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FLASH GENE
Symbol TDP1 contributors: mct/npt/pgu - updated : 27-11-2015
HGNC name tyrosyl-DNA phosphodiesterase 1
HGNC id 18884
Corresponding disease
SCAN1 spinocerebellar ataxia with axonal neuropathy
Location 14q32.11      Physical location : 90.422.245 - 90.511.106
Synonym name Tyr-DNA phosphodiesterase 1
Synonym symbol(s) SCAN1, FLJ11090, MGC104252
EC.number 3.1.4.-
DNA
TYPE functioning gene
STRUCTURE 88.86 kb     17 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
GALC 14q31 galactosylceramidase (Krabbe disease) GPR65 14q31.1 G protein-coupled receptor 65 LOC283587 14q31.3 hypothetical protein LOC283587 KCNK10 14q31 potassium channel, subfamily K, member 10 SPATA7 14q31.3 spermatogenesis associated 7 PTPN21 14q31.1 protein tyrosine phosphatase, non-receptor type 21 FLJ11806 14q31.3 nuclear protein UKp68 EML5 14q31.3 echinoderm microtubule associated protein like 5 TTC8 14q31.3 tetratricopeptide repeat domain 8 LOC390501 14 similar to MPPE1 protein CHES1 14q24.3-q31 checkpoint suppressor 1 C14orf116 14q31.3 chromosome 14 open reading frame 116 CAP2P1 14 CAP, adenylate cyclase-associated protein, 2 (yeast) pseudogene 1 PRO1768 14q32.11 PRO1768 protein CHORDC2P 14 cysteine and histidine-rich domain (CHORD)-containing 2 pseudogene C14orf143 14q32.11 chromosome 14 open reading frame 143 TDP1 14q32.11 tyrosyl-DNA phosphodiesterase 1 KCNK13 14q24.1-q24.3 potassium channel, subfamily K, member 13 GLRXP2 14q32.13-q32.2 glutaredoxin pseudogene 2 PSMC1 19p13.3 proteasome (prosome, macropain) 26S subunit, ATPase, 1 C14orf102 14q32.11 chromosome 14 open reading frame 102 RPL21P11 14q32.11 ribosomal protein L21 pseudogene 11 CALM1 14q24-q31 calmodulin 1 (phosphorylase kinase, delta) TTC7L1 14q32.12 tetratricopeptide repeat domain 7 like 1 RPS18P2 14 ribosomal protein S18 pseudogene 2 LOC283588 14q32.12 hypothetical protein LOC283588 RPS6KA5 14q31-q32.1 ribosomal protein S6 kinase, 90kDa, polypeptide 5 C14orf159 14q32.12 chromosome 14 open reading frame 159 GPR68 14q31 G protein-coupled receptor 68 KIAA1509 14q32.12 KIAA1509 LOC388005 14 similar to RIKEN cDNA 0610010D24 KIAA2010 14q32.12 KIAA2010 C14orf161 14q32.12 chromosome 14 open reading frame 161 MTAC2D1 14q32.12 membrane targeting (tandem) C2 domain containing 1 FBLN5 14q32.1 fibulin 5 TRIP11 14q31-q32 thyroid hormone receptor interactor 11
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 splicing 3763 68 608 - 2001 11572945
  • encoding the same isoform
  • 16 splicing 3540 68 608 - 2001 11572945
  • differing in the 5' UTR compared to variant 1
  • encoding the same isoform
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   moderately
     thymus   highly
    Reproductivemale systemtestis  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Mus musculus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two unusual HKD signature motifs
  • two PLD phosphodiesterase domains
  • mono polymer monomer
    HOMOLOGY
    interspecies homolog to murine Tdp1
    Homologene
    FAMILY
  • phospholipase D superfamily
  • tyrosyl-DNA phosphodiesterase family
  • CATEGORY enzyme , DNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus
    text
  • a fraction of the TDP1 encoded by the nuclear TDP1 gene localizes to mitochondria
  • basic FUNCTION
  • involved in repairing covalent topo-isomerase 1-DNA complexes
  • remove glycolate from single-stranded DNA containing a 3'- phosphoglycolate, suggesting a role in repair of
  • free-radical mediated DNA double-strand breaks
  • required for repair of chromosomal single-strand breaks arising independently of DNA replication from abortive top1 activity or oxidative stress
  • playing a role in the repair of DNA damage mediated by topoisomerase II
  • required for neural homeostasis
  • critical for DNA chromosomal single-strand breaks repair in primary neural cells and required to prevent progressive cerebellar atrophy
  • hydrolyzes the phosphodiester bond between a tyrosyl moiety and a DNA 3prime-end
  • playing a role in repair of 3'-phosphoglycolate-terminated DNA double-strand breaks (Zhou 2009)
  • its optimal function requires its phosphorylation by ATM and/or (Das 2009)
  • required for efficient repair of oxidative damage in mitochondrial DNA, and is a novel mitochondrial enzyme
  • role of TDP1 in protecting against oxidative DNA damage in mitochondria
  • involvement of TOP1, TDP1 , and single-strand break repair (SSBR) in modulating transcription-dependent CAG repeat contractions
  • TDP1 and TDP2 fulfil overlapping roles following TOP1-induced DNA damage, but not following TOP2A-induced DNA damage
  • role of cytoplasmic TDP1 is the repair of mitochondrial DNA lesions arising from oxidative stress
  • role of TDP1 and APTX in mitochondrial DNA repair
  • not only excises trapped topoisomerases I (Top1 in the nucleus and Top1mt in mitochondria), but also repairs oxidative damage-induced 3'-phosphoglycolates and alkylation damage-induced DNA breaks
  • catalyzes the repair of 3prime-DNA adducts, such as the 3prime-phosphotyrosyl linkage of DNA topoisomerase I to DNA
  • a role for TDP1 during the early stages of mammalian NHEJ (non-homologous end joining)
  • functional significance of PARP1 and TDP1 interaction in the process of DNA repair
  • DNA repair enzyme that removes irreversible protein-linked 3' DNA complexes, 3' phosphoglycolates, alkylation damage-induced DNA breaks, and 3' deoxyribose nucleosides
  • potential role of TDP1 in both canonical non-homologous end joining and alternative end joining, but not in the homologous recombination repair pathway
  • CELLULAR PROCESS nucleotide, repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • sequestered into multi-protein single-strand break repair (SSBR) complexes by direct interaction with DNA ligase III and that these complexes are catalytically inactive in SCAN1 cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DNA ligase III
  • interacting with topoisomerase II
  • is a substrate for modification by the small ubiquitin-like modifier SUMO
  • DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway
  • active role of TDP1 in the repair of TOP2A-induced DNA damage
  • cell & other
    REGULATION
    Other phosphorylation at S81 mediated by the protein kinases: ataxia-telangiectasia-mutated (ATM) and DNA-dependent protein kinase PRKDC (TDP1 post-translational regulation by ATM and PRKDC)
    S81 phosphorylation enhancing TDP1 interactions with XRCC1 and promotes the recruitment of TDP1 to DNA damage sites
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAN1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone
    Susceptibility To Tourette syndrome (TS)
    Variant & Polymorphism other
  • polymorphism at position rs28365054 in the TDP1 gene had a significant difference between the TS patients (AG genotype was a risk factor for TS)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS