Cloned (Comment) | Organism |
---|---|
gene CMPK1, genotyping in cervical tumour cell lines | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
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 |
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 |
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] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.02 | - |
CMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
0.1 | - |
UMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
0.11 | - |
dCMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
0.123 | - |
CMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.25 | - |
UMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.315 | - |
cytarabine | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
0.327 | - |
cytarabine | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.97 | - |
dCMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
1.034 | - |
dUMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
2.08 | - |
5-aza-cidofovir | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
2.3 | - |
Cidofovir | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + 5-aza-cidofovir | Homo sapiens | - |
ADP + phospho-5-aza-cidofovir | - |
? | |
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 | - |
? | |
ATP + CMP | Homo sapiens | - |
ADP + CDP | - |
? | |
ATP + cytarabine | Homo sapiens | anticancer drug, phosphorylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells | ADP + phospho-cytarabine | - |
? | |
ATP + dCMP | Homo sapiens | - |
ADP + dCDP | - |
? | |
ATP + dUMP | Homo sapiens | - |
ADP + dUDP | - |
? | |
ATP + gemcitabine | Homo sapiens | i.e. 2',2'-difluorodeoxycytidine | ADP + phospho-gemcitabine | - |
? | |
ATP + UMP | Homo sapiens | - |
ADP + UDP | - |
? | |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P30085 | gene CMPK1 | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HaCaT cell | cidofovir-resistant tumour cell line, no infection with human papilloma virus | Homo sapiens | - |
HeLa cell | cidofovir-resistant tumour cell line, infection with human papilloma virus | Homo sapiens | - |
SiHa cell | cidofovir-resistant tumour cell line, infection with human papilloma virus | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + 5-aza-cidofovir | - |
Homo sapiens | ADP + phospho-5-aza-cidofovir | - |
? | |
ATP + 5-aza-cidofovir | wild-type enzyme | Homo sapiens | ADP + phospho-5-aza-cidofovir | - |
? | |
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 | - |
? | |
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 | - |
? | |
ATP + CMP | - |
Homo sapiens | ADP + CDP | - |
? | |
ATP + CMP | wild-type enzyme and mutant P64T | Homo sapiens | ADP + CDP | - |
? | |
ATP + cytarabine | anticancer drug, phosphorylation catalyzed by the enzyme in cidofovir-resistant HaCaT cells | Homo sapiens | ADP + phospho-cytarabine | - |
? | |
ATP + cytarabine | i.e. araC, wild-type enzyme and mutant P64T | Homo sapiens | ADP + phospho-cytarabine | - |
? | |
ATP + dCMP | - |
Homo sapiens | ADP + dCDP | - |
? | |
ATP + dCMP | wild-type enzyme and mutant P64T | Homo sapiens | ADP + dCDP | - |
? | |
ATP + dUMP | - |
Homo sapiens | ADP + dUDP | - |
? | |
ATP + dUMP | wild-type enzyme | Homo sapiens | ADP + dUDP | - |
? | |
ATP + gemcitabine | i.e. 2',2'-difluorodeoxycytidine | Homo sapiens | ADP + phospho-gemcitabine | - |
? | |
ATP + gemcitabine | i.e. 2',2'-difluorodeoxycytidine, wild-type enzyme | Homo sapiens | ADP + phospho-gemcitabine | - |
? | |
ATP + UMP | - |
Homo sapiens | ADP + UDP | - |
? | |
ATP + UMP | wild-type enzyme and mutant P64T | Homo sapiens | ADP + UDP | - |
? | |
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 | ? | - |
? | |
additional information | mutants P64T/R134M and R134M show no activity with all substrates | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
CMPK1 | - |
Homo sapiens |
UMP/CMP kinase 1 | - |
Homo sapiens |
UMP/CMPK1 | - |
Homo sapiens |
Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
---|---|---|---|
70 | - |
inactivation of wild-type enzyme and mutant R134M enzyme, only partial denaturation of mutant P64T | Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.019 | - |
cytarabine | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.036 | - |
dCMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.09 | - |
Cidofovir | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
0.31 | - |
CMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.35 | - |
UMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.47 | - |
5-aza-cidofovir | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
5.8 | - |
dUMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
13.4 | - |
dCMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
125 | - |
CMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
130 | - |
cytarabine | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
188 | - |
UMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
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 |
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 |
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 |
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 Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.037 | - |
dCMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.04 | - |
Cidofovir | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
0.058 | - |
cytarabine | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
0.226 | - |
5-aza-cidofovir | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
1.4 | - |
UMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
2.52 | - |
CMP | pH and temperature not specified in the publication, recombinant mutant P64T | Homo sapiens | |
5.61 | - |
dUMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
122 | - |
dCMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
410 | - |
cytarabine | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
1880 | - |
UMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens | |
6250 | - |
CMP | pH and temperature not specified in the publication, recombinant wild-type enzyme | Homo sapiens |