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FLASH GENE
Symbol APTX contributors: mct/pgu - updated : 26-11-2010
HGNC name aprataxin
HGNC id 15984
Corresponding disease
AOA1 ataxia-ocular apraxia 1
Location 9p21.1      Physical location : 32.972.604 - 33.001.639
Synonym name forkhead-associated domain histidine triad-like protein
Synonym symbol(s) AOA, EAOH, FLJ20157, AXA1, EOAHA, FHA-HIT, EOAHA, MGC1072
EC.number 3.-.-.-
DNA
TYPE functioning gene
STRUCTURE 29.02 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
text structure putative DNA binding site
MAPPING cloned Y linked Y status confirmed
Physical map
LOC392301 9 similar to ADP,ATP carrier protein, fibroblast isoform (ADP/ATP translocase 2) (Adenine nucleotide translocator 2) (ANT 2) ACO1 9p22-p13 aconitase 1, soluble RIG-I 9p12 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide TOPORS 9p21 topoisomerase I binding, arginine/serine-rich NDUFB6 9p13.2 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6, 17kDa TAF1L 9p13.3 TAF1-like RNA polymerase II, TATA box binding protein (TBP)-associated factor, 210kDa LOC389710 9 similar to hypothetical protein (L1H 3 region) - human LOC392302 9 similar to argininosuccinate synthetase APTX 9p13.3 aprataxin DNAJA1 9p13-p12 DnaJ (Hsp40) homolog, subfamily A, member 1 SMU-1 9p12 homolog of C. elegans smu-1 B4GALT1 9p13 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1 SPINK4 9p12 serine protease inhibitor, Kazal type 4 BAG1 9p12 BCL2-associated athanogene HSPC177 NFX1 9p12 nuclear transcription factor, X-box binding 1 AQP7 9p13 aquaporin 7 AQP3 9p13 aquaporin 3 NOL6 9p13.2 nucleolar protein family 6 (RNA-associated) bA255A11.3 9p12 FLJ35740 pseudogene LOC389711 9 similar to hypothetical protein DKFZp434F1719
RNA
TRANSCRIPTS type messenger
text three transcripts are not completely described
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 2116 38.9 342 highly expressed in cerebral cortex and cerebellum, and is largely nuclear 2011 21502511
  • starting from exon 1 full exon 3
  • a nuclear localization signal located near the amino terminus
  • isoform a, which lacks this N-terminal extension
  • interacting with ERCC1
  • - - 2010 - 356 - 2006 16439205
    also called isoform e
    8 initiation site 1836 19.6 168 lower expression 2006 16439205
  • eight exons
  • using a downstream codon initiation, resulting in a protein (isoform d) with a shorter N-terminus compared to isoform a
  • 8 - 2046 34.8 306 - 2011 21502511
  • isoform b
  • using an upstream codon initiation resulting in a protein (isoform b) with distinct N- and C-termini compared to isoform a
  • one of the isoforms that has the putative mitochondrial localization N-terminal signal
  • - - 2179 - 342 - 2006 16439205
    also called isoform a
    - - 1848 - 302 - 2006 16439205
    also called isoform f
    - - 2152 - 292 - 2006 16439205
    also called isoform g
    - - 1794 - 284 - 2006 16439205
    also called isoform i
    - - 1870 - 288 - 2006 16439205
    also called isoform h
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveesophagus   highly
     liver    
     salivary gland   highly
    Endocrineparathyroid   highly
    Nervousbrainhindbraincerebellum predominantly Homo sapiens
     brainlimbic systemhippocampus highly Homo sapiens
    Reproductivefemale systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    NervousPurkinje cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal domain homolog to polynucleotide kinase 3'-phosphatase (PKNT) domain and FHA domain, mediating complex formation with XRCC1-DNA ligase III by interaction with phosphorylated residues in XRCC1 , targeting certain isoforms of the protein to the mitochondrial intracellular compartment
  • a nuclear localization signal (NLS)
  • a middle region including the histidine triad motif HIT, having enzymatic activity that is negatively regulated by the intramolecular interaction of the N-terminal domain
  • one C2H2 type zinc finger
  • C-terminal domain implicated in possessing general DNA binding capacity
  • HOMOLOGY
    interspecies homolog to murine Aptx (87.1pc)
    homolog to rattus Aptx (84.4pc)
    Homologene
    FAMILY
  • histidine triad superfamily of nucleotide hydrolases and transferases
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • cross-dependence between aprataxin and nucleolin in the nucleolus and its nucleolar localization is dependent on rRNA synthesis
  • localizes to mitochondria in human cells
  • Purkinje cells had both nuclear and cytoplasmic aprataxin
  • basic FUNCTION
  • involved in DNA repair in the nucleolus, through its interactions with deadenylating XRCC1 and/or other components of DNA repair
  • influencing the cellular response to genotoxic stress very likely by its capacity to interact with a number of proteins involved in DNA repair
  • may have a general proofreading function in DNA repair, removing DNA adenylates as they arise during single-strand break repair, double-strand break repair, and in base excision repair
  • having an important and direct role in single-strand break repair, that is, it removes blocking molecules from DNA 3'-ends
  • first protein to adopt canonical histidine triad-type reaction chemistry for the repair of DNA
  • possesses nick sensor activity, which is ideally suited to locate and repair 5'-DNA adenylates
  • direct and indirect modulating functions on base excision repair
  • catalyzes removal of adenosine monophosphate (AMP) from the 5 prime end of a DNA strand, which results from an aborted attempt to ligate a strand break containing a damaged end
  • having potentially a direct role in mtDNA processing
  • plays an important role in the repair of mtDNA and that defects in aprataxin expression and/or function lead to mitochondrial dysfunction and oxidative stress
  • role of TDP1 and APTX in mitochondrial DNA repair
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, repair, base excision repair
    nucleotide, repair, nucleotide excision repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
  • constitute with XRCC1 a multiprotein complex involved in single-strand DNA break repair
  • INTERACTION
    DNA binding
    RNA binding
    small molecule
    protein
  • interacting with XRCC1, ADPRT, TP53, XRCC4
  • interacting with several nucleolar proteins, including nucleolin, nucleophosmin and upstream binding factor-1 (UBF-1), involved in ribosomal RNA (rRNA) synthesis and cellular stress signaling
  • interaction with PARP1, APEX1 (synergistic functions of aprataxin, PARP1 and APEX1 in the cellular response to DNA damage and the modulating function of aprataxin on base excision and long patch repair)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AOA1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    result in mitochondrial dysfunction and an accumulation of mtDNA damage
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    aprataxin resolves abortive DNA ligation intermediates in Aptrx-/- mouse primary neural cells