BRENDA - Enzyme Database
show all sequences of 2.7.4.14

Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1

Topalis, D.; Nogueira, T.C.; De Schutter, T.; El Amri, C.; Krecmerova, M.; Naesens, L.; Balzarini, J.; Andrei, G.; Snoeck, R.; Oncotarget 7, 10386-10401 (2016)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
gene CMPK1, genotyping in cervical tumour cell lines
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
additional information
modeling studies of the P64T and R134M amino acid changes, structure-function relationship analysis of mutant UMP/CMPK1s, effect of the two mutations on the stability of the UMP/CMPK1 protein is assessed by circular dichroism, overview
Homo sapiens
P64T
naturally occuring mutation, involved in alterations of cidofovir metabolism and resistance against cidofovir in cervical tumour cell lines, thermoresistant mutant compared to the wild-type enzyme. The P64T substitution may modify the distance between Ile62, Val63 and CMP, and therefore reduce the intensity or abolish the interactions observed in the wild-type UMP/CMPK1 at this position
Homo sapiens
R134M
naturally occuring mutation, involved in alterations of cidofovir metabolism and resistance against cidofovir in cervical tumour cell lines, thermosensitive similar to the wild-type enzyme. The typical interactions established between an arginine to bridge the phosphate of ATP and CMP for the enzymatic reaction are abolished in the presence of Met134
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.02
-
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.1
-
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.11
-
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.123
-
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.25
-
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.315
-
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.327
-
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.97
-
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
1.034
-
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
2.08
-
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
2.3
-
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ATP + 5-aza-cidofovir
Homo sapiens
-
ADP + phospho-5-aza-cidofovir
-
-
?
ATP + cidofovir
Homo sapiens
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid
ADP + phospho-cidofovir
-
-
?
ATP + CMP
Homo sapiens
-
ADP + CDP
-
-
?
ATP + cytarabine
Homo sapiens
anticancer drug, phosporylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells
ADP + phospho-cytarabine
-
-
?
ATP + dCMP
Homo sapiens
-
ADP + dCDP
-
-
?
ATP + dUMP
Homo sapiens
-
ADP + dUDP
-
-
?
ATP + gemcitabine
Homo sapiens
i.e. 2',2'-difluorodeoxycytidine
ADP + phospho-gemcitabine
-
-
?
ATP + UMP
Homo sapiens
-
ADP + UDP
-
-
?
additional information
Homo sapiens
hyperensitivity and resistance against anti-cancer drugs in the different cervical tumour cell lines, effects of changes on UMP/CMPK1 expression on CTP and UTP synthesis , overview
?
-
-
-
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
P30085
gene CMPK1
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
HaCaT cell
cidofovir-resistant tumour cell line, no infection with human papilloma virus
Homo sapiens
-
HeLa cell
cidofovir-resistant tumour cell line, infection with human papilloma virus
Homo sapiens
-
SiHa cell
cidofovir-resistant tumour cell line, infection with human papilloma virus
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ATP + 5-aza-cidofovir
-
739215
Homo sapiens
ADP + phospho-5-aza-cidofovir
-
-
-
?
ATP + 5-aza-cidofovir
wild-type enzyme
739215
Homo sapiens
ADP + phospho-5-aza-cidofovir
-
-
-
?
ATP + cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid
739215
Homo sapiens
ADP + phospho-cidofovir
-
-
-
?
ATP + cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid, wild-type enzyme
739215
Homo sapiens
ADP + phospho-cidofovir
-
-
-
?
ATP + CMP
-
739215
Homo sapiens
ADP + CDP
-
-
-
?
ATP + CMP
wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + CDP
-
-
-
?
ATP + cytarabine
anticancer drug, phosporylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells
739215
Homo sapiens
ADP + phospho-cytarabine
-
-
-
?
ATP + cytarabine
i.e. araC, wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + phospho-cytarabine
-
-
-
?
ATP + dCMP
-
739215
Homo sapiens
ADP + dCDP
-
-
-
?
ATP + dCMP
wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + dCDP
-
-
-
?
ATP + dUMP
-
739215
Homo sapiens
ADP + dUDP
-
-
-
?
ATP + dUMP
wild-type enzyme
739215
Homo sapiens
ADP + dUDP
-
-
-
?
ATP + gemcitabine
i.e. 2',2'-difluorodeoxycytidine
739215
Homo sapiens
ADP + phospho-gemcitabine
-
-
-
?
ATP + gemcitabine
i.e. 2',2'-difluorodeoxycytidine, wild-type enzyme
739215
Homo sapiens
ADP + phospho-gemcitabine
-
-
-
?
ATP + UMP
-
739215
Homo sapiens
ADP + UDP
-
-
-
?
ATP + UMP
wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + UDP
-
-
-
?
additional information
hyperensitivity and resistance against anti-cancer drugs in the different cervical tumour cell lines, effects of changes on UMP/CMPK1 expression on CTP and UTP synthesis , overview
739215
Homo sapiens
?
-
-
-
-
additional information
mutants P64T/R134M and R134M show no activity with all substrates
739215
Homo sapiens
?
-
-
-
-
Temperature Stability [°C]
Temperature Stability Minimum [°C]
Temperature Stability Maximum [°C]
Commentary
Organism
70
-
inactivation of wild-type enzyme and mutant R134M enzyme, only partial denaturation of mutant P64T
Homo sapiens
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.019
-
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.036
-
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.09
-
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.31
-
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.35
-
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.47
-
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
5.8
-
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
13.4
-
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
125
-
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
130
-
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
188
-
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
Cofactor
Cofactor
Commentary
Organism
Structure
ATP
-
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
gene CMPK1, genotyping in cervical tumour cell lines
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
ATP
-
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
additional information
modeling studies of the P64T and R134M amino acid changes, structure-function relationship analysis of mutant UMP/CMPK1s, effect of the two mutations on the stability of the UMP/CMPK1 protein is assessed by circular dichroism, overview
Homo sapiens
P64T
naturally occuring mutation, involved in alterations of cidofovir metabolism and resistance against cidofovir in cervical tumour cell lines, thermoresistant mutant compared to the wild-type enzyme. The P64T substitution may modify the distance between Ile62, Val63 and CMP, and therefore reduce the intensity or abolish the interactions observed in the wild-type UMP/CMPK1 at this position
Homo sapiens
R134M
naturally occuring mutation, involved in alterations of cidofovir metabolism and resistance against cidofovir in cervical tumour cell lines, thermosensitive similar to the wild-type enzyme. The typical interactions established between an arginine to bridge the phosphate of ATP and CMP for the enzymatic reaction are abolished in the presence of Met134
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.02
-
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.1
-
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.11
-
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.123
-
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.25
-
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.315
-
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.327
-
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.97
-
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
1.034
-
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
2.08
-
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
2.3
-
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ATP + 5-aza-cidofovir
Homo sapiens
-
ADP + phospho-5-aza-cidofovir
-
-
?
ATP + cidofovir
Homo sapiens
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid
ADP + phospho-cidofovir
-
-
?
ATP + CMP
Homo sapiens
-
ADP + CDP
-
-
?
ATP + cytarabine
Homo sapiens
anticancer drug, phosporylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells
ADP + phospho-cytarabine
-
-
?
ATP + dCMP
Homo sapiens
-
ADP + dCDP
-
-
?
ATP + dUMP
Homo sapiens
-
ADP + dUDP
-
-
?
ATP + gemcitabine
Homo sapiens
i.e. 2',2'-difluorodeoxycytidine
ADP + phospho-gemcitabine
-
-
?
ATP + UMP
Homo sapiens
-
ADP + UDP
-
-
?
additional information
Homo sapiens
hyperensitivity and resistance against anti-cancer drugs in the different cervical tumour cell lines, effects of changes on UMP/CMPK1 expression on CTP and UTP synthesis , overview
?
-
-
-
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
HaCaT cell
cidofovir-resistant tumour cell line, no infection with human papilloma virus
Homo sapiens
-
HeLa cell
cidofovir-resistant tumour cell line, infection with human papilloma virus
Homo sapiens
-
SiHa cell
cidofovir-resistant tumour cell line, infection with human papilloma virus
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ATP + 5-aza-cidofovir
-
739215
Homo sapiens
ADP + phospho-5-aza-cidofovir
-
-
-
?
ATP + 5-aza-cidofovir
wild-type enzyme
739215
Homo sapiens
ADP + phospho-5-aza-cidofovir
-
-
-
?
ATP + cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid
739215
Homo sapiens
ADP + phospho-cidofovir
-
-
-
?
ATP + cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid, wild-type enzyme
739215
Homo sapiens
ADP + phospho-cidofovir
-
-
-
?
ATP + CMP
-
739215
Homo sapiens
ADP + CDP
-
-
-
?
ATP + CMP
wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + CDP
-
-
-
?
ATP + cytarabine
anticancer drug, phosporylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells
739215
Homo sapiens
ADP + phospho-cytarabine
-
-
-
?
ATP + cytarabine
i.e. araC, wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + phospho-cytarabine
-
-
-
?
ATP + dCMP
-
739215
Homo sapiens
ADP + dCDP
-
-
-
?
ATP + dCMP
wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + dCDP
-
-
-
?
ATP + dUMP
-
739215
Homo sapiens
ADP + dUDP
-
-
-
?
ATP + dUMP
wild-type enzyme
739215
Homo sapiens
ADP + dUDP
-
-
-
?
ATP + gemcitabine
i.e. 2',2'-difluorodeoxycytidine
739215
Homo sapiens
ADP + phospho-gemcitabine
-
-
-
?
ATP + gemcitabine
i.e. 2',2'-difluorodeoxycytidine, wild-type enzyme
739215
Homo sapiens
ADP + phospho-gemcitabine
-
-
-
?
ATP + UMP
-
739215
Homo sapiens
ADP + UDP
-
-
-
?
ATP + UMP
wild-type enzyme and mutant P64T
739215
Homo sapiens
ADP + UDP
-
-
-
?
additional information
hyperensitivity and resistance against anti-cancer drugs in the different cervical tumour cell lines, effects of changes on UMP/CMPK1 expression on CTP and UTP synthesis , overview
739215
Homo sapiens
?
-
-
-
-
additional information
mutants P64T/R134M and R134M show no activity with all substrates
739215
Homo sapiens
?
-
-
-
-
Temperature Stability [°C] (protein specific)
Temperature Stability Minimum [°C]
Temperature Stability Maximum [°C]
Commentary
Organism
70
-
inactivation of wild-type enzyme and mutant R134M enzyme, only partial denaturation of mutant P64T
Homo sapiens
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.019
-
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.036
-
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.09
-
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.31
-
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.35
-
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.47
-
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
5.8
-
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
13.4
-
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
125
-
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
130
-
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
188
-
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
General Information
General Information
Commentary
Organism
malfunction
mutations P64T and R134M as well as downregulation of UMP/CMPK1 expression are observed in SiHaCDV and HeLaCDV, respectively, leading to alterations of cidofovir metabolism and resistance against cidofovir in the cervical tumour cell lines. In HaCaTCDV, no mutations of the uck gene are found and no impairment of UMP/CMPK1 activity is observed
Homo sapiens
metabolism
the first and last phosphorylation steps of cytidine 2'-deoxynucleoside analogues are catalyzed, respectively, by deoxycytidine kinase (dCK) and nucleoside diphosphate kinase (NDPK)
Homo sapiens
additional information
anticancer drugs, analogues of 2'-deoxycytidine (dC) (i.e. lamivudine and emtricitabine) or 2'-deoxycytidine monophosphate (dCMP) (i.e. CDV), require phosphorylation by UMP/CMPK. The anticancer agents cytarabine (araC) and gemcitabine (dFdC) are activated by UMP/CMPK1 following prior conversion to their 5?-monophosphate forms by dCK
Homo sapiens
physiological function
the cytosolic UMP/CMP kinase 1, is a key enzyme in the activation of antiviral and anticancer drugs and catalyzes the phosphorylation of (d)CMP analogues to their diphosphate forms
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
malfunction
mutations P64T and R134M as well as downregulation of UMP/CMPK1 expression are observed in SiHaCDV and HeLaCDV, respectively, leading to alterations of cidofovir metabolism and resistance against cidofovir in the cervical tumour cell lines. In HaCaTCDV, no mutations of the uck gene are found and no impairment of UMP/CMPK1 activity is observed
Homo sapiens
metabolism
the first and last phosphorylation steps of cytidine 2'-deoxynucleoside analogues are catalyzed, respectively, by deoxycytidine kinase (dCK) and nucleoside diphosphate kinase (NDPK)
Homo sapiens
additional information
anticancer drugs, analogues of 2'-deoxycytidine (dC) (i.e. lamivudine and emtricitabine) or 2'-deoxycytidine monophosphate (dCMP) (i.e. CDV), require phosphorylation by UMP/CMPK. The anticancer agents cytarabine (araC) and gemcitabine (dFdC) are activated by UMP/CMPK1 following prior conversion to their 5?-monophosphate forms by dCK
Homo sapiens
physiological function
the cytosolic UMP/CMP kinase 1, is a key enzyme in the activation of antiviral and anticancer drugs and catalyzes the phosphorylation of (d)CMP analogues to their diphosphate forms
Homo sapiens
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
0.037
-
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.04
-
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.058
-
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.226
-
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
1.4
-
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
2.52
-
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
5.61
-
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
122
-
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
410
-
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
1880
-
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
6250
-
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
KCat/KM [mM/s] (protein specific)
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
0.037
-
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.04
-
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
0.058
-
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
0.226
-
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
1.4
-
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
2.52
-
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
Homo sapiens
5.61
-
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
122
-
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
410
-
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
1880
-
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
6250
-
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Homo sapiens
Other publictions for EC 2.7.4.14
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
739215
Topalis
Resistance to the nucleotide a ...
Homo sapiens
Oncotarget
7
10386-10401
2016
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1
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18
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11
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4
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11
739700
Liu
Prognostic significance of nuc ...
Homo sapiens
Sci. Rep.
6
32027
2016
-
1
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1
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2
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-
737991
Tsao
The contribution of CMP kinase ...
Homo sapiens
Cell Cycle
14
354-363
2015
-
-
-
-
1
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7
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3
3
-
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-
702166
Liou
Modulation of human UMP/CMP ki ...
Homo sapiens
Biochem. Pharmacol.
79
381-388
2010
-
-
1
-
-
-
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2
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7
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-
692040
Kocabas
Gemcitabine pharmacogenomics: ...
Homo sapiens
Drug Metab. Dispos.
36
1951-1959
2008
-
-
1
-
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-
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2
1
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-
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-
693063
Xu
Human UMP-CMP kinase 2, a nove ...
Homo sapiens
J. Biol. Chem.
283
1563-1571
2008
-
-
1
-
2
-
-
4
2
1
-
1
-
2
-
-
1
-
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6
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6
-
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5
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1
-
-
-
-
-
-
-
-
-
693656
Lorenz
The influence of proline isome ...
Dictyostelium discoideum
J. Mol. Biol.
381
443-455
2008
-
-
-
-
-
-
-
-
-
-
1
-
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3
-
-
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-
-
-
673598
Topalis
Nucleotide binding to human UM ...
Homo sapiens
FEBS J.
274
3704-3714
2007
-
1
1
1
-
-
6
5
-
1
-
-
-
2
-
-
1
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5
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-
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-
-
676227
Alexandre
Enantioselectivity of human AM ...
Homo sapiens
Nucleic Acids Res.
35
4895-4904
2007
-
-
1
-
-
-
1
12
-
-
-
-
-
2
-
-
1
-
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12
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-
694478
Topalis
Looking for new pyrimidine acy ...
Homo sapiens
Nucleosides Nucleotides Nucleic Acids
26
1369-1373
2007
-
-
-
-
-
-
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1
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-
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-
694479
Alexandre
Enantio-selectivity of human n ...
Homo sapiens
Nucleosides Nucleotides Nucleic Acids
26
1375-1379
2007
-
-
-
-
-
-
-
11
-
1
-
4
-
1
-
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-
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4
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12
-
1
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-
1
-
-
-
-
-
-
-
-
-
663161
Hewitt
Effects of phosphate limitatio ...
Arabidopsis thaliana
Plant Physiol. Biochem.
43
91-99
2005
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
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-
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1
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1
-
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-
-
-
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-
-
-
-
-
-
645155
Curbo
The Drosophila melanogaster UM ...
Drosophila melanogaster
Biochem. Biophys. Res. Commun.
311
440-445
2003
-
-
1
-
-
-
-
4
2
-
-
-
-
4
-
-
-
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-
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4
-
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-
-
-
-
-
-
-
645162
Pasti
Reaction of human UMP-CMP kina ...
Dictyostelium sp., Homo sapiens
Eur. J. Biochem.
270
1784-1790
2003
-
-
1
-
-
-
2
16
-
-
-
3
-
4
-
-
-
-
-
-
-
-
12
-
-
-
-
14
-
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-
4
-
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-
-
1
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-
-
2
4
16
-
-
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3
-
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-
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-
-
-
-
12
-
-
-
-
14
-
-
-
-
-
-
-
-
-
-
645161
Liou
Characterization of human UMP/ ...
Homo sapiens
Cancer Res.
62
1624-1631
2002
-
-
1
-
-
-
4
16
1
-
-
3
-
3
-
-
1
-
-
1
-
-
27
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
4
-
16
1
-
-
3
-
-
-
1
-
1
-
-
27
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645160
Pearman
Characterization of human UMP- ...
Homo sapiens
Life Sci.
69
2361-2370
2001
-
-
-
-
-
-
-
-
-
1
1
1
-
2
-
-
-
-
-
21
-
-
3
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
-
-
-
-
1
1
1
-
-
-
-
-
21
-
-
3
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645152
Hutter
Phosphoryl transfer by a conce ...
Dictyostelium discoideum
Protein Sci.
9
2225-2231
2000
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
1
-
-
-
-
1
-
-
-
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-
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-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645156
Van Rompay
Phosphorylation of deoxycytidi ...
Homo sapiens
Mol. Pharmacol.
56
562-569
1999
-
-
1
-
-
-
-
5
2
-
-
-
-
3
-
-
-
-
-
-
-
-
9
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
5
2
-
-
-
-
-
-
-
-
-
-
-
9
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645153
Zhou
Cloning, expression in Escheri ...
Arabidopsis thaliana
Plant Physiol.
117
245-254
1998
-
-
1
-
-
-
1
4
-
-
1
-
-
5
-
-
1
1
-
-
-
-
2
1
-
-
1
2
1
-
-
-
2
-
-
-
-
1
-
-
-
-
-
1
2
4
-
-
1
-
-
-
-
1
-
-
-
-
2
1
-
-
1
2
1
-
-
-
-
-
-
-
-
-
645157
Okajima
Exchange of nucleoside monopho ...
Sus scrofa
J. Biochem.
124
359-367
1998
-
-
-
-
1
-
-
-
2
-
-
-
-
3
-
-
-
-
-
3
-
-
2
-
-
-
3
3
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
2
-
-
-
-
-
-
-
-
3
-
-
2
-
-
-
3
3
-
-
-
-
-
-
-
-
-
-
645158
Zhou
Site-specific mutations of con ...
Arabidopsis thaliana
Arch. Biochem. Biophys.
358
297-302
1998
-
-
-
-
7
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645150
Seagrave
Pyrimidine nucleoside monophos ...
Rattus norvegicus
Arch. Biochem. Biophys.
254
518-525
1987
-
-
-
-
-
-
2
4
-
-
-
-
-
2
-
-
-
1
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
4
-
-
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-
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-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645147
Seagrave
Pyrimidine nucleoside monophos ...
Rattus norvegicus
Arch. Biochem. Biophys.
247
76-83
1986
-
-
-
-
-
2
5
-
-
-
2
-
-
3
-
-
-
-
-
3
-
2
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
2
-
5
-
-
-
-
2
-
-
-
-
-
-
3
-
2
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
209853
Neale
Enzymes of pyrimidine deoxyrib ...
Mycoplasma mycoides
J. Bacteriol.
156
1001-1005
1983
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645149
Kohno
-
Purification and properties of ...
Saccharomyces cerevisiae
Agric. Biol. Chem.
47
19-24
1983
1
-
-
-
-
-
5
4
-
3
1
-
-
1
-
-
1
-
-
-
1
-
3
-
-
-
1
-
1
1
1
-
-
-
-
1
-
-
-
-
-
-
-
5
-
4
-
3
1
-
-
-
-
1
-
-
1
-
3
-
-
-
1
-
1
1
1
-
-
-
-
-
-
-
645141
Scott
Kinetics and equilibria of pyr ...
Homo sapiens
Biochim. Biophys. Acta
571
45-54
1979
-
-
-
-
-
2
-
-
-
1
-
-
-
2
-
-
1
1
-
2
1
1
5
-
-
-
1
-
-
-
2
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
1
-
-
-
-
-
1
-
2
1
1
5
-
-
-
1
-
-
-
2
-
-
-
-
-
-
-
645139
Orengo
Pyrimidine nucleoside monophos ...
Rattus norvegicus
Methods Enzymol.
51
321-331
1978
1
-
-
-
-
-
5
18
-
6
-
-
-
2
-
-
1
-
-
4
4
1
8
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
5
-
18
-
6
-
-
-
-
-
1
-
4
4
1
8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
645140
Anderson
UMP-CMP kinase from Tetrahymen ...
Tetrahymena pyriformis
Methods Enzymol.
51
331-337
1978
-
-
-
-
-
1
1
3
-
-
-
-
-
2
-
-
1
-
-
-
1
-
4
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
3
-
-
-
-
-
-
-
1
-
-
1
-
4
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
645144
Kobayashi
NADPH activation of deoxycytid ...
Rattus norvegicus
Biochem. Biophys. Res. Commun.
74
1249-1255
1977
1
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
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1
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1
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645142
Maness
Activation of rat liver pyrimi ...
Rattus norvegicus
Biochim. Biophys. Acta
429
182-190
1976
2
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1
1
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2
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2
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1
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2
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645146
Teng
Human erythrocyte pyrimidine n ...
Homo sapiens
J. Biol. Chem.
251
4179-4183
1976
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4
6
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2
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1
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4
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4
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4
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6
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1
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2
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4
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4
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645143
Maness
A pyrimidine nucleoside monoph ...
Rattus norvegicus
Biochemistry
14
1484-1489
1975
6
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2
6
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2
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2
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1
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2
1
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16
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6
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2
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6
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2
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1
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2
1
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16
-
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645148
Gravey
ATP:UMP-CMP phosphotransferase ...
Tetrahymena pyriformis
Biochim. Biophys. Acta
302
38-49
1973
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1
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645137
Ruffner
Adenosine triphosphate: uridin ...
Tetrahymena pyriformis
J. Biol. Chem.
244
5994-6002
1969
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2
5
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1
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1
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1
1
3
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1
1
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2
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5
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1
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1
1
3
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1
1
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645138
Hurwitz
The enzymatic incorporation of ...
Escherichia coli, Escherichia coli B / ATCC 11303
J. Biol. Chem.
234
2351-2358
1959
-
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177
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1
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4
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1
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