand break repair • protein dephosphorylation • cellular response to DNA damage stimulus • regulation of protein stability • response to hydrogen peroxide • nucleic acid phosphodiester bond hydrolysis • polynucleotide 3' dephosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	54840	66408
Ensembl	ENSG00000137074	ENSMUSG00000028411
UniProt	Q7Z2E3	Q7TQC5
RefSeq (mRNA)	NM_001195248	NM_001025444
RefSeq (protein)	NP_001182177	NP_001020615
Location (UCSC)	Chr 9: 32.97 – 33.03 Mb	Chr 4: 40.68 – 40.7 Mb
PubMed search

Aprataxin is a protein that in humans is encoded by the APTX gene.^[1][2][3]

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.^[3]

Function

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.^[4][5]

Interactions

Aprataxin has been shown to interact with:

• PARP1,^[6][7]
• P53,^[7]
• XRCC1,^[6][7] and
• XRCC4.^[8]

References

1. 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.
2. 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.
3. "Entrez Gene: APTX aprataxin".
4. 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.
5. 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.
6. 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.
7. 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.
8. 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

• Aicardi J, Barbosa C, Andermann E; et al. (1989). "Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia.". Ann. Neurol. 24 (4): 497–502. doi:10.1002/ana.410240404. PMID 3239952.
• Gascon GG, Abdo N, Sigut D; et al. (1995). "Ataxia-oculomotor apraxia syndrome.". J. Child Neurol. 10 (2): 118–22. doi:10.1177/088307389501000210. PMID 7782601.
• Hannan MA, Sigut D, Waghray M, Gascon GG (1995). "Ataxia-ocular motor apraxia syndrome: an investigation of cellular radiosensitivity of patients and their families.". J. Med. Genet. 31 (12): 953–6. doi:10.1136/jmg.31.12.953. PMC 1016697. PMID 7891378.
• Moreira MC, Barbot C, Tachi N; et al. (2001). "Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity.". Am. J. Hum. Genet. 68 (2): 501–8. doi:10.1086/318191. PMC 1235299. PMID 11170899.
• Brenner C (2002). "Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases.". Biochemistry 41 (29): 9003–14. doi:10.1021/bi025942q. PMC 2571077. PMID 12119013.
• Shimazaki H, Takiyama Y, Sakoe K; et al. (2002). "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.". Neurology 59 (4): 590–5. doi:10.1212/wnl.59.4.590. PMID 12196655.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Tranchant C, Fleury M, Moreira MC; et al. (2004). "Phenotypic variability of aprataxin gene mutations.". Neurology 60 (5): 868–70. doi:10.1212/01.wnl.0000048562.88536.a4. PMID 12629250.
• Le Ber I, Moreira MC, Rivaud-Péchoux S; et al. (2003). "Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies.". Brain 126 (Pt 12): 2761–72. doi:10.1093/brain/awg283. PMID 14506070.
• Sekijima Y, Hashimoto T, Onodera O; et al. (2004). "Severe generalized dystonia as a presentation of a patient with aprataxin gene mutation.". Mov. Disord. 18 (10): 1198–200. doi:10.1002/mds.10526. PMID 14534929.
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Sano Y, Date H, Igarashi S; et al. (2004). "Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.". Ann. Neurol. 55 (2): 241–9. doi:10.1002/ana.10808. PMID 14755728.
• Gueven N, Becherel OJ, Kijas AW; et al. (2004). "Aprataxin, a novel protein that protects against genotoxic stress.". Hum. Mol. Genet. 13 (10): 1081–93. doi:10.1093/hmg/ddh122. PMID 15044383.
• Humphray SJ, Oliver K, Hunt AR; et al. (2004). "DNA sequence and analysis of human chromosome 9.". Nature 429 (6990): 369–74. doi:10.1038/nature02465. PMC 2734081. PMID 15164053.
• Habeck M, Zühlke C, Bentele KH; et al. (2004). "Aprataxin mutations are a rare cause of early onset ataxia in Germany.". J. Neurol. 251 (5): 591–4. doi:10.1007/s00415-004-0374-7. PMID 15164193.
• Hirano M, Nishiwaki T, Kariya S; et al. (2004). "Novel splice variants increase molecular diversity of aprataxin, the gene responsible for early-onset ataxia with ocular motor apraxia and hypoalbuminemia.". Neurosci. Lett. 366 (2): 120–5. doi:10.1016/j.neulet.2004.05.034. PMID 15276230.
• Amouri R, Moreira MC, Zouari M; et al. (2005). "Aprataxin gene mutations in Tunisian families.". Neurology 63 (5): 928–9. doi:10.1212/01.wnl.0000137044.06573.46. PMID 15365154.
• Clements PM, Breslin C, Deeks ED; et al. (2005). "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.

External links

• GeneReviews/NCBI/NIH/UW entry on Ataxia with Oculomotor Apraxia Type 1
• OMIM entries on Ataxia with Oculomotor Apraxia Type 1