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Information on EC 2.7.1.78 - polynucleotide 5'-hydroxyl-kinase and Organism(s) Mus musculus and UniProt Accession Q9JLV6
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2.7.1.78 polynucleotide 5'-hydroxyl-kinaseIUBMB Comments
Also acts on 5'-dephospho-RNA 3'-mononucleotides.
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Word Map
- 2.7.1.78
- termini
- strand
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single-stranded
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gamma-32patp
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exonuclease
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32p-postlabeling
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5\'-hydroxyl
- bacteriophage
- phosphodiesterase
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3'-phosphatase
- nick
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32p-labeled
- duplex
- 3'-monophosphate
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5'-phosphorylated
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5'-terminal
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postlabeling
- dsdna
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anticodon
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5\'-termini
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klenow
- xrcc4
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dinucleoside
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micrococcal
- 3',5'-bisphosphate
- synthesis
- primase
-
carcinogen-dna
-
phosphotriester
-
t4-infected
- oligoribonucleotide
- analysis
- biotechnology
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
pnk, polynucleotide kinase, t4 polynucleotide kinase, t4 pnk, hd-pnk, dna kinase, hpnkp, 5'-oh polynucleotide kinase, cleavage and polyadenylation factor i subunit, 5'-hydroxyl polynucleotide kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5'-hydroxyl polynucleotide kinase
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5'-hydroxyl polyribonucleotide kinase
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5'-hydroxyl RNA kinase
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ATP:5'-dephosphopolynucleotide 5'-phosphatase
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DNA 5'-hydroxyl kinase
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DNA kinase
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kinase (phosphorylating), polynucleotide 5'-hydroxyl
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PNK
polynucleotide 5'-hydroxyl kinase (phosphorylating)
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polynucleotide 5'-hydroxyl-kinase
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polynucleotide kinase
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PNK
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:5'-dephosphopolynucleotide 5'-phosphotransferase
Also acts on 5'-dephospho-RNA 3'-mononucleotides.
CAS REGISTRY NUMBER
COMMENTARY
37211-65-7
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 5'-dephospho-RNA
ADP + 5'-phospho-RNA
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much more efficient as substrate than DNA
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?
ATP + synthetic oligonucleotide
ADP + oligonucleotide 5'-phosphate
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5'-hydroxyl poly(A)
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-
?
ATP + 5'-dephospho-DNA
ADP + 5'-phospho-DNA
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micrococcal-nuclease-treated calf thymus DNA is not effectively phosphorylated
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?
additional information
?
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prefers double-stranded substrates with recessed 5-termini
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?
additional information
?
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PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
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PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(3-bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-N1-cyclohexyl-N2-[2-(1H-imidazol-4-yl)ethyl]piperazine-1,2-dicarboxamide
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4-(3-bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-N1-cyclohexyl-N2-[3-(1H-imidazol-4-yl)propyl]piperazine-1,2-dicarboxamide
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ATP
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the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp396 that activates the 5'-OH for attack on the ATP gamma-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione
A12B4C3
additional information
-
productive engagement of a 3'-phosphate terminus may block access of a 5'-hydroxyl to the kinase active site
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
XRCC1
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mechanism underlying XRCC1-induced stimulation of PNKP, XRCC1 displaces PNKP from the reaction product, and addition of XRCC1 increases PNKP enzymatic turnover. Phosphorylation of XRCC1 by CK2 stimulates the kinase and phosphatase activities of PNKP
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 9.4
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pH 7.5: about 50% of activity maximum, pH 8.4 and pH 9.4: about 85% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
mice with PNKP inactivation in neural progenitors manifest neurodevelopmental abnormalities and postnatal death. The phenotype involves defective base excision repair and nonhomologous end-joining. Mice homozygous for the T424GfsX48 frame-shift allele are lethal embryonically, and attenuated PNKP levels akin to microcephaly with seizures syndrome show general neurodevelopmental defects. Directed postnatal neural inactivation of PNKP affects specific subpopulations including oligodendrocytes
physiological function
additional information
physiological function
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bifunctional polynucleotide kinase/phosphatase contains both DNA 5'-kinase and 3'-phosphatase activities required for restoration of 3'-hydroxyls and 5'-phosphates needed to seal the broken DNA. Cellular DNA is constantly assaulted by ionizing radiation and reactive oxygen species. This damage, along with the products of some DNA repair enzymes, may contain 5' hydroxyls or 3' phosphates. These are converted by PNK to 5' phosphates and 3' hydroxyls, which are required for DNA polymerases and DNA ligases to complete repair of the damaged DNA. Productive engagement of a 3'-phosphate terminus may block access of a 5'-hydroxyl to the kinase active site
physiological function
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polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini
additional information
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molecular architecture of the enzyme, overview. The mammalian enzyme preferentially phosphorylates 5'-hydroxyl termini within nicked, gapped or DSBs with single-stranded 3' overhanging ends, whereas single-stranded 5'-termini or blunt double-stranded ends are phosphorylated less efficiently. The selective recognition of the larger, double-stranded DNA substrates is effected by a broad DNA recognition groove composed of two distinct positively charged surfaces. Mechanisms of single-strand break and double-strand break repairs, and base excision repair, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PNKP_MOUSE
522
0
57223
Swiss-Prot
Mitochondrion (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
strcuture has three compact domains with kinase domain at the C-terminus
additional information
-
PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains. The forkhead-associated domain is linked to the catalytic domain through a flexible polypeptide segment and acts to selectively bind acidic casein kinase 2-phosphorylated regions in XRCC1 and XRCC4, which are key scaffolding proteins in the repair of DNA single and double strand breaks, respectively. Two catalytic active sites are positioned on the same side of the protein
additional information
-
separate kinase and phosphatase catalytic activities are located in two halves of an interconnected bilobed catalytic domain that is flexibly linked to an aminoterminal phosphoprotein-binding forkhead-associated domain
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
inactivated PNK mutant protein with several 3'-phosphorylated DNAs of different sequence bound in the phosphatase active site
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sertic-Pritsos, K.; Vinocour, M.; Winicov, I.
5-Hydroxyl RNA kinase from mouse L cells
Eur. J. Biochem.
144
47-55
1984
Mus musculus
Bernstein, N.K.; Williams, R.S.; Rakovszky, M.L.; Cui, D.; Green, R.; Karimi-Busheri, F.; Mani, R.S.; Galicia, S.; Koch, C.A.; Cass, C.E.; Durocher, D.; Weinfeld, M.; Glover, J.N.
The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase
Mol. Cell
17
657-670
2005
Mus musculus (Q9JLV6)
Freschauf, G.K.; Karimi-Busheri, F.; Ulaczyk-Lesanko, A.; Mereniuk, T.R.; Ahrens, A.; Koshy, J.M.; Rasouli-Nia, A.; Pasarj, P.; Holmes, C.F.; Rininsland, F.; Hall, D.G.; Weinfeld, M.
Identification of a small molecule inhibitor of the human DNA repair enzyme polynucleotide kinase/phosphatase
Cancer Res.
69
7739-7746
2009
Tequatrovirus T4, Homo sapiens, Schizosaccharomyces pombe, Mus musculus (Q9JLV6)
Weinfeld, M.; Mani, R.S.; Abdou, I.; Aceytuno, R.D.; Glover, J.N.
Tidying up loose ends: the role of polynucleotide kinase/phosphatase in DNA strand break repair
Trends Biochem. Sci.
36
262-271
2011
Tequatrovirus T4, Homo sapiens, Mus musculus, Schizosaccharomyces pombe
Schellenberg, M.; Williams, R.
DNA end processing by polynucleotide kinase/phosphatase
Proc. Natl. Acad. Sci. USA
108
20855-20856
2011
Homo sapiens, Mus musculus
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