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Uridine-cytidine kinase 2 (UCK2)

Target
UCK2
Molecular classification
Enzyme
01

Overview

Uridine-cytidine kinase 2 (UCK2) is a human enzyme encoded by the UCK2 gene, predominantly found in the cytoplasm. It catalyzes the phosphorylation of uridine and cytidine to form uridine monophosphate (UMP) and cytidine monophosphate (CMP), respectively—the initial and rate-limiting step in the pyrimidine salvage pathway required for RNA and DNA synthesis[1][3][4][5]. UCK2 is structurally a tetramer with a characteristic active site that selects ribonucleosides over deoxyribonucleosides. It is abundantly expressed in various cancers and placenta but has limited expression in most normal tissues, making it both a marker and functional contributor to tumor proliferation[3]. UCK2 is exploited in cancer treatment to selectively activate cytotoxic nucleoside drugs within tumor cells, but also has non-catalytic roles in promoting oncogenic signaling and is under investigation as a dual-pathway therapeutic target[3][4].

Other names
Cytidine monophosphokinase 2UCK 2UMPKUridine monophosphokinase 2Testis-specific protein TSA903EC 2.7.1.48
02

Mechanism of action

Prodrug activation via phosphorylation of pyrimidine nucleoside analogs, enabling their cytotoxic effects in cancer therapy[3][4]

03

Biological functions

Pyrimidine salvageNucleotide biosynthesisCell proliferationNucleoside metabolism
04

Disease associations

CancerOther (nonhumoral immunity to certain infections)
05

Safety considerations

Off-target toxicity of nucleoside analog drugsPotential roles of UCK2 in normal tissues (e.g., placenta)
06

Interacting drugs

Cytotoxic nucleoside analogs (e.g., 5-fluorouridine, 6-azauridine, 5-fluorocytidine, 5-bromouridine, 4-thiouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, N(4)-anisoylcytidine, 2-thiocytidine, 5-methylcytidine)
07

Biomarkers

High UCK2 expression as a biomarker of poor prognosis in certain cancers (e.g., hepatocellular carcinoma, pancreatic cancer, lung cancer)

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