3kt9

Structural highlights

Disease

APTX_HUMAN Defects in APTX are the cause of ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920. AOA is an autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.^{[1] [2] [3] [4] [5] [6] [7]}

Function

APTX_HUMAN DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity.^{[8] [9] [10] [11] [12]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet. 2001 Oct;29(2):184-8. PMID:11586299 doi:10.1038/ng1001-184
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. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet. 2001 Oct;29(2):189-93. PMID:11586300 doi:10.1038/ng1001-189
3. ↑ Shimazaki H, Takiyama Y, Sakoe K, Ikeguchi K, Niijima K, Kaneko J, Namekawa M, Ogawa T, Date H, Tsuji S, Nakano I, Nishizawa M. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations. Neurology. 2002 Aug 27;59(4):590-5. PMID:12196655
4. ↑ Tranchant C, Fleury M, Moreira MC, Koenig M, Warter JM. Phenotypic variability of aprataxin gene mutations. Neurology. 2003 Mar 11;60(5):868-70. PMID:12629250
5. ↑ Le Ber I, Moreira MC, Rivaud-Pechoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Said G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Durr A. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003 Dec;126(Pt 12):2761-72. Epub 2003 Sep 23. PMID:14506070 doi:10.1093/brain/awg283
6. ↑ Criscuolo C, Mancini P, Menchise V, Sacca F, De Michele G, Banfi S, Filla A. Very late onset in ataxia oculomotor apraxia type I. Ann Neurol. 2005 May;57(5):777. PMID:15852392 doi:10.1002/ana.20463
7. ↑ Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M. Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology. 2005 Feb 8;64(3):539-41. PMID:15699391 doi:10.1212/01.WNL.0000150588.75281.58
8. ↑ Sano Y, Date H, Igarashi S, Onodera O, Oyake M, Takahashi T, Hayashi S, Morimatsu M, Takahashi H, Makifuchi T, Fukuhara N, Tsuji S. Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein. Ann Neurol. 2004 Feb;55(2):241-9. PMID:14755728 doi:10.1002/ana.10808
9. ↑ Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF. Aprataxin, a novel protein that protects against genotoxic stress. Hum Mol Genet. 2004 May 15;13(10):1081-93. Epub 2004 Mar 25. PMID:15044383 doi:10.1093/hmg/ddh122
10. ↑ Kijas AW, Harris JL, Harris JM, Lavin MF. Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA/RNA binding and nucleotide hydrolase activities. J Biol Chem. 2006 May 19;281(20):13939-48. Epub 2006 Mar 16. PMID:16547001 doi:M507946200
11. ↑ Ahel I, Rass U, El-Khamisy SF, Katyal S, Clements PM, McKinnon PJ, Caldecott KW, West SC. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature. 2006 Oct 12;443(7112):713-6. Epub 2006 Sep 10. PMID:16964241 doi:10.1038/nature05164
12. ↑ Rass U, Ahel I, West SC. Actions of aprataxin in multiple DNA repair pathways. J Biol Chem. 2007 Mar 30;282(13):9469-74. Epub 2007 Feb 2. PMID:17276982 doi:M611489200