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Information on EC 3.6.1.23 - dUTP diphosphatase and Organism(s) Homo sapiens and UniProt Accession P33316
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3.6.1.23 dUTP diphosphataseIUBMB Comments
The enzyme catalyses the Mg2+-dependent hydrolysis of dUTP to dUMP, providing the substrate for EC 2.1.1.45, thymidylate synthase, leading to production of thymidine nucleotides. By reducing the effective ratio of dUTP to TTP, the enzyme also reduces the possibility of dUTP incorporation into DNA.
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Word Map
- 3.6.1.23
- uracil
- dump
- trimer
- thymidylate
-
misincorporation
- glycosylase
-
herpes
-
uracil-dna
- simplex
- drug development
-
homotrimeric
- herpesviruses
-
integrase
-
fluoropyrimidines
-
uracil-containing
- lentiviruses
- pyrophosphatases
-
sapis
-
ebv-encoded
- herv-k
- 2'-deoxyuridine
-
varicella-zoster
- fiv
- diagnostics
- medicine
- pharmacology
- synthesis
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
dutpase, deoxyuridine triphosphatase, deoxyuridine triphosphate nucleotidohydrolase, deoxyuridine 5'-triphosphate nucleotidohydrolase, dut-n, deoxyuridine 5'-triphosphate, dutp pyrophosphatase, dutp nucleotidohydrolase, orf 54, dcd-dut, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dUTPase
-
desoxyuridine 5'-triphosphatase
-
-
-
-
desoxyuridine 5'-triphosphate nucleotidohydrolase
-
-
-
-
desoxyuridine-triphosphatase
-
-
-
-
dUTP pyrophosphatase
dUTPase
P18
-
-
-
-
PIP4
-
-
-
-
dUTP pyrophosphatase
-
-
-
-
dUTPase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphorous acid anhydride hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
dUTP nucleotidohydrolase
The enzyme catalyses the Mg2+-dependent hydrolysis of dUTP to dUMP, providing the substrate for EC 2.1.1.45, thymidylate synthase, leading to production of thymidine nucleotides. By reducing the effective ratio of dUTP to TTP, the enzyme also reduces the possibility of dUTP incorporation into DNA.
CAS REGISTRY NUMBER
COMMENTARY
37289-34-2
-
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
2',3'-dideoxyUTP + H2O
2',3'-dideoxy-UMP + diphosphate
-
76% of the activity with dUTP
-
-
?
2'-deoxy-5-fluoro-UTP + H2O
2'-deoxy-5-fluoro-UMP + diphosphate
-
most specific substrate
-
-
?
dUDP + H2O
deoxyuridine + diphosphate
-
the enzyme is highly specific for deoxyuridine nucleotides
-
-
?
dUTP + H2O
?
-
the enzyme may generally perform an essential role in DNA replication and therefore can serve as a target enzyme for the development of chemotherapeutic compounds
-
-
?
dUTP + H2O
dUMP + diphosphate
dUTPase is essential for DNA integrity and is an important survival factor for cancer cells
-
-
?
dUTP + H2O
dUMP + diphosphate
dUTPase is essential in controlling relative cellular levels of dTTP/dUTP, both of which can be incorporated into DNA
-
-
?
dUTP + H2O
dUMP + diphosphate
enzyme inhibition is involved in apoptosis in cancer cells and decreases the sensitivity of cells for 5-fluorouracil, overview
-
-
?
dUTP + H2O
dUMP + diphosphate
substrate synthesis, overview, the enzymatic cycle is limited by a single rate-limiting step that occurs before or is concomitant with proton release
-
-
?
dUTP + H2O
dUMP + diphosphate
dUTP is constantly produced in the pyrimidine biosynthesis network. To prevent uracil incorporation into DNA, representatives of the dUTP nucleotidohydrolase enzyme family eliminate excess dUTP as one moethod to avoid uracil nucleotides incorporation into DNA, besides exchanging dUTP for dTTP as a second method, overview
dUMP is required for de novo biosynthesis of thymine
-
?
dUTP + H2O
dUMP + diphosphate
catalysis proceeds by way of an SN2 mechanism, a water molecule initiates in-line nucleophilic attack, conformational changes during the reaction take place in the C-terminus. The dUTPase binding pocket is highly specific for uracil, structural basis, overview. Phosphate chain coordination involves Mg2+ and is analogous to that of DNA polymerases. Catalytically competent and noncompetent conformation of the bound substrate, nodelling, overview
-
-
?
dUTP + H2O
dUMP + diphosphate
-
-
-
-
?
dUTP + H2O
dUMP + diphosphate
-
the enzyme is one of the primary enzymes that prevent the incorporation and accumulation of deoxyuridine in genomic DNA, and is essential for viability
-
-
?
dUTP + H2O
dUMP + diphosphate
-
dUTPase catalyzes the hydrolysis of dUTP to dUMP and diphosphate controlling the incorporation of uracil into DNA genomes
-
-
?
dUTP + H2O
dUMP + diphosphate
-
the enzyme is highly specific for deoxyuridine nucleotides
-
-
?
additional information
?
-
-
overexpression of dUTPase is associated with resistance to chemotherapeutic agents targeting thymidilate biosynthesis
-
-
?
additional information
?
-
-
the enzyme limits the activation or degradation of 5-fluorouracil, overview. The expression of dUTPase is significantly different between primary tumours and their corresponding metastatic tumour
-
-
?
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
dUTP + H2O
?
-
the enzyme may generally perform an essential role in DNA replication and therefore can serve as a target enzyme for the development of chemotherapeutic compounds
-
-
?
dUTP + H2O
dUMP + diphosphate
dUTPase is essential for DNA integrity and is an important survival factor for cancer cells
-
-
?
dUTP + H2O
dUMP + diphosphate
dUTPase is essential in controlling relative cellular levels of dTTP/dUTP, both of which can be incorporated into DNA
-
-
?
dUTP + H2O
dUMP + diphosphate
enzyme inhibition is involved in apoptosis in cancer cells and decreases the sensitivity of cells for 5-fluorouracil, overview
-
-
?
dUTP + H2O
dUMP + diphosphate
dUTP is constantly produced in the pyrimidine biosynthesis network. To prevent uracil incorporation into DNA, representatives of the dUTP nucleotidohydrolase enzyme family eliminate excess dUTP as one moethod to avoid uracil nucleotides incorporation into DNA, besides exchanging dUTP for dTTP as a second method, overview
dUMP is required for de novo biosynthesis of thymine
-
?
dUTP + H2O
dUMP + diphosphate
-
the enzyme is one of the primary enzymes that prevent the incorporation and accumulation of deoxyuridine in genomic DNA, and is essential for viability
-
-
?
dUTP + H2O
dUMP + diphosphate
-
dUTPase catalyzes the hydrolysis of dUTP to dUMP and diphosphate controlling the incorporation of uracil into DNA genomes
-
-
?
additional information
?
-
-
overexpression of dUTPase is associated with resistance to chemotherapeutic agents targeting thymidilate biosynthesis
-
-
?
additional information
?
-
-
the enzyme limits the activation or degradation of 5-fluorouracil, overview. The expression of dUTPase is significantly different between primary tumours and their corresponding metastatic tumour
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
Mg2+
activates, phosphate chain coordination involves Mg2+, binding structure, overview. Mg2+ probably dissociates from the enzyme with the product PPi and not with dUMP
Mg2+
-
dialyzed enzyme is activated 2fold by 5 mM MgCl2, reverses inhibition by EDTA
Mg2+
-
required for full activity, In the absence of divalent cations, dUTPase retains about 50% of the catalytic rate observed in the presence of Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-3-(2,2-difluoroethoxy)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
-
(E)-3-(cyclopentyloxy)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
-
(E)-3-(cyclopropylmethoxy)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
-
(E)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)-3-methoxybenzenesulfonamide
-
(E)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
-
(R)-1-(3-(2-(hydroxydiphenylmethyl)-pyrrolidin-1-ylsulfonyl)propyl)pyrimidine-2,4(1H,3H)-dione
-
(R)-1-(4-(2-(hydroxydiphenylmethyl)-pyrrolidin-1-yl)-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
-
(R)-N-(1-(3-(2,2-difluoroethoxy)phenyl)ethyl)-4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzenesulfonamide
-
(R)-N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzenesulfonamide
-
(R)-N-(1-(3-(cyclopropylmethoxy)phenyl)ethyl)-4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-benzenesulfonamide
-
(R,E)-N-(1-(3-(2,2-difluoroethoxy)phenyl)ethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pent-3-ene-1-sulfonamide
-
(R,E)-N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pent-3-ene-1-sulfonamide
-
(R,E)-N-(1-(3-(cyclopropylmethoxy)phenyl)ethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pent-3-ene-1-sulfonamide
-
(S)-1-(4-(2-(hydroxydiphenylmethyl)-pyrrolidin-1-yl)-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
-
1-(3-[[(2S)-2-[hydroxy[bis(2-methoxyphenyl)]methyl]pyrrolidin-1-yl]sulfonyl]propyl)pyrimidine-2,4(1H,3H)-dione
-
1-(3-[[(2S)-2-[hydroxy[bis(3-methoxyphenyl)]methyl]pyrrolidin-1-yl]sulfonyl]propyl)pyrimidine-2,4(1H,3H)-dione
-
1-(4-[(2S)-2-[bis(3-chlorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
-
1-(4-[(2S)-2-[bis(3-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
-
1-(4-[(2S)-2-[bis(4-chlorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
-
1-(4-[(2S)-2-[bis(4-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
-
1-[(1E,8E)-5-([[(E)-(3,4-dihydroxy-5-methoxybenzylidene)amino]oxy]methyl)-1-(3,4-dihydroxy-5-methoxyphenyl)-3,7-dioxa-2,8-diazadeca-1,8-dien-10-yl]pyrimidine-2,4(1H,3H)-dione
-
1-[(1Z,8E)-5-([[(E)-(3,4-dihydroxy-5-methoxybenzylidene)amino]oxy]methyl)-1-(3,4-dihydroxy-5-methoxyphenyl)-3,7-dioxa-2,8-diazadeca-1,8-dien-10-yl]pyrimidine-2,4(1H,3H)-dione
-
1-[3-([(2R)-2-[hydroxy(diphenyl)methyl]pyrrolidin-1-yl]sulfonyl)propyl]pyrimidine-2,4(1H,3H)-dione
-
1-[3-([(2S)-2-[bis(3-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]sulfonyl)propyl]pyrimidine-2,4(1H,3H)-dione
-
1-[3-([(2S)-2-[bis(4-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]sulfonyl)propyl]pyrimidine-2,4(1H,3H)-dione
-
1-[3-[(2S)-2-(diphenylmethyl)pyrrolidin-1-yl]-3-oxopropyl]pyrimidine-2,4(1H,3H)-dione
-
1-[4-[(2S)-2-(diphenylmethyl)pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
-
1-[4-[(2S)-2-[bis[2-(benzyloxy)phenyl](hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
-
1-[4-[(2S)-2-[bis[3-(benzyloxy)phenyl](hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
-
1-[4-[(2S)-2-[bis[4-(benzyloxy)phenyl](hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
-
1-[4-[(2S)-2-[hydroxy[di(thiophen-3-yl)]methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
-
3'-deoxy-5'-O-(hydroxy{[hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl)uridine
-
3-(2,2-difluoroethoxy)-N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)phenyl)propan-2-yl)-benzenesulfonamide
-
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,4,4-trimethylpentan-2-yl)propanamide
-
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-methylbutan-2-yl)propanamide
-
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-phenylethyl)propanamide
-
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(3-ethylhexan-3-yl)propanamide
-
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(3-phenylpropyl)propanamide
-
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(diphenylmethyl)propanamide
-
3-(cyclopentyloxy)-N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)phenyl)propan-2-yl)-benzenesulfonamide
-
3-(cyclopropylmethoxy)-N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)phenyl)propan-2-yl)-benzenesulfonamide
-
3-(cyclopropylmethoxy)-N-[5-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]-2-methylpentan-2-yl]benzenesulfonamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(1-hydroxy-2-methyl-1,1-diphenylpropan-2-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(1-hydroxy-2-methylpropan-2-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,2-diphenylethyl)-N-methylbutanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,2-diphenylethyl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,4,4-trimethylpentan-2-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-hydroxy-2,2-diphenylethyl)-N-methylbutanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-methyl-1-phenylpropan-2-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-methyl-4-phenylbutan-2-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-phenylpropan-2-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(3-ethylpentan-3-yl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(diphenylmethyl)butanamide
-
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-[2-methyl-1-(naphthalen-2-yl)propan-2-yl]butanamide
-
beta-hydroxyisovalerylshikonin
an ATP-noncompetitive inhibitor of protein tyrosine kinases, induces apoptosis in human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase activity, acts synergistically with 5-fluorouracil, overview
N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-phenyl)propan-2-yl)-3-methoxybenzenesulfonamide
-
N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-phenyl)propan-2-yl)benzenesulfonamide
-
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]ethyl]-3-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]propane-1-sulfonamide
-
N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-3-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]propane-1-sulfonamide
-
N-[2-[3-(cyclopropylmethoxy)phenyl]propan-2-yl]-3-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]propane-1-sulfonamide
-
N-[5-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]-2-methylpentan-2-yl]benzenesulfonamide
-
siRNAdUT3
a 21 base-pair double-stranded RNA molecule targeted against the motif 3 of the enzyme, time- and dose-dependent decrease in the dUTPase activity in transfected cells
-
3'-O-tert-butyldimethylsilyl-2',5'-dideoxyuridine 5'-N-diphenylphosphoramidate
-
-
additional information
-
inhibitor in vivo activity against the parasite, overview
-
additional information
-
enzyme inhibitor development by high-throughput screening of triskelion libraries, a uracil-aldehyde ligand is covalently tethered to one position of a trivalent alkyloxyamine linker via an oxime linkage, and then the vacant linker positions are derivatized with a library of aldehydes, screening of triskelion oximes for inhibitory potency, overview
-
additional information
-
programmed cell death protein 4 downregulates dUTPase in certain cell types, overview
-
additional information
-
the enzyme is not inhibited by 3'-azido-2',3'-dideoxy-UTP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0061
2'-deoxy-5-fluoro-UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.523
beta-L-2'-dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.687
dCTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.761
dTTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.54
UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.001
dUTP
-
wild type enzyme, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
0.0011
dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.0036
dUTP
-
mutant enzyme F158W, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
0.0052
dUTP
-
mutant enzyme F158A, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
additional information
additional information
detailed pre-steady-state and steady-state kinetic analysis, quantitative kinetic model of the human dUTPase catalytic cycle, overview
-
additional information
additional information
-
detailed pre-steady-state and steady-state kinetic analysis, quantitative kinetic model of the human dUTPase catalytic cycle, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
dUTP
-
mutant enzyme D49N/F158W, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
0.32
dUTP
-
mutant enzyme F158A, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
5.8
dUTP
-
wild type enzyme, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
6.3
dUTP
-
mutant enzyme F158W, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
6.8
dUTP
-
mutant enzyme F158W, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
600
2'-deoxy-5-fluoro-UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.0061
beta-L-2'-dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.1616
dCTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.01971
dTTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.01278
UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
62
dUTP
-
mutant enzyme F158A, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
1900
dUTP
-
mutant enzyme F158W, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
5800
dUTP
-
wild type enzyme, in 1 mM HEPES pH 7.5 containing 100 mM KCl and 5 mM MgCl2, at 20°C
6600
dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0033
1-[(1Z,8E)-5-([[(E)-(3,4-dihydroxy-5-methoxybenzylidene)amino]oxy]methyl)-1-(3,4-dihydroxy-5-methoxyphenyl)-3,7-dioxa-2,8-diazadeca-1,8-dien-10-yl]pyrimidine-2,4(1H,3H)-dione
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.017
1-[[2-(trityloxy)ethoxy]methyl]pyrimidine-2,4(1H,3H)-dione
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.018
2'-deoxyuridine 5'-(alpha,beta-imido)triphosphate
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000021
N-[(1R)-1-[3-(cyclopropylmethoxy)-4-fluorophenyl]ethyl]-3-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]propane-1-sulfonamide
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.232
3'-O-tert-butyldimethylsilyl-2',5'-dideoxyuridine 5'-N-diphenylphosphoramidate
-
-
0.156
3-[5-(trityloxy)tetrahydrofuran-2-yl]pyridine-2,6(1H,3H)-dione
-
pH 8.0, 25°C
0.807
5'-(2,2-dimethyl-1,1-diphenylpropan-1-yl)-3'-methyl-2',3'-dideoxyuracil
-
pH 8.0, 25°C
0.547
5'-adamantoyl-3'-methyl-2',3'-dideoxyuracil
-
pH 8.0, 25°C, recombinant enzyme
additional information
2'-deoxy-5'-phenylmethylaminouracil
-
above 1 mM, pH 8.0, 25°C
additional information
5'-(2,2-dimethyl-1,1-diphenylpropan-1-yl)-2',3'-dideoxyuracil
-
above 1 mM, pH 8.0, 25°C
additional information
5'-(2,3,3-trimethylbutan-2-yl)-3'-methyl-2',3'-dideoxyuracil
-
above 1 mM, pH 8.0, 25°C
additional information
5'-(2,4-dimethyl-3-(1-methylethyl)pentan-3-yl)-2'-deoxyuracil
-
above 1 mM, pH 8.0, 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000026
(E)-3-(2,2-difluoroethoxy)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000033
(E)-3-(cyclopentyloxy)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000028
(E)-3-(cyclopropylmethoxy)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00034
(E)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)-3-methoxybenzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0016
(E)-N-(7-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methylhept-5-en-2-yl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.01
(R)-1-(4-(2-(hydroxydiphenylmethyl)-pyrrolidin-1-yl)-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00041
(R)-N-(1-(3-(2,2-difluoroethoxy)phenyl)ethyl)-4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00043
(R)-N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00082
(R)-N-(1-(3-(cyclopropylmethoxy)phenyl)ethyl)-4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000082
(R,E)-N-(1-(3-(2,2-difluoroethoxy)phenyl)ethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pent-3-ene-1-sulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000041
(R,E)-N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pent-3-ene-1-sulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000039
(R,E)-N-(1-(3-(cyclopropylmethoxy)phenyl)ethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pent-3-ene-1-sulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-(3-[[(2S)-2-[hydroxy[bis(2-methoxyphenyl)]methyl]pyrrolidin-1-yl]sulfonyl]propyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-(3-[[(2S)-2-[hydroxy[bis(3-methoxyphenyl)]methyl]pyrrolidin-1-yl]sulfonyl]propyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00058
1-(4-[(2S)-2-[bis(3-chlorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00035
1-(4-[(2S)-2-[bis(3-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-(4-[(2S)-2-[bis(4-chlorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0006
1-(4-[(2S)-2-[bis(4-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl)pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0094
1-[3-([(2R)-2-[hydroxy(diphenyl)methyl]pyrrolidin-1-yl]sulfonyl)propyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00028
1-[3-([(2S)-2-[bis(3-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]sulfonyl)propyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00031
1-[3-([(2S)-2-[bis(4-fluorophenyl)(hydroxy)methyl]pyrrolidin-1-yl]sulfonyl)propyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-[3-[(2S)-2-(diphenylmethyl)pyrrolidin-1-yl]-3-oxopropyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00015
1-[4-[(2S)-2-(diphenylmethyl)pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-[4-[(2S)-2-[bis[2-(benzyloxy)phenyl](hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-[4-[(2S)-2-[bis[3-(benzyloxy)phenyl](hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.001
1-[4-[(2S)-2-[bis[4-(benzyloxy)phenyl](hydroxy)methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.001 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00023
1-[4-[(2S)-2-[hydroxy[di(thiophen-3-yl)]methyl]pyrrolidin-1-yl]-4-oxobutyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.3
1-[[2-(trityloxy)ethoxy]methyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
IC50 above 0.3 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.015
2'-deoxyuridine 5'-(alpha,beta-imido)triphosphate
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000073
3-(2,2-difluoroethoxy)-N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)phenyl)propan-2-yl)-benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,4,4-trimethylpentan-2-yl)propanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-methylbutan-2-yl)propanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-phenylethyl)propanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.022
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(3-ethylhexan-3-yl)propanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(3-phenylpropyl)propanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(diphenylmethyl)propanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000031
3-(cyclopentyloxy)-N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)phenyl)propan-2-yl)-benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000073
3-(cyclopropylmethoxy)-N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)phenyl)propan-2-yl)-benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.000035
3-(cyclopropylmethoxy)-N-[5-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]-2-methylpentan-2-yl]benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0025
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(1-hydroxy-2-methyl-1,1-diphenylpropan-2-yl)butanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(1-hydroxy-2-methylpropan-2-yl)butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0013
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,2-diphenylethyl)-N-methylbutanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.016
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,2-diphenylethyl)butanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2,4,4-trimethylpentan-2-yl)butanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0011
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-hydroxy-2,2-diphenylethyl)-N-methylbutanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-methyl-1-phenylpropan-2-yl)butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.021
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-methyl-4-phenylbutan-2-yl)butanamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(2-phenylpropan-2-yl)butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(3-ethylpentan-3-yl)butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-(diphenylmethyl)butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-phenylbutanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-N-[2-methyl-1-(naphthalen-2-yl)propan-2-yl]butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
N,N-dibenzyl-3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00127
N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-phenyl)propan-2-yl)-3-methoxybenzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0018
N-(2-(4-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-phenyl)propan-2-yl)benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.03
N-benzyl-4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)butanamide
Homo sapiens
IC50 above 0.03 mM, in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00004
N-[(1R)-1-[3-(cyclopropylmethoxy)phenyl]ethyl]-3-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]propane-1-sulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.00034
N-[2-[3-(cyclopropylmethoxy)phenyl]propan-2-yl]-3-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]propane-1-sulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0039
N-[5-[(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy]-2-methylpentan-2-yl]benzenesulfonamide
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
0.0073
1-[3-(4-benzylpiperidin-1-yl)-3-oxopropyl]pyrimidine-2,4(1H,3H)-dione
Homo sapiens
in 0.2 M Tris buffer (pH 7.4), 16 mM MgCl2, at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
primary cancer, patients after surgery, expression levels of the enzyme in the primary colorectal cancer of patients with and without distant metastases, the expression level is 3fold higher in the first case, overview
additional information
enzyme form DUT-N is approximately 30fold more abundant in HeLa cells than in DUT-M cells
additional information
-
intracellular labeling of the enzyme in intracranial tumors with marker Ki-67, overview
additional information
-
several astrocytoma, oligodendrogliomas, oligoastrocytomas, meningiomas, ependymomas, and metastatic acrcinomas, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
intracellular labeling of the enzyme in intracranial tumors with marker Ki-67, overview
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the enzyme contributes to the cellular response to the anti-cancer nucleoside decitabine. Exposure of HeLa cells to decitabine upregulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase. dUTPase down-regulation enhances the cytotoxic effect of decitabine producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA
malfunction
dUTPase down-regulation increases decitabine-induced toxicity in HeLa and MRC-5 cells at a wide range of doses
metabolism
the enzyme is involved de novo biosynthesis of dTTP and sanitizing the deoxynucleotide pool by the specific removal of dUTP
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). DUT_HUMAN
252
0
26563
Swiss-Prot
Mitochondrion (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotrimer
homotrimer
with interfaces formed between subunit surfaces, in the central channel, and by C-terminal beta-strand swapping. Analysis of intersubunit interactions reveals an important cohesive role for the C-terminus
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
nuclear dUTPase is phosphorylated by the phosphorylated cyclin-cdc2 complex
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with inhibitor alpha,beta-imino-dUTP and Mg2+, 0.282 mM dUTPase, 1.25 mM alpha,beta-imino-dUTP, and 10 mM MgCl2 in 10 mM Tris-HCl, 50 mM NaCl, and 0.1 mM TCEP, pH 7.0, are mixed with reservoir solution containing 0.1 M Na-HEPES buffer, pH 7.5, and 18-20% PEG 3350, generation of rhombohedral crystals, X-ray diffraction structure determination and analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D49N/F158W
-
the Asp/Asn mutation within motif I results in approximately 1000fold decrease of steady-state rate and significantly weakens the interaction of the protein with alpha,beta-imido-dUTP (4fold) whereas dUMP binding is only slightly affected
F158A
-
the mutant shows severely decreased catalytic activity compared to the wild type enzyme
F158W
additional information
F158W
-
the mutant shows decreased catalytic activity compared to the wild type enzyme
F158W
-
the mutation has no significant effect on the catalytic properties of dUTPase
additional information
increase in the expression of dUTPase in human lung and ovarian tumor cell lines is known to result in resistance to 5-fluorouracil
additional information
-
increase in the expression of dUTPase in human lung and ovarian tumor cell lines is known to result in resistance to 5-fluorouracil
additional information
mutations of a suggested hinge proline destabilize human dUTPase without preventing trimeric organization. But trimer formation is prevented in the human enzyme by truncating the C-terminus before the swapping arm
additional information
-
mutations of a suggested hinge proline destabilize human dUTPase without preventing trimeric organization. But trimer formation is prevented in the human enzyme by truncating the C-terminus before the swapping arm
additional information
-
overexpression of programmed cell death protein 4, Pdcd4, in a human endocrine pancreatic cell line Bon-1 decreases levels of dUTPase, but does not in colon carcinoma cell line HCT116, treatment of a human breast adenocarcinoma cell line MCF-7, with 5-fluorouracil results in regulated expression of Pdcd4 and dUTPase, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
heat-induced denaturation, unfolding is irreversible in all samples
additional information
-
heat-induced denaturation, unfolding is irreversible in all samples
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged wild-type dUTPase and mutant F158W by nickel affinity chromatography
recombinant enzyme from Escherichia coli by phosphocellulose chromatography and gel filtration to near homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
exposure of HeLa cells to decitabine upregulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
diagnostics
-
the enzyme can be a biomarker for exposure to N-methyl-N'-nitro-N-nitrosoguanidine exposure since the compound leads to release of the enzyme, besides other proteins, to the extracellular compartment from amnion epithelial cells, overview
drug development
the nuclear isoform of the enzyme is a target for anticancer chemotherapeutic strategies
drug development
dUTPase family of enzymes are promising targets for anticancer and antimicrobial therapies
drug development
the enzyme is a factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Williams, M.V.; Cheng, Y.
Human deoxyuridine triphosphate nucleotidohydrolase. Purification and characterization of the deoxyuridine triphosphate nucleotidohydrolase from acute lymphocytic leukemia
J. Biol. Chem.
254
2897-2901
1979
Homo sapiens
Wist, E.
Partial purification of deoxyuridine triphosphate nucleotidohydrolase and its effect on DNA synthesis in isolated HeLa cell nuclei
Biochim. Biophys. Acta
565
98-106
1979
Homo sapiens
Ingraham, H.A.; Goulian, M.
Deoxyuridine triphosphatase: a potential site of interaction with pyrimidine nucleotide analogues
Biochem. Biophys. Res. Commun.
109
746-752
1982
Homo sapiens
Caradonna, S.J.; Adamkiewicz, D.M.
Purification and properties of the deoxyuridine triphosphate nucleotidohydrolase enzyme derived from HeLa S3 cells. Comparison to a distinct dUTP nucleotidohydrolase induced in herpes simplex virus-infected HeLa S3 cells
J. Biol. Chem.
259
5459-5464
1984
Human alphaherpesvirus 1, Homo sapiens
Williams, M.V.
Deoxyuridine triphosphate nucleotidohydrolase induced by herpes simplex virus type 1. Purification and characterization of induced enzyme
J. Biol. Chem.
259
10080-10084
1984
Human alphaherpesvirus 1, Homo sapiens
Ladner, R.D.; McNulty, D.E.; Carr, S.A.; Roberts, G.D.; Caradonna, S.J.
Characterization of distinct nuclear and mitochondrial forms of human deoxyuridine triphosphate nucleotidohydrolase
J. Biol. Chem.
271
7745-7751
1996
Homo sapiens (P33316), Homo sapiens
McIntosh, E.M.; Ager, D.D.; Gadsen, M.H.; Haynes, R.H.
Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme
Proc. Natl. Acad. Sci. USA
89
8020-8024
1992
Homo sapiens
Studebaker, A.W.; Lafuse, W.P.; Kloesel, R.; Williams, M.V.
Modulation of human dUTPase using small interfering RNA
Biochem. Biophys. Res. Commun.
327
306-310
2005
Homo sapiens (P33316), Homo sapiens
Nguyen, C.; Kasinathan, G.; Leal-Cortijo, I.; Musso-Buendia, A.; Kaiser, M.; Brun, R.; Ruiz-Perez, L.M.; Johansson, N.G.; Gonzalez-Pacanowska, D.; Gilbert, I.H.
Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target
J. Med. Chem.
48
5942-5954
2005
Homo sapiens, Leishmania donovani, Leishmania major, Plasmodium falciparum
Nguyen, C.; Ruda, G.F.; Schipani, A.; Kasinathan, G.; Leal, I.; Musso-Buendia, A.; Kaiser, M.; Brun, R.; Ruiz-Perez, L.M.; Sahlberg, B.L.; Johansson, N.G.; Gonzalez-Pacanowska, D.; Gilbert, I.H.
Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase
J. Med. Chem.
49
4183-4195
2006
Homo sapiens, Plasmodium falciparum
Romeike, B.F.; Boeckeler, A.; Kremmer, E.; Sommer, P.; Krick, C.; Graesser, F.
Immunohistochemical detection of dUTPase in intracranial tumors
Pathol. Res. Pract.
201
727-732
2005
Homo sapiens
Wu, M.; Shen, J.; Zhan, J.; Yu, Y.
dUTP pyrophosphatase, its appearance in extracellular compartment may serve as a potential biomarker for N-methyl-N-nitro-N-nitrosoguanidine exposure in mammalian cells
Proteomics
6
3001-3007
2006
Homo sapiens
Lankat-Buttgereit, B.; Lenschen, B.; Schmidt, H.; Goeke, R.
The action of Pdcd4 may be cell type specific: evidence that reduction of dUTPase levels might contribute to its tumor suppressor activity in Bon-1 cells
Apoptosis
13
157-164
2008
Homo sapiens
Kajimoto, S.; Horie, M.; Manabe, H.; Masuda, Y.; Shibayama-Imazu, T.; Nakajo, S.; Gong, X.F.; Obama, T.; Itabe, H.; Nakaya, K.
A tyrosine kinase inhibitor, beta-hydroxyisovalerylshikonin, induced apoptosis in human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase activity
Biochim. Biophys. Acta
1782
41-50
2008
Homo sapiens (P33316), Homo sapiens
Jiang, Y.L.; Chung, S.; Krosky, D.J.; Stivers, J.T.
Synthesis and high-throughput evaluation of triskelion uracil libraries for inhibition of human dUTPase and UNG2
Bioorg. Med. Chem.
14
5666-5672
2006
Homo sapiens
Varga, B.; Barabas, O.; Kovari, J.; Toth, J.; Hunyadi-Gulyas, E.; Klement, E.; Medzihradszky, K.F.; Toelgyesi, F.; Fidy, J.; Vertessy, B.G.
Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase
FEBS Lett.
581
4783-4788
2007
Homo sapiens (P33316), Homo sapiens
Toth, J.; Varga, B.; Kovacs, M.; Malnasi-Csizmadia, A.; Vertessy, B.G.
Kinetic mechanism of human dUTPase, an essential nucleotide pyrophosphatase enzyme
J. Biol. Chem.
282
33572-33582
2007
Homo sapiens (P33316), Homo sapiens
Vertessy, B.G.; Toth, J.
Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases
Acc. Chem. Res.
42
97-106
2009
Homo sapiens (P33316), Homo sapiens
Takacs, E.; Barabas, O.; Petoukhov, M.V.; Svergun, D.I.; Vertessy, B.G.
Molecular shape and prominent role of beta-strand swapping in organization of dUTPase oligomers
FEBS Lett.
583
865-871
2009
Escherichia coli (P06968), Escherichia coli, Homo sapiens (P33316), Homo sapiens, Drosophila melanogaster (Q9V3I1)
Kawahara, A.; Akagi, Y.; Hattori, S.; Mizobe, T.; Shirouzu, K.; Ono, M.; Yanagawa, T.; Kuwano, M.; Kage, M.
Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer
J. Clin. Pathol.
62
364-369
2009
Homo sapiens
Musso-Buendia, J.A.; Vidal, A.E.; Kasinthan, G.; Nguyen, C.; Carrero-Lerida, J.; Ruiz-Perez, L.M.; Wilson, K.; Johansson, N.G.; Gilbert, I.H.; Gonzalez-Pacanowska, D.
Kinetic properties and inhibition of the dimeric dUTPase-dUDPase from Campylobacter jejuni
J. Enzyme Inhib. Med. Chem.
24
111-116
2009
Campylobacter jejuni, Homo sapiens
Quesada-Soriano, I.; Casas-Solvas, J.M.; Recio, E.; Ruiz-Perez, L.M.; Vargas-Berenguel, A.; Gonzalez-Pacanowska, D.; Garcia-Fuentes, L.
Kinetic properties and specificity of trimeric Plasmodium falciparum and human dUTPases
Biochimie
92
178-186
2010
Homo sapiens, Plasmodium falciparum
Takacs, E.; Nagy, G.; Leveles, I.; Harmat, V.; Lopata, A.; Toth, J.; Vertessy, B.G.
Direct contacts between conserved motifs of different subunits provide major contribution to active site organization in human and mycobacterial dUTPases
FEBS Lett.
584
3047-3054
2010
Homo sapiens, Mycobacterium tuberculosis (P9WNS5), Mycobacterium tuberculosis H37Rv (P9WNS5)
Palmen, L.G.; Kvassman, J.O.
Differential inhibition of homotrimeric dUTPases by the 3-azido derivative of dideoxy-UTP
J. Enzyme Inhib. Med. Chem.
25
146-150
2010
Escherichia coli, equine infectious anemia virus, Homo sapiens
Pecsi, I.; Leveles, I.; Harmat, V.; Vertessy, B.G.; Toth, J.
Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase
Nucleic Acids Res.
38
7179-7186
2010
Homo sapiens, Mycobacterium tuberculosis (P9WNS5), Mycobacterium tuberculosis H37Rv (P9WNS5)
Miyakoshi, H.; Miyahara, S.; Yokogawa, T.; Chong, K.T.; Taguchi, J.; Endoh, K.; Yano, W.; Wakasa, T.; Ueno, H.; Takao, Y.; Nomura, M.; Shuto, S.; Nagasawa, H.; Fukuoka, M.
Synthesis and discovery of N-carbonylpyrrolidine- or N-sulfonylpyrrolidine-containing uracil derivatives as potent human deoxyuridine triphosphatase inhibitors
J. Med. Chem.
55
2960-2969
2012
Homo sapiens (P33316), Homo sapiens
Miyahara, S.; Miyakoshi, H.; Yokogawa, T.; Chong, K.T.; Taguchi, J.; Muto, T.; Endoh, K.; Yano, W.; Wakasa, T.; Ueno, H.; Takao, Y.; Fujioka, A.; Hashimoto, A.; Itou, K.; Yamamura, K.; Nomura, M.; Nagasawa, H.; Shuto, S.; Fukuoka, M.
Discovery of highly potent human deoxyuridine triphosphatase inhibitors based on the conformation restriction strategy
J. Med. Chem.
55
5483-5496
2012
Homo sapiens (P33316), Homo sapiens
Guiomar, P.; Andras, H.; Beata, G.; Luis, M.; Dolores, G.; Requena, C.; Vidal, A.
The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine
Biochem. J.
473
2635-2643
2016
Homo sapiens, Homo sapiens (P33316)
Rotoli, S.M.; Jones, J.L.; Caradonna, S.J.
Cysteine residues contribute to the dimerization and enzymatic activity of human nuclear dUTP nucleotidohydrolase (nDut)
Protein Sci.
27
1797-1809
2018
Homo sapiens (P33316), Homo sapiens
Hizi, A.; Herzig, E.
dUTPase the frequently overlooked enzyme encoded by many retroviruses
Retrovirology
12
70
2015
bovine immunodeficiency virus, Caenorhabditis elegans, Caprine arthritis encephalitis virus, equine infectious anemia virus, Escherichia coli (P06968), feline immunodeficiency virus, Homo sapiens (P33316), Homo sapiens, Human endogenous retrovirus K, Human gammaherpesvirus 4, Human gammaherpesvirus 8, Jembrana disease virus, Mason-Pfizer monkey virus, mouse mammary tumor virus, Murid gammaherpesvirus 4, Mycobacterium tuberculosis, Plasmodium falciparum, Saccharomyces cerevisiae, Visna-maedi virus
Nyiri, K.; Mertens, H.D.T.; Tihanyi, B.; Nagy, G.N.; Kohegyi, B.; Matejka, J.; Harris, M.J.; Szabo, J.E.; Papp-Kadar, V.; Nemeth-Pongracz, V.; Ozohanics, O.; Vekey, K.; Svergun, D.I.; Borysik, A.J.; Vertessy, B.G.
Structural model of human dUTPase in complex with a novel proteinaceous inhibitor
Sci. Rep.
8
4326
2018
Homo sapiens
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