Information on EC 2.7.4.14 - UMP/CMP kinase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.7.4.14
-
RECOMMENDED NAME
GeneOntology No.
UMP/CMP kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + UMP = ADP + UDP
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
CMP phosphorylation
-
-
Metabolic pathways
-
-
pyrimidine deoxyribonucleotide phosphorylation
-
-
pyrimidine metabolism
-
-
Pyrimidine metabolism
-
-
UTP and CTP de novo biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:CMP(UMP) phosphotransferase
This eukaryotic enzyme is a bifunctional enzyme that catalyses the phosphorylation of both CMP and UMP with similar efficiency. dCMP can also act as acceptor. Different from the monofunctional prokaryotic enzymes EC 2.7.4.25, CMP kinase and EC 2.7.4.22, UMP kinase.
CAS REGISTRY NUMBER
COMMENTARY hide
37278-21-0
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
strain B
-
-
Manually annotated by BRENDA team
subsp. mycoides
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine
ADP + (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine
show the reaction diagram
-
Cidofovir
-
-
-
ATP + 1-beta-D-arabinofuranosylcytosine
ADP + ?
show the reaction diagram
-
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + ?
show the reaction diagram
-
-
-
?
ATP + 2'-azido-CMP
ADP + 2'-azido-CDP
show the reaction diagram
-
4fold higher activity with 2'-azido-dCMP than with 2'-azido-CMP
-
-
?
ATP + 2'-azido-dCMP
ADP + 2'-azido-dCDP
show the reaction diagram
-
4fold higher activity with 2'-azido-dCMP than with 2'-azido-CMP
-
-
?
ATP + 2'-azido-dUMP
ADP + 2'-azido-dUDP
show the reaction diagram
-
similar activity with 2'-azido-UMP and 2'-azido-dUMP
-
-
?
ATP + 2'-azido-UMP
ADP + 2'-azido-UDP
show the reaction diagram
-
similar activity with 2'-azido-UMP and 2'-azido-dUMP
-
-
?
ATP + AMP
ADP + ADP
show the reaction diagram
ATP + ara-CMP
ADP + ara-CDP
show the reaction diagram
ATP + beta-D-2',3'-dideoxy-CMP + H2O
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + beta-D-2'-azido-2'-dCMP
ADP + beta-D-2'-azido-2'-dCDP
show the reaction diagram
-
-
-
-
?
ATP + beta-D-2'-azido-2'-dUMP
ADP + beta-D-2'-azido-2'-dUDP
show the reaction diagram
-
-
-
-
?
ATP + beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluoro-CMP
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
ADP + beta-L-2',3'-dideoxy-3'-thiacytidine diphosphate
show the reaction diagram
-
-
-
-
?
ATP + beta-L-2',3'-dideoxy-CMP + H2O
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + beta-L-2'-azido-2'-dCMP
ADP + beta-L-2'-azido-2'-dCDP
show the reaction diagram
-
-
-
-
?
ATP + beta-L-2'-azido-2'-dUMP
ADP + beta-L-2'-azido-2'-dUDP
show the reaction diagram
-
-
-
-
?
ATP + beta-L-dioxolane-cytidine
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + CMP
ADP + CDP
show the reaction diagram
ATP + D-CMP
ADP + D-CDP
show the reaction diagram
-
-
-
-
?
ATP + D-dCMP
ADP + D-dCDP
show the reaction diagram
-
-
-
-
?
ATP + D-dUMP
ADP + D-dUDP
show the reaction diagram
-
-
-
-
?
ATP + D-UMP
ADP + D-UDP
show the reaction diagram
-
-
-
-
?
ATP + dAMP
ADP + dADP
show the reaction diagram
-
-
-
?
ATP + dCMP
ADP + dCDP
show the reaction diagram
ATP + dUMP
ADP + dUDP
show the reaction diagram
ATP + gemcitabine
ADP + gemcitabine monophosphate
show the reaction diagram
activity of DCK
i.e. 2',2'-difluorodeoxycytidine 5'-monophosphate
-
?
ATP + gemcitabine monophosphate
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + gemcitabine phosphate
ADP + gemcitabine diphosphate
show the reaction diagram
activity of CMPK
i.e. 2',2'-difluorodeoxycytidine 5'-diphosphate
-
?
ATP + L-(-)-2',3'-dideoxy-3'-thia-CMP
ADP + L-(-)-2',3'-dideoxy-3'-thia-CDP
show the reaction diagram
ATP + L-(-)-2',3'-dideoxy-5-fluoro-3'-thia-CMP
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + L-3TCMP
ADP + L-3TCMP
show the reaction diagram
-
-
-
-
?
ATP + L-CMP
ADP + L-CDP
show the reaction diagram
ATP + L-dCMP
ADP + L-dCDP
show the reaction diagram
ATP + L-dUMP
ADP + L-dUDP
show the reaction diagram
ATP + UMP
ADP + UDP
show the reaction diagram
CTP + CMP
CDP + CDP
show the reaction diagram
dATP + CMP
dADP + CDP
show the reaction diagram
dATP + dCMP
dADP + dCDP
show the reaction diagram
-
-
-
-
?
dATP + UMP
dADP + ADP
show the reaction diagram
dCTP + CMP
dCDP + CDP
show the reaction diagram
-
-
-
-
?
dCTP + dCMP
dCDP + dCDP
show the reaction diagram
-
-
-
-
?
dCTP + UMP
dGDP + UDP
show the reaction diagram
-
-
-
-
?
dGTP + CMP
dGDP + CDP
show the reaction diagram
dGTP + UMP
dGDP + UDP
show the reaction diagram
-
-
-
-
?
dTTP + CMP
dTDP + CDP
show the reaction diagram
-
-
-
-
?
dUTP + CMP
dUDP + CDP
show the reaction diagram
-
-
-
-
?
GTP + CMP
GDP + CDP
show the reaction diagram
GTP + dCMP
GDP + dCDP
show the reaction diagram
-
-
-
-
?
GTP + UMP
GDP + UDP
show the reaction diagram
-
-
-
-
?
ITP + CMP
IDP + CDP
show the reaction diagram
-
-
-
-
?
ITP + UMP
IDP + UDP
show the reaction diagram
-
-
-
-
?
TTP + CMP
TDP + CDP
show the reaction diagram
-
-
-
-
?
TTP + dCMP
TDP + dCMP
show the reaction diagram
-
-
-
-
?
TTP + UMP
TDP + UDP
show the reaction diagram
-
-
-
-
?
UTP + CMP
UDP + CDP
show the reaction diagram
-
-
-
-
?
XTP + CMP
XDP + CDP
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + CMP
ADP + CDP
show the reaction diagram
ATP + dCMP
ADP + dCDP
show the reaction diagram
ATP + dUMP
ADP + dUDP
show the reaction diagram
-
higher activity with the D-enantiomer compared to the L-enantiomer
-
-
?
ATP + UMP
ADP + UDP
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
required for the phosphorylation of CMP, IUMP and dCMP by either ATP or dCTP. With CMP as phosphate acceptor and ATP as phosphate donor, Mn2+, Ni2+ and Ca2+ are able to substitute for Mg2+ but are less effective. The relative rates are Mg2+ (100%), Mn2+ (42%), Ni2+ (16%), and Ca2+ (13%)
Co2+
-
divalent cation required, Mn2+ can substitute for Mg2+
Na2SO4
-
250 mM, stimulates
NaCl
-
250 mM, stimulates
Ni2+
-
required for the phosphorylation of CMP, IUMP and dCMP by either ATP or dCTP. With CMP as phosphate acceptor and ATP as phosphate donor, Mn2+, Ni2+ and Ca2+ are able to substitute for Mg2+ but are less effective. The relative rates are Mg2+ (100%), Mn2+ (42%), Ni2+ (16%), and Ca2+ (13%)
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-Br-uracil vinylphosphonate
-
-
5-Cl-uracil vinylphosphonate
-
-
5-F-Phe-uracil vinylphosphonate
-
-
5-Phe-S-uracil vinylphosphonate
-
-
5-Phe-uracil vinylphosphonate
-
-
CTP
-
inhibits reaction with ATP and UMP, CMP or dCMP
CuSO4
-
0.25 mM, 96% inhibition of enzyme form UMPK1 and 92% inhibition of enzyme form UMPK2
dCMP
-
competitive inhibition of UMP phosphorylation
dCTP
-
inhibits reaction with ATP and UMP, CMP or dCMP
DTNB
-
0.009 mM, 50% inhibition
F-
-
complete inhibition at 25 mM
iodoacetamide
-
-
iodoacetate
-
0.05 mM, 50% inhibition
L-CMP
-
excess of L-CMP
lead nitrate
-
0.25 mM, 52% inhibition of enzyme form UMPK1 and 40% inhibition of enzyme form UMPK2
MgATP2-
-
competitive with UMP
NaClO
-
250 mM
NaSCN
-
250 mM
p-hydroxymercuribenzoate
-
0.02 mM, 50% inhibition
p-Hydroxymercuriphenyl sulfonate
-
0.02 mM, 50% inhibition
P1,P5-di(adenosine-5')pentaphosphate
-
PCMB
-
0.1 mM, 69% loss of activity
TTP
-
inhibits reaction with ATP and UMP, CMP or dCMP
UDP
-
product inhibition
UMP
-
substrate inhibition above 0.2 mM
uracil vinylphosphonate
-
-
UTP
-
inhibits reaction with ATP and UMP, CMP or dCMP
ZnCl2
-
0.25 mM, 55% inhibition of enzyme form UMPK1 and 30% inhibition of enzyme form UMPK2
additional information
-
no substrate inhibition with 3 mM dCMP and 1 mM UMP
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
dithiothreitol
glutathione
-
activates
L-Cys
-
activates
NADPH
-
NADPH-dependent activation system is composed of at least two protein factors: one is heat-stable and the other is indistinguishable from NADPH-dependent disulfide reductase
reduced DL-alpha-lipoic acid
-
activates
-
thioredoxin
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.45
2',2'-difluorodeoxycytidine
-
pH 8.0, 37C
0.36
2'-azido-D-dCMP
-
pH 7.4, 37C
0.9
2'-azido-D-dUMP
-
pH 7.4, 37C
1.2
2'-azido-L-dCMP
-
pH 7.4, 37C
1.3
2'-azido-L-dUMP
-
pH 7.4, 37C
0.26 - 0.917
ara-CMP
1.4
araCMP
-
pH 8.0, 37C
0.029 - 0.68
ATP
0.272 - 1.037
beta-D-2',3'-dideoxy-CMP
0.36
beta-D-2'-azido-2'-dCMP
-
-
0.9
beta-D-2'-azido-2'-dUMP
-
-
0.228
beta-L-(-)-2',3'-dideoxy-2',3'-didehydro-5-fluoro-CMP
-
37C
-
0.15 - 2
beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
0.697
beta-L-2',3'-dideoxy-CMP
-
37C
1.2
beta-L-2'-azido-2'-dCMP
-
-
1.3
beta-L-2'-azido-2'-dUMP
-
-
2
cCMP
-
pH 7.4, 37C
1
Cidofovir
-
-
0.0053 - 3.09
CMP
0.02
D-CMP
1
D-dCMP
1.3
D-dUMP
0.05
D-UMP
0.074 - 0.61
dATP
0.017 - 2.77
dCMP
0.82
dCTP
-
reaction with CMP, liver enzyme
0.1 - 8.5
dUMP
0.0146
gemcitabine
wild-type DCK
0.581
gemcitabine monophosphate
-
37C
0.246
gemcitabine phosphate
wild-type CMPK
0.494
L-(-)-2',3'-dideoxy-3'-thia-CMP
-
37C
0.25
L-(-)-2',3'-dideoxy-5-fluoro-3'-thia-CMP
-
37C, His-tagged UMP/CMP kinase
0.15
L-3TCMP
-
-
0.75
L-CMP
0.73
L-dCMP
0.7
L-dUMP
0.02 - 6.3
UMP
additional information
additional information
Km values of mutant enzymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
45 - 150
ara-CMP
10 - 36
beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
8.57 - 410
CMP
22 - 73
dCMP
0.65 - 217
UMP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017
5-Br-uracil vinylphosphonate
-
-
0.016
5-Cl-uracil vinylphosphonate
-
-
0.028
5-Phe-S-uracil vinylphosphonate
-
-
0.12 - 0.5
CMP
0.0012 - 0.00653
P1,P5-di(adenosine-5') pentaphosphate
0.5 - 1.5
UMP
0.7
uracil vinylphosphonate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.035
5-Br-uracil vinylphosphonate
Homo sapiens
-
-
0.03
5-Cl-uracil vinylphosphonate
Homo sapiens
-
-
0.23
5-F-Phe-uracil vinylphosphonate
Homo sapiens
-
-
0.05 - 0.12
5-Phe-S-uracil vinylphosphonate
1.2
uracil vinylphosphonate
Homo sapiens
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.2
-
reaction with CMP and ATP
4.98
-
reaction with dCMP and ATP
8.76
-
reaction with UMP and dCMP
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
7.5
-
reaction with UMP and ATP
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 9
-
pH 4.0: about 40% of maximal activity, pH 9.0: about 65% of maximal activity, reaction with UMP and ATP
6.2 - 8.6
-
50% of maximal activity at pH 6.2 and at pH 8.6
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.7 - 4.8
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
lung carcinoma
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
melanoma cell
Manually annotated by BRENDA team
high expression
Manually annotated by BRENDA team
-
promyelocytic leukemia
Manually annotated by BRENDA team
-
growth for 14 days without phosphate, increase in enzyme transkript level, coordinate regulation of aspartate transcarbamoylase, ATCase, EC 2.1.3.2, carbamoyl phosphate synthetase, CPSase, EC 6.3.5.5, UMP synthase, EC 2.4.1.10, EC 4.1.1.23, uracil phosphoribosyltransferase, UPRTase, EC 2.4.2.9, UMP kinase, EC 2.7.4.14
Manually annotated by BRENDA team
-
colorectal adenocarcinoma cell
Manually annotated by BRENDA team
additional information
-
two mRNA species are expressed in all immune tissues examined, an all cases the 3.4 kb form is the more prominent RNA species
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22500
-
sucrose density gradient centrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
of the selenomethionine labelled protein in complex with UMP, CMP, ADP, AMP-PCP, cidofovor and P1-(5-adenosyl) P5-(5-uridyl) pentaphosphate
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
-
more stable than at higher pH
645141
7
-
at pH 7.0, the enzyme is most stable when kept at 4C
645149
additional information
-
more stable in histidine buffer than in phosphate buffer
645141
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
-
in absence of glycerol, the half-life of a preparation with a specific activity of 80 is about 10 min, inactivation is partially reversed by addition of 2-mercaptoethanol
25
-
30 min, stable
40
-
30 min, enzyme form UMPK2 loses 70% of maximal activity, enzyme form UMPK1 loses 30% of its activity
45
-
30 min, enzyme form UMPK2 loses more than 80% of maximal activity, enzyme form UMPK1 loses more than 60% of its activity
51
-
midpoint denaturation temperature of UMP/CMP kinase
52
-
midpoint denaturation temperature of the UAU chimeric enzyme
58
10 min, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin, 0.1 mg/ml, is completely effective in preventing the loss of activity in the dilute preparation
-
dialysis against 20 mM phosphate, 1 mM MgCl2, 20% ethylene glycol, pH 8.0, 90% loss of activity
-
freeze-thawing inactivates
-
more stable in histidine than in phosphate buffer
-
the enzyme is unstable when fully activated, anions promoting hydrophobic interactions stabilize the active conformation
-
the purified enzyme is notably unstable
-
three-fold dilution of a preparation of 0.2 mg of protein per ml results in less of 50% of the activity in 1 h
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, 30% loss of activity within 2 months
-
-20C, concentrated enzyme solution in 30% glycerol, less than 5% loss of activity per month
-
-20C, in 25 mM Tris-acetate buffer, pH 7.5, 50 mM 2-mercaptoethanol, 50% glycerol, stable for at least 2 months
-
-80C, up to 12 months
-
4C, 0.2 mg/ml, 2 weeks, 20% loss of activity
-
4C, considerable loss of activity within 24 h, DTT stabilizes, more stable in 20 mM phosphate buffer, pH 8 than in Tris-HCl buffer
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
of the recombinant protein
-
of the recombinant proteins
-
partial, two allelic gene products UMPK1 and UMPK2
-
recombinant His6-tagged mutant UMP-CMPK2DELTA21 from Spodoptera frugiperda Sf9 cells by affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA is subcloned into pGEX-4T-3 and expressed as a glutathione S-transferase fusion protein in Escherichia coli
expressed in HCT-8 cell
-
expression in Escherichia coli
-
expression in Escherichia coli. The 228-aa and the 196-11 form are expressed as His-tagged fusion protein. The 196-aa UMP/CMP kinase is the actual form of the enzyme
-
expression of His-tagged UMP-CMP kinase and UMP-CMP kinase fusion protein with glutathione S-transferase
-
overexpression in Escherichia coli
-
overexpression in Escherichia coli, wild type and selenomethionine labelled protein
-
transient expression of wild-type and mutant DCK/CMPK enzymes in COS-1 cells
UMP-CMPK2, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression of His6-tagged mutant UMP-CMPK2DELTA21, lacking the mitochondrial targeting sequence, in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system, expression of GFP-tagged wild-type and E448G mutant enzymes in HeLa cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G21A
-
mutant enzyme is degraded during the purification phase
G22A
-
mutant enzyme with decreased turnover-number/KmATP value. Turnover-number is 59% of that of the wild-type enzyme
G24A
-
mutant enzyme with decreased turnover-number/KmATP value. Turnover-number is 48% of that of the wild-type enzyme
G26A
-
mutant enzyme with decreased turnover-number/KmATP value
G27R
-
mutant enzyme is degraded during the purification phase. Turnover-number is 45% of that of the wild-type enzyme
K27E
-
mutant enzyme with 2600fold decreased turnover-number/KmATP value. Turnover-number is 21% of that of the wild-type enzyme
K27M
-
mutant enzyme with 1000fold decreased turnover-number/KmATP value. Turnover-number is 22% of that of the wild-type enzyme
E448G
site-directed mutagenesis
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
after treatment with urea, UmpK protein unfolding and refolding kinetics, and folding mechanism, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
screening of acyclic phosphonate analogs to find antimetabolites for antivirus and anticancer therapies
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