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FLASH GENE
Symbol TDP2 contributors: mct/pgu - updated : 25-11-2015
HGNC name tyrosyl-DNA phosphodiesterase 2
HGNC id 17768
Corresponding disease
SCAR23 spinocerebellar ataxia, autosomal recessive 23
Location 6p22.3      Physical location : 24.650.205 - 24.667.115
Synonym name
  • ETS1-associated protein 2
  • TRAF and TNF receptor associated protein
  • 5prime-tyrosyl-DNA phosphodiesterase
  • tyrosyl-RNA phosphodiesterase
  • Synonym symbol(s) AD022, EAP2, MGC111021, MGC9099, EAPII , dJ30M3.3, RP1-30M3.3, dJ30M3.3, TTRAP
    EC.number 3.1.4.-
    DNA
    TYPE functioning gene
    STRUCTURE 17.01 kb     7 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1940 - 362 - 2008 18706885
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine   highly
    Reproductivefemale systemuteruscervix highly
    Urinarybladder   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four conserved catalytic motifs shared by Mg2+-dependent endonucleases, such as APE1
  • structure for the C-terminal core of TDP2 (AAs 113–362) contains three beta-sheets sandwiched by two alpha-helices on either side, forming a potential DNA binding groove
  • HOMOLOGY
    Homologene
    FAMILY
  • AP endonuclease family 1
  • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,nucleolus
    text
  • predominantly localized to the nucleus of mammalian cells
  • in the nucleolus, contributes to control levels of ribosomal RNA precursor and processing intermediates
  • basic FUNCTION
  • inhibitor of NFKB activation
  • negatively modulates ETS1 transcriptional activity and attenuates synergistic transactivation by ETS1 and AP-1
  • ETS1 modulator that regulates specific aspects of the ETS1 functions
  • may be possessing an antiviral activity like other PML NBs-associated proteins
  • might play an important role in PML NBs-mediated antiviral activity
  • promyelocytic leukemia protein nuclear bodies-associated protein
  • is the major 5prime-tyrosyl DNA phosphodiesterase activity in vertebrate cells and is critical for cellular resistance to TOP2A-induced DNA damage
  • is a multifunctional protein that can act in the nucleus as a 5'-tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling
  • function for TDP2 and nucleolar cavities in ribosome biogenesis under stress
  • adaptor molecule that is a novel component of the non-canonical TGFB1 pathway
  • TDP2 contributes to cellular 3prime-TDP activity in the absence of TDP1
  • TDP1 and TDP2 fulfil overlapping roles following TOP1-induced DNA damage, but not following TOP2A-induced DNA damage
  • is not only specific but also efficient in recognizing and processing trapped TOP2A cleavage complexes even in the form of a longer peptide
  • having preferential action at abortive TOP2A and possibly TOP3A cleavage complexes
  • multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage
  • is essential for the life cycle of picornaviruses (important human and bovine pathogens)and is involved in signal transduction
  • repair function of TDP2 is devoted to the excision of topoisomerase II- and potentially topoisomerases III-DNA adducts
  • latest identified cytosolic protein that serves as a negative regulator for TNF signaling pathway
  • is a critical factor in grouper immune response to virus infection
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TNFRSF5 (CD40), TNFRSF8 (CD30), TNF-R75
  • interacts with ETS1 and other Ets proteins (ETS2 and FLI1)
  • colocalized and interacted with PML, SP100 and DAXX
  • interacts with HIV1- integrase to facilitate viral integration
  • MAPK6, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against TOP2 inhibitors-induced DNA damage and growth inhibition
  • cell & other
    REGULATION
    induced by IFN-gamma, representing a common feature of PML NBs-associated proteins
    Phosphorylated by MAPK6
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAR23
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS