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Literature summary extracted from

  • Eriksson, S.; Munch-Petersen, B.; Johansson, K.; Eklund, H.
    Structure and function of cellular deoxyribonucleoside kinases (2002), Cell. Mol. Life Sci., 59, 1327-1346.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.1.113 Triton X-100
-
Homo sapiens

Application

EC Number Application Comment Organism
2.7.1.145 medicine enzyme with increased specificity towards certain analogues can be used as a suicide gene in combined gene/chemotherapy treatment of cancer Bombyx mori
2.7.1.145 medicine enzyme with increased specificity towards certain analogues can be used as a suicide gene in combined gene/chemotherapy treatment of cancer Drosophila melanogaster
2.7.1.145 synthesis enzyme can be utilized in industrial large-scale production of dNTPs and analogues, used for DNA synthetic reactions, giving a higher yield and less toxic byproducts compared to chemical processes Drosophila melanogaster
2.7.1.145 synthesis enzyme can be utilized in industrial large-scale production of dNTPs and analogues, used forDNA synthetic reactions, giving a higher yield and less toxic byproducts compared to chemical processes Bombyx mori

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.74 the single copy gene is located on chromosome 4q13.3-q21.1 Homo sapiens
2.7.1.113 gene is localized on chromosome 2q13 Homo sapiens
2.7.1.145 DNA and amino acid sequence determination and analysis, gene is located on chromosome 3 at position 91D-91E, expression of wild-type and mutant enzymes in Escherichia coli TK-deficient strain KY895 Drosophila melanogaster

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.1.113 enzyme in complex with ATP Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.145 N45D/N64D site-directed mutagenesis, mutant shows increased drug sensitivity and decreased inhibition by dTTP compared to the wild-type enzyme Drosophila melanogaster

General Stability

EC Number General Stability Organism
2.7.1.113 Triton X-100 and ATP stabilize Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.74 dCTP feedback inhibition, competitive versus phosphate donors Homo sapiens
2.7.1.113 dATP feedback inhibition Homo sapiens
2.7.1.113 dGTP feedback inhibition Homo sapiens
2.7.1.145 dTTP competitive versus ATP, feedback inhibition Bombyx mori
2.7.1.145 dTTP competitive versus ATP, feedback inhibition Drosophila melanogaster
2.7.1.145 additional information no inhibition by dNTPs other than dTTP Bombyx mori
2.7.1.145 additional information no inhibition by dNTPs other than dTTP Drosophila melanogaster

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.1.74 additional information
-
additional information no Michaelis-Menten kinetics, but negative cooperativity Homo sapiens
2.7.1.145 additional information
-
additional information positive cooperativity with all 4 natural deoxyribonucleosides, no hyperbolic Michaelis-Menten substrate kinetics Bombyx mori
2.7.1.145 additional information
-
additional information straight forward hyperbolic kinetic reaction mechanism following a compulsory ordered steady-state reaction mechanism with formation of a ternary complex Drosophila melanogaster

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.74 cytoplasm
-
Homo sapiens 5737
-
2.7.1.74 nucleus enzyme possesses a nuclear localization signal at the N-terminus Homo sapiens 5634
-
2.7.1.113 mitochondrial matrix
-
Homo sapiens 5759
-
2.7.1.113 mitochondrion enzyme possesses an N-terminal mitochondrial import signal Homo sapiens 5739
-
2.7.1.113 additional information the enzyme leaks out into the cytosol during cell apoptosis Homo sapiens
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.74 Mg2+
-
Homo sapiens
2.7.1.113 Mg2+
-
Homo sapiens
2.7.1.145 Mg2+ dependent on Bombyx mori
2.7.1.145 Mg2+ dependent on Drosophila melanogaster

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.7.1.113 30000
-
2 * 30000 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.74 ATP + 2'-deoxycytidine Homo sapiens
-
ADP + 2'-deoxycytidine 5'-phosphate
-
?
2.7.1.74 UTP + 2'-deoxycytidine Homo sapiens
-
UDP + 2'-deoxycytidine 5'-phosphate
-
?
2.7.1.113 ATP + 2'-deoxyadenosine Homo sapiens
-
ADP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.113 ATP + 2'-deoxyguanosine Homo sapiens
-
ADP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.113 UTP + 2'-deoxyadenosine Homo sapiens
-
UDP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.113 UTP + 2'-deoxyguanosine Homo sapiens
-
UDP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxyadenosine Drosophila melanogaster
-
ADP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxycytidine Drosophila melanogaster
-
ADP + 2'-deoxycytidine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxyguanosine Drosophila melanogaster
-
ADP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxythymidine Drosophila melanogaster
-
ADP + 2'-deoxythymidine 5'-phosphate
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.74 Homo sapiens P27707
-
-
2.7.1.113 Homo sapiens Q16854 constitutive expression
-
2.7.1.145 Bombyx mori
-
-
-
2.7.1.145 Drosophila melanogaster Q9XZT6 dNK is the only deoxyriconucleoside kinase in the fruitfly
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.1.74 additional information posttranscriptional regulation of the enzyme Homo sapiens

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.1.113 enzyme activity is stabilized during purification in presence of Triton X-100 and ATP Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
2.7.1.74 NTP + deoxycytidine = NDP + dCMP substrate-enzyme interactions, bi bi random reaction mechanism with ATP, but ordered with UTP binding before the acceptor substrate, substrate binding site structures Homo sapiens
2.7.1.113 ATP + deoxyguanosine = ADP + dGMP substrate interactions, reaction mechanism Homo sapiens
2.7.1.145 ATP + a 2'-deoxyribonucleoside = ADP + a 2'-deoxyribonucleoside 5'-phosphate positive cooperativity mechanism, substrate and nucleotide interactions and binding sites, overview Bombyx mori
2.7.1.145 ATP + a 2'-deoxyribonucleoside = ADP + a 2'-deoxyribonucleoside 5'-phosphate straight forward hyperbolic kinetic reaction mechanism following a compulsory ordered steady-state reaction mechanism with formation of a ternary complex, substrate interactions Drosophila melanogaster

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.74 colonic mucosa
-
Homo sapiens
-
2.7.1.74 kidney very low enzyme expression Homo sapiens
-
2.7.1.74 liver very low enzyme expression Homo sapiens
-
2.7.1.74 lymphoid tissue high enzyme expression Homo sapiens
-
2.7.1.74 additional information tissue specific enzyme expression Homo sapiens
-
2.7.1.74 muscle very low enzyme expression Homo sapiens
-
2.7.1.74 pancreas very low enzyme expression Homo sapiens
-
2.7.1.113 brain
-
Homo sapiens
-
2.7.1.113 liver
-
Homo sapiens
-
2.7.1.113 lymphoid tissue
-
Homo sapiens
-
2.7.1.113 skin
-
Homo sapiens
-
2.7.1.113 spleen
-
Homo sapiens
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2.7.1.74 additional information
-
substrate specificity Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.74 ATP + 2',3'-dideoxycytidine i.e. zalcitabine Homo sapiens ADP + 2',3'-dideoxycytidine 5'-phosphate
-
?
2.7.1.74 ATP + 2'-deoxyadenosine
-
Homo sapiens ADP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.74 ATP + 2'-deoxycytidine
-
Homo sapiens ADP + 2'-deoxycytidine 5'-phosphate
-
?
2.7.1.74 ATP + 2'-deoxyguanosine
-
Homo sapiens ADP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.74 ATP + 2-chloro-2'-deoxyadenosine i.e. cladribine Homo sapiens ADP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.74 ATP + arabinosyl adenine
-
Homo sapiens ADP + arabinosyl adenine 5'-phosphate
-
?
2.7.1.74 ATP + arabinosyl cytosine i.e. cytosar Homo sapiens ADP + arabinosyl cytosine 5'-phosphate
-
?
2.7.1.74 ATP + beta-L-2',3'-dideoxy-3'-thiacytidine
-
Homo sapiens ADP + beta-L-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
-
?
2.7.1.74 ATP + difluoro-arabinofuranosyl adenine i.e. fludarabine Homo sapiens ADP + difluoro-arabinofuranosyl adenine 5'-phosphate
-
?
2.7.1.74 ATP + difluorodeoxycytidine i.e. gemcitabine Homo sapiens ADP + difluorodeoxycytidine 5'-phosphate
-
?
2.7.1.74 additional information substrate-enzyme interactions, overview, enzyme prefers nucleosides with sugars in the S-conformation, i.e C2'-endo-C3'-exo, binding of substrate induces conformational changes, the phosphate donor influences the acceptor substrate specificity, mechanism, overview Homo sapiens ?
-
?
2.7.1.74 UTP + 2',3'-dideoxycytidine i.e. zalcitabine Homo sapiens UDP + 2',3'-dideoxycytidine 5'-phosphate
-
?
2.7.1.74 UTP + 2'-deoxyadenosine
-
Homo sapiens UDP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.74 UTP + 2'-deoxycytidine
-
Homo sapiens UDP + 2'-deoxycytidine 5'-phosphate
-
?
2.7.1.74 UTP + 2'-deoxyguanosine
-
Homo sapiens UDP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.74 UTP + 2-chloro-2'-deoxyadenosine i.e. cladribine Homo sapiens UDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.74 UTP + arabinosyl adenine
-
Homo sapiens UDP + arabinosyl adenine 5'-phosphate
-
?
2.7.1.74 UTP + arabinosyl cytosine i.e. cytosar Homo sapiens UDP + arabinosyl cytosine 5'-phosphate
-
?
2.7.1.74 UTP + beta-L-2',3'-dideoxy-3'-thiacytidine
-
Homo sapiens UDP + beta-L-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
-
?
2.7.1.74 UTP + beta-L-dioxolane-cytidine antitumor drug Homo sapiens UDP + beta-L-dioxolane-cytidine 5'-phosphate
-
?
2.7.1.74 UTP + difluoro-arabinofuranosyl adenine i.e. fludarabine Homo sapiens UDP + difluoro-arabinofuranosyl adenine 5'-phosphate
-
?
2.7.1.74 UTP + difluorodeoxycytidine i.e. gemcitabine Homo sapiens UDP + difluorodeoxycytidine 5'-phosphate
-
?
2.7.1.113 ATP + 1-beta-D-arabinofuranosyladenine
-
Homo sapiens ADP + 1-beta-D-arabinofuranosyladenine 5'-phosphate
-
?
2.7.1.113 ATP + 2',2'-difluorodeoxyguanosine
-
Homo sapiens ADP + 2',2'-difluorodeoxyguanosine 5'-phosphate
-
?
2.7.1.113 ATP + 2'-deoxyadenosine
-
Homo sapiens ADP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.113 ATP + 2'-deoxyguanosine
-
Homo sapiens ADP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.113 ATP + 2'-deoxyinosine
-
Homo sapiens ADP + 2'-deoxyinosine 5'-phosphate
-
?
2.7.1.113 ATP + 2-chloro-2'-arabinofluoro-2'-deoxyadenosine
-
Homo sapiens ADP + 2-chloro-2'-arabinofluoro-2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.113 ATP + 2-chlorodeoxyadenosine
-
Homo sapiens ADP + 2-chlorodeoxyadenosine 5'-phosphate
-
?
2.7.1.113 ATP + 9-beta-D-arabinofuranosylguanine
-
Homo sapiens ADP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
-
?
2.7.1.113 ATP + ganciclovir i.e. 9-(1,3-dihydroxy-2-propoxymethyl)-guanine, low activity Homo sapiens ADP + ganciclovir phosphate
-
?
2.7.1.113 ATP + penciclovir i.e. 9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-guanine, low activity Homo sapiens ADP + penciclovir 5'-phosphate
-
?
2.7.1.113 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 Homo sapiens ?
-
?
2.7.1.113 UTP + 2'-deoxyadenosine
-
Homo sapiens UDP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.113 UTP + 2'-deoxyguanosine
-
Homo sapiens UDP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.113 UTP + 2'-deoxyinosine
-
Homo sapiens UDP + 2'-deoxyinosine 5'-phosphate
-
?
2.7.1.145 ATP + 1-beta-D-arabinofuranosylcytosine
-
Drosophila melanogaster ADP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
?
2.7.1.145 ATP + 1-beta-D-arabinofuranosylthymine
-
Drosophila melanogaster ADP + 1-beta-D-arabinofuranosylthymine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxyadenosine
-
Drosophila melanogaster ADP + 2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxycytidine
-
Drosophila melanogaster ADP + 2'-deoxycytidine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxyguanosine
-
Drosophila melanogaster ADP + 2'-deoxyguanosine 5'-phosphate
-
?
2.7.1.145 ATP + 2'-deoxythymidine
-
Drosophila melanogaster ADP + 2'-deoxythymidine 5'-phosphate
-
?
2.7.1.145 ATP + 2-chloro-2'-deoxyadenosine
-
Drosophila melanogaster ADP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
?
2.7.1.145 ATP + 5-fluoro-2'-deoxyuridine
-
Drosophila melanogaster ADP + 5-fluoro-2'-deoxyuridine 5'-phosphate
-
?
2.7.1.145 ATP + E-5-(2-bromovinyl)-2'-deoxyuridine
-
Drosophila melanogaster ADP + E-5-(2-bromovinyl)-2'-deoxyuridine phosphate
-
?
2.7.1.145 additional information broad substrate specificity Drosophila melanogaster ?
-
?
2.7.1.145 additional information substrate specificity, no activity with purine ribonucleosides and dideoxynucleosides Bombyx mori ?
-
?

Subunits

EC Number Subunits Comment Organism
2.7.1.74 More 3D-structure analysis, dCK structure model, overview Homo sapiens
2.7.1.113 dimer 2 * 30000 Homo sapiens
2.7.1.113 More ternary and quarternary structure analysis, overview Homo sapiens
2.7.1.145 dimer
-
Bombyx mori
2.7.1.145 dimer
-
Drosophila melanogaster
2.7.1.145 More ternary and quarternary structure analysis, overview Bombyx mori
2.7.1.145 More ternary and quarternary structure analysis, overview Drosophila melanogaster

Synonyms

EC Number Synonyms Comment Organism
2.7.1.74 dCK
-
Homo sapiens
2.7.1.74 NTP:deoxycytidine 5'-phosphotransferase
-
Homo sapiens
2.7.1.113 DGK
-
Homo sapiens
2.7.1.113 nucleoside triphosphate: deoxyguanosine 5'-phosphotransferase
-
Homo sapiens
2.7.1.145 dNK
-
Bombyx mori
2.7.1.145 dNK
-
Drosophila melanogaster
2.7.1.145 More the enzyme belongs to the thymidine kinase 2-like, i.e. TK2-like, family of enzymes Bombyx mori
2.7.1.145 More the enzyme belongs to the thymidine kinase 2-like, i.e. TK2-like, family of enzymes Drosophila melanogaster
2.7.1.145 multisubstrate deoxyribonucleoside kinase
-
Bombyx mori
2.7.1.145 multisubstrate deoxyribonucleoside kinase
-
Drosophila melanogaster
2.7.1.145 nucleoside triphosphate: deoxyribonucleoside 5'-phosphotransferase
-
Drosophila melanogaster

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.74 ATP
-
Homo sapiens
2.7.1.74 additional information enzyme lalso utilizes other nucleoside triphosphates as phosphate donors Homo sapiens
2.7.1.74 UTP
-
Homo sapiens
2.7.1.113 ATP binding site structure and interactions, Gln111, Arg118, Met99, and Asp147 are involved, overview Homo sapiens
2.7.1.113 additional information enzyme accepts several triphosphate donor substrates with preference for ATP and UTP Homo sapiens
2.7.1.113 UTP
-
Homo sapiens
2.7.1.145 ATP
-
Drosophila melanogaster