Property Summary

NCBI Gene PubMed Count 43
PubMed Score 52.50
PubTator Score 96.28

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (4)

Disease log2 FC p
psoriasis 2.100 1.3e-05
osteosarcoma -1.381 9.9e-04
tuberculosis 1.500 2.0e-08
ovarian cancer 1.800 5.6e-05

Protein-protein Interaction (3)

Gene RIF (25)

PMID Text
25728773 We identified homozygous or compound-heterozygous PNKP mutations in eight of the nine Portuguese families we studied, suggesting that, in Portugal, mutations in PNKP are the most frequent cause of ataxia with oculomotor apraxia.
25633985 Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity
25590633 We now report that the mutant ATXN3 protein interacts with and inactivates PNKP (polynucleotide kinase 3'-phosphatase), an essential DNA strand break repair enzyme
23883586 we show that modest inhibition of PNKP in a PTEN knockout background enhances cellular radiosensitivity, suggesting that such a "synthetic sickness" approach involving the combination of PNKP inhibition with radiotherapy
23224214 Mutations in PNKP have previously been associated with a syndrome of microcephaly, seizures and developmental delay (MIM 613402), and is now associated with a neurodegenerative disorder.
22992732 the interaction between PNKP and XRCC1 has roles in the retention of XRCC1 at DNA damage sites and in DNA alkylation damage repair
22508754 The data suggest that all four known mutations associated with microcephaly, seizures and developmental delay reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5'-kinase activity and all of the mutations greatly reducing cellular DNA 3'-phosphatase activity.
22174317 HIV-1 Rev interacting protein, polynucleotide kinase 3'-phosphatase (PNKP), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells
22171004 PNKP distorts target DNA structures to access damaged substrate DNA ends, thus providing a molecular mechanism for the involvement of PNKP in the repair of both single- and double-strand breaks.
22130663 the critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome.
21824916 Results reveal that ionizing radiation-induced phosphorylation of PNKP by ATM and DNA-PK regulates PNKP function at DNA double strand breaks.
21353781 Studies indicate that PNKP serves a crucial role in the repair of DNA strand breaks through interactions with other DNA repair proteins, notably XRCC1 and XRCC4.
20852255 CK2-mediated phosphorylation of XRCC4 can have different effects on PNKP activity.
20574454 Observational study of gene-disease association. (HuGE Navigator)
20522537 Observational study of gene-disease association. (HuGE Navigator)
20226869 Observational study of gene-disease association. (HuGE Navigator)
20118933 The neurological abnormalities in individuals with microcephaly, early onset, intractable seizures and develomental delays may reflect a role for PNKP in several DNA repair pathways.
19155274 the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex.
18414202 The PNKP T5644G variant does not seem to be involved in adenoma recurrence in the Polyp Prevention Trial.
18414202 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17650498 XRCC1 enhances the capacity of hPNK to discriminate between strand breaks with 5'-OH termini and those with 5'-phosphate termini; and XRCC1 stimulates hPNK activity by displacing hPNK from the phosphorylated DNA product
17638872 polynucleotide kinase participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination
16364363 Data show that polynucleotide kinase is associated with the PARP-1-dependent end-joining pathway, and show functional parallels between the PARP-1 and DNA-PK-dependent end-joining processes.
14556639 First direct physical evidence for ternary complex formation involving a polynucleotide kinase, AMP-PNP, and an oligonucleotide, supports a reaction mechanism in which ATP and DNA bind simultaneously to the enzyme.
12032095 Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining

AA Sequence

MGEVEAPGRLWLESPPGGAPPIFLPSDGQALVLGRGPLTQVTDRKCSRTQVELVADPETRTVAVKQLGVN      1 - 70
PSTTGTQELKPGLEGSLGVGDTLYLVNGLHPLTLRWEETRTPESQPDTPPGTPLVSQDEKRDAELPKKRM     71 - 140
RKSNPGWENLEKLLVFTAAGVKPQGKVAGFDLDGTLITTRSGKVFPTGPSDWRILYPEIPRKLRELEAEG    141 - 210
YKLVIFTNQMSIGRGKLPAEEFKAKVEAVVEKLGVPFQVLVATHAGLYRKPVTGMWDHLQEQANDGTPIS    211 - 280
IGDSIFVGDAAGRPANWAPGRKKKDFSCADRLFALNLGLPFATPEEFFLKWPAAGFELPAFDPRTVSRSG    281 - 350
PLCLPESRALLSASPEVVVAVGFPGAGKSTFLKKHLVSAGYVHVNRDTLGSWQRCVTTCETALKQGKRVA    351 - 420
IDNTNPDAASRARYVQCARAAGVPCRCFLFTATLEQARHNNRFREMTDSSHIPVSDMVMYGYRKQFEAPT    421 - 490
LAEGFSAILEIPFRLWVEPRLGRLYCQFSEG                                           491 - 521
//

Text Mined References (52)

PMID Year Title
27232581 2016 Microcephalic primordial dwarfism in an Emirati patient with PNKP mutation.
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
25728773 2015 Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4.
25633985 2015 The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia type 3 pathogenesis.
25609649 2015 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
25590633 2015 Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.
25416956 2014 A proteome-scale map of the human interactome network.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23883586 2013 Synthetic lethal targeting of PTEN-deficient cancer cells using selective disruption of polynucleotide kinase/phosphatase.
23224214 2013 Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22992732 2012 The interaction between polynucleotide kinase phosphatase and the DNA repair protein XRCC1 is critical for repair of DNA alkylation damage and stable association at DNA damage sites.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22508754 2012 Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair.
22171004 2011 Structural basis for the phosphatase activity of polynucleotide kinase/phosphatase on single- and double-stranded DNA substrates.
22130663 2012 Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome.
21824916 2011 Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage.
21637298 2011 ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair.
21531765 2011 High-throughput RNAi screening reveals novel regulators of telomerase.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21353781 2011 Tidying up loose ends: the role of polynucleotide kinase/phosphatase in DNA strand break repair.
21269460 2011 Initial characterization of the human central proteome.
20852255 2010 Dual modes of interaction between XRCC4 and polynucleotide kinase/phosphatase: implications for nonhomologous end joining.
20574454 2010 Polymorphisms in the base excision repair pathway and graft-versus-host disease.
20522537 2010 Variation within DNA repair pathway genes and risk of multiple sclerosis.
20226869 2010 Association between genetic variants in the base excision repair pathway and outcomes after hematopoietic cell transplantations.
20118933 2010 Mutations in PNKP cause microcephaly, seizures and defects in DNA repair.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19946888 2010 Defining the membrane proteome of NK cells.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19155274 2009 Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18414202 2008 Polynucleotide kinase 3' phosphatase variant, dietary variables and risk of adenoma recurrence in the Polyp Prevention Trial.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17650498 2007 XRCC1 stimulates polynucleotide kinase by enhancing its damage discrimination and displacement from DNA repair intermediates.
17638872 2007 Human polynucleotide kinase participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16364363 2006 Involvement of polynucleotide kinase in a poly(ADP-ribose) polymerase-1-dependent DNA double-strand breaks rejoining pathway.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15635413 2005 Nucleolar proteome dynamics.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15385968 2004 Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV.
15231748 2004 Functional proteomics mapping of a human signaling pathway.
15057824 2004 The DNA sequence and biology of human chromosome 19.
14556639 2003 Spectroscopic studies of DNA and ATP binding to human polynucleotide kinase: evidence for a ternary complex.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12032095 2002 Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining.
11163244 2001 XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair.
10446193 1999 Molecular characterization of a human DNA kinase.
10446192 1999 Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage.