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Literature summary extracted from

  • Sato, A.; Takano, T.; Hiramoto, A.; Naito, T.; Matsuda, A.; Fukushima, M.; Wataya, Y.; Kim, H.S.
    Role of the uridine/cytidine kinase 2 mutation in cellular sensitiveness toward 3-ethynylcytidine treatment of human cancer cells (2017), Anticancer Drugs, 28, 781-786 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.48 gene OCK2, quantitative real-time PCR analysis of UCK2 mRNA expression Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.48 additional information several functional point mutations, including the splice-site mutation of the UCK2 gene IVS5+5 G>A, are identified in the UCK2 enzyme protein. The IVS5+5 G>A variant generates an aberrant mRNA transcript, namely, truncated mRNA is produced and normal mRNA levels are markedly decreased in the ECyd-resistant cancer cell line HT1080. Effect of the IVS5+5G>A variation on pre-mRNA splicing. The IVS5+ 5 A/A genotype that is 98 bp shorter than a normal PCR product is detected. This variant-type UCK2 mRNA in HT1080/EUrd generates an aberrant stop codon and it produces an UCK2 protein without the C-terminal region. The wild-type UCK2 protein consists of 261 amino acid residues. In contrast, although the variant-type UCK2 mRNA conserves 166 amino acids in part of the N-terminus of UCK2, codons 167-171 are substituted by other amino acids by the frameshift mutation and parts of the C-terminal, codons 172-261, are missing (truncated). This missing region has been considered the substrate recognition site (LID domain) as well as the tetramer stabilization site. In addition, the mRNA with premature translation termination codon and coding nonfunctional protein is known to be eliminated by nonsense-mediated mRNA decay. It is possible that deletion of this region causes loss of stabilization and specific substrate recognition in UCK2 functions Homo sapiens
2.7.1.48 V84A missense mutation Homo sapiens

Metals/Ions

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.48 ATP + 3'-C-ethynylcytidine Homo sapiens i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine ADP + 3'-C-ethynylcytidine 5'-phosphate
-
 ir
2.7.1.48 ATP + 3'-C-ethynylcytidine 5'-diphosphate Homo sapiens
-
 ADP + 3'-C-ethynylcytidine 5'-triphosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynylcytidine 5'-phosphate Homo sapiens
-
 ADP + 3'-C-ethynylcytidine 5'-diphosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynyluridine Homo sapiens i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine ADP + 3'-C-ethynyluridine 5'-phosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynyluridine 5'-diphosphate Homo sapiens
-
 ADP + 3'-C-ethynyluridine 5'-triphosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynyluridine 5'-phosphate Homo sapiens
-
 ADP + 3'-C-ethynyluridine 5'-diphosphate
-
 ?
2.7.1.48 ATP + cytidine Homo sapiens
-
 ADP + CMP
-
 ?
2.7.1.48 ATP + uridine Homo sapiens
-
 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 HT-1080 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.48 ATP + 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine
-
 Homo sapiens ADP + 3'-ethynylcytidine 5'-monophosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynylcytidine i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine Homo sapiens ADP + 3'-C-ethynylcytidine 5'-phosphate
-
 ir
2.7.1.48 ATP + 3'-C-ethynylcytidine 5'-diphosphate
-
 Homo sapiens ADP + 3'-C-ethynylcytidine 5'-triphosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynylcytidine 5'-phosphate
-
 Homo sapiens ADP + 3'-C-ethynylcytidine 5'-diphosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynyluridine i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine Homo sapiens ADP + 3'-C-ethynyluridine 5'-phosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynyluridine 5'-diphosphate
-
 Homo sapiens ADP + 3'-C-ethynyluridine 5'-triphosphate
-
 ?
2.7.1.48 ATP + 3'-C-ethynyluridine 5'-phosphate
-
 Homo sapiens ADP + 3'-C-ethynyluridine 5'-diphosphate
-
 ?
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 + cytidine
-
 Homo sapiens ADP + CMP
-
 ?
2.7.1.48 ATP + uridine
-
 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
2.7.1.48 uridine/cytidine kinase 2
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.1.48 drug target 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) is a potent inhibitor of RNA polymerase I and shows anticancer activity to various human solid tumors. ECyd is phosphorylated to 3'-ethynylcytidine 5'-monophosphate by uridine/cytidine kinase 2 (UCK2) and subsequently further to diphosphate and triphosphate (3'-ethyntlcytidine 5'-diphosphate, 3'-ethyntlcytidine 5'-triphosphate). 3'-Ethyntlcytidine 5'-triphosphate is an active metabolite that can inhibit RNA polymerase I competitively. IVS5 + 5 G > A mutation would affect the expression level of the UCK2 transcript and result in decreased sensitivity to ECyd. The UCK2 is a key drug-response predictive marker for innate or acquired resistance to uridine/cytidine-type nucleoside analogs Homo sapiens
2.7.1.48 malfunction role of a uridine/cytidine kinase 2 mutation in cellular sensitiveness toward 3'-ethynylcytidine (ECyd) treatment of human cancer cells. The splice-site mutation of the UCK2 gene resulting in the IVS5+5 G>A variant affects the expression level of the UCK2 transcript, causing decreased sensitivity to ECyd. The IVS5+5 G>A variant generates an aberrant mRNA transcript, namely, truncated mRNA is produced and normal mRNA levels are markedly decreased in the ECyd-resistant cancer cell line HT1080. Relationship of UCK2 mutations and drug sensitivity with ECyd in several cancer cell lines, overview. Detection of the aberrant mRNA transcript in the ECyd/EUrd-resistant cancer cells with the IVS5 +5 A/A genotype Homo sapiens
2.7.1.48 physiological function a nucleosidic medicine, 1-(3-C-ethynyl-beta-D-ribopentofuranosyl) cytosine [3'-ethynylcytidine (ECyd)], is a potent inhibitor of RNA polymerase I and shows anticancer activity to various human solid tumors in vitro and in vivo. ECyd is phosphorylated to 3'-ethynylcytidine 5'-monophosphate by uridine/cytidine kinase 2 (UCK2) and subsequently further to diphosphate and triphosphate (3'-ethynylcytidine 5'-diphosphate, 3'-ethynylcytidine 5'-triphosphate). 3'-ethynylcytidine 5'-triphosphate is an active metabolite that can inhibit RNA polymerase I competitively, causing cancer cell death Homo sapiens