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Literature summary extracted from

  • 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 (2016), Oncotarget, 7, 10386-10401.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.4.14 gene CMPK1, genotyping in cervical tumour cell lines Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.4.14 additional information modeling studies of the P64T and R134M amino acid changes, structure-function relationship analysis of mutant UMP/CMPK1s, effect of the two mutations on the stability of the UMP/CMPK1 protein is assessed by circular dichroism, overview Homo sapiens
2.7.4.14 P64T naturally occuring mutation, involved in alterations of cidofovir metabolism and resistance against cidofovir in cervical tumour cell lines, thermoresistant mutant compared to the wild-type enzyme. The P64T substitution may modify the distance between Ile62, Val63 and CMP, and therefore reduce the intensity or abolish the interactions observed in the wild-type UMP/CMPK1 at this position Homo sapiens
2.7.4.14 R134M naturally occuring mutation, involved in alterations of cidofovir metabolism and resistance against cidofovir in cervical tumour cell lines, thermosensitive similar to the wild-type enzyme. The typical interactions established between an arginine to bridge the phosphate of ATP and CMP for the enzymatic reaction are abolished in the presence of Met134 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.4.14 0.02
-
 CMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 0.1
-
 UMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 0.11
-
 dCMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 0.123
-
 CMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.25
-
 UMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.315
-
 cytarabine pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 0.327
-
 cytarabine pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.97
-
 dCMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 1.034
-
 dUMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 2.08
-
 5-aza-cidofovir pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 2.3
-
 Cidofovir pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.4.14 cytosol
-
 Homo sapiens 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.4.14 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.4.14 ATP + 5-aza-cidofovir Homo sapiens
-
 ADP + phospho-5-aza-cidofovir
-
 ?
2.7.4.14 ATP + cidofovir Homo sapiens i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid ADP + phospho-cidofovir
-
 ?
2.7.4.14 ATP + CMP Homo sapiens
-
 ADP + CDP
-
 ?
2.7.4.14 ATP + cytarabine Homo sapiens anticancer drug, phosphorylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells ADP + phospho-cytarabine
-
 ?
2.7.4.14 ATP + dCMP Homo sapiens
-
 ADP + dCDP
-
 ?
2.7.4.14 ATP + dUMP Homo sapiens
-
 ADP + dUDP
-
 ?
2.7.4.14 ATP + gemcitabine Homo sapiens i.e. 2',2'-difluorodeoxycytidine ADP + phospho-gemcitabine
-
 ?
2.7.4.14 ATP + UMP Homo sapiens
-
 ADP + UDP
-
 ?
2.7.4.14 additional information Homo sapiens hyperensitivity and resistance against anti-cancer drugs in the different cervical tumour cell lines, effects of changes on UMP/CMPK1 expression on CTP and UTP synthesis , overview ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.4.14 Homo sapiens P30085 gene CMPK1
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.4.14 HaCaT cell cidofovir-resistant tumour cell line, no infection with human papilloma virus Homo sapiens
-
2.7.4.14 HeLa cell cidofovir-resistant tumour cell line, infection with human papilloma virus Homo sapiens
-
2.7.4.14 SiHa cell cidofovir-resistant tumour cell line, infection with human papilloma virus Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.4.14 ATP + 5-aza-cidofovir
-
 Homo sapiens ADP + phospho-5-aza-cidofovir
-
 ?
2.7.4.14 ATP + 5-aza-cidofovir wild-type enzyme Homo sapiens ADP + phospho-5-aza-cidofovir
-
 ?
2.7.4.14 ATP + cidofovir i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid Homo sapiens ADP + phospho-cidofovir
-
 ?
2.7.4.14 ATP + cidofovir i.e. (S)-[1-(4-amino-2-oxo-pyrimidin-1-yl)-3-hydroxy-propan-2-yl]oxy-methylphosphonic acid, wild-type enzyme Homo sapiens ADP + phospho-cidofovir
-
 ?
2.7.4.14 ATP + CMP
-
 Homo sapiens ADP + CDP
-
 ?
2.7.4.14 ATP + CMP wild-type enzyme and mutant P64T Homo sapiens ADP + CDP
-
 ?
2.7.4.14 ATP + cytarabine anticancer drug, phosphorylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells Homo sapiens ADP + phospho-cytarabine
-
 ?
2.7.4.14 ATP + cytarabine i.e. araC, wild-type enzyme and mutant P64T Homo sapiens ADP + phospho-cytarabine
-
 ?
2.7.4.14 ATP + dCMP
-
 Homo sapiens ADP + dCDP
-
 ?
2.7.4.14 ATP + dCMP wild-type enzyme and mutant P64T Homo sapiens ADP + dCDP
-
 ?
2.7.4.14 ATP + dUMP
-
 Homo sapiens ADP + dUDP
-
 ?
2.7.4.14 ATP + dUMP wild-type enzyme Homo sapiens ADP + dUDP
-
 ?
2.7.4.14 ATP + gemcitabine i.e. 2',2'-difluorodeoxycytidine Homo sapiens ADP + phospho-gemcitabine
-
 ?
2.7.4.14 ATP + gemcitabine i.e. 2',2'-difluorodeoxycytidine, wild-type enzyme Homo sapiens ADP + phospho-gemcitabine
-
 ?
2.7.4.14 ATP + UMP
-
 Homo sapiens ADP + UDP
-
 ?
2.7.4.14 ATP + UMP wild-type enzyme and mutant P64T Homo sapiens ADP + UDP
-
 ?
2.7.4.14 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 Homo sapiens ?
-
 ?
2.7.4.14 additional information mutants P64T/R134M and R134M show no activity with all substrates Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.4.14 CMPK1
-
 Homo sapiens
2.7.4.14 UMP/CMP kinase 1
-
 Homo sapiens
2.7.4.14 UMP/CMPK1
-
 Homo sapiens

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
2.7.4.14 70
-
 inactivation of wild-type enzyme and mutant R134M enzyme, only partial denaturation of mutant P64T Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.7.4.14 0.019
-
 cytarabine pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.036
-
 dCMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.09
-
 Cidofovir pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 0.31
-
 CMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.35
-
 UMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.47
-
 5-aza-cidofovir pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 5.8
-
 dUMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 13.4
-
 dCMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 125
-
 CMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 130
-
 cytarabine pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 188
-
 UMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.4.14 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.4.14 malfunction mutations P64T and R134M as well as downregulation of UMP/CMPK1 expression are observed in SiHaCDV and HeLaCDV, respectively, leading to alterations of cidofovir metabolism and resistance against cidofovir in the cervical tumour cell lines. In HaCaTCDV, no mutations of the uck gene are found and no impairment of UMP/CMPK1 activity is observed Homo sapiens
2.7.4.14 metabolism the first and last phosphorylation steps of cytidine 2'-deoxynucleoside analogues are catalyzed, respectively, by deoxycytidine kinase (dCK) and nucleoside diphosphate kinase (NDPK) Homo sapiens
2.7.4.14 additional information anticancer drugs, analogues of 2'-deoxycytidine (dC) (i.e. lamivudine and emtricitabine) or 2'-deoxycytidine monophosphate (dCMP) (i.e. CDV), require phosphorylation by UMP/CMPK. The anticancer agents cytarabine (araC) and gemcitabine (dFdC) are activated by UMP/CMPK1 following prior conversion to their 5?-monophosphate forms by dCK Homo sapiens
2.7.4.14 physiological function the cytosolic UMP/CMP kinase 1, is a key enzyme in the activation of antiviral and anticancer drugs and catalyzes the phosphorylation of (d)CMP analogues to their diphosphate forms Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.7.4.14 0.037
-
 dCMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.04
-
 Cidofovir pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 0.058
-
 cytarabine pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 0.226
-
 5-aza-cidofovir pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 1.4
-
 UMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 2.52
-
 CMP pH and temperature not specified in the publication, recombinant mutant P64T Homo sapiens
2.7.4.14 5.61
-
 dUMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 122
-
 dCMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 410
-
 cytarabine pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 1880
-
 UMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens
2.7.4.14 6250
-
 CMP pH and temperature not specified in the publication, recombinant wild-type enzyme Homo sapiens