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3kt9
From Proteopedia
Aprataxin FHA Domain
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. Publication Abstract from PubMedAprataxin, 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
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Categories: Human | Cherry, A L | Smerdon, S J | Amp hydrolase | Beta sandwich | Beta sheet | Disease mutation | Dna damage | Dna repair | Dna-binding | Fha domain | Hydrolase | Metal-binding | Neurodegeneration | Nucleus | Zinc-finger
