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Information on EC 2.7.4.14 - UMP/CMP kinase and Organism(s) Homo sapiens and UniProt Accession Q5EBM0
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2.7.4.14 UMP/CMP kinaseIUBMB Comments
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, (d)CMP kinase and EC 2.7.4.22, UMP kinase.
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Word Map
- 2.7.4.14
- dcmp
- deoxycytidine
- gemcitabine
- cidofovir
-
nmp-binding
- umpks
- medicine
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
cmpk2, cmpk, cmp kinase, ump-cmp kinase, cmpk1, ump/cmp kinase, cytidylate kinase, pyrimidine nucleoside monophosphate kinase, cytidine monophosphate kinase, cytidine/uridine monophosphate kinase 2, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP:UMP-CMP phosphotransferase
-
-
-
-
CMP kinase
CMPK
CTP:CMP phosphotransferase
-
-
-
-
cytidine monophosphate kinase
cytidylate kinase
kinase, cytidylate (phosphorylating)
-
-
-
-
MssA protein
-
-
-
-
P25
-
-
-
-
pyrimidine nucleoside monophosphate kinase
-
-
-
-
UCK
UMP-CMP kinase
UMP/CMP kinase
UMPK
-
-
-
-
additional information
mitochondrial UMP-CMPK2 belongs to a distinct nucleoside monophosphate kinase family, closer to thymidylate kinase than to cytosolic UMP-CMP kinase
CMP kinase
-
-
-
-
CMPK
-
-
-
-
cytidine monophosphate kinase
-
-
-
-
cytidylate kinase
-
-
-
-
UCK
-
-
-
-
UMP-CMP kinase
-
-
-
-
UMP/CMP kinase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + UMP = ADP + UDP
formation of a ternary complex, addition of substrates is random
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -
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, (d)CMP kinase and EC 2.7.4.22, UMP kinase.
CAS REGISTRY NUMBER
COMMENTARY
37278-21-0
-
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
ATP + (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine
ADP + (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine
Cidofovir
-
-
?
ATP + 2'-azido-CMP
ADP + 2'-azido-CDP
-
4fold higher activity with 2'-azido-dCMP than with 2'-azido-CMP
-
-
?
ATP + 2'-azido-dCMP
ADP + 2'-azido-dCDP
-
4fold higher activity with 2'-azido-dCMP than with 2'-azido-CMP
-
-
?
ATP + 2'-azido-dUMP
ADP + 2'-azido-dUDP
-
similar activity with 2'-azido-UMP and 2'-azido-dUMP
-
-
?
ATP + 2'-azido-UMP
ADP + 2'-azido-UDP
-
similar activity with 2'-azido-UMP and 2'-azido-dUMP
-
-
?
ATP + beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
ADP + beta-L-2',3'-dideoxy-3'-thiacytidine diphosphate
-
-
-
-
?
ATP + gemcitabine
ADP + gemcitabine monophosphate
activity of DCK
i.e. 2',2'-difluorodeoxycytidine 5'-monophosphate
-
?
ATP + gemcitabine phosphate
ADP + gemcitabine diphosphate
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
-
-
-
-
?
ATP + 5-aza-cidofovir
ADP + phospho-5-aza-cidofovir
wild-type enzyme
-
-
?
ATP + cidofovir
ADP + phospho-cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid
-
-
?
ATP + cidofovir
ADP + phospho-cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid, wild-type enzyme
-
-
?
ATP + CMP
ADP + CDP
-
the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis
-
-
?
ATP + CMP
ADP + CDP
-
the enzyme catalyses an important step in the phosphorylation of UTP, CTP and dCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies
-
-
?
ATP + cytarabine
ADP + phospho-cytarabine
anticancer drug, phosphorylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells
-
-
?
ATP + cytarabine
ADP + phospho-cytarabine
i.e. araC, wild-type enzyme and mutant P64T
-
-
?
ATP + dCMP
ADP + dCDP
-
the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis
-
-
?
ATP + dCMP
ADP + dCDP
-
the enzyme catalyses an important step in the phosphorylation of UTP, CTP and cCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies
-
-
?
ATP + dCMP
ADP + dCDP
-
higher activity with the D-enantiomer compared to the L-enantiomer
-
-
?
ATP + dUMP
ADP + dUDP
-
higher activity with the D-enantiomer compared to the L-enantiomer
-
-
?
ATP + gemcitabine
ADP + phospho-gemcitabine
i.e. 2',2'-difluorodeoxycytidine
-
-
?
ATP + gemcitabine
ADP + phospho-gemcitabine
i.e. 2',2'-difluorodeoxycytidine, wild-type enzyme
-
-
?
ATP + L-dCMP
ADP + L-dCDP
slower phosphorylation than the D-enantiomers
-
-
?
ATP + L-dUMP
ADP + L-dUDP
slower phosphorylation than the D-enantiomers
-
-
?
ATP + UMP
ADP + UDP
-
the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis
-
-
?
ATP + UMP
ADP + UDP
-
the enzyme catalyses an important step in the phosphorylation of UTP, CTP and cCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies
-
-
?
additional information
?
-
UMP-CMPK2 may have other functions in addition to the supply of substrates for mtDNA synthesis, it is highly expressed in leukemia cells, in bone marrow, and is tightly correlated with macrophage activation and inflammatory response
-
-
?
additional information
?
-
-
UMP-CMPK2 may have other functions in addition to the supply of substrates for mtDNA synthesis, it is highly expressed in leukemia cells, in bone marrow, and is tightly correlated with macrophage activation and inflammatory response
-
-
?
additional information
?
-
-
formation of a ternary complex, addition of substrates is random
-
-
?
additional information
?
-
-
the UMP-CMP kinase has a relaxed enantiospecificity for the nucleoside monophosphate acceptor site, but it is restricted to D-nucleotides at the donor site
-
-
?
additional information
?
-
the enzyme is involved in the phosphorylation of nucleic acid precursors, and is critical in the ribo- and deoxyribonucleoside salvage pathway, as well as the anabolic phosphorylation of nucleoside analogues used in viral and anticancer therapies, e.g. cidofovir, which is activated by the enzyme, overview
-
-
?
additional information
?
-
-
the enzyme is involved in the phosphorylation of nucleic acid precursors, and is critical in the ribo- and deoxyribonucleoside salvage pathway, as well as the anabolic phosphorylation of nucleoside analogues used in viral and anticancer therapies, e.g. cidofovir, which is activated by the enzyme, overview
-
-
?
additional information
?
-
substrate/product binding site determination and kinetics using MABA-CDP in a competition assay, overview
-
-
?
additional information
?
-
-
substrate/product binding site determination and kinetics using MABA-CDP in a competition assay, overview
-
-
?
additional information
?
-
-
the enzyme shows enantioselectivity, acceptor-binding site structure of human UMP-CMP kinase in the closed form or in ligand-bound forms, overview
-
-
?
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
-
-
?
additional information
?
-
CMP and UMP are the preferred substrates for purified CMPK, and it has lower affinity to dCMP and dUMP
-
-
?
additional information
?
-
mutants P64T/R134M and R134M show no activity with all substrates
-
-
?
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
ATP + cidofovir
ADP + phospho-cidofovir
i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid
-
-
?
ATP + cytarabine
ADP + phospho-cytarabine
anticancer drug, phosphorylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells
-
-
?
ATP + gemcitabine
ADP + phospho-gemcitabine
i.e. 2',2'-difluorodeoxycytidine
-
-
?
ATP + CMP
ADP + CDP
-
the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis
-
-
?
ATP + CMP
ADP + CDP
-
the enzyme catalyses an important step in the phosphorylation of UTP, CTP and dCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies
-
-
?
ATP + dCMP
ADP + dCDP
-
the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis
-
-
?
ATP + dCMP
ADP + dCDP
-
the enzyme catalyses an important step in the phosphorylation of UTP, CTP and cCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies
-
-
?
ATP + dCMP
ADP + dCDP
-
higher activity with the D-enantiomer compared to the L-enantiomer
-
-
?
ATP + dUMP
ADP + dUDP
-
higher activity with the D-enantiomer compared to the L-enantiomer
-
-
?
ATP + UMP
ADP + UDP
-
the enzyme plays a crucial role in the formation of UDP, CDP and dCDP which are required for cellular nucleic acid synthesis
-
-
?
ATP + UMP
ADP + UDP
-
the enzyme catalyses an important step in the phosphorylation of UTP, CTP and cCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies
-
-
?
additional information
?
-
UMP-CMPK2 may have other functions in addition to the supply of substrates for mtDNA synthesis, it is highly expressed in leukemia cells, in bone marrow, and is tightly correlated with macrophage activation and inflammatory response
-
-
?
additional information
?
-
-
UMP-CMPK2 may have other functions in addition to the supply of substrates for mtDNA synthesis, it is highly expressed in leukemia cells, in bone marrow, and is tightly correlated with macrophage activation and inflammatory response
-
-
?
additional information
?
-
the enzyme is involved in the phosphorylation of nucleic acid precursors, and is critical in the ribo- and deoxyribonucleoside salvage pathway, as well as the anabolic phosphorylation of nucleoside analogues used in viral and anticancer therapies, e.g. cidofovir, which is activated by the enzyme, overview
-
-
?
additional information
?
-
-
the enzyme is involved in the phosphorylation of nucleic acid precursors, and is critical in the ribo- and deoxyribonucleoside salvage pathway, as well as the anabolic phosphorylation of nucleoside analogues used in viral and anticancer therapies, e.g. cidofovir, which is activated by the enzyme, overview
-
-
?
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
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CuSO4
-
0.25 mM, 96% inhibition of enzyme form UMPK1 and 92% inhibition of enzyme form UMPK2
lead nitrate
-
0.25 mM, 52% inhibition of enzyme form UMPK1 and 40% inhibition of enzyme form UMPK2
ZnCl2
-
0.25 mM, 55% inhibition of enzyme form UMPK1 and 30% inhibition of enzyme form UMPK2
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
doxorubicin
binding of doxorubicin to the enzyme (CMPK1) activates the phosphorylation of CMP, dCMP, and UMP. Doxorubicin might bind to the nonactive site of CMPK1 and regulate its activity with magnesium
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.08
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
additional information
additional information
Km values of mutant enzymes, overview
-
0.15
beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
-
pH 7.4, 37°C, His-tagged UMP/CMP kinase
0.3
beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
-
pH 7.4, 37°C, GST fusion UMP-CMP kinase
2.3
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.02
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.123
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
0.315
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.327
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
0.11
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.97
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
1.034
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.1
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.25
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.47
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.09
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
5.8
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
14
beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
-
pH 7.4, 37°C, GST fusion UMP/CMP kinase
36
beta-L-2',3'-dideoxy-3'-thiacytidine monophosphate
-
pH 7.4, 37°C, His-tagged UMP-CMP kinase
0.31
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
125
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.019
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
130
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.036
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
13.4
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.35
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
188
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.226
5-aza-cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.04
Cidofovir
pH and temperature not specified in the publication, recombinant wild-type enzyme
5.61
dUMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
2.52
CMP
pH and temperature not specified in the publication, recombinant mutant P64T
6250
CMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.058
cytarabine
pH and temperature not specified in the publication, recombinant mutant P64T
410
cytarabine
pH and temperature not specified in the publication, recombinant wild-type enzyme
0.037
dCMP
pH and temperature not specified in the publication, recombinant mutant P64T
122
dCMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
1.4
UMP
pH and temperature not specified in the publication, recombinant mutant P64T
1880
UMP
pH and temperature not specified in the publication, recombinant wild-type enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
distribution of the enzyme expression in different cancer tissue samples, overview
cidofovir-resistant tumour cell line, no infection with human papilloma virus
cidofovir-resistant tumour cell line, infection with human papilloma virus
cidofovir-resistant tumour cell line, infection with human papilloma virus
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UMP-CMPK2 contains an N-terminal mitochondrial targeting sequence
localization of enzyme CMPK at DNA damage sites, co-localization and complex formation with Tip60 and ribonucleotide reductase
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the first and last phosphorylation steps of cytidine 2'-deoxynucleoside analogues are catalyzed, respectively, by deoxycytidine kinase (dCK) and nucleoside diphosphate kinase (NDPK)
physiological function
additional information
malfunction
knockdown of CMPK delays DNA repair during recovery from UV damage in serum-deprived cells but not in the cells without serum deprivation. Exogenous supply of cytidine or deoxycytidine facilitates DNA repair dependent on CMPK in serum-deprived cells. But CMPK knockdown does not affect the steady state level of dCTP in serum-deprived cells. Re-expression of wild-type but not N-terminus deleted CMPK restores the efficiency of DNA repair in CMPK knockdown cells
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
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
physiological function
the enzyme catalyzes phosphorylation of pyrimidine nucleoside monophosphates, which is essential for de novo biosynthesis of pyrimidines. Nuclear CMPK1 isozyme is indicative of poor prognosis in triple negative breast cancers, TNBC, and its expression may be related to dysregulation of extracellular matrix and cell cycle molecules, clinical significance of CMPK1 in TNBC patients., overview. CMPK1 performs a crucial role in activation of nucleoside analogues used as chemotherapy against human cancers and pathogenic viruses
physiological function
the enzyme enzyme catalyzes CDP formation in DNA repair, the synthesis of dCDP or CDP determines the rate of repair. The N-terminal 32-amino-acid of enzyme CMPK is required for its recruitment to DNA damage sites in a Tip60-dependent manner, complex of CMPK/RNR/Tip60 and the recruitment to the sites of DNA damage, overview. Site-specific dCDP formation via CMPK provides a means to facilitate DNA repair in serum-deprived cells, analysis of functional contribution of CMPK to dCTP pool and the rate of DNA compared in MCF-7 cells in serum-containing and serum-deprived conditions
additional information
analysis of gene expression data associated to nuclear CMPK1 expression, overview
additional information
-
analysis of gene expression data associated to nuclear CMPK1 expression, overview
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
additional information
the N-terminal region of CMPK is essential for the complex formation and recruitment to DNA damage sites
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). CMPK2_HUMAN
449
0
49448
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
DCK and CMPK structural models from crystal structures, overview
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
additional information
additional information
construction of a UMP-CMPK2DELTA21 mutant lacking the mitochondrial targeting sequence
additional information
-
construction of a UMP-CMPK2DELTA21 mutant lacking the mitochondrial targeting sequence
additional information
determination and analysis of 28 polymorphisms in DCK/CMPK enzymes, genotyping with humans of different ethnic origins, overview. Variant allozyme enzyme activities range from 32 to 105% of the wild-type enzyme for DCK and from 78 to 112% of wild-type enzyme for CMPK, with no significant differences in apparent Km values for either enzyme except for a DCK Val24/Ser122 double variant allozyme, overview
additional information
enzyme knockdown in MCF-7 cells using a CMPK shRNA lentivirus
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
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
more stable in histidine buffer than in phosphate buffer
645141
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
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
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
70
inactivation of wild-type enzyme and mutant R134M enzyme, only partial denaturation of mutant P64T
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, concentrated enzyme solution in 30% glycerol, less than 5% loss of activity per month
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged mutant UMP-CMPK2DELTA21 from Spodoptera frugiperda Sf9 cells by affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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, wild type and selenomethionine labelled protein
transient expression of wild-type and mutant DCK/CMPK enzymes in COS-1 cells
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 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
ORGANISM
UNIPROT
LITERATURE
CMPK2 expression and NLRP3 inflammasome activation, downstream pro-IL-18 and pro-IL-1beta expression, and IL-18 and IL-1beta release, are all significantly increased in missed abortion tissues or LPS-induced HTR8/SVneo cells. Pigment epithelium-derived factor reverses the increase in CMPK2 expression
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
lipopolysaccharide-induced human chorionic trophoblast HTR8/SVneo cell model to mimic missed abortion in vitro. CMPK2 expression and NLRP3 inflammasome activation, downstream pro-IL-18 and pro-IL-1beta expression, and IL-18 and IL-1beta release, are all significantly increased in missed abortion tissues or LPS-induced HTR8/SVneo cells. Pigment epithelium-derived factor reverses the increase in CMPK2 expression and activation of the NLRP3 inflammasome axis and downregulates the production of mitochondrial reactive oxygen species and mitochondrial DNA release
diagnostics
UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer. Analysis of 461 breast adenocarcinoma samples, overview. While cytoplasmic CMPK1 does not show any association to metastasis free survival (MFS), nuclear CMPK1 is associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses
medicine
screening of acyclic phosphonate analogs to find antimetabolites for antivirus and anticancer therapies
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Scott, E.M.; Wright, R.C.
Kinetics and equilibria of pyrimidine nucleoside monophosphate kinase from human erythrocytes
Biochim. Biophys. Acta
571
45-54
1979
Homo sapiens
Teng, Y.S.; Chen, S.H.; Scott, C.R.
Human erythrocyte pyrimidine nucleoside monophosphate kinase. Partial purification and properties of two allelic gene products
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251
4179-4183
1976
Homo sapiens
Van Rompay, A.R.; Johansson, M.; Karlsson, A.
Phosphorylation of deoxycytidine analog monophosphates by UMP-CMP kinase: molecular characterization of the human enzyme
Mol. Pharmacol.
56
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1999
Homo sapiens (P30085), Homo sapiens
Pearman, A.T.; Castro-Faria-Neto, H.C.; McIntyre, T.M.; Prescott, S.M.; Stafforini, D.M.
Characterization of human UMP-CMP kinase enzymatic activity and 5' untranslated region
Life Sci.
69
2361-2370
2001
Homo sapiens
Liou, J.Y.; Dutschman, G.E.; Lam, W.; Jiang, Z.; Cheng, Y.C.
Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates
Cancer Res.
62
1624-1631
2002
Homo sapiens
Pasti, C.; Gallois-Montbrun, S.; Munier-Lehmann, H.; Veron, M.; Gilles, A.M.; Deville-Bonne, D.
Reaction of human UMP-CMP kinase with natural and analog substrates
Eur. J. Biochem.
270
1784-1790
2003
Dictyostelium sp., Homo sapiens
Topalis, D.; Kumamoto, H.; Amaya Velasco, M.F.; Dugue, L.; Haouz, A.; Alexandre, J.A.; Gallois-Montbrun, S.; Alzari, P.M.; Pochet, S.; Agrofoglio, L.A.; Deville-Bonne, D.
Nucleotide binding to human UMP-CMP kinase using fluorescent derivatives - a screening based on affinity for the UMP-CMP binding site
FEBS J.
274
3704-3714
2007
Homo sapiens (P30085), Homo sapiens
Alexandre, J.A.; Roy, B.; Topalis, D.; Pochet, S.; Perigaud, C.; Deville-Bonne, D.
Enantioselectivity of human AMP, dTMP and UMP-CMP kinases
Nucleic Acids Res.
35
4895-4904
2007
Homo sapiens (P30085), Homo sapiens
Kocabas, N.A.; Aksoy, P.; Pelleymounter, L.L.; Moon, I.; Ryu, J.S.; Gilbert, J.A.; Salavaggione, O.E.; Eckloff, B.W.; Wieben, E.D.; Yee, V.; Weinshilboum, R.M.; Ames, M.M.
Gemcitabine pharmacogenomics: deoxycytidine kinase and cytidylate kinase gene resequencing and functional genomics
Drug Metab. Dispos.
36
1951-1959
2008
Homo sapiens (P30085)
Xu, Y.; Johansson, M.; Karlsson, A.
Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria
J. Biol. Chem.
283
1563-1571
2008
Homo sapiens (Q5EBM0), Homo sapiens
Topalis, D.; Kumamoto, H.; Alexandre, J.A.; Dugue, L.; Pochet, S.; Berteina-Raboin, S.; Agrofoglio, L.A.; Deville-Bonne, D.
Looking for new pyrimidine acyclic nucleotide analogues designed for phosphorylation by human UMP-CMP kinase
Nucleosides Nucleotides Nucleic Acids
26
1369-1373
2007
Homo sapiens (P30085), Homo sapiens
Alexandre, J.A.; Roy, B.; Topalis, D.; Perigaud, C.; Deville-Bonne, D.
Enantio-selectivity of human nucleoside monophosphate kinases
Nucleosides Nucleotides Nucleic Acids
26
1375-1379
2007
Homo sapiens
Liou, J.Y.; Lai, H.R.; Hsu, C.H.; Chang, W.L.; Hsieh, M.J.; Huang, Y.C.; Cheng, Y.C.
Modulation of human UMP/CMP kinase affects activation and cellular sensitivity of deoxycytidine analogs
Biochem. Pharmacol.
79
381-388
2010
Homo sapiens
Tsao, N.; Lee, M.H.; Zhang, W.; Cheng, Y.C.; Chang, Z.F.
The contribution of CMP kinase to the efficiency of DNA repair
Cell Cycle
14
354-363
2015
Homo sapiens (P30085)
Topalis, D.; Nogueira, T.C.; De Schutter, T.; El Amri, C.; Krecmerova, M.; Naesens, L.; Balzarini, J.; Andrei, G.; Snoeck, R.
Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1
Oncotarget
7
10386-10401
2016
Homo sapiens (P30085)
Liu, N.Q.; De Marchi, T.; Timmermans, A.; Trapman-Jansen, A.M.; Foekens, R.; Look, M.P.; Smid, M.; van Deurzen, C.H.; Span, P.N.; Sweep, F.C.; Brask, J.B.; Timmermans-Wielenga, V.; Foekens, J.A.; Martens, J.W.; Umar, A.
Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients
Sci. Rep.
6
32027
2016
Homo sapiens (P30085), Homo sapiens
Zhang, X.; Zhang, K.; Zhang, Y.
Pigment epithelium-derived factor facilitates NLRP3 inflammasome activation through downregulating cytidine monophosphate kinase 2 A potential treatment strategy for missed abortion
Int. J. Mol. Med.
45
1436-1446
2020
Homo sapiens (Q5EBM0), Homo sapiens
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