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Information on EC 2.7.1.21 - thymidine kinase and Organism(s) Homo sapiens and UniProt Accession P04183

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EC Tree
IUBMB Comments
Deoxyuridine can also act as acceptor, and dGTP can act as a donor. The deoxypyrimidine kinase complex induced by Herpes simplex virus catalyses this reaction as well as those of EC 2.7.1.114 (AMP---thymidine kinase), EC 2.7.1.118 (ADP---thymidine kinase) and EC 2.7.4.9 (dTMP-kinase).
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This record set is specific for:
Homo sapiens
UNIPROT: P04183
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
thymidine kinase, hsv1-tk, calmodulin-binding protein, thymidine kinase 1, thymidylate kinase, type 1 thymidine kinase, hsv-1 tk, thymidine kinase 2, mitochondrial thymidine kinase, cam-binding protein, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
thymidine kinase-1
-
type II thymidine kinase 1
-
2'-deoxythymidine kinase
ATP-thymidine 5'-phosphotransferase
-
-
-
-
beta-thymidine kinase-1
-
-
beta-thymidine kinase-2
-
-
dThd kinase-1
-
-
dThd kinase-2
-
-
EC 2.7.1.75
-
-
-
-
kinase, deoxythymidine (phosphorylating)
-
-
-
-
kinase, thymidine (phosphorylating)
-
-
-
-
mitochondrial thymidine kinase
-
-
TdR kinase
-
-
-
-
thymidine kinase
-
-
thymidine kinase 1
-
-
thymidine kinase 2
thymidine kinase 2, mitochondrial
-
thymidine kinase I
-
-
thymidine kinase-1
-
-
thymidine kinase-2
-
-
TK-1
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + thymidine = ADP + dTMP
show the reaction diagram
ATP + thymidine = ADP + dTMP
show the reaction diagram
molecular docking of substrates and inhibitors, active site structure modeling
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:thymidine 5'-phosphotransferase
Deoxyuridine can also act as acceptor, and dGTP can act as a donor. The deoxypyrimidine kinase complex induced by Herpes simplex virus catalyses this reaction as well as those of EC 2.7.1.114 (AMP---thymidine kinase), EC 2.7.1.118 (ADP---thymidine kinase) and EC 2.7.4.9 (dTMP-kinase).
CAS REGISTRY NUMBER
COMMENTARY hide
9002-06-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1-(beta-D-arabinofuranosyl)thymine
ADP + 1-(beta-D-arabinofuranosyl)thymine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyuridine
ADP + 2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 3'-(4-(2-phenylethyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine
ADP + 3'-(4-(2-phenylethyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
2.4% activity compared to thymidine
-
-
?
ATP + 3'-(4-(2-pyridine)-1,2,3-triazole-1-yl)-3'-deoxythymidine
ADP + 3'-(4-(2-pyridine)-1,2,3-triazole-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
3.1% activity compared to thymidine
-
-
?
ATP + 3'-(4-(3-chloropropyl)-1,2,3-triazol-1-yl)-3'-deoxythymidine
ADP + 3'-(4-(3-chloropropyl)-1,2,3-triazol-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
2.7% activity compared to thymidine
-
-
?
ATP + 3'-(4-(4-fluorophenyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine
ADP + 3'-(4-(4-fluorophenyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
2.6% activity compared to thymidine
-
-
?
ATP + 3'-(4-benzyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
ADP + 3'-(4-benzyl-1,2,3-triazol-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
4.8% activity compared to thymidine
-
-
?
ATP + 3'-(4-pentyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
ADP + 3'-(4-pentyl-1,2,3-triazol-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
2.9% activity compared to thymidine
-
-
?
ATP + 3'-(4-phenyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
ADP + 3'-(4-phenyl-1,2,3-triazol-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
2.1% activity compared to thymidine
-
-
?
ATP + 3'-(4-propyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
ADP + 3'-(4-propyl-1,2,3-triazol-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
1.9% activity compared to thymidine
-
-
?
ATP + 3'-(4-tert-butyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
ADP + 3'-(4-tert-butyl-1,2,3-triazol-1-yl)-3'-deoxythymidine 5'-phosphate
show the reaction diagram
2.2% activity compared to thymidine
-
-
?
ATP + 3'-azido-3'-deoxythymidine
ADP + 3'-azido-3'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + thymidine
ADP + dTMP
show the reaction diagram
ATP + 1-(beta-D-arabinofuranosyl)thymine
ADP + 1-(beta-D-arabinofuranosyl)thymine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyuridine
ADP + 2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
ir
ATP + 3-(benzylcarbamimidoyl)thymidine
ADP + 3-(benzylcarbamimidoyl)thymidine 5'-phosphate
show the reaction diagram
-
14.9% activity compared to thymidine
-
-
?
ATP + 3-(butylcarbamimidoyl)thymidine
ADP + 3-(butylcarbamimidoyl)thymidine 5'-phosphate
show the reaction diagram
-
1.2% activity compared to thymidine
-
-
?
ATP + 3-(phenylcarbamimidoyl)thymidine
ADP + 3-(phenylcarbamimidoyl)thymidine 5'-phosphate
show the reaction diagram
-
1.9% activity compared to thymidine
-
-
?
ATP + 3-(tetrazol-5-ylmethyl)thymidine
ADP + 3-(tetrazol-5-ylmethyl)thymidine 5'-phosphate
show the reaction diagram
-
39.5% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-ylmethyl]thymidine
ADP + 3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-ylmethyl]thymidine 5'-phosphate
show the reaction diagram
-
63.7% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-yl]thymidine
ADP + 3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-yl]thymidine 5'-phosphate
show the reaction diagram
-
42.5% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-closo-1,7-carboranylethyltetrazol-5-ylmethyl]thymidine
ADP + 3-[1(2)-closo-1,7-carboranylethyltetrazol-5-ylmethyl]thymidine 5'-phosphate
show the reaction diagram
-
52.4% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-closo-1,7-carboranylethyltetrazol-5-yl]thymidine
ADP + 3-[1(2)-closo-1,7-carboranylethyltetrazol-5-yl]thymidine 5'-phosphate
show the reaction diagram
-
55.6% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-ylmethyl]thymidine
ADP + 3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-ylmethyl]thymidine 5'-phosphate
show the reaction diagram
-
58.2% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-yl]thymidine
ADP + 3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-yl]thymidine 5'-phosphate
show the reaction diagram
-
42.9% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-propyltetrazol-5-ylmethyl]thymidine
ADP + 3-[1(2)-propyltetrazol-5-ylmethyl]thymidine 5'-phosphate
show the reaction diagram
-
55.7% activity compared to thymidine
-
-
?
ATP + 3-[1(2)-propyltetrazol-5-yl]thymidine
ADP + 3-[1(2)-propyltetrazol-5-yl]thymidine 5'-phosphate
show the reaction diagram
-
57.6% activity compared to thymidine
-
-
?
ATP + 3-[2-(closo-1,7-carboranyl)ethylcarbamimidoyl]thymidine
ADP + 3-[2-(closo-1,7-carboranyl)ethylcarbamimidoyl]thymidine 5'-phosphate
show the reaction diagram
-
16.3% activity compared to thymidine
-
-
?
ATP + 3-[2-imino-2-(benzylamino)ethyl]thymidine
ADP + 3-[2-imino-2-(benzylamino)ethyl]thymidine 5'-phosphate
show the reaction diagram
-
16.8% activity compared to thymidine
-
-
?
ATP + 3-[2-imino-2-(butylamino)ethyl]thymidine
ADP + 3-[2-imino-2-(butylamino)ethyl]thymidine 5'-phosphate
show the reaction diagram
-
2.3% activity compared to thymidine
-
-
?
ATP + 3-[2-imino-2-(phenylamino)ethyl]thymidine
ADP + 3-[2-imino-2-(phenylamino)ethyl]thymidine 5'-phosphate
show the reaction diagram
-
11.3% activity compared to thymidine
-
-
?
ATP + 3-[2-imino-2-(propylamino)ethyl]thymidine
ADP + 3-[2-imino-2-(propylamino)ethyl]thymidine 5'-phosphate
show the reaction diagram
-
1.9% activity compared to thymidine
-
-
?
ATP + 3-[2-imino-2-[2-(closo-1,7-carboranyl)ethylamino]ethyl]thymidine
ADP + 3-[2-imino-2-[2-(closo-1,7-carboranyl)ethylamino]ethyl]thymidine 5'-phosphate
show the reaction diagram
-
3.0% activity compared to thymidine
-
-
?
ATP + 3-[2-imino-2-[2-(closo-1,7-carboranyl)propylamino]ethyl]thymidine
ADP + 3-[2-imino-2-[2-(closo-1,7-carboranyl)propylamino]ethyl]thymidine 5'-phosphate
show the reaction diagram
-
5.6% activity compared to thymidine
-
-
?
ATP + 3-[3-(closo-1,7-carboranyl)propylcarbamimidoyl]thymidine
ADP + 3-[3-(closo-1,7-carboranyl)propylcarbamimidoyl]thymidine 5'-phosphate
show the reaction diagram
-
15.5% activity compared to thymidine
-
-
?
ATP + 3-[4-(closo-1,7-carboranyl)butylcarbamimidoyl]thymidine
ADP + 3-[4-(closo-1,7-carboranyl)butylcarbamimidoyl]thymidine 5'-phosphate
show the reaction diagram
-
27.3% activity compared to thymidine
-
-
?
ATP + 5-bromo-2'-deoxyuridine
ADP + 5-bromo-2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-diaza-2'-deoxyuridine
ADP + 5-diaza-2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-iodo-2'-deoxyuridine
ADP + 5-iodo-2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + arabinosyl cytosine
?
show the reaction diagram
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + difluorodeoxycytidine
?
show the reaction diagram
-
-
-
?
ATP + difluorodeoxyuridine
?
show the reaction diagram
-
-
-
?
ATP + methylthymidine
ADP + methylthymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + thymidine
?
show the reaction diagram
-
involved in DNA replication
-
-
?
ATP + thymidine
ADP + dTMP
show the reaction diagram
ATP + thymidine
ADP + thymidine 5'-phosphate
show the reaction diagram
ATP + [methyl-3H]thymidine
ADP + [methyl-3H]thymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
CTP + thymidine
CDP + thymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
GTP + thymidine
GDP + thymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + thymidine
UDP + dTMP
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyuridine
ADP + 2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyuridine
ADP + 2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
ir
ATP + thymidine
?
show the reaction diagram
-
involved in DNA replication
-
-
?
ATP + thymidine
ADP + thymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
MgATP2-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
can partially substitute for Mg2+
Cu2+
-
can partially substitute for Mg2+
Fe2+
-
can partially substitute for Mg2+
Mn2+
-
can partially substitute for Mg2+
Zn2+
-
can partially substitute for Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-[(2Z)-4-(dibenzylamino)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: above 0.5 mM
3'-(4-(2-phenyl-ethyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine
-
3'-(4-(2-pyridine)-1,2,3-triazole-1-yl)-3'-deoxythymidine
-
3'-(4-(3-chloro-propyl)-1,2,3-triazol-1-yl)-3'-deoxythymidine
-
3'-(4-(4-fluorophenyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine
-
3'-(4-benzyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
-
3'-(4-pentyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
-
3'-(4-phenyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
-
3'-(4-propyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
-
3'-(4-tert-butyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
-
3'-azido-3'-deoxythymidine
-
5-(E)-(2-bromovinyl)-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
IC50: 0.1 mM
5-fluoro-2'-deoxyuridine
concentration dependent reduction of activity
5-methyl-1-[(2Z)-4-(tritylamino)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: above 0.5 mM
5-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: above 0.1 mM
trifluridine
concentration dependent reduction of activity
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl 3,3-dimethylbutanoate
IC50: 0.028 mM
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl benzoate
IC50: 0.03 mM
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl diphenylacetate
IC50: 0.0046 mM
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl dodecanoate
IC50: 0.019 mM
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl heptanoate
IC50: 0.011 mM
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl pivalate
IC50: 0.04 mM
(4E)-N-(diphenylmethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hex-4-enamide
IC50: 0.265 mM
(4E)-N-[cyano(phenyl)methyl]-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hex-4-enamide
IC50: 0.371 mM
(E)-5-(2-bromovinyl)-1-beta-D-(arabinofuranosyl)uracil
-
-
1-(3'-deoxy-5'-O-triphenylmethyl-beta-D-thymidin-3'-yl)-3-(4-chloro-3-(trifluoromethyl)-phenyl)-thiourea
-
-
1-(3,4-dichlorobenzyl)-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
-
-
1-(3,4-dichlorophenyl)-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
-
-
1-benzyl-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
-
-
1-beta-D-(arabinofuranosyl)thymine
-
-
1-[(2Z)-4-(4-benzylpiperazin-1-yl)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.18 mM
1-[(2Z)-4-(benzylamino)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.057 mM
1-[(2Z)-4-(benzyloxy)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.022 mM
1-[(2Z)-4-(dibenzylamino)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.0035 mM
1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-5,6-dihydrothymine
IC50: 0.01 mM
1-[(2Z)-4-hydroxybut-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.173 mM
1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine
-
-
1-[2,3-dihydroxy-4-(trityloxy)butyl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.017 mM
1-[3-hydroxy-4-(trityloxy)butyl]-5-methylpyrimidine-2,4(1H,3H)-dione
IC50: 0.0036 mM
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(2S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]thiourea
-
-
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(2S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]urea
-
-
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
-
-
1-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]-3-phenylthiourea
-
-
2-(4-chlorophenyl)-N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]acetamide
IC50: 0.023 mM
2-biphenyl-4-yl-N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]acetamide
IC50: 0.0041 mM
3'-(1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
-
-
3'-(4-benzyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
-
-
3'-(4-butyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
-
-
3'-(4-chlorobenzylamino)-3'-deoxy-beta-D-thymidine
-
-
3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridine
-
-
3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
-
-
3'-(4-cyclopentylmethyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
-
-
3'-(5-(4-chlorophenyl)-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
-
-
3'-([[(4-chlorophenyl)carbamothioyl]amino]methyl)-3'-deoxythymidine
-
-
3'-([[4-chloro-3-(trifluoromethyl)phenyl]carbamothioyl]amino)-2',3'-dideoxy-3,4-dihydrothymidine
-
-
3'-azido-2',3'-dideoxy-3,4-dihydrothymidine
-
inhibits thymidine phosphorylation catalyzed by thymidine kinase 2
3'-benzylamino-3'-deoxy-beta-D-thymidine
-
-
3'-deoxy-3'-(4-(3,4-dichlorophenyl)-1,2,3-triazol-1-yl)-beta-D-thymidine
-
-
3'-deoxy-3'-(4-phenyl-1,2,3-triazol-1-yl)-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridine
-
-
3'-deoxy-3'-(4-phenyl-1,2,3-triazol-1-yl)-beta-D-thymidine
-
-
3'-deoxy-3'-(4-pyridin-2-yl-1,2,3-triazol-1-yl)-beta-D-thymidine
-
-
3'-deoxy-3'-(5-phenyl-1,2,3-triazol-1-yl)-beta-D-thymidine
-
-
3'-deoxy-3'-([[(3,4-dichlorophenyl)carbamothioyl]amino]methyl)thymidine
-
-
3'-deoxy-3'-([[(4-methoxyphenyl)carbamothioyl]amino]methyl)thymidine
-
-
3'-deoxy-3'-([[(4-methylphenyl)carbamothioyl]amino]methyl)thymidine
-
-
3'-deoxy-3'-fluorothymidine
-
inhibits thymidine phosphorylation catalyzed by thymidine kinase 2
3'-hexanoylamino-3'-deoxythymidine
-
very potent inhibitor of thymidine kinase 2
3'-O-ethyl-2'-deoxyuridine
-
3'-O-methyl-2'-deoxyuridine
-
3'-spiro-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)-5-methyluridine
inhibits phosphorylation of 2'-deoxythymidine, IC50: 0.0046 mM
3'-[(3-trifluoromethyl-4-chloro)-benzylamino]-3'-deoxy-beta-D-thymidine
-
-
3'-[([[4-(benzyloxy)phenyl]carbamothioyl]amino)methyl]-3'-deoxythymidine
-
-
3'-[([[4-chloro-3-(trifluoromethyl)phenyl]carbamothioyl]amino)methyl]-3'-deoxythymidine
-
-
4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-tritylbutanamide
IC50: 0.44 mM
4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-[2-oxo-2-(tritylamino)ethyl]butanamide
IC50: 0.194 mM
5'-deoxy-5'-[(tricyclo[3.3.1.13,7]dec-1-ylcarbamothioyl)amino]thymidine
-
-
5'-deoxy-5'-[[(diphenylmethyl)carbamothioyl]amino]thymidine
-
-
5'-O-(4,4'-dimethoxytrityl)thymidine
IC50: 0.468 mM
5-(3'-amino-3'-deoxy-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridin-3'Nyl)-1-(4-chloro-3-trifluoromethylphenyl)-tetrazole
-
-
5-(3'-amino-3'-deoxy-beta-D-thymidin-3'N-yl)-1-(4-chloro-3-trifluoromethylphenyl)-tetrazole
-
-
5-(3'-amino-3'-deoxy-beta-D-thymidin-3'N-yl)-1-benzyl-tetrazole
-
-
5-(E)-(2-bromovinyl)-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
IC50: 0.0013 mM
5-(E)-(2-bromovinyl)uridine
5-benzylamino-(3'-deoxy-beta-D-thymidin-3'N-yl)-tetrazole
-
-
5-ethyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
IC50: 0.02 mM
5-iodo-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
IC50: 0.0046 mM
5-methyl-1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: 0.025 mM
5-methyl-1-[(2Z)-4-(4-methylpiperazin-1-yl)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: 0.491 mM
5-methyl-1-[(2Z)-4-(tritylamino)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: 0.0023 mM
5-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-cytosine
IC50: 0.484 mM
5-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: 0.0015 mM
5-methyl-1-[4-(trityloxy)but-2-yn-1-yl]pyrimidine-2,4(1H,3H)-dione
IC50: 0.404 mM
5-methyl-1-[4-(trityloxy)butyl]pyrimidine-2,4(1H,3H)-dione
IC50: 0.0033 mM
5-[(4-chloro-3-trifluoromethylphenyl)amino]-1-(3'-deoxy-beta-D-thymidin-3'N-yl)-tetrazole
-
-
5-[(E)-2-bromoethenyl]-2'-O-decanoyluridine
competitive with respect to 2'-deoxythymidine, IC50: 0.0012 mm
5-[(E)-2-bromoethenyl]-2'-O-octanoyluridine
5-[amino-(4-chloro-3-trifluoromethylphenyl)]-1-(3'-deoxy-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridin-3'N-yl)-tetrazole
-
-
6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-tritylhexanamide
IC50: 0.019 mM
9-[(2Z)-4-(trityloxy)but-2-en-1-yl]-guanine
IC50: above 0.5 mM
dATP
-
strong feedback inhibition, tight binding at the active site in stoichiometric amount
deoxcytidine
dTMP
-
-
N-(2-cyanoethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
IC50: 0.46 mM
N-(2-cyanoethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
IC50: 0.353 mM
N-(2-[[cyano(phenyl)methyl]amino]-2-oxoethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
IC50: 0.318 mM
N-(3'-deoxy-beta-D-thymidin-3'-yl)-N'-(4-chloro-3-trifluoromethylphenyl)-benzylguanidine
-
-
N-(3'-deoxy-beta-D-thymidin-3'-yl)-N'-(4-chloro-3-trifluoromethylphenyl)-guanidine
-
-
N-(3'-deoxy-beta-D-thymidin-3'-yl)-N'-(4-chloro-3-trifluoromethylphenyl)-isopropylguanidine
-
-
N-(cyanomethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
IC50: 0.268 mM
N-(diphenylmethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
IC50: 0.238 mM
N-(diphenylmethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
IC50: 0.038 mM
N-methyl-4-[[[8-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)octyl]oxy](diphenyl)methyl]benzamide
-
-
N-methyl-4-[{[8-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)octyl]oxy}(diphenyl)methyl]benzamide
-
-
N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]-2,2-diphenylacetamide
IC50: 0.027 mM
N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]-3-(trifluoromethyl)benzamide
IC50: 0.028 mM
N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]-9H-xanthene-9-carboxamide
IC50: 0.033 mM
N-[2-[(diphenylmethyl)amino]-2-oxoethyl]-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
IC50: 0.287 mM
N-[cyano(phenyl)methyl]-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
IC50: 0.208 mM
N-[cyano(phenyl)methyl]-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
IC50: 0.075 mM
N3-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-thymine
IC50: above 0.5 mM
P1-(Adenosine-5')-P3-(thymidine-5')-triphosphate
-
-
P1-(adenosine-5')-P4-(thymidine-5')-tetraphosphate
-
-
P1-(Adenosine-5')-P5-(thymidine-5')-pentaphosphate
-
-
P1-(Adenosine-5')-P6-(thymidine-5')-hexaphosphate
-
-
thymidine
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3'-azido-3'-deoxythymidine
-
stimulates deoxycytidine phosphorylation catalyzed by thymidine kinase 2
3'-deoxy-3'-fluorothymidine
-
stimulates deoxycytidine phosphorylation catalyzed by thymidine kinase 2
ATP
-
binding of ATP induces enzyme tetramerization, which leads to activation of the enzyme, the dimeric enzyme form is probably less active, 50-100% activation at up to 5 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00043 - 0.254
3'-azido-3'-deoxythymidine
0.0005 - 0.349
thymidine
0.004 - 0.025
2'-deoxycytidine
0.0058 - 0.054
2'-deoxythymidine
0.0563
3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0174
3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0318
3-[1(2)-closo-1,7-carboranylethyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0356
3-[1(2)-closo-1,7-carboranylethyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0552
3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0799
3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0373
3-[1(2)-propyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0552
3-[1(2)-propyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.0028 - 0.162
ATP
0.15
CTP
-
pH 7.4, 37°C
0.003 - 0.568
deoxycytidine
0.066
difluorodeoxycytidine
-
0.029
difluorodeoxyuridine
-
0.3
GTP
-
pH 7.4, 37°C
0.0003 - 0.043
thymidine
0.26
UTP
-
pH 7.4, 37°C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.24 - 3.5
3'-azido-3'-deoxythymidine
1.4 - 9.5
thymidine
0.47
3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.32
3-[1(2)-closo-1,7-carboranylbutyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.44
3-[1(2)-closo-1,7-carboranylethyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.35
3-[1(2)-closo-1,7-carboranylethyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.39
3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.37
3-[1(2)-closo-1,7-carboranylpropyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.45
3-[1(2)-propyltetrazol-5-ylmethyl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.34
3-[1(2)-propyltetrazol-5-yl]thymidine
-
in 25 mM Tris-HCl (pH 7.6), 5 mM MgCl2, 125 mM KCl, 10 mM dithiothreitol, and 0.5 mg/ml bovine serum albumin, at 37°C
0.46 - 282
thymidine
additional information
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0031 - 1.7
3'-azido-3'-deoxythymidine
0.0068 - 4.5
thymidine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0039
3'-azido-2',3'-dideoxy-3,4-dihydrothymidine
-
pH and temperature not specified in the publication
0.0014
3'-deoxy-3'-fluorothymidine
-
pH and temperature not specified in the publication
0.0104
5-(E)-(2-bromovinyl)uridine
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
6.5
ADP
-
pH 7.4, 37°C
0.00036 - 0.002
dCTP
0.004 - 0.63
deoxycytidine
0.00089 - 0.01
dTTP
0.0036 - 0.006
thymidine
0.63
TMP
-
pH 7.4, 37°C
0.0085 - 0.0135
TTP
additional information
additional information
-
bisubstrate analogs with adenosine and thymidine joined at their 5' positions by polyphorphoryl linkages of varying lengths
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.5
1-[(2Z)-4-(dibenzylamino)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: above 0.5 mM
0.06
3'-(4-(2-phenyl-ethyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.053
3'-(4-(2-pyridine)-1,2,3-triazole-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.105
3'-(4-(3-chloro-propyl)-1,2,3-triazol-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.044
3'-(4-(4-fluorophenyl)-1,2,3-triazole-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.078
3'-(4-benzyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.086
3'-(4-pentyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.099
3'-(4-phenyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.311
3'-(4-propyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.114
3'-(4-tert-butyl-1,2,3-triazol-1-yl)-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.003
3'-azido-3'-deoxythymidine
Homo sapiens
in 50 mM Tris/HCl pH 7.6, 5 mM MgCl2, at 37°C
0.1
5-(E)-(2-bromovinyl)-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
Homo sapiens
IC50: 0.1 mM
0.5
5-methyl-1-[(2Z)-4-(tritylamino)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: above 0.5 mM
0.1
5-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: above 0.1 mM
0.028
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl 3,3-dimethylbutanoate
Homo sapiens
IC50: 0.028 mM
0.03
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl benzoate
Homo sapiens
IC50: 0.03 mM
0.0046
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl diphenylacetate
Homo sapiens
IC50: 0.0046 mM
0.019
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl dodecanoate
Homo sapiens
IC50: 0.019 mM
0.011
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl heptanoate
Homo sapiens
IC50: 0.011 mM
0.04
(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl pivalate
Homo sapiens
IC50: 0.04 mM
0.265
(4E)-N-(diphenylmethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hex-4-enamide
Homo sapiens
IC50: 0.265 mM
0.371
(4E)-N-[cyano(phenyl)methyl]-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hex-4-enamide
Homo sapiens
IC50: 0.371 mM
0.043
(E)-5-(2-bromovinyl)-1-beta-D-(arabinofuranosyl)uracil
Homo sapiens
-
-
0.5
1-(3'-deoxy-5'-O-triphenylmethyl-beta-D-thymidin-3'-yl)-3-(4-chloro-3-(trifluoromethyl)-phenyl)-thiourea
Homo sapiens
-
IC50 above 0.5 mM, thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.041
1-(3,4-dichlorobenzyl)-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
Homo sapiens
-
-
0.057
1-(3,4-dichlorophenyl)-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
Homo sapiens
-
-
0.099
1-benzyl-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
Homo sapiens
-
-
0.285
1-beta-D-(arabinofuranosyl)thymine
Homo sapiens
-
-
0.18
1-[(2Z)-4-(4-benzylpiperazin-1-yl)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.18 mM
0.057
1-[(2Z)-4-(benzylamino)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.057 mM
0.022
1-[(2Z)-4-(benzyloxy)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.022 mM
0.0035
1-[(2Z)-4-(dibenzylamino)but-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.0035 mM
0.01
1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-5,6-dihydrothymine
Homo sapiens
IC50: 0.01 mM
0.173
1-[(2Z)-4-hydroxybut-2-en-1-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.173 mM
0.0015
1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.017
1-[2,3-dihydroxy-4-(trityloxy)butyl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.017 mM
0.0036
1-[3-hydroxy-4-(trityloxy)butyl]-5-methylpyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.0036 mM
0.00015
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(2S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]thiourea
Homo sapiens
-
-
0.00042
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(2S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]urea
Homo sapiens
-
-
0.038
1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]thiourea
Homo sapiens
-
-
0.405
1-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl]-3-phenylthiourea
Homo sapiens
-
-
0.023
2-(4-chlorophenyl)-N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]acetamide
Homo sapiens
IC50: 0.023 mM
0.0041
2-biphenyl-4-yl-N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]acetamide
Homo sapiens
IC50: 0.0041 mM
0.0047
3'-(1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.0003
3'-(4-benzyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.00023
3'-(4-butyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.0033
3'-(4-chlorobenzylamino)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.000036
3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.000046
3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.00015
3'-(4-cyclopentylmethyl-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.004
3'-(5-(4-chlorophenyl)-1,2,3-triazol-1-yl)-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.0012
3'-([[(4-chlorophenyl)carbamothioyl]amino]methyl)-3'-deoxythymidine
Homo sapiens
-
-
0.000036 - 0.00015
3'-([[4-chloro-3-(trifluoromethyl)phenyl]carbamothioyl]amino)-2',3'-dideoxy-3,4-dihydrothymidine
0.0046
3'-benzylamino-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.000042
3'-deoxy-3'-(4-(3,4-dichlorophenyl)-1,2,3-triazol-1-yl)-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.00025
3'-deoxy-3'-(4-phenyl-1,2,3-triazol-1-yl)-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.00032
3'-deoxy-3'-(4-phenyl-1,2,3-triazol-1-yl)-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.0013
3'-deoxy-3'-(4-pyridin-2-yl-1,2,3-triazol-1-yl)-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.0011
3'-deoxy-3'-(5-phenyl-1,2,3-triazol-1-yl)-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml bovine serum albumin, at 37°C
0.00064
3'-deoxy-3'-([[(3,4-dichlorophenyl)carbamothioyl]amino]methyl)thymidine
Homo sapiens
-
-
0.0031
3'-deoxy-3'-([[(4-methoxyphenyl)carbamothioyl]amino]methyl)thymidine
Homo sapiens
-
-
0.0012
3'-deoxy-3'-([[(4-methylphenyl)carbamothioyl]amino]methyl)thymidine
Homo sapiens
-
-
0.0046
3'-spiro-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)-5-methyluridine
Homo sapiens
inhibits phosphorylation of 2'-deoxythymidine, IC50: 0.0046 mM
0.00033
3'-[(3-trifluoromethyl-4-chloro)-benzylamino]-3'-deoxy-beta-D-thymidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.00043
3'-[([[4-(benzyloxy)phenyl]carbamothioyl]amino)methyl]-3'-deoxythymidine
Homo sapiens
-
-
0.00047
3'-[([[4-chloro-3-(trifluoromethyl)phenyl]carbamothioyl]amino)methyl]-3'-deoxythymidine
Homo sapiens
-
-
0.44
4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-tritylbutanamide
Homo sapiens
IC50: 0.44 mM
0.194
4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-[2-oxo-2-(tritylamino)ethyl]butanamide
Homo sapiens
IC50: 0.194 mM
0.031
5'-deoxy-5'-[(tricyclo[3.3.1.13,7]dec-1-ylcarbamothioyl)amino]thymidine
Homo sapiens
-
-
0.11
5'-deoxy-5'-[[(diphenylmethyl)carbamothioyl]amino]thymidine
Homo sapiens
-
-
0.468
5'-O-(4,4'-dimethoxytrityl)thymidine
Homo sapiens
IC50: 0.468 mM
0.000014
5-(3'-amino-3'-deoxy-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridin-3'Nyl)-1-(4-chloro-3-trifluoromethylphenyl)-tetrazole
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.000035
5-(3'-amino-3'-deoxy-beta-D-thymidin-3'N-yl)-1-(4-chloro-3-trifluoromethylphenyl)-tetrazole
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.0009
5-(3'-amino-3'-deoxy-beta-D-thymidin-3'N-yl)-1-benzyl-tetrazole
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.0013
5-(E)-(2-bromovinyl)-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
Homo sapiens
IC50: 0.0013 mM
0.0026
5-benzylamino-(3'-deoxy-beta-D-thymidin-3'N-yl)-tetrazole
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.02
5-ethyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
Homo sapiens
IC50: 0.02 mM
0.0046
5-iodo-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-uracil
Homo sapiens
IC50: 0.0046 mM
0.025
5-methyl-1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.025 mM
0.491
5-methyl-1-[(2Z)-4-(4-methylpiperazin-1-yl)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.491 mM
0.0023
5-methyl-1-[(2Z)-4-(tritylamino)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.0023 mM
0.484
5-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-cytosine
Homo sapiens
IC50: 0.484 mM
0.0015
5-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.0015 mM
0.404
5-methyl-1-[4-(trityloxy)but-2-yn-1-yl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.404 mM
0.0033
5-methyl-1-[4-(trityloxy)butyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50: 0.0033 mM
0.00059
5-[(4-chloro-3-trifluoromethylphenyl)amino]-1-(3'-deoxy-beta-D-thymidin-3'N-yl)-tetrazole
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.0012
5-[(E)-2-bromoethenyl]-2'-O-decanoyluridine
Homo sapiens
competitive with respect to 2'-deoxythymidine, IC50: 0.0012 mM
0.00015 - 0.006
5-[(E)-2-bromoethenyl]-2'-O-octanoyluridine
0.0004
5-[amino-(4-chloro-3-trifluoromethylphenyl)]-1-(3'-deoxy-beta-(E)-5-(2-bromovinyl)-2'-deoxyuridin-3'N-yl)-tetrazole
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.019
6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-tritylhexanamide
Homo sapiens
IC50: 0.019 mM
0.5
9-[(2Z)-4-(trityloxy)but-2-en-1-yl]-guanine
Homo sapiens
IC50: above 0.5 mM
0.46
N-(2-cyanoethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
Homo sapiens
IC50: 0.46 mM
0.353
N-(2-cyanoethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
Homo sapiens
IC50: 0.353 mM
0.318
N-(2-[[cyano(phenyl)methyl]amino]-2-oxoethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
Homo sapiens
IC50: 0.318 mM
0.0013
N-(3'-deoxy-beta-D-thymidin-3'-yl)-N'-(4-chloro-3-trifluoromethylphenyl)-benzylguanidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.00043
N-(3'-deoxy-beta-D-thymidin-3'-yl)-N'-(4-chloro-3-trifluoromethylphenyl)-guanidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.00058
N-(3'-deoxy-beta-D-thymidin-3'-yl)-N'-(4-chloro-3-trifluoromethylphenyl)-isopropylguanidine
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.268
N-(cyanomethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
Homo sapiens
IC50: 0.268 mM
0.238
N-(diphenylmethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
Homo sapiens
IC50: 0.238 mM
0.038
N-(diphenylmethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
Homo sapiens
IC50: 0.038 mM
0.000046
N-methyl-4-[[[8-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)octyl]oxy](diphenyl)methyl]benzamide
Homo sapiens
-
thymidine kinase 2, in 50 mM Tris/HCl, pH 8.0, 2.5 mM MgCl2, 10 mM dithiothreitol, 0.5 mM CHAPS, 3 mg/ml obvine serum albumin, at 37°C
0.027
N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]-2,2-diphenylacetamide
Homo sapiens
IC50: 0.027 mM
0.028
N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]-3-(trifluoromethyl)benzamide
Homo sapiens
IC50: 0.028 mM
0.033
N-[(2Z)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)but-2-en-1-yl]-9H-xanthene-9-carboxamide
Homo sapiens
IC50: 0.033 mM
0.287
N-[2-[(diphenylmethyl)amino]-2-oxoethyl]-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
Homo sapiens
IC50: 0.287 mM
0.208
N-[cyano(phenyl)methyl]-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
Homo sapiens
IC50: 0.208 mM
0.075
N-[cyano(phenyl)methyl]-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanamide
Homo sapiens
IC50: 0.075 mM
0.5
N3-methyl-1-[(2Z)-4-(trityloxy)but-2-en-1-yl]-thymine
Homo sapiens
IC50: above 0.5 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.031
-
liver enzyme
0.094
-
placenta enzyme
0.124 - 0.183
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.2
-
fetal liver
7 - 8.5
-
adult liver
7.4 - 7.8
-
mitochondrial enzyme
7.6 - 7.8
-
cytoplasmic enzyme
8
-
assay at
9
-
bimodal pH profile with a peak at pH 7.4 and a minor peak at pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 37
highest activity within this temperature range at 37°C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.1
-
linear pH gradient
9.1
-
linear pH gradient between pH 7 and pH 11
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
embryonal
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
malfunction
-
depletion of thymidine kinase 1 decreases the efficiency of DNA repair during recovery from DNA damage and generates more cell death
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
KITH_HUMAN
234
0
25469
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25000
x * 25000, SDS-PAGE
25400
4 * 25400, calculated from amino acid sequence
58000
gel filtration
100000
24000
24840
-
calculated from amino acid sequence
25000
340000
-
oligomeric form, gel filtration
44000
-
2 * 44000, SDS-PAGE in presence of 2-mercaptoethanol
48000
-
2 * 48000, SDS-PAGE
48800
recombinant enzyme, gel filtration
49000
-
gel filtration
50000
70000 - 74000
84000 - 98000
92000
-
gel filtration, sucrose density gradient centrifugation
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 25000, SDS-PAGE
dimer
the truncated, dimeric enzyme form is fully active
homotetramer
4 * 25400, calculated from amino acid sequence
tetramer
?
-
x * 24000, about, SDS-PAGE
dimer
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
phosphorylation at Ser13 has regulatory function
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant enzyme T163S, hanging drop vapor diffusion method, using 0.1 M sodium citrate (pH 5.6), 20% (v/v) 2-propanol and 17% (w/v) polyethylene glycol 4000
purified recombinant C-terminally truncated enzyme in complex with inhibitor dTTP, hanging drop vapour diffusion method, 7-13 mg/ml protein in solution with 5 mM dTTP mixed with an equal volume of crystallization solution containing 0.1 M Na-citrate, pH 5.6, 20% 2-propanol, and 14-16% PEG 4000, 15°C, X-ray diffraction structure determination and analysis at 2.4-3.5 A resolution
purified recombinant truncated enzyme comprising residues 15-194 of the wild-type enzyme without His-tag, hanging drop vapour diffusion method, 7 mg/ml protein in 5 mM Tris-HCl, pH 7.2, 10 mM NaCl, and 10 mM DTT, mixed at equal volumes with crystallization buffer containing 0.095 mM tri-sodium citrate, pH 5.5, 12% PEG 4000, 10% isopropanol, 23°C, equilibration against a reservoir of 0.5 ml crystallization buffer, 3 days, X-ray diffraction structure determination and analysis at 1.7 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
L124A
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
M28A
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
M28I
the mutation has a negative impact on enzyme activity with thymidine as the substrate, affecting both the Km (250fold increase) and the kcat (6fold increase) values. The mutant has no activity with deoxycytidine
T163S
the mutation results in a kinase with a 140fold lower Km for 3’-azido-3’-deoxythymidine
H121N
similar subunit structure to wild-type enzyme, decreased enzyme activity
I212N
similar subunit structure to wild-type enzyme, less than 1% activity compared to wild-type
I59H
-
the mutant shows imcreased Km compared to the wild type enzyme
I59L
-
the mutant shows imcreased Km compared to the wild type enzyme
I59V
-
the mutant shows imcreased Km compared to the wild type enzyme
I59Y
-
the mutant shows decreased Km compared to the wild type enzyme
S13D
-
site-directed mutagenesis, ATP-induced tetramerization is perturbed, mutant is less activated by ATP and shows reduced activity compared to the wild-type enzyme
V106A
-
site-directed mutagenesis, mutant is similar to the wild-type enzyme in size, conformation and polarity, unaltered activity and oligomerization pattern
V106G
-
site-directed mutagenesis, mutant differs in size, conformation and polarity from the wild-type enzyme, reduced activity, permanent tetrameric form irrespective of the presence of ATP
V106H
-
site-directed mutagenesis, mutant differs in size, conformation and polarity from the wild-type enzyme, reduced activity, permanent tetrameric form irrespective of the presence of ATP
V106I
-
site-directed mutagenesis, mutant is similar to the wild-type enzyme in size, conformation and polarity, unaltered activity and oligomerization pattern
V106K
-
site-directed mutagenesis, mutant differs in size, conformation and polarity from the wild-type enzyme, reduced activity, permanent tetrameric form irrespective of the presence of ATP
V106L
-
site-directed mutagenesis, mutant differs in size, conformation and polarity from the wild-type enzyme, reduced activity, permanent tetrameric form irrespective of the presence of ATP
V106M
V106Q
-
site-directed mutagenesis, mutant differs in size, conformation and polarity from the wild-type enzyme, reduced activity, permanent tetrameric form irrespective of the presence of ATP
V106T
-
site-directed mutagenesis, mutant is similar to the wild-type enzyme in size, conformation and polarity, unaltered activity and oligomerization pattern
additional information
-
deletion of the 20 C-terminal amino acids decreases half-life at 20°C from 83 min for wild-type enzyme to 78 min, deletion of the 40 C-terninal amino acids increases half-life to 335 min, deletion of the 44 C-terminal amino acids increases half-life to 500 min
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9
-
-
641139
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15
-
rLyTK1Met-106: 50% loss of activity within 41 min, rLyTK1Val-106: 50% loss of activity after 392 min
20
-
deletion of the 20 C-terminal amino acids decreases half-life at 20°C from 83 min for wild-type enzyme to 78 min, deletion of the 40 C-terninal amino acids increases half-life to 335 min, deletion of the 44 C-terminal amino acids increases half-life to 500 min
25
-
50% loss of activity within 4 min, rLyTK1Met-106
25 - 40
-
40 min stable
40
-
enzyme TK-A: half-life 8 h, enzyme TK-C: half-life 30 min
45
-
5 min, fetal liver: 50% loss of activity, adult liver: 10% loss of activity
additional information
-
irreversible thermal denaturation following a two-state irrversible denaturation model, study with ligand-bound and free enzyme, respectively, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
binding of dNTP inhibitors and substrates, i.e. 2'-deoxycytidine, Mg-2'-deoxyCTP, 2'-deoxythymidine, and Mg-2'-deoxyTTP structurally stabilizes the enzyme, ligand-bound enzyme is less susceptible to aggregation, proteolysis by trypsin, and thermal denaturation
-
bovine serum albumin, 0.5 mg/ml stabilizes
-
digitonin stabilizes
-
dithiothreitol essential for stability
-
not stabilized by 10% glycerol, 5 mM 2-mercaptoethanol, 5 mM EDTA, 1 mg/ml bovine serum albumin
-
stable in the presence of ATP, bovine serum albumin and CHAPS
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50% glycerol, relatively stable
-
-20°C, or 4°C, 24 h, more than 50% loss of activity
-
-80°C, 2 weeks, no loss of activity in presence of digitonin
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GST affinity column chromatography
glutathione-Sepharose column chromatography
-
partial
-
recombinant enzyme as maltose binding fusion protein from Escherichia coli
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli by GST affinity chromatography, cleaving of the tag
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain B834(DE3) by nickel affinity chromatography
-
rLyTK1Val-106 and rLyTK1Met-106
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 cells
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
expression of C-terminally truncated enzyme lacking 41 amino acid residues
N-terminal thrombin-cleavable His6-tagged enzyme, missing 14 amino acids of the N-terminus and 40 amino acids of the C-terminus, in Escherichia coli
DNA and amino acid sequence determination, expression in Escherichia coli as maltose binding fusion protein in inclusion bodies, coexpression of GroEL/ES molecular chaperone system and 3% v/v ethanol supplementation
-
DNA and amino acid sequence determination, expression in Escherichia coli as maltose binding fusion protein in inclusion bodies, coexpression of GroEL/ES molecular chaperone system improves enzyme solubility only marginally, but ethanol supplementation contributes to enzyme recovery due to activation of heat shock response
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3)pLysS cells
-
expressed in Escherichia coli Rosetta(DE3) cells as a fusion protein to glutathione transferase
-
expression in Escherichia coli
expression of wild-type and Val106 mutants in an enzyme-deficient Escherichia coli strain as GST-fusion proteins
-
overexpression of His-tagged wild-type and mutant enzymes in Escherichia coli strain B834(DE3), transient expression as Flag-tagged enzyme in LM-tk- cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
doxorubicin treatment leads to upregulation of thymidine kinase 1
treatment with hydrogen peroxide results in induction of thymidine kinase 1, however, the thymidine kinase 1 activity does not correlate with thymidine kinase 1 protein levels, indicating that TK1 protein is inactive
trifluridine and 5-fluoro-2'-deoxyuridine lead to concentration dependent reduction of thymidine kinase 1 expression
upregulated after araC and dFdC treatment
0.001 mM of the mitogenic extracellular kinase 1/2 inhibitor PD0325901 rapidly decreases thymidine kinase 1 protein levels and mRNA expression in SKMEL-28 human melanoma cells with maximum reduction at 48 h posttreatment
-
DNA damage causes up-regulation of thymidine kinase 1 in tumor cells
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
coexpression of GroEL/ES molecular chaperone system improves recombinant enzyme solubility from inclusion bodies only marginally, but ethanol supplementation contributes to enzyme recovery due to activation of heat shock response
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
synthesis
enzyme can be useful in drug design
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sherley, J.L.; Kelly, T.J.
Human cytosolic thymidine kinase. Purification and physical characterization of the enzyme from HeLa cells
J. Biol. Chem.
263
375-382
1988
Homo sapiens
Manually annotated by BRENDA team
Cheng, Y.C.
Thymidine kinase from blast cells of myelocytic leukemia
Methods Enzymol.
51
365-371
1978
Homo sapiens
Manually annotated by BRENDA team
Bone, R.; Cheng, Y.C.; Wolfenden, R.
Inhibition of thymidine kinase by P1-(adenosine-5)-P5-(thymidine-5)-pentaphosphate
J. Biol. Chem.
261
5731-5735
1986
Homo sapiens
Manually annotated by BRENDA team
Kit, S.
Thymidine kinase
Microbiol. Sci.
2
369-375
1985
Gallus gallus, Cytomegalovirus, Homo sapiens, Betapolyomavirus macacae
Manually annotated by BRENDA team
Gan, T.E.; Brumley, J.L.; van der Weyden, M.B.
Human thymidine kinase. Purification and properties of the cytosolic enzyme of placenta
J. Biol. Chem.
258
7000-7004
1983
Homo sapiens
Manually annotated by BRENDA team
Ellims, P.H.; van der Weyden, M.B.
Kinetic mechanism and inhibition of human liver thymidine kinase
Biochim. Biophys. Acta
660
238-242
1981
Homo sapiens
Manually annotated by BRENDA team
Ellims, P.H.; van der Weyden, M.B.
Human liver thymidine kinase. Purification and some properties of the enzyme
J. Biol. Chem.
255
11290-11295
1980
Homo sapiens
Manually annotated by BRENDA team
Lee, L.S.; Cheng, Y.C.
Human deoxythymidine kinase. I. Purification and general properties of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute myelocytic leukemia
J. Biol. Chem.
251
2600-2604
1976
Homo sapiens
Manually annotated by BRENDA team
Kit, S.; Leung, W.C.; Trkula, D.
Properties of mitochondrial thymidine kinases of parental and enzyme-deficient HeLa cells
Arch. Biochem. Biophys.
158
503-513
1973
Homo sapiens
Manually annotated by BRENDA team
Taylor, A.T.; Stafford, M.A.; Jones, O.W.
Properties of thymidine kinase partially purified from human fetal and adult tissue
J. Biol. Chem.
247
1930-1935
1972
Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Saada, A.; Eriksson, S.
Kinetic properties of mutant human thymidine kinase 2 suggest a mechanism for mitochondrial DNA depletion myopathy
J. Biol. Chem.
278
6963-6968
2003
Homo sapiens (O00142), Homo sapiens
Manually annotated by BRENDA team
Zhang, F.; Shao, X.; Li, H.; Robison, J.G.; Murray, B.K.; O'Neill, K.L.
A monoclonal antibody specific for human thymidine kinase 1
Hybridoma
20
25-34
2001
Homo sapiens
Manually annotated by BRENDA team
Berenstein, D.; Christensen, J.F.; Kristensen, T.; Hofbauer, R.; Munch-Petersen, B.
Valine, not methionine, is amino acid 106 in human cytosolic thymidine kinase (TK1). Impact on oligomerization, stability, and kinetic properties
J. Biol. Chem.
275
32187-32192
2000
Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Munch-Petersen, B.; Herrstrom Sjoberg, A.; Hellman, U.; Bergman, T.; Jornvall, H.; Eriksson, S.
Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates
FEBS Lett.
443
170-174
1999
Homo sapiens (O00142), Homo sapiens
Manually annotated by BRENDA team
Li, C.L.; Lu, C.Y.; Ke, P.Y.; Chang, Z.F.
Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site
Biochem. Biophys. Res. Commun.
313
587-593
2004
Homo sapiens
Manually annotated by BRENDA team
Barroso, J.F.; Elholm, M.; Flatmark, T.
Tight binding of deoxyribonucleotide triphosphates to human thymidine kinase 2 expressed in Escherichia coli. Purification and partial characterization of its dimeric and tetrameric forms
Biochemistry
42
15158-15169
2003
Homo sapiens (O00142), Homo sapiens
Manually annotated by BRENDA team
Barroso, J.F.; Carvalho, R.N.; Flatmark, T.
Kinetic analysis and ligand-induced conformational changes in dimeric and tetrameric forms of human thymidine kinase 2
Biochemistry
44
4886-4896
2005
Homo sapiens
Manually annotated by BRENDA team
Frederiksen, H.; Berenstein, D.; Munch-Petersen, B.
Effect of valine 106 on structure-function relation of cytosolic human thymidine kinase. Kinetic properties and oligomerization pattern of nine substitution mutants of V106
Eur. J. Biochem.
271
2248-2256
2004
Homo sapiens
Manually annotated by BRENDA team
Birringer, M.S.; Claus, M.T.; Folkers, G.; Kloer, D.P.; Schulz, G.E.; Scapozza, L.
Structure of a type II thymidine kinase with bound dTTP
FEBS Lett.
579
1376-1382
2005
Leishmania major, Vaccinia virus (O57203), Homo sapiens (P04183), Homo sapiens, Mycoplasma pneumoniae (P75070)
Manually annotated by BRENDA team
Welin, M.; Kosinska, U.; Mikkelsen, N.E.; Carnrot, C.; Zhu, C.; Wang, L.; Eriksson, S.; Munch-Petersen, B.; Eklund, H.
Structures of thymidine kinase 1 of human and mycoplasmic origin
Proc. Natl. Acad. Sci. USA
101
17970-17975
2004
Ureaplasma urealyticum, Homo sapiens (P04183), Homo sapiens
Manually annotated by BRENDA team
Votava, T.; Topolcan, O.; Holubec, L.; Cerna, Z.; Sasek, L.; Finek, J.; Kormunda, S.
Changes of serum thymidine kinase in children with acute leukemia
Anticancer Res.
27
1925-1928
2007
Homo sapiens
Manually annotated by BRENDA team
Perez-Perez, M.J.; Hernandez, A.I.; Priego, E.M.; Rodriguez-Barrios, F.; Gago, F.; Camarasa, M.J.; Balzarini, J.
Mitochondrial thymidine kinase inhibitors
Curr. Top. Med. Chem.
5
1205-1219
2005
Human alphaherpesvirus 1, Homo sapiens (O00142), Homo sapiens (P04183)
Manually annotated by BRENDA team
Sandrini, M.P.; Clausen, A.R.; Munch-Petersen, B.; Piskur, J.
Thymidine kinase diversity in bacteria
Nucleosides Nucleotides Nucleic Acids
25
1153-1158
2006
Bacillus cereus, Bacillus subtilis, Clostridium perfringens, Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, Xanthomonas campestris, Streptomyces coelicolor (O50519), Gallus gallus (P04047), Homo sapiens (P04183), Mus musculus (P04184), Yersinia enterocolitica (Q0H7D6), Solanum lycopersicum (Q71F77), Salmonella enterica subsp. enterica serovar Typhi (Q8XFQ8), Clostridium acetobutylicum (Q97F65), Arabidopsis thaliana (Q9FN47), Arabidopsis thaliana (Q9S750), Ureaplasma parvum (Q9PPP5), Deinococcus radiodurans (Q9RSY5)
Manually annotated by BRENDA team
Zhu, C.; Harlow, L.S.; Berenstein, D.; Munch-Petersen, S.; Munch-Petersen, B.
Effect of C-terminal of human cytosolic thymidine kinase (TK1) on in vitro stability and enzymatic properties
Nucleosides Nucleotides Nucleic Acids
25
1185-1188
2006
Homo sapiens
Manually annotated by BRENDA team
Perez-Perez, M.J.; Priego, E.M.; Hernandez, A.I.; Familiar, O.; Camarasa, M.J.; Negri, A.; Gago, F.; Balzarini, J.
Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future
Med. Res. Rev.
28
797-820
2008
Homo sapiens
Manually annotated by BRENDA team
Leyton, J.; Smith, G.; Lees, M.; Perumal, M.; Nguyen, Q.D.; Aigbirhio, F.I.; Golovko, O.; He, Q.; Workman, P.; Aboagye, E.O.
Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901
Mol. Cancer Ther.
7
3112-3121
2008
Homo sapiens
Manually annotated by BRENDA team
Balzarini, J.; Van Daele, I.; Negri, A.; Solaroli, N.; Karlsson, A.; Liekens, S.; Gago, F.; Van Calenbergh, S.
Human mitochondrial thymidine kinase is selectively inhibited by 3-thiourea derivatives of beta-thymidine: identification of residues crucial for both inhibition and catalytic activity
Mol. Pharmacol.
75
1127-1136
2009
Homo sapiens, Human alphaherpesvirus 1 (P03176), Human alphaherpesvirus 1
Manually annotated by BRENDA team
Lin, J.; Roy, V.; Wang, L.; You, L.; Agrofoglio, L.A.; Deville-Bonne, D.; McBrayer, T.R.; Coats, S.J.; Schinazi, R.F.; Eriksson, S.
3-(1,2,3-Triazol-1-yl)-3-deoxythymidine analogs as substrates for human and Ureaplasma parvum thymidine kinase for structure-activity investigations
Bioorg. Med. Chem.
18
3261-3269
2010
Homo sapiens (P04183), Homo sapiens, Ureaplasma parvum (Q9PPP5), Ureaplasma parvum
Manually annotated by BRENDA team
Agarwal, H.K.; McElroy, C.A.; Sjuvarsson, E.; Eriksson, S.; Darby, M.V.; Tjarks, W.
Synthesis of N3-substituted carboranyl thymidine bioconjugates and their evaluation as substrates of recombinant human thymidine kinase 1
Eur. J. Med. Chem.
60
456-468
2013
Homo sapiens
Manually annotated by BRENDA team
Skovgaard, T.; Uhlin, U.; Munch-Petersen, B.
Comparative active-site mutation study of human and Caenorhabditis elegans thymidine kinase 1
FEBS J.
279
1777-1787
2012
Caenorhabditis elegans, Homo sapiens (P04183), Homo sapiens
Manually annotated by BRENDA team
Mutahir, Z.; Clausen, A.R.; Andersson, K.M.; Wisen, S.M.; Munch-Petersen, B.; Piskur, J.
Thymidine kinase 1 regulatory fine-tuning through tetramer formation
FEBS J.
280
1531-1541
2013
Anolis carolinensis (C3VAL3), Caenorhabditis elegans (G5EEZ5), Gallus gallus (P04047), Homo sapiens (P04183), Homo sapiens, Rattus norvegicus (P27158), Bacillus cereus (Q0H0H6), Dictyostelium discoideum (Q27564), Xenopus tropicalis (Q5I0A2), Danio rerio (Q803Y1), Arabidopsis thaliana (Q9S750 and Q9FN47)
Manually annotated by BRENDA team
Chen, Y.L.; Eriksson, S.; Chang, Z.F.
Regulation and functional contribution of thymidine kinase 1 in repair of DNA damage
J. Biol. Chem.
285
27327-27335
2010
Homo sapiens
Manually annotated by BRENDA team
Van Poecke, S.; Negri, A.; Gago, F.; Van Daele, I.; Solaroli, N.; Karlsson, A.; Balzarini, J.; Van Calenbergh, S.
3-[4-Aryl-(1,2,3-triazol-1-yl)]-3-deoxythymidine analogues as potent and selective inhibitors of human mitochondrial thymidine kinase
J. Med. Chem.
53
2902-2912
2010
Homo sapiens
Manually annotated by BRENDA team
Sun, R.; Eriksson, S.; Wang, L.
Identification and characterization of mitochondrial factors modulating thymidine kinase 2 activity
Nucleosides Nucleotides Nucleic Acids
29
382-385
2010
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Van Poecke, S.; Negri, A.; Janssens, J.; Solaroli, N.; Karlsson, A.; Gago, F.; Balzarini, J.; Van Calenbergh, S.
Synthesis, modeling and evaluation of 3-(1-aryl-1H-tetrazol-5-ylamino)-substituted 3-deoxythymidine derivatives as potent and selective human mitochondrial thymidine kinase inhibitors
Org. Biomol. Chem.
9
892-901
2011
Homo sapiens
Manually annotated by BRENDA team
Jagarlamudi, K.; Hansson, L.; Eriksson, S.
Breast and prostate cancer patients differ significantly in their serum Thymidine kinase 1 (TK1) specific activities compared with those hematological malignancies and blood donors: Implications of using serum TK1 as a biomarker
BMC Cancer
15
66
2015
Homo sapiens (P04183), Homo sapiens
Manually annotated by BRENDA team
Szantho, E.; Bhattoa, H.P.; Csoban, M.; Antal-Szalmas, P.; Ujfalusi, A.; Kappelmayer, J.; Hevessy, Z.
Serum thymidine kinase activity: analytical performance, age-related reference ranges and validation in chronic lymphocytic leukemia
PLoS ONE
9
e91647
2014
Homo sapiens
Manually annotated by BRENDA team
Zhang, S.Y.; Lin, B.D.; Li, B.R.
Evaluation of the diagnostic value of alpha-L-fucosidase, alpha-fetoprotein and thymidine kinase 1 with ROC and logistic regression for hepatocellular carcinoma
FEBS open bio
5
240-244
2015
Homo sapiens (P04183), Homo sapiens
Manually annotated by BRENDA team
Okamura, S.; Osaki, T.; Nishimura, K.; Ohsaki, H.; Shintani, M.; Matsuoka, H.; Maeda, K.; Shiogama, K.; Itoh, T.; Kamoshida, S.
Thymidine kinase-1/CD31 double immunostaining for identifying activated tumor vessels
Biotech. Histochem.
94
60-64
2019
Homo sapiens (P04183)
Manually annotated by BRENDA team
Cabel, L.; Rosenblum, D.; Lerebours, F.; Brain, E.; Loirat, D.; Bergqvist, M.; Cottu, P.; Donnadieu, A.; Bethune, A.; Kiavue, N.; Rodrigues, M.; Pierga, J.; Tanguy, M.; Bidard, F.
Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy
Breast Cancer Res.
22
98
2020
Homo sapiens (P04183), Homo sapiens
Manually annotated by BRENDA team
Sun, R.; Eriksson, S.; Wang, L.
The expression and activity of thymidine kinase 1 and deoxycytidine kinase are modulated by hydrogen peroxide and nucleoside analogs
Nucleosides Nucleotides Nucleic Acids
39
1347-1358
2020
Homo sapiens (P04183)
Manually annotated by BRENDA team
Larsson, A.M.; Bendahl, P.O.; Aaltonen, K.; Jansson, S.; Forsare, C.; Bergqvist, M.; Jorgensen, C.L.T.; Ryden, L.
Serial evaluation of serum thymidine kinase activity is prognostic in women with newly diagnosed metastatic breast cancer
Sci. Rep.
10
4484
2020
Homo sapiens (P04183), Homo sapiens
Manually annotated by BRENDA team