Any feedback?
Information on EC 2.7.1.113 - deoxyguanosine kinase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC2.7.1.113Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.7.1.113 deoxyguanosine kinaseIUBMB Comments
Deoxyinosine can also act as acceptor.
Specify your search results
Word Map
- 2.7.1.113
- deoxycytidine
- mtdna
- thymidine
-
hepatocerebral
- deoxyribonucleoside
- deoxynucleoside
- ophthalmoplegia
- sucla2
- twinkle
- 9-beta-d-arabinofuranosylguanine
- cladribine
- c10orf2
-
nystagmus
- 2-chlorodeoxyadenosine
- deoxyinosine
-
2.7.1.74
- 2-chloro-2'-deoxyadenosine
-
mngie
-
neurogastrointestinal
- medicine
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
deoxyguanosine kinase, dguok, 2'-deoxyguanosine kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(dihydroxypropoxymethyl)guanine kinase
-
-
-
-
2'-deoxyguanosine kinase
-
-
-
-
DGK
DGUOK
kinase, deoxyguanosine (phosphorylating)
-
-
-
-
NTP-deoxyguanosine 5'-phosphotransferase
-
-
-
-
nucleoside triphosphate: deoxyguanosine 5'-phosphotransferase
DGK
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + deoxyguanosine = ADP + dGMP
active site residues are Glu70, Lys142, and Arg142
-
ATP + deoxyguanosine = ADP + dGMP
substrate interactions and binding mechanism, and active site structure
ATP + deoxyguanosine = ADP + dGMP
substrate interactions, reaction mechanism
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:deoxyguanosine 5'-phosphotransferase
Deoxyinosine can also act as acceptor.
CAS REGISTRY NUMBER
COMMENTARY
39471-28-8
-
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'-deoxyadenosine-3'-fluoro-3'-triphosphate + 2'-deoxyguanosine
2'-deoxyadenosine-3'-fluoro-3'-diphosphate + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
2'-deoxyadenosine-3'-fluoroara-3'-triphosphate + 2'-deoxyguanosine
2'-deoxyadenosine-3'-fluoroara-3'-diphosphate + 2'-deoxyguanosine 5'-phosphate
-
low activity
-
-
?
2'-deoxyadenosine-3'-triphosphate + 2'-deoxyguanosine
2'-deoxyadenosine-3'-diphosphate + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
3'-deoxyadenosine-2'-triphosphate + 2'-deoxyguanosine
3'-deoxyadenosine-2'-diphosphate + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
3'-deoxyadenosine-3'-fluoro-2'-triphosphate + 2'-deoxyguanosine
3'-deoxyadenosine-3'-fluoro-2'-diphosphate + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
3'-deoxyadenosine-3'-fluoroxylo-2'-triphosphate + 2'-deoxyguanosine
3'-deoxyadenosine-3'-fluoroxylo-2'-diphosphate + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
ATP + 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril
ADP + ?
-
4.4% of the activity with 2'-deoxyguanosine
-
-
?
ATP + 1-(2-deoxy-beta-D-ribofuranosyl)-isocarbostyril
ADP + ?
-
poor substrate, 1.1% of the activity with 2'-deoxyguanosine
-
-
?
ATP + 1-beta-D-arabinofuranosyladenine
ADP + 1-beta-D-arabinofuranosyladenine 5'-phosphate
-
-
-
?
ATP + 2',2'-difluorodeoxyguanosine
ADP + 2',2'-difluorodeoxyguanosine 5'-phosphate
-
-
-
?
ATP + 2',3'-dideoxyguanosine
ADP + 2',3'-dideoxyguanosine 5'-monophosphate
-
recombinant deoxyguanosine kinase, 14% of activity with deoxyguanosine
-
?
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
-
-
-
?
ATP + 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
ADP + 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine 5'-monophosphate
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + 2-chloro-2'-arabinofluoro-2'-deoxyadenosine
ADP + 2-chloro-2'-arabinofluoro-2'-deoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-monophosphate
-
-
-
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2-fluoro-arabinosyl-adenine
ADP + 2-fluoro-arabinosyl-adenine 5'-monophosphate
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + 2-fluoroadenine-beta-D-arabinofuranoside
ADP + 2-fluoroadenine-beta-D-arabinofuranoside 5'-monophosphate
-
-
-
-
?
ATP + 3'-fluoro-2',3'-dideoxyguanosine
ADP + 3'-fluoro-2',3'-dideoxyguanosine 5'-monophosphate
-
recombinant deoxyguanosine kinase, 14% of activity with deoxyguanosine
-
?
ATP + 9-(1,3-dihydroxy-2-propoxymethyl)guanine
ADP + 9-(1,3-dihydroxy-2-propoxymethyl)guanine 5'-monophosphate
-
antiherpesvirus drug ganciclovir, recombinant mitochondrial deoxyguanosine kinase, 6% of activity with deoxyguanosine
-
?
ATP + 9-(4-hydroxy-3-hydroxymethylbutyl-1-yl)guanine
ADP + 9-(4-hydroxy-3-hydroxymethylbutyl-1-yl)guanine 5'-monophosphate
-
antiherpesvirus drug penciclovir, recombinant mitochondrial deoxyguanosine kinase, 50% of activity with deoxyguanosine
-
?
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-monophosphate
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
-
-
-
?
ATP + 9-beta-D-arabinosylguanine
ADP + 9-beta-D-arabinosylguanine 5'-monophosphate
-
-
-
?
ATP + arabinosyl adenine
ADP + arabinosyl adenine 5'-monophosphate
-
recombinant mitochondrial deoxyguanosine kinase, very low activity
-
?
ATP + arabinosyl guanine
ADP + arabinosyl guanine 5'-monophosphate
-
recombinant mitochondrial deoxyguanosine kinase, better substrate than deoxyguanosine kinase
-
?
ATP + dideoxyinosine
ADP + dideoxyinosine 5'-monophosphate
-
recombinant mitochondrial deoxyguanosine kinase, very low activity
-
?
ATP + ganciclovir
ADP + ganciclovir phosphate
i.e. 9-(1,3-dihydroxy-2-propoxymethyl)-guanine, low activity
-
-
?
ATP + penciclovir
ADP + penciclovir 5'-phosphate
i.e. 9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-guanine, low activity
-
-
?
CTP + deoxyguanosine
CDP + dGMP
-
62% of activity with ATP at pH 6.0, 1.8fold higher activity than with ATP at pH 7.0
-
?
dTTP + deoxyguanosine
dTDP + dGMP
-
83% of activity with ATP at pH 6.0, 2.8fold higher activity than with ATP at pH 7.0
-
?
dUTP + deoxyguanosine
dUDP + dGMP
-
69% of activity with ATP at pH 6.0, 1.7fold higher activity than with ATP at pH 7.0
-
?
triphosphate + 2'-deoxyguanosine
diphosphate + 2'-deoxyguanosine 5'-phosphate
-
triphosphate is active with 2'deoxyguanosine, 50% of the activity with ATP
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
UTP + 9-beta-D-arabinofuranosylguanine
UDP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
i.e. nelarabine, activation of the anticancer drug
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
key enzyme in mitochondrial DNA precursor synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
key enzyme in mitochondrial DNA precursor synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
important enzyme for the phosphorylation/activation of 2'-deoxyguanosine
-
-
ir
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
one of the two mitochondrial deoxynucleoside salvage pathway enzymes involved in precursor synthesis for mitochondrial DNA replication, DGUOK is responsible for the initial rate-limiting phosphorylation of the purine deoxynucleosides, mutations of the enzyme are associated with the hepato-specific and hepatocerebral forms of the mtDNA depletion syndrome
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine monophosphate
-
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine monophosphate
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-monophosphate
-
-
-
-
?
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-monophosphate
-
guanosine analog with activity in patients with T-cell malignancies
-
?
ATP + deoxyadenosine
ADP + dAMP
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + deoxyadenosine
ADP + dAMP
-
4.8%, 25.8% and 93.5% of activity with deoxyguanosine at 0.01 mM, 0.1 mM and 1 mM deoxyguanosine, respectively
-
?
ATP + deoxycytidine
ADP + dCMP
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + deoxyguanosine
ADP + dGMP
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
-
recombinant mitochondrial deoxyguanosine kinase does not discriminate between beta-D-2'-deoxyguanosine and beta-L-2'-deoxyguanosine
-
?
ATP + deoxyguanosine
ADP + dGMP
-
ATP can be replaced by dTTP, CTP, dCTP and UTP
-
?
ATP + deoxyinosine
ADP + dIMP
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + deoxyinosine
ADP + dIMP
-
recombinant mitochondrial deoxyguanosine kinase, may be the preferred substrate in vivo
-
?
ATP + dioxolane guanosine
ADP + dioxolane guanosine 5'-phosphate
-
low activity, step in anabolism of amdoxovir, i.e. (-)-beta-D-2,6-diaminopurine dioxolane, a prodrug of dioxolane guanosine
-
-
?
ATP + dioxolane guanosine
ADP + dioxolane guanosine 5'-phosphate
-
0.02% of the activity with 2'-deoxyguanosine
-
-
?
additional information
?
-
-
no activity with diphosphate as phosphate donor
-
-
?
additional information
?
-
de novo synthesis and salvage of ribonucleotides and deoxyribonucleotides, metabolism overview
-
-
?
additional information
?
-
-
enzyme defect due to genetic alterations leads to tissue-specific mitochondrial DNA depletion causing multi-systemic disease or devastating liver disease
-
-
?
additional information
?
-
-
th enzyme catalyzes the initial phosphorylation of purine deoxynucleosides, enzyme deficiency leads to severe mitochondrial DNA depletion diseases
-
-
?
additional information
?
-
the earliest nucleotide kinase in evolution, probably encoded by the so-called dCK/dGK/TK2-like gene, is the progenitor gene, several duplications of it are the reason for evolutionary occurring of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
?
additional information
?
-
anticancer drugs 2-chloro-2'-deoxyadenosine, i.e. cladribine, and 2-fluoro-9-beta-D-arabinofuranosyladenine, i.e. clofarabine, are poor substrates
-
-
?
additional information
?
-
-
no activity with several difluorophenyl nucleoside analogues, overview
-
-
?
additional information
?
-
substrate interactions, overview, enzyme shows relaxed enantioselectivity, accepting D- and L-enantiomers of beta-deoxyguanosine but with lower activity than alpha-L-deoxyguanosine, and beta-L-deoxyadenosine, enzyme accepts purine deoxynucleosides and analogues as substrates utilizing a triphosphate donor substrate
-
-
?
additional information
?
-
the enzyme is highly specific for purine substrates, Arg118 is responsible for the substrate specificity
-
-
?
additional information
?
-
-
the enzyme is highly specific for purine substrates, Arg118 is responsible for the substrate specificity
-
-
?
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 + deoxyinosine
ADP + dIMP
-
recombinant mitochondrial deoxyguanosine kinase, may be the preferred substrate in vivo
-
?
ATP + dioxolane guanosine
ADP + dioxolane guanosine 5'-phosphate
-
low activity, step in anabolism of amdoxovir, i.e. (-)-beta-D-2,6-diaminopurine dioxolane, a prodrug of dioxolane guanosine
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
key enzyme in mitochondrial DNA precursor synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
key enzyme in mitochondrial DNA precursor synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
important enzyme for the phosphorylation/activation of 2'-deoxyguanosine
-
-
ir
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
one of the two mitochondrial deoxynucleoside salvage pathway enzymes involved in precursor synthesis for mitochondrial DNA replication, DGUOK is responsible for the initial rate-limiting phosphorylation of the purine deoxynucleosides, mutations of the enzyme are associated with the hepato-specific and hepatocerebral forms of the mtDNA depletion syndrome
-
-
?
additional information
?
-
de novo synthesis and salvage of ribonucleotides and deoxyribonucleotides, metabolism overview
-
-
?
additional information
?
-
-
enzyme defect due to genetic alterations leads to tissue-specific mitochondrial DNA depletion causing multi-systemic disease or devastating liver disease
-
-
?
additional information
?
-
-
th enzyme catalyzes the initial phosphorylation of purine deoxynucleosides, enzyme deficiency leads to severe mitochondrial DNA depletion diseases
-
-
?
additional information
?
-
the earliest nucleotide kinase in evolution, probably encoded by the so-called dCK/dGK/TK2-like gene, is the progenitor gene, several duplications of it are the reason for evolutionary occurring of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
-
ATP
binding site structure and interactions, Gln111, Arg118, Met99, and Asp147 are involved, overview
additional information
enzyme accepts several triphosphate donor substrates with preference for ATP and UTP
-
additional information
enzyme can use several phosphate donors, but UTP is preferred in vitro
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
not inhibited by deoxycytidine, adenosine; not inhibited by dTTP; not inhibited by inosine, cytidine, uridine, deoxythymidine, deoxyuridine
-
dGTP
-
0.001 mM, 50% inhibition, 1 mM, complete inhibition, reversed by 0.2 mM dTTP
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.019
1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril
-
pH 7.6, 37°C, recombinant enzyme
0.056
2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.078
2-chloro-2'-deoxyadenosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.46
2-fluoro-arabinosyl-adenine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.033
arabinosyl guanine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.008
2-chlorodeoxyadenosine
-
pH 7.6, 37°C, recombinant deoxguanosine kinase, cosubstrate UTP
0.062
2-chlorodeoxyadenosine
-
pH 7.6, 37°C, recombinant deoxguanosine kinase, cosubstrate ATP
0.0028
deoxyguanosine
-
pH 7.6, 37°C, recombinant deoxguanosine kinase, cosubstrate ATP
0.0037
deoxyguanosine
-
pH 7.6, 37°C, recombinant deoxguanosine kinase, cosubstrate UTP
additional information
additional information
-
reaction of the mutant L250S with 2'-deoxyguanosine follows Michaelis-Menten kinetics, while the reaction with 2'-deoxyadenosine shows biphasic kinetics
-
additional information
additional information
-
the reaction with triphosphate follows strict Michaelis-Menten kinetics, while ATP exhibits negative cooperativity
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril
-
pH 7.6, 37°C, recombinant enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.028
-
using 9-beta-D-arabinofuranosylguanine as substrate, in the presence of 1 mM deoxycytidine, in 50 mM Tris-HCl (pH 7.6) containing 5 mM ATP, 4 mM dithiothreitol, 10 mM sodium fluoride and 5 mM MgCl2
0.058
-
using deoxyguanosine as substrate, in the presence of 1 mM deoxycytidine, in 50 mM Tris-HCl (pH 7.6) containing 5 mM ATP, 4 mM dithiothreitol, 10 mM sodium fluoride and 5 mM MgCl2
0.073
-
using 2-chlorodeoxyadenosine as substrate, in the presence of 1 mM deoxycytidine, in 50 mM Tris-HCl (pH 7.6) containing 5 mM ATP, 4 mM dithiothreitol, 10 mM sodium fluoride and 5 mM MgCl2
additional information
additional information
-
catalytic efficiencies of the purified recombinant enzyme
additional information
-
catalytic efficiencies of wild-type and muztant enzymes
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
640553, 640555, 640556, 640557, 640559, 640560, 640562, 640563, 640568, 660855, 661034, 661040, 661728
-
-
3 patients, one with N46S/L266R double mutation who is clinically healthy at age of 10 years, 2 patients with lethal mutations who died at 2 and 3 month of age and parents and healthy controls
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
enzyme is expressed in most tissues, enzyme expression throughout the cell cycle
-
genotyping of the enzyme splicing variants and mutants in fibroblast cell lines
human lung adenocarcinoma cell line PDC-027
human lung adenocarcinoma cell line PDC-236
human lung adenocarcinoma cell line PDC-251
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
the enzyme leaks out into the cytosol during cell apoptosis
-
-
-
640555, 640556, 640559, 661040, 661728, 662882, 662992, 671801, 671890, 673472, 705750, 737461, 737599
-
mitochondrial deoxguanosine kinase is redistributed to the cytosol during apoptosis
enzyme possesses an N-terminal mitochondrial import signal
N-terminal enzyme sequence contains a mitochondrial import signal
-
deoxyguanosine kinase is encoded by the nuclear DNA and transported into the mitochondria
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
deoxyguanosine kinase deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype, deoxyguanosine kinase deficiency is associated with a variable clinical phenotype, long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival
malfunction
-
dGK depletion in cells results in lower sensitivity to 2-fluoro-9-beta-D-arabinofuranosyladenine, gemcitabine, clofarabine, and 9-beta-D-arabinofuranosylguanine, but slightly higher sensitivity to cladribine and cytarabine
malfunction
-
mitochondrial DNA depletion due to deoxyguanosine kinase deficiency is a devastating mitochondrial disease of infancy characterized by liver failure and encephalopathy and invariably a fatal outcome. The cytoplasmic deoxycytine kinase supplemented with external substrates may compensate for the deficient deoxyguanosine kinase
malfunction
mutations in deoxyguanosine kinase cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus, and hypotonia
malfunction
-
deoxyguanosine kinase deficiency associated with mutations in the deoxyguanosine kinase gene is responsible for hepatic mitochondrial depletion syndrome phenotype, the disease is characterized by tissue-specific pathology. Deoxyguanosine kinase gene mutations combined with impaired glucose homeostasis and iron overload features cause lethal progressive liver failure in infants
malfunction
-
loss of enzyme function results in the depletion of mitochondrial DNA relative to nuclear DNA. Recessive deoxyguanosine kinase deficiency causes juvenile onset mitochondrial myopathy and is the cause of an infantile onset hepatocerebral mitochondrial disease including significant hepatic failure with nystagmus and hypotonia. Mitochondrial DNA depletion in cells from a patient presenting with mitochondrial myopathy caused by a mutation in the enzyme
malfunction
the depletion of the enzyme robustly inhibits lung adenocarcinoma tumor growth, metastasis, and cancer stem-like cell self-renewal
physiological function
-
deoxyguanosine kinase is responsible for phosphorylation of purine deoxyribonucleosides in the mitochondrial matrix. The main supply of purine dNTPs for mtDNA synthesis comes from the salvage pathway initiated by the enzyme
physiological function
the enzyme is required for cancer cell stemness in lung adenocarcinoma. The enzyme is required for the biogenesis of respiratory complex I and mitochondrial oxidative phosphorylation, which in turn regulates cancer stem-like cell self-renewal through AMP-activated kinase-YAP1 signaling
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). DCK_HUMAN
260
0
30519
Swiss-Prot
other Location (Reliability: 5)
DGUOK_HUMAN
277
0
32056
Swiss-Prot
Mitochondrion (Reliability: 2)
P78533_HUMAN
15
0
1706
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
ternary and quarternary structure analysis, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, hanging drop vapour diffusion method, enzyme solution containing 7 mg/ml protein, 5 mM MgCl2, and 5 mM ATP, mixed with an equal volume of cyrstallization solution containing 0.1 M Na-citrate, pH 6.5, 0.2 M ammonium acetate, and 30% w/v PEG 4000, X-ray diffraction structure determination and analysis at 2.8 A resolution, molecular replacement method
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A2S
-
resulting from a base change G to T at position 4, a G base change immediately after the start codon is likely to affect start codon recognition by the ribosome the patient has an additional base change G to A at position 591 results in skipping of exon 4, very low residual activity
E165V
-
naturally occuring enzyme mutation involved in mitochondrial depletion syndrome
E227K
-
site-directed mutagenesis, mutation is naturally found in patients, unaltered Km but very low Vmax for all substrates compared to the wild-type enzyme
F256X
-
naturally occuring enzyme mutation involved in mitochondrial depletion syndrome
H226R
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
I43T
the mutation is associated with infantile mitochondrial DNA depletion syndrome
K51Q
the p.K51Q alteration changes the basic amino acid lysine to the uncharged polar amino acid glutamine in the ATP binding site and is expected to interfere with enzymatic function, the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
L250S
-
naturally occurring mutation in a patient with mitochondrial DNA depletion syndrome, patient shows rapidly progressing, early onset fatal liver failure associated with profoundly decreased mtDNA levels in liver and, to a lesser extent, in skeletal muscle, mutation is introduced into the enzyme cDNA via site-directed mutagenesis, the mutant enzyme shows 0.5% remaining activity compared to the wild-type enzyme
L266R
M1I
-
naturally occuring enzyme mutation involved in mitochondrial depletion syndrome
N46S
N46S/L266R
R105*
the mutation is associated with infantile mitochondrial DNA depletion syndrome
R118C
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
R142K
-
site-directed mutagenesis, mutation is naturally found in patients, low activity with dG, no activity with dA compared to the wild-type enzyme
W178X
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
W65X
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
Y191C
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
additional information
L266R
-
father of patient with double mutant, 42 of the mean control value for 2'-deoxyguanosine, and 41 of the mean control value for 2'-deoxyadenosine
N46S
-
mother and brother of patient with double mutant, 61 and 45% of the mean control value for 2'-deoxyguanosine, and 59 and 44% of the mean control value for 2'-deoxyadenosine
N46S
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
N46S
the mutation is associated with familial idiopathic noncirrhotic portal hypertension
N46S/L266R
-
naturally occuring mutation, 14 and 10% residual activity as compared with controls with deoxyguanosine and deoxyadenosine, patient shows improved liver tests starting from age 46 month, at age 10 years clinically healthy
additional information
-
C-terminally truncated mutants are catalytically inactive, naturally occuring genetic defects/mutations, overview
additional information
-
duplication of bases 763 to 766 in exon 6 results in a truncated non-functional protein, very low residual activity
additional information
frame shift mutation c.80delC causes a truncated polypeptide of 64 amino acids and frame shift mutation c763_c766dupGATT results in a truncated polypeptide of 256 amino acids, the c.591G>A nucleotide substitution, located at the end of exon 4 does not result in amino acid change (p.Q197Q), but it changes the consensus splice site sequence, this is predicted to result in aberrant splicing, the frame shift mutation c.605_c.606delGA produces a premature stop codon and a truncated protein of 214 amino acids
additional information
-
frame shift mutation c.80delC causes a truncated polypeptide of 64 amino acids and frame shift mutation c763_c766dupGATT results in a truncated polypeptide of 256 amino acids, the c.591G>A nucleotide substitution, located at the end of exon 4 does not result in amino acid change (p.Q197Q), but it changes the consensus splice site sequence, this is predicted to result in aberrant splicing, the frame shift mutation c.605_c.606delGA produces a premature stop codon and a truncated protein of 214 amino acids
additional information
-
identification of deoxyguanosine kinase gene mutations. Most frequent mutation identified in patients with liver pathology is the c.3G>A substitution in the DGUOK exon 1, potentially causing a severe impairment in the synthesis of the protein, geno-y and phenotypes, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, affinity chromatography on AMP-Sepharose and Blue-Sepharose, DEAE-cellulose, Sephadex G-75
-
enzyme activity is stabilized during purification in presence of Triton X-100 and ATP
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of wild-type and mutant L250S enzymes in Escherichia coli with similar expression levels, the mutant enzyme is poorly soluble
-
expresssion of mitochondrial deoxyguanosine kinase-green fluorescent protein fusion in pancreatic cancer cells
-
genetic organization, located on chromosome 2p13, expression as GFP-fusion protein in CHO cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is downregulated by didanosine (2',3'-dideoxyinosine) to about 40%
-
treatment with 3'-azido-2',3'-dideoxythymidine (zidovudine) treatment leads to downregulation of the mitochondrial enzyme in U2OS cells. Incubation with 1 mM tert-butylhydroperoxide results in 80% and 65% reductions in mitochondrial protein levels. Similarly, incubation with 2 mM diamide leads to about 50% decreases in enzyme expression
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
enzyme is useful in anticancer therapy due to activation of anticancer drugs through phosphorylation
medicine
the enzyme activates a number of medically important nucleoside analogues
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yamada, Y.; Goto, H.; Ogasawara, N.
Deoxyguanosine kinase from human placenta
Biochim. Biophys. Acta
709
265-272
1982
Homo sapiens
Sjoberg, A.H.; Wang, L.; Eriksson, S.
Substrate specificity of human recombinant mitochondrial deoxyguanosine kinase with cytostatic and antiviral purine and pyrimidine analogs
Mol. Pharmacol.
53
270-273
1998
Homo sapiens
Zhu, C.; Johansson, M.; Permert, J.; Karlsson, A.
Enhanced cytotoxicity of nucleoside analogs by overexpression of mitochondrial deoxyguanosine kinase in cancer cell lines
J. Biol. Chem.
273
14707-14711
1998
Homo sapiens
Gaubert, G.; Gosselin, G.; Boudou, V.; Imbach, J.L.; Eriksson, S.; Maury, G.
Low enantioselectivities of human deoxycytidine kinase and human deoxyguanosine kinase with respect to 2'-deoxyadenosine, 2'-deoxyguanosine and their analogs
Biochimie
81
1041-1047
1999
Homo sapiens
Jullig, M.; Eriksson, S.
Mitochondrial and submitochondrial localization of human deoxyguanosine kinase
Eur. J. Biochem.
267
5466-5472
2000
Homo sapiens
Jullig, M.; Eriksson, S.
Apoptosis induces efflux of the mitochondrial matrix enzyme deoxyguanosine kinase
J. Biol. Chem.
276
24000-24004
2001
Homo sapiens
Herrstrom Sjoberg, A.; Wang, L.; Eriksson, S.
Antiviral guanosine analogs as substrates for deoxyguanosine kinase: implications for chemotherapy
Antimicrob. Agents Chemother.
45
739-742
2001
Bos taurus, Homo sapiens
Lotfi, K.; Mansson, E.; Peterson, C.; Eriksson, S.; Albertioni, F.
Low level of mitochondrial deoxyguanosine kinase is the dominant factor in acquired resistance to 9-beta-D-arabinofuranosylguanine cytotoxicity
Biochem. Biophys. Res. Commun.
293
1489-1496
2002
Homo sapiens
Rodriguez, C.O., Jr.; Mitchell, B.S.; Ayres, M.; Eriksson, S.; Gandhi, V.
Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase
Cancer Res.
62
3100-3105
2002
Homo sapiens
Krawiec, K.; Kierdaszuk, B.; Shugar, D.
Inorganic tripolyphosphate (PPP(i)) as a phosphate donor for human deoxyribonucleoside kinases
Biochem. Biophys. Res. Commun.
301
192-197
2003
Homo sapiens
Feng, J.Y.; Parker, W.B.; Krajewski, M.L.; Deville-Bonne, D.; Veron, M.; Krishnan, P.; Cheng, Y.C.; Borroto-Esoda, K.
Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases
Biochem. Pharmacol.
68
1879-1888
2004
Homo sapiens
Rylova, S.N.; Albertioni, F.; Flygh, G.; Eriksson, S.
Activity profiles of deoxynucleoside kinases and 5'-nucleotidases in cultured adipocytes and myoblastic cells: insights into mitochondrial toxicity of nucleoside analogs
Biochem. Pharmacol.
69
951-960
2005
Homo sapiens
Eriksson, S.; Munch-Petersen, B.; Johansson, K.; Eklund, H.
Structure and function of cellular deoxyribonucleoside kinases
Cell. Mol. Life Sci.
59
1327-1346
2002
Homo sapiens (Q16854)
Wang, L.; Eriksson, S.
Mitochondrial deoxyguanosine kinase mutations and mitochondrial DNA depletion syndrome
FEBS Lett.
554
319-322
2003
Homo sapiens
Piskur, J.; Sandrini, M.P.B.; Knecht, W.; Munch-Petersen, B.
Animal deoxyribonucleoside kinases: 'forward' and 'retrograde' evolution of their substrate specificity
FEBS Lett.
560
3-6
2004
Homo sapiens (Q16854)
Wang, L.; Limongelli, A.; Vila, M.R.; Carrara, F.; Zeviani, M.; Eriksson, S.
Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes
Mol. Genet. Metab.
84
75-82
2005
Homo sapiens
Johansson, K.; Ramaswamy, S.; Ljungcrantz, C.; Knecht, W.; Piskur, J.; Munch-Petersen, B.; Eriksson, S.; Eklund, H.
Structural basis for substrate specificities of cellular deoxyribonucleoside kinases
Nat. Struct. Biol.
8
616-620
2001
Homo sapiens (Q16854), Homo sapiens
Krawiec, K.; Kierdaszuk, B.; Kalinichenko, E.N.; Rubinova, E.B.; Mikhailopulo, I.A.; Eriksson, S.; Munch-Petersen, B.; Shugar, D.
Ability of adenosine-2'(3')-deoxy-3'(2')-triphosphates and related analogues to replace ATP as phosphate donor for all human and Drosphila melanogaster deoxyribonucleoside kinases
Nucleosides Nucleotides Nucleic Acids
22
1525-1529
2003
Homo sapiens
Al-Madhoun, A.S.; Eriksson, S.; Wang, Z.X.; Naimi, E.; Knaus, E.E.; Wiebe, L.I.
Phosphorylation of isocarbostyril- and difluorophenyl-nucleoside thymidine mimics by the human deoxynucleoside kinases
Nucleosides Nucleotides Nucleic Acids
23
1865-1874
2004
Homo sapiens
Van Rompay, A.R.; Johansson, M.; Karlsson, A.
Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases
Pharmacol. Ther.
100
119-139
2003
Homo sapiens (Q16854)
Fyrberg, A.; Albertioni, F.; Lotfi, K.
Cell cycle effect on the activity of deoxynucleoside analogue metabolising enzymes
Biochem. Biophys. Res. Commun.
357
847-853
2007
Homo sapiens
Mousson de Camaret, B.; Taanman, J.W.; Padet, S.; Chassagne, M.; Mayencon, M.; Clerc-Renaud, P.; Mandon, G.; Zabot, M.T.; Lachaux, A.; Bozon, D.
Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion
Biochem. J.
402
377-385
2007
Homo sapiens
Lotfi, K.; Karlsson, K.; Fyrberg, A.; Juliusson, G.; Jonsson, V.; Peterson, C.; Eriksson, S.; Albertioni, F.
The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia
Biochem. Pharmacol.
71
882-890
2006
Homo sapiens
Franco, M.; Johansson, M.; Karlsson, A.
Depletion of mitochondrial DNA by down-regulation of deoxyguanosine kinase expression in non-proliferating HeLa cells
Exp. Cell Res.
313
2687-2694
2007
Homo sapiens
Dimmock, D.P.; Zhang, Q.; Dionisi-Vici, C.; Carrozzo, R.; Shieh, J.; Tang, L.Y.; Truong, C.; Schmitt, E.; Sifry-Platt, M.; Lucioli, S.; Santorelli, F.M.; Ficicioglu, C.H.; Rodriguez, M.; Wierenga, K.; Enns, G.M.; Longo, N.; Lipson, M.H.; Vallance, H.; Craigen, W.J.; Scaglia, F.; Wong, L.J.
Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase
Hum. Mutat.
29
330-331
2008
Homo sapiens (Q16854), Homo sapiens
Dimmock, D.P.; Dunn, J.K.; Feigenbaum, A.; Rupar, A.; Horvath, R.; Freisinger, P.; Mousson de Camaret, B.; Wong, L.J.; Scaglia, F.
Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency
Liver Transpl.
14
1480-1485
2008
Homo sapiens
Saada, A.
Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency
Mol. Genet. Metab.
95
169-173
2008
Homo sapiens
Fyrberg, A.; Albertioni, F.; Lotfi, K.
RNAi depletion of deoxycytidine and deoxyguanosine kinase in human leukemic CEM cells
Nucleosides Nucleotides Nucleic Acids
27
712-719
2008
Homo sapiens
Pronicka, E.; Weglewska-Jurkiewicz, A.; Taybert, J.; Pronicki, M.; Szymanska-Debinska, T.; Karkucinska-Wieckowska, A.; Jakobkiewicz-Banecka, J.; Kowalski, P.; Piekutowska-Abramczuk, D.; Pajdowska, M.; Socha, P.; Sykut-Cegielska, J.; Wegrzyn, G.
Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure
J. Appl. Genet.
52
61-66
2011
Homo sapiens
Buchaklian, A.H.; Helbling, D.; Ware, S.M.; Dimmock, D.P.
Recessive deoxyguanosine kinase deficiency causes juvenile onset mitochondrial myopathy
Mol. Genet. Metab.
107
92-94
2012
Homo sapiens
Sun, R.; Eriksson, S.; Wang, L.
Zidovudine induces downregulation of mitochondrial deoxynucleoside kinases: implications for mitochondrial toxicity of antiviral nucleoside analogs
Antimicrob. Agents Chemother.
58
6758-6766
2014
Homo sapiens
Sun, R.; Eriksson, S.; Wang, L.
Down-regulation of mitochondrial thymidine kinase 2 and deoxyguanosine kinase by didanosine: implication for mitochondrial toxicities of anti-HIV nucleoside analogs
Biochem. Biophys. Res. Commun.
450
1021-1026
2014
Homo sapiens
Vilarinho, S.; Sari, S.; Yilmaz, G.; Stiegler, A.L.; Boggon, T.J.; Jain, D.; Akyol, G.; Dalgic, B.; Guenel, M.; Lifton, R.P.
Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension
Hepatology
63
1977-1986
2016
Homo sapiens (Q16854), Homo sapiens
Lin, S.; Huang, C.; Sun, J.; Bollt, O.; Wang, X.; Martine, E.; Kang, J.; Taylor, M.D.; Fang, B.; Singh, P.K.; Koomen, J.; Hao, J.; Yang, S.
The mitochondrial deoxyguanosine kinase is required for cancer cell stemness in lung adenocarcinoma
EMBO Mol. Med.
11
e10849
2019
Homo sapiens (Q16854)
EXTERNAL LINKS (specific for EC-Number 2.7.1.113)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
