2.7.1.74: deoxycytidine kinase
This is an abbreviated version!
For detailed information about deoxycytidine kinase, go to the full flat file.
Word Map on EC 2.7.1.74
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2.7.1.74
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leukemia
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gemcitabine
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thymidine
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triphosphate
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deaminase
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purine
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ribonucleotide
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deoxynucleoside
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pyrimidine
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deoxyguanosine
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salvage
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myeloid
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arabinoside
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cytarabine
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prodrugs
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deoxyadenosine
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1-beta-d-arabinofuranosylcytosine
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deoxyribonucleoside
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5'-nucleotidase
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cladribine
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cross-resistance
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ara-ctp
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2-chlorodeoxyadenosine
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2',2'-difluorodeoxycytidine
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fludarabine
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dttp
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antileukemic
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ccrf-cem
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dfdctp
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2-chloro-2'-deoxyadenosine
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gemcitabine-resistant
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dado
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deoxycytidylate
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kinase-deficient
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clofarabine
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2',3'-dideoxycytidine
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5'-phosphorylation
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arabinosyl
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deoxypyrimidine
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t-lymphoblastoid
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deoxycoformycin
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medicine
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2'-deoxyadenosine
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deoxythymidine
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l-nucleoside
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dideoxycytidine
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t-lymphoblasts
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2',3'-dideoxyinosine
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tetrahydrouridine
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arabinosylcytosine
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anabolites
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pharmacology
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analysis
- 2.7.1.74
- leukemia
- gemcitabine
- thymidine
- triphosphate
- deaminase
- purine
- ribonucleotide
- deoxynucleoside
- pyrimidine
- deoxyguanosine
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salvage
- myeloid
- arabinoside
- cytarabine
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prodrugs
- deoxyadenosine
- 1-beta-d-arabinofuranosylcytosine
- deoxyribonucleoside
- 5'-nucleotidase
- cladribine
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cross-resistance
- ara-ctp
- 2-chlorodeoxyadenosine
- 2',2'-difluorodeoxycytidine
- fludarabine
- dttp
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antileukemic
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ccrf-cem
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dfdctp
- 2-chloro-2'-deoxyadenosine
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gemcitabine-resistant
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dado
- deoxycytidylate
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kinase-deficient
- clofarabine
- 2',3'-dideoxycytidine
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5'-phosphorylation
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arabinosyl
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deoxypyrimidine
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t-lymphoblastoid
- deoxycoformycin
- medicine
- 2'-deoxyadenosine
- deoxythymidine
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l-nucleoside
- dideoxycytidine
- t-lymphoblasts
- 2',3'-dideoxyinosine
- tetrahydrouridine
- arabinosylcytosine
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anabolites
- pharmacology
- analysis
Reaction
Synonyms
2'-deoxycytidine kinase, ara-C kinase, arabinofuranosylcytosine kinase, dC kinase, dCK, deoxycytidine kinase, deoxycytidine-cytidine kinase, dNTP:deoxycytidine 5'-phosphotransferase, kinase, deoxycytidine (phosphorylating), NTP:deoxycytidine 5'-phosphotransferase
ECTree
2.7.1.74 deoxycytidine kinaseAdvanced search results
results (
results (Engineering
Engineering on EC 2.7.1.74 - deoxycytidine kinase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A100V/R104M/D133A
A100V/R104M/D133S
A100V/R104M/D133S/E196A
the mutant shows low activity for D-deoxycytidine and D-thymidine
A100V/R104M/D133S/F96Y
the mutant shows low activity for D-deoxycytidine and D-thymidine
A100V/R104M/D133S/W58V
the mutant shows low activity for D-deoxycytidine and D-thymidine
A119G
C185A
lower efficiency with dCyd as the substrate with ATP und UTP, nearly 2-fold higher efficiency than wild-type dCK with dAdo as substrate and UTP as the phosphate donor
C9S/C45S/C59S/C146S
C9S/C45S/C59S/S74E/R104M/D133A/C146S
site-directed mutagenesis, crystallization mutant
D133A
D47E/R104Q/D133G/N163I/F242L
1.5fold increase in ratio kcat/Km for deoxycytidine
DEL65-79
construction of an enzyme variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as the wild type
I24V
P122S
R104I/D133A
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104L/D133A
R104M
R104M/D133A
R104M/D133A/S74E
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site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
R104M/D133N
R104M/D133N/L102Y
the mutant shows low activity for D-deoxycytidine and D-thymidine
R104M/D133N/L191A
the mutant shows low activity for D-deoxycytidine and D-thymidine
R104M/D133N/M85Y
the mutant shows low activity for D-deoxycytidine and D-thymidine
R104M/D133N/V130T
the mutant shows low activity for D-deoxycytidine and D-thymidine
R104M/D133N/V130T/L191A
the mutant shows low activity for D-deoxycytidine and D-thymidine
R104M/D133N/V55E
the mutant shows very low activity for D-deoxycytidine and D-thymidine
R104M/D133N/V55F
the mutant shows very low activity for D-deoxycytidine and D-thymidine
R104M/D133N/V55F/V130T
the mutant shows very low activity for D-deoxycytidine and D-thymidine
R104M/D133N/V55F/V130T/L191A
the mutant shows very low activity for D-deoxycytidine and D-thymidine
R104M/D133T
mutant with reversed substrate specificity, with elevated specific constant for thymidine phosphorylation and decreased activity for deeoxycytidine, deoxyadenosine, and deoxyguanosine
R104Q/D133A
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104Q/D133G
mutant is a generalist kinase with broader specificity and elevated turnover compared with wild-type
S11A
S11E
S15A
S15E
S74A
S74E
T3A
T3E
additional information
A100V/R104M/D133A
site-directed mutagenesis, mutations alter the residues to the multisubstrate nucleoside kinase, EC 2.7.1.145, mutant shows 30fold increased kcat for deoxycytidine compared to the wild-type enzyme
A100V/R104M/D133S
the mutant shows exquisitely high activity for D-deoxycytidine and D-thymidine
A119G
naturally occurring mutation, 66% of activity of the wild type protein
A119G
genetic polymorphism, 66% of wild-type activity, decrease in Km value
C9S/C45S/C59S/C146S
engineered protein has a significantly improved crystallization behaviour compared with the wild type protein
C9S/C45S/C59S/C146S
mutation of the four surface-exposed Cys residues, constructued for crystallization. Mutant displays moderate kinetic differences in the catalytic efficiency when compared with wild-type
C9S/C45S/C59S/C146S
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mutation of the four surface-exposed Cys residues, constructued for crystallization. Mutant displays moderate kinetic differences in the catalytic efficiency when compared with wild-type
D133A
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site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
D133A
site-directed mutagenesis, the mutation renders the enzyme capable of thymidine binding
I24V
naturally occurring mutation, 85% of activity of the wild type protein
P122S
naturally occurring mutation, 43% of activity of the wild type protein
P122S
genetic polymorphism, 43% of wild-type activity, decrease in Km value
R104L/D133A
the double mutant does also accept L- and D-thymidine as substrates
R104L/D133A
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104M
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site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
R104M
site-directed mutagenesis, the mutation renders the enzyme capable of thymidine binding
R104M/D133A
site-directed mutagenesis, mutations alter the residues to the multisubstrate nucleoside kinase, EC 2.7.1.145, the mutant gains the ability to phosphorylate deoxythymidine
R104M/D133A
the double mutant is a pyrimidine-specific enzyme due to large Km values with purines and does also accept L- and D-thymidine as substrates
R104M/D133A
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104M/D133N
the mutant shows low activity for D-deoxycytidine and D-thymidine
S15E
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site-directed mutagenesis, replacement of the phosphorylation site, the mutant shows a slight, but significant, reduction of Ser74 phosphorylation
S74A
the mutation abrogates phosphorylation of the protein. The ratio of phospho-Akt/Akt, phospho-mTOR/mTOR, phospho-P70S6K/P70S6K does not significantly decrease in mutant cells following ionizing radiation treatment
S74E
mutation mimicking phosphorylation, results in 11fold increase in kcat value for deoxycytidine. Mutation has no effect on cellular localization
S74E
site-directed mutagenesis, replacing the serine with a glutamic acid mimic phosphorylation of Ser74, the enzyme containing the S74E mutation adopts the open state, but wild-type dCK can adopt the open state also in the absence of the S74E mutation
S74E
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site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
S74E
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site-directed mutagenesis, the mutation sensitizes the enzyme to feedback inhibition by dCTP, regardless of the phosphoryl donor. Mimicking Ser74 phosphorylation by a S74E mutation increases the enzyme activity toward pyrimidine analogues. The S74E mutation increased the kcat for cladribine by 8 or 3fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine by about 2fold with both ATP and UTP, and for fludarabine by 2fold, but only with UTP
S74E
the mutation mimics phosphorylation of the protein. The ratio of phospho-Akt/Akt, phospho-mTOR/mTOR, phospho-P70S6K/P70S6K significantly decreases in mutant cells following ionizing radiation treatment
T3A
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site-directed mutagenesis, replacement of the phosphorylation site, the mutant shows a slight, but significant, reduction of Ser74 phosphorylation
T3E
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site-directed mutagenesis, replacement of the phosphorylation site, the mutant shows a slight, but significant, reduction of Ser74 phosphorylation
additional information
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in gemcitabine-resistant pancreatic cancer cells, expression of deoxycytidine kinase is significantly reduced compared with that of parental cells. Treatment with siRNA targeted to deoxycytidine kinase reduces gemcitabine sensitivity without affecting cell proliferation. Downregulation of gemcitabine-related genes RRM1 and RRM2 by siRNA increases gemcitabine sensitivity and reduces cell proliferation even without gemcitabine treatment
additional information
R104 and D133 are key residues for substrate specificity
additional information
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R104 and D133 are key residues for substrate specificity
additional information
sequencing of deoxycytidine kinase and cytidine monophosphate kinase using 240 DNA samples reveals 28 polymorphisms in deoxycytidine kinase. Variant allozyme enzyme activities range from 32% to 105% of the wild type activity with no significant differences in apparent Km values except for a V24/S122 double variant enzyme. Relative levels of immunoreactive protein after expression in COS-1 cells parallel relative levels of enzyme activity
additional information
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sequencing of gene from European and African individuals reveals 64 genetic polymorphisms. In general, African ancestry subjects show higher mRNA expression compared with subjects with European ancestry. In both groups, single nucleotide polymorphism 35708 C>T of a 3'-untranslated region is significanlty associated with lower mRNA expression and with lower blast 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in acute myeloid leukemia patients
additional information
sequencing of gene from European and African individuals reveals 64 genetic polymorphisms. In general, African ancestry subjects show higher mRNA expression compared with subjects with European ancestry. In both groups, single nucleotide polymorphism 35708 C>T of a 3'-untranslated region is significanlty associated with lower mRNA expression and with lower blast 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in acute myeloid leukemia patients
additional information
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cotruction of a loss-of--function mutant dCK containing an altered ATP-binding site
additional information
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mutants of dCK with rationally designed active sites, that make them thymidine-activating, are stably introduced into cells by recombinant lentiviral vectors. Transduced cells maintain growth kinetics and function. These dCK mutants efficiently activate bromovinyl-deoxyuridine, L-deoxythymidine, and L-deoxyuridine, which are otherwise not toxic to wild-type cells, overview. Mutant dCK-expressing Jurkat, Molt-4, and U87-MG cells could be efficiently eliminated in vitro and in xenogeneic leukemia and tumor models in vivo
additional information
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stable enzyme knockout in HeLa cells by expression of dCK-siRNA or shRNA
additional information
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deletion of exon 3 inactivates dCK function. Generation of enzyme knockout mice that show 90fold decrease in thymic cellularity compared to wild-type, lymphocyte numbers in the dCK KO mice are 5 to 13fold below normal values
additional information
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for enzyme knockout, MLE12 cells are transfected with DCK siRNA
