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Uracil phosphoribosyltransferase homolog (UPRT) is a protein-coding enzyme encoded by the *UPRT* gene, classified as EC 2.4.2.9. It catalyzes the formation of UMP from uracil and PRPP—a critical step in the pyrimidine salvage pathway, especially in microorganisms and lower eukaryotes[5][1]. In humans and other higher eukaryotes, UPRT homologs exist but may have limited or context-dependent enzymatic activity[4][3]. Its central biochemical role makes it a target for chemotherapy (by converting prodrugs like 5-FU into toxic metabolites in cancer or parasites) and molecular biology (such as cell-specific labeling)[4][3][5]. UPRT is evolutionarily conserved, but catalytic differences exist between species, particularly at the active site[4][1]. Expression is observed in diverse tissues including blood leukocytes, liver, spleen, and thymus, with nuclear and cytoplasmic localization[4][5]. Safety issues stem from potential cross-reactivity and non-selective activity of exogenous UPRT in transgenic or gene therapy contexts[3].
Drugs/prodrugs such as 5-FU are converted by UPRT to cytotoxic nucleotides, leading to cell death in targeted cells (e.g., cancer or parasite)
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