Homo sapiens L. (human) [HSA]

FULL NAME: Polynucleotide 3'-phosphatase


DESCRIPTION:
Catalyzes the phosphorylation of DNA at 5'-hydroxyl termini and can dephosphorylate its 3'-phosphate termini. Plays an important function in DNA repair following ionizing radiation or oxidative damage.
Polynucleotide kinase/phosphatase (PNKP) is a bifunctional enzyme that can phosphorylate the 5'-OH termini and dephosphorylate the 3'-phosphate termini of DNA. It is a DNA repair enzyme involved in the processing of strand break termini, which permits subsequent repair proteins to replace missing nucleotides and rejoin broken strands.

Polynucleotide kinase as a potential target for enhancing cytotoxicity by ionizing radiation and topoisomerase I inhibitors.
The cytotoxicity of many antineoplastic agents is due to their capacity to damage DNA and there is evidence indicating that DNA repair contributes to the cellular resistance to such agents. DNA strand breaks constitute a significant proportion of the lesions generated by a broad range of genotoxic agents, either directly, or during the course of DNA repair. Strand breaks that are caused by many agents including ionizing radiation, topoisomerase I inhibitors, and DNA repair glycosylases such as NEIL1 and NEIL2, often contain 5'-hydroxyl and/or 3'-phosphate termini. These ends must be converted to 5'-phosphate and 3'-hydroxyl termini in order to allow DNA polymerases and ligases to catalyze repair synthesis and strand rejoining. A key enzyme involved in this end-processing is polynucleotide kinase (PNK), which possesses two enzyme activities, a DNA 5'-kinase activity and a 3'-phosphatase activity. PNK participates in the single-strand break repair pathway and the non-homologous end joining pathway for double-strand break repair. RNAi-mediated down-regulation of PNK renders cells more sensitive to ionizing radiation and camptothecin, a topoisomerase I inhibitor. Structural analysis of PNK revealed the protein is composed of three domains, the kinase domain at the C-terminus, the phosphatase domain in the centre and a forkhead associated (FHA) domain at the N-terminus. The FHA domain plays a critical role in the binding of PNK to other DNA repair proteins. Thus each PNK domain may be a suitable target for small molecule inhibition to effectively reduce resistance to ionizing radiation and topoisomerase I inhibitors.


MISCELLANEOUS:
Expressed in many tissues with highest expression in spleen and testis, and lowest expression in small intestine. Expressed in higher amount in pancreas, heart and kidney and at lower levels in brain, lung and liver.


STRUCTURE SIMILARITY:
In the N-terminal section; belongs to the DNA 3' phosphatase family.


CATALYTIC ACTIVITY:
ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA.
A 3'-phosphopolynucleotide + H(2)O = a polynucleotide + phosphate.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated upon DNA damage, probably by ATM or ATR.


PROTEIN TYPE(S):
kinase
phosphatase


RELATED DISEASE(S):
microcephaly seizures and development delay (MCSZ)


RELATED DAMAGE:
3'-P


Amino acids sequence

        10         20         30         40         50         60
MGEVEAPGRL WLESPPGGAP PIFLPSDGQA LVLGRGPLTQ VTDRKCSRTQ VELVADPETR
        70         80         90        100        110        120
TVAVKQLGVN PSTTGTQELK PGLEGSLGVG DTLYLVNGLH PLTLRWEETR TPESQPDTPP
       130        140        150        160        170        180
GTPLVSQDEK RDAELPKKRM RKSNPGWENL EKLLVFTAAG VKPQGKVAGF DLDGTLITTR
       190        200        210        220        230        240
SGKVFPTGPS DWRILYPEIP RKLRELEAEG YKLVIFTNQM SIGRGKLPAE EFKAKVEAVV
       250        260        270        280        290        300
EKLGVPFQVL VATHAGLYRK PVTGMWDHLQ EQANDGTPIS IGDSIFVGDA AGRPANWAPG
       310        320        330        340        350        360
RKKKDFSCAD RLFALNLGLP FATPEEFFLK WPAAGFELPA FDPRTVSRSG PLCLPESRAL
       370        380        390        400        410        420
LSASPEVVVA VGFPGAGKST FLKKHLVSAG YVHVNRDTLG SWQRCVTTCE TALKQGKRVA
       430        440        450        460        470        480
IDNTNPDAAS RARYVQCARA AGVPCRCFLF TATLEQARHN NRFREMTDSS HIPVSDMVMY
       490        500        510        520
GYRKQFEAPT LAEGFSAILE IPFRLWVEPR LGRLYCQFSE G 

Encoded by PNKP gene

FULL NAME: polynucleotide kinase 3'-phosphatase


OTHER NAME(S):
EIEE10
MCSZ
PNK


DESCRIPTION:
This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]


Nucleic acid sequence

        10         20         30         40         50         60
atgggcgagg tggaggcccc gggccgcttg tggctcgaga gcccccctgg gggagcgccc
        70         80         90        100        110        120
cccatcttcc tgccctcgga cgggcaagcc ctggtcctgg gcaggggacc cctgacccag
       130        140        150        160        170        180
gttacggacc ggaagtgctc cagaactcaa gtggagctgg tcgcagatcc tgagacccgg
       190        200        210        220        230        240
acagtggcag tgaaacagct gggagttaac ccctcaacta ccgggaccca ggagttgaag
       250        260        270        280        290        300
ccggggttgg agggctctct gggggtgggg gacacactgt atttggtcaa tggcctccac
       310        320        330        340        350        360
ccactgaccc tgcgctggga agagacccgc acaccagaat cccagccaga tactccgcct
       370        380        390        400        410        420
ggcacccctc tggtgtccca agatgagaag agagatgctg agctgccgaa gaagcgtatg
       430        440        450        460        470        480
cggaagtcaa accccggctg ggagaacttg gagaagttgc tagtgttcac cgcagctggg
       490        500        510        520        530        540
gtgaaacccc agggcaaggt ggctggcttt gatctggacg ggacgctcat caccacacgc
       550        560        570        580        590        600
tctgggaagg tctttcccac tggccccagt gactggagga tcttgtaccc agagattccc
       610        620        630        640        650        660
cgtaagctcc gagagctgga agccgagggc tacaagctgg tgatcttcac caaccagatg
       670        680        690        700        710        720
agcatcgggc gcgggaagct gccagccgag gagttcaagg ccaaggtgga ggctgtggtg
       730        740        750        760        770        780
gagaagctgg gggtcccctt ccaggtgctg gtggccacgc acgcaggctt gtaccggaag
       790        800        810        820        830        840
ccggtgacgg gcatgtggga ccatctgcag gagcaggcca acgacggcac gcccatatcc
       850        860        870        880        890        900
atcggggaca gcatctttgt gggagacgca gccggacgcc cggccaactg ggccccgggg
       910        920        930        940        950        960
cggaagaaga aagacttctc ctgcgccgat cgcctgtttg ccctcaacct tggcctgccc
       970        980        990       1000       1010       1020
ttcgccacgc ctgaggagtt ctttctcaag tggccagcag ccggcttcga gctcccagcc
      1030       1040       1050       1060       1070       1080
tttgatccga ggactgtctc ccgctcaggg cctctctgcc tccccgagtc cagggccctc
      1090       1100       1110       1120       1130       1140
ctgagcgcca gcccggaggt ggttgtcgca gtgggattcc ctggggccgg gaagtccacc
      1150       1160       1170       1180       1190       1200
tttctcaaga agcacctcgt gtcggccgga tatgtccacg tgaacaggga cacgctaggc
      1210       1220       1230       1240       1250       1260
tcctggcagc gctgtgtgac cacgtgtgag acagccctga agcaagggaa acgggtcgcc
      1270       1280       1290       1300       1310       1320
atcgacaaca caaacccaga cgccgcgagc cgcgccaggt acgtccagtg tgcccgagcc
      1330       1340       1350       1360       1370       1380
gcgggcgtcc cctgccgctg cttcctcttc accgccactc tggagcaggc gcgccacaac
      1390       1400       1410       1420       1430       1440
aaccggtttc gagagatgac ggactcctct catatccccg tgtcagacat ggtcatgtat
      1450       1460       1470       1480       1490       1500
ggctacagga agcagttcga ggccccaacg ctggctgaag gcttctctgc catcctggag
      1510       1520       1530       1540       1550       1560
atcccgttcc ggctatgggt ggagccgagg ctggggcggc tgtactgcca gttctccgag

ggctga     

Last modification date: Oct. 16, 2011