Any feedback?
Literature summary for 2.7.1.48 extracted from
- Involvement of the uridine cytidine kinase 2 enzyme in cancer cell death a molecular crosstalk between the enzyme and cellular apoptosis induction (2019), Biomed. Pharmacother., 109, 1506-1510 .
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | role of UCK2-dependant nucleoside analogues in cancer therapy, overview. Nucleoside antimetabolites are amongst the most important chemotherapeutic agents currently used or under clinical trials against several cancers. This included the important clinically used nucleoside analogue, 5-fluorouracil. UCK2 is also involved in the phosphorylation of ribonucleoside analogues, 5-azacytidine, cyclopentenyl cytosine/uracil, 5-fluorocytidine, 6-azauridine, 3-deazauridine, 5-fluorouridine as well as ethynyl cytidine and uridine. To exert their pharmacological actions, these cytotoxic drugs depend on the action of the UCK2 enzyme to sequentially transform them into nucleoside 5'-triphosphate, thereby interfering with gene synthesis vital for metabolic processes required for cancer cell growth and maintenance | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| CTP | feedback inhibition | Homo sapiens |  |
| UTP | feedback inhibition | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Homo sapiens | 5829 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + cytidine | Homo sapiens | - |
ADP + CMP | - |
? | |
| ATP + cytidine | Homo sapiens | the enzyme is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis | ADP + CMP | - |
? | |
| ATP + uridine | Homo sapiens | - |
ADP + UMP | - |
? | |
| ATP + uridine | Homo sapiens | the enzyme is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis | ADP + UMP | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q9BZX2 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| carcinoma cell | - |
Homo sapiens | - |
| additional information | isoenzyme UCK2 (but not UCK1) is most abundantly overexpressed in numerous tumour cells | Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + 3'-ethynylcytidine | i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine | Homo sapiens | ADP + 3'-ethynylcytidine 5'-monophosphate | - |
? | |
| ATP + 3'-ethynylcytidine 5'-diphosphate | - |
Homo sapiens | ADP + 3'-ethynylcytidine 5'-triphosphate | - |
? | |
| ATP + 3'-ethynylcytidine 5'-monophosphate | - |
Homo sapiens | ADP + 3'-ethynylcytidine 5'-diphosphate | - |
? | |
| ATP + 3'-ethynyluridine | i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine | Homo sapiens | ADP + 3'-ethynyluridine 5'-monophosphate | - |
? | |
| ATP + 3'-ethynyluridine 5'-diphosphate | - |
Homo sapiens | ADP + 3'-ethynyluridine 5'-triphosphate | - |
? | |
| ATP + 3'-ethynyluridine 5'-monophosphate | - |
Homo sapiens | ADP + 3'-ethynyluridine 5'-diphosphate | - |
? | |
| ATP + 3-deazauridine | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + 5-azacytidine | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + 5-fluorocytidine | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + 5-fluorouridine | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + 6-azauridine | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + cyclopentenyl cytosine | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + cyclopentenyl uracil | - |
Homo sapiens | ADP + ? | - |
? | |
| ATP + cytidine | - |
Homo sapiens | ADP + CMP | - |
? | |
| ATP + cytidine | the enzyme is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis | Homo sapiens | ADP + CMP | - |
? | |
| ATP + uridine | - |
Homo sapiens | ADP + UMP | - |
? | |
| ATP + uridine | the enzyme is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis | Homo sapiens | ADP + UMP | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| UCK2 | - |
Homo sapiens |
| uridine cytidine kinase 2 | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| drug target | inhibition of enzyme (UCK2) induces nucleolar stress, probably by depleting nucleotide biosynthesis, thereby destabilising ribosomal biogenesis and subsequently causing cancer cell arrest and apoptotic cell death induction | Homo sapiens |
| malfunction | probable ribosomal stress condition during inhibition of the UCK2 enzyme, overview. The released and subsequent activation of p53 leads towards apoptosis induction | Homo sapiens |
| metabolism | UCK2 is feedback inhibited by UTP and CTP to adjust cellular needs and prevent overproduction of the nucleotides. In the course of cancer cell proliferation, these nucleotides are continuously synthesized to sustain protein synthesis. During gene degradation, some NMPs are released and recycled via the salvage pathway by the action of UCK2, thereby facilitating the prevention of energy loss and the waste of valuable precursors. Molecular crosstalks between UCK2 and cell death, the role of ribosomal proteins, MDM2 and p53 in regulation of cell death, and the role of UCK2 in regulation of cell death | Homo sapiens |
| metabolism | the enzyme is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis | Homo sapiens |
| physiological function | UCK2 is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis. Uridine-cytidine kinase 2 (UCK2) is linked to cell apoptosis induction. Molecular crosstalk involving UCK2 protein and cancer cell death through cell cycle arrest and triggering of apoptosis involving proteins, MDM2 and the subsequent activation of p53. UCK2 is also involved in the phosphorylation of ribonucleoside analogues, 5-azacytidine, cyclopentenyl cytosine/uracil, 5-fluorocytidine, 6-azauridine, 3-deazauridine, 5-fluorouridine as well as ethynyl cytidine and uridine. These cytotoxic drugs depends on the action of the UCK2 enzyme to sequentially transformed into nucleoside 5'-triphosphate, thereby interfering with gene synthesis vital for metabolic processes required for cancer cell growth and maintenance | Homo sapiens |
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
