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Literature summary extracted from

  • Malami, I.; Abdul, A.B.
    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 .
    View publication on PubMed

Application

EC Number Application Comment Organism
2.7.1.48 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

EC Number Inhibitors Comment Organism Structure
2.7.1.48 CTP feedback inhibition Homo sapiens
2.7.1.48 UTP feedback inhibition Homo sapiens

Localization

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.48 ATP + cytidine Homo sapiens
-
 ADP + CMP
-
 ?
2.7.1.48 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
-
 ?
2.7.1.48 ATP + uridine Homo sapiens
-
 ADP + UMP
-
 ?
2.7.1.48 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

EC Number Organism UniProt Comment Textmining
2.7.1.48 Homo sapiens Q9BZX2
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.48 carcinoma cell
-
 Homo sapiens
-
2.7.1.48 additional information isoenzyme UCK2 (but not UCK1) is most abundantly overexpressed in numerous tumour cells Homo sapiens
-
2.7.1.48 placenta
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.48 ATP + 3'-ethynylcytidine i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine Homo sapiens ADP + 3'-ethynylcytidine 5'-monophosphate
-
 ?
2.7.1.48 ATP + 3'-ethynylcytidine 5'-diphosphate
-
 Homo sapiens ADP + 3'-ethynylcytidine 5'-triphosphate
-
 ?
2.7.1.48 ATP + 3'-ethynylcytidine 5'-monophosphate
-
 Homo sapiens ADP + 3'-ethynylcytidine 5'-diphosphate
-
 ?
2.7.1.48 ATP + 3'-ethynyluridine i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine Homo sapiens ADP + 3'-ethynyluridine 5'-monophosphate
-
 ?
2.7.1.48 ATP + 3'-ethynyluridine 5'-diphosphate
-
 Homo sapiens ADP + 3'-ethynyluridine 5'-triphosphate
-
 ?
2.7.1.48 ATP + 3'-ethynyluridine 5'-monophosphate
-
 Homo sapiens ADP + 3'-ethynyluridine 5'-diphosphate
-
 ?
2.7.1.48 ATP + 3-deazauridine
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + 5-azacytidine
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + 5-fluorocytidine
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + 5-fluorouridine
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + 6-azauridine
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + cyclopentenyl cytosine
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + cyclopentenyl uracil
-
 Homo sapiens ADP + ?
-
 ?
2.7.1.48 ATP + cytidine
-
 Homo sapiens ADP + CMP
-
 ?
2.7.1.48 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
-
 ?
2.7.1.48 ATP + uridine
-
 Homo sapiens ADP + UMP
-
 ?
2.7.1.48 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

EC Number Synonyms Comment Organism
2.7.1.48 UCK2
-
 Homo sapiens
2.7.1.48 uridine cytidine kinase 2
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.1.48 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
2.7.1.48 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
2.7.1.48 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
2.7.1.48 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
2.7.1.48 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