3.6.1.71	evolution	aprataxin (APTX) belongs to a family of histidine triad (HIT) enzymes. Mutation of His138 to alanine does not completely abolish the catalytic activity; the residual activity is 25% of the wild-type enzyme activity. The DNA deadenylation reaction catalyzed by the H138A mutant can proceed by the protonated substrate	750307	
3.6.1.71	malfunction	APTX human mutations cause the neurodegenerative disorder ataxia with oculomotor ataxia 1 (AOA1). AOA1 mutagenic effects on APTX solubility, stability, and catalytic activity, and molecular basis for APTX inactivation in AOA1, APTX mutations variably impact protein folding and activity, overview	750417	
3.6.1.71	malfunction	ataxia oculomotor apraxia-1 (AOA1) is a recessive human neurodegenerative disorder linked to more than 20 distinct mutations in the gene encoding APTX. Although reminiscent of ataxia-telangiectasia, primary AOA1 fibroblasts exhibit only mild hypersensitivity to ionizing radiation	750390	
3.6.1.71	malfunction	lack of aprataxin impairs mitochondrial functions, independent of its role in mitochondrial DNA repair, via downregulation of the APE1/NRF1/NRF2 pathway. Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency is identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized to mitochondria in neuroblastoma cells, where it enhances preservation of mitochondrial function. The bioenergetics defect in AOA1-mutant fibroblasts and APTX-depleted Hela cells is caused by decreased expression of SDHA and genes encoding CoQ biosynthetic enzymes, in association with reductions of APE1, NRF1 and NRF2. APE1 depletion impairs NRF1 expression in Hela cells and resembles APTX knockdown clones, mitochondrial genes are downregulated in APE1-deficient cells owing to the regulatory role of APE1 on DNA-binding and transcriptional activity of NRF1	750720	
3.6.1.71	malfunction	mutation of aprataxin (APTX) is causing the heritable neurological disorder ataxia with oculomotor apraxia 1 (AOA1)	752086	
3.6.1.71	malfunction	mutations of the APTX gene cause neurological diseases such as ataxia oculomotor aparaxia type 1 (AOA1)	750307	
3.6.1.71	malfunction	while hnt3DELTA single mutants are not sensitive to DNA damaging agents, loss of HNT3 causes synergistic sensitivity to H2O2 in backgrounds that accumulate strand breaks with blocked termini, including apn1DELTA/apn2DELTA/tpp1DELTA and ntg1DELTA/ntg2DELTA/ogg1DELTA. Loss of HNT3 in rad27DELTA cells, which are deficient in long-patch base excision repair (LP-BER), results in synergistic sensitivity to H2O2 and methylmethane sulfonate, indicating that Hnt3 and LP-BER provide parallel pathways for processing 5'-AMPs. Loss of HNT3 also increases the sister chromatid exchange frequency. HNT3 deletion partially rescues H2O2 sensitivity in recombination deficient rad51DELTA and rad52DELTA cells, suggesting that Hnt3 promotes formation of a repair intermediate that is resolved by recombination. Expression of Myc-NLS-tagged human aprataxin from a plasmid complements HNT3 deletion	750390	
3.6.1.71	additional information	active site structure of APTX, and molecular reaction mechanism, modeling, overview. General acid-base catalysis of APTX with and important role of His138 as a general acid. The second step, the histidine-AMP intermediate hydrolysis, can proceed with the aid of the product DNA phosphate without a general base residue	750307	
3.6.1.71	additional information	two highly conserved amino acid sequence motifs typify the HIT-Znf region of APTX. The first is the histidine triad motif HXHXHXX (X = hydrophobic residue) of the HIT domain, and the second is a C-terminal Zn-binding (Znf) domain with a sequence motif C(x2)C(x11-12)H(x3)H/E (x = any amino acid). This core HIT-Znf architecture is conserved in APTX orthologs with bona-fide polynucleotide adenylate hydrolase activity including plant, yeast and vertebrate homologues, suggesting that the Znf domain imparts critical substrate specificity to the aprataxins. The APTX Zn2+-binding betabetaalpha core is structurally related to the ubiquitous family of DNA binding C2H2 transcription factors including the prototypical Zif268. APTX Zn2+ ligands can be of either the C2H2 (Cys2-His2 in vertebrate APTX) or C2HE (Cys2-His-Glu in fungal Aptx), which both fold into very similar DNA damage recognition elements	752086	
3.6.1.71	physiological function	5'-AMP DNA hydrolysis of aprataxin, energy profile of the APTX catalytic reaction and the protonate states, by quantum mechanical/molecular mechanical (QM/MM) calculations and modeling, overview. Aprataxin hydrolyses abnormal 5'-AMP DNA termini formed in abortive DNA ligations, it is an important DNA repair enzyme	750307