PNKP
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PNKP


PNKP
Protein PNKP PDB 2brf.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPNKP, EIEE10, MCSZ, PNK, AOA4, polynucleotide kinase 3'-phosphatase
External IDsOMIM: 605610 MGI: 1891698 HomoloGene: 5247 GeneCards: PNKP
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for PNKP
Genomic location for PNKP
Band19q13.33Start49,859,882 bp[1]
End49,878,351 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)

n/a

Location (UCSC)Chr 19: 49.86 - 49.88 MbChr 7: 44.86 - 44.86 Mb
PubMed search[3][4]
Wikidata

Bifunctional polynucleotide phosphatase/kinase is an enzyme that in humans is encoded by the PNKP gene.[5][6][7]

Interactions

PNKP has been shown to interact with DNA polymerase beta[8] and XRCC1.[8][9]

Role in Neurologic Disease[10]

The human gene encoding PNKP was observed to be mutated in patients [11][12][13] with microcephaly, seizures and defects in DNA repair. A type of recessive ataxia is also associated with PNKP mutations.[14] There are also newly characterized pathological variants of PNKP.[15] Model organisms such as mice and Drosophila have been used to generate further insights.[16][17]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000039650 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002963 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Jilani A, Ramotar D, Slack C, Ong C, Yang XM, Scherer SW, Lasko DD (September 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". J. Biol. Chem. 274 (34): 24176-86. doi:10.1074/jbc.274.34.24176. PMID 10446192.
  6. ^ Karimi-Busheri F, Daly G, Robins P, Canas B, Pappin DJ, Sgouros J, Miller GG, Fakhrai H, Davis EM, Le Beau MM, Weinfeld M (September 1999). "Molecular characterization of a human DNA kinase". J. Biol. Chem. 274 (34): 24187-94. doi:10.1074/jbc.274.34.24187. PMID 10446193.
  7. ^ "Entrez Gene: PNKP polynucleotide kinase 3'-phosphatase".
  8. ^ a b Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko DD, Weinfeld M, Caldecott KW (January 2001). "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair". Cell. 104 (1): 107-17. doi:10.1016/S0092-8674(01)00195-7. PMID 11163244.
  9. ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  10. ^ Dumitrache, Lavinia C.; McKinnon, Peter J. (2017). "Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease". Mechanisms of Ageing and Development. 161 (Pt A): 121-129. doi:10.1016/j.mad.2016.04.009. PMC 5161711. PMID 27125728.
  11. ^ Shen, Jun; Gilmore, Edward C; Marshall, Christine A; Haddadin, Mary; Reynolds, John J; Eyaid, Wafaa; Bodell, Adria; Barry, Brenda; Gleason, Danielle; Allen, Kathryn; Ganesh, Vijay S (2010). "Mutations in PNKP cause microcephaly, seizures and defects in DNA repair". Nat Genet. 42 (3): 245-249. doi:10.1038/ng.526. ISSN 1061-4036. PMC 2835984. PMID 20118933.
  12. ^ Issa, Lina; Mueller, Katrin; Seufert, Katja; Kraemer, Nadine; Rosenkotter, Henning; Ninnemann, Olaf; Buob, Michael; Kaindl, Angela M; Morris-Rosendahl, Deborah J (2013). "Clinical and cellular features in patients with primary autosomal recessive microcephaly and a novel CDK5RAP2 mutation". Orphanet Journal of Rare Diseases. 8 (1): 59. doi:10.1186/1750-1172-8-59. ISSN 1750-1172. PMC 3639195. PMID 23587236.
  13. ^ Kalasova, Ilona; Hanzlikova, Hana; Gupta, Neerja; Li, Yun; Altmüller, Janine; Reynolds, John J.; Stewart, Grant S.; Wollnik, Bernd; Yigit, Gökhan; Caldecott, Keith W. (2019). "Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ". Neurol Genet. 5 (2): e320. doi:10.1212/NXG.0000000000000320. ISSN 2376-7839. PMC 6454307. PMID 31041400.
  14. ^ Bras, Jose; Alonso, Isabel; Barbot, Clara; Costa, Maria Manuela; Darwent, Lee; Orme, Tatiana; Sequeiros, Jorge; Hardy, John; Coutinho, Paula; Guerreiro, Rita (2015). "Mutations in PNKP Cause Recessive Ataxia with Oculomotor Apraxia Type 4". The American Journal of Human Genetics. 96 (3): 474-479. doi:10.1016/j.ajhg.2015.01.005. PMC 4375449. PMID 25728773.
  15. ^ Gatti, Marta; Magri, Stefania; Nanetti, Lorenzo; Sarto, Elisa; Di Bella, Daniela; Salsano, Ettore; Pantaleoni, Chiara; Mariotti, Caterina; Taroni, Franco (2019). "From congenital microcephaly to adult onset cerebellar ataxia: Distinct and overlapping phenotypes in patients with PNKP gene mutations". American Journal of Medical Genetics Part A. 179 (11): 2277-2283. doi:10.1002/ajmg.a.61339. ISSN 1552-4825. PMID 31436889.
  16. ^ Shimada, Mikio; Dumitrache, Lavinia C; Russell, Helen R; McKinnon, Peter J (2015). "Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability". The EMBO Journal. 34 (19): 2465-2480. doi:10.15252/embj.201591363. ISSN 0261-4189. PMC 4601665. PMID 26290337.
  17. ^ Chakraborty, Anirban; Tapryal, Nisha; Venkova, Tatiana; Mitra, Joy; Vasquez, Velmarini; Sarker, Altaf H.; Duarte-Silva, Sara; Huai, Weihan; Ashizawa, Tetsuo; Ghosh, Gourisankar; Maciel, Patricia (2020-04-07). "Deficiency in classical nonhomologous end-joining-mediated repair of transcribed genes is linked to SCA3 pathogenesis". Proceedings of the National Academy of Sciences. 117 (14): 8154-8165. doi:10.1073/pnas.1917280117. ISSN 0027-8424. PMC 7148577. PMID 32205441.

Further reading



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PNKP
 



 



 
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