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3kt9

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Revision as of 08:41, 1 November 2017

Aprataxin FHA Domain

Structural highlights

3kt9 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	APTX, AXA1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Publication Abstract from PubMed

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1.

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response.,Becherel OJ, Jakob B, Cherry AL, Gueven N, Fusser M, Kijas AW, Peng C, Katyal S, McKinnon PJ, Chen J, Epe B, Smerdon SJ, Taucher-Scholz G, Lavin MF Nucleic Acids Res. 2010 Mar;38(5):1489-503. Epub 2009 Dec 14. PMID:20008512^[13]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Becherel OJ, Jakob B, Cherry AL, Gueven N, Fusser M, Kijas AW, Peng C, Katyal S, McKinnon PJ, Chen J, Epe B, Smerdon SJ, Taucher-Scholz G, Lavin MF. CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response. Nucleic Acids Res. 2010 Mar;38(5):1489-503. Epub 2009 Dec 14. PMID:20008512 doi:10.1093/nar/gkp1149

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3kt9"

@@ Line 1: / Line 1: @@
 ==Aprataxin FHA Domain==
 <StructureSection load='3kt9' size='340' side='right' caption='[[3kt9]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[3kt9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KT9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KT9 FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APTX, AXA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kt9 OCA], [http://pdbe.org/3kt9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kt9 RCSB], [http://www.ebi.ac.uk/pdbsum/3kt9 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kt9 OCA], [http://pdbe.org/3kt9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kt9 RCSB], [http://www.ebi.ac.uk/pdbsum/3kt9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kt9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 36: / Line 37: @@
 [[Category: Cherry, A L]]
 [[Category: Smerdon, S J]]
+[[Category: Alternative splicing]]
 [[Category: Amp hydrolase]]
 [[Category: Beta sandwich]]
@@ Line 48: / Line 50: @@
 [[Category: Neurodegeneration]]
 [[Category: Nucleus]]
+[[Category: Zinc]]
 [[Category: Zinc-finger]]

3kt9

From Proteopedia

Revision as of 08:41, 1 November 2017

Aprataxin FHA Domain

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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