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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
Corresponding disease
AOA4 ataxia-oculomotor apraxia 4
MCSZ microcephaly, seizures, and developmental delay
Location 19q13.33      Physical location : 50.364.459 - 50.370.822
Synonym name
  • polydeoxyribonucleotide kinase 1
  • polynucleotide kinase 3'-phosphatase, amino acids 68-521
  • DNA 5'-kinase/3'-phosphatase
  • Synonym symbol(s) PNK, PDNAK1, EIEE10, MCSZ
    EC.number 2.7.1.78, 3.1.3.32
    DNA
    TYPE functioning gene
    STRUCTURE 6.36 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    TIP39 19q13.33 tuberoinfundibular 39 residue protein precursor LOC390955 19 similar to ENSANGP00000004655 SLC17A7 19q13 solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7 FLJ20643 19q13.33 hypothetical protein FLJ20643 MGC10204 19q13.33 hypothetical protein MGC10204 FLT3LG 19q13.3 fms-related tyrosine kinase 3 ligand RPL13A 19q13.4 ribosomal protein L13a RPS11 19q13.3 ribosomal protein S11 FCGRT 19q13.3 Fc fragment of IgG, receptor, transporter, alpha RCN3 19q13.33 reticulocalbin 3, EF-hand calcium binding domain NOSIP 19q13.3 nitric oxide synthase interacting protein PRRG2 19q13.33 proline-rich Gla (G-carboxyglutamic acid) polypeptide 2 KIAA1205 19q13.33 KIAA1205 RRAS 19q13.3-q13.4 related RAS viral (r-ras) oncogene homolog SR-A1 19q13.3-q13.4 serine arginine-rich pre-mRNA splicing factor SR-A1 IRF3 19q13.3 interferon regulatory factor 3 BCL2L12 19q13.3 BCL2-like 12 (proline rich) HRMT1L2 19q13-3 HMT1 hnRNP methyltransferase-like 2 (S. cerevisiae) LOC199800 19q13.33 hypothetical protein LOC199800 CPT1C 19q13.33 hypothetical protein LOC199800 LOC388556 19 hypothetical gene supported by NM_001013 TSKS 19q13.3 hypothetical gene supported by NM_001013 AP2A1 19q13.3 adaptor-related protein complex 2, alpha 1 subunit FLJ22688 19q13.33 hypothetical protein FLJ22688 TCBAP0758 19q13.3 hypothetical protein TCBAP0758 PTOV1 19q13.33 prostate tumor over expressed gene 1 PNKP 19q13.3-q13.4 polynucleotide kinase 3'-phosphatase MGC2865 19q13.33 hypothetical protein MGC2865 FLJ12168 IL4I1 19q13.3-q13.4 interleukin 4 induced 1 NUP62 19q13.33 nucleoporin 62kDa ATF5 19q13.3 activating transcription factor 5 SIGLEC11 19q13.33 sialic acid binding Ig-like lectin 11 VRK3 19q13 vaccinia related kinase 3 ZNF473 19q13.33 zinc finger protein 473 LOC342917 19q13.33 similar to kruppel-related zinc finger protein MGC33947 19q13.33 hypothetical protein MGC33947 MYH14 19q13.33 myosin, heavy polypeptide 14
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 1745 - 521 - 2002 12032095
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrinepancreas   highly
    Reproductivefemale systemuteruscervix highly
     female systemovary  highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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