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FLASH GENE
Symbol PNKP contributors: mct/npt/pgu - updated : 25-03-2016
HGNC name polynucleotide kinase 3'-phosphatase
HGNC id 9154
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a putative ATP binding site
  • a 3'phosphatase domain with similarity to L-2-haloacid dehalogenases
  • a P-loop motif, and a second motif associated with several different phosphatases
    • HOMOLOGY
    Homologene
    FAMILY
  • DNA 3' phosphatase family (in the N-terminal section)
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • presence of NEIL2 and PNKP in mitochondria
    • basic FUNCTION
  • 5'-DNA kinase and 3'phosphatase facilitating DNA repair of DNA single strand breaks caused by ionizing radiation or oxidative damage
  • direct, specific role in double-strand break repair
  • bifunctional enzyme possessing a 5'-DNA kinase activity and a 3'-phosphatase activity
  • required to process unligatable strand break termini generated directly by many genotoxic agents
  • participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination
  • involved in multiple repair pathways (BER, SSBR, and double strand break repair), so its abundance may be a requirement for the cells
  • involved in a poly(ADP-ribose) polymerase-1-dependent DNA double-strand breaks rejoining pathway
  • may have a role in several DNA repair pathways
  • implicated in repair of both double-strand breaks (DSBs) and single-strand breaks
  • critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome
  • is a relatively abundant DNA repair protein in mitochondria
  • plays a major role in repair of oxidized bases in the mitochondrial genome
  • is a dual-function enzyme with a key role in different pathways of DNA damage repair. DNA repair disorders can result in accelerated cell death, leading to underdevelopment and neurodegeneration
  • dual-function enzyme with a key role in different pathways of DNA-damage repair
    • CELLULAR PROCESS nucleotide, repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • unphosphorylated XRCC4 interacts with PNKP through a lower affinity interaction site within the catalytic domain and this interaction stimulates the turnover of PNKP
  • XRCC1 can interact with the catalytic domain of PNKP and stimulate PNKP activity
  • interacting with XRCC1 (a major function of XRCC1 is to stimulate PNKP activity by displacing PNKP from the phosphorylated DNA product)
  • binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain
  • PNKP is an ATM target
  • co-association of NEIL2 and PNKP with POLG on the mitochondrial genome
  • interact with DNA repair proteins involved in the onset of polyneuropathy and cerebellar degeneration
  • DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway
  • overlapping roles for PARP1 and PARP2 in the recruitment of endogenous XRCC1 and PNKP into oxidized chromatin
  • XRCC1 and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 and a forkhead-associated domain in PNKP
  • repair function of PNKP is facilitated by its binding to the scaffold protein XRCC1, and phosphorylation of XRCC1 by CSNK2A2 at several consensus sites enables PNKP binding and recruitment to DNA damage
    • cell & other
    REGULATION
    activated by XRCC1 at damaged DNA termini in order to accelerate DNA single strand break repair
    Phosphorylated by ATM (ATM-mediated phosphorylation of PNKP is required for effective DNA double-strand break repair)
    ASSOCIATED DISORDERS
    corresponding disease(s) MCSZ , AOA4
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS