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Uracil phosphoribosyltransferase homolog (UPRT)

Target
UPRT
Molecular classification
Enzyme, Glycosyltransferase (EC 2.4.2.9), Pentosyltransferase, Phosphoribosyltransferase family
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Overview

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].

Other names
UPRTDKFZp781E1243MGC23937FUR1RP11-311P8.3UPPUMP pyrophosphorylaseUPRTaseuracil phosphoribosyltransferase (FUR1) homolog
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Mechanism of action

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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Biological functions

Pyrimidine salvage pathwayNucleotide metabolismCell survival/growth (especially in lower eukaryotes and microbes)
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Disease associations

Infection (especially parasitic infections, e.g., Toxoplasmosis)Cancer (as a tool for suicide-gene therapy)Other: coccidiosis, geotrichosis
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Safety considerations

Expression of microbial or exogenous UPRT in higher eukaryotes can lead to inadvertent cytotoxicity or off-target effectsBackground incorporation of nucleotides due to endogenous UPRT expression complicates mRNA labeling strategies in higher eukaryotes
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Interacting drugs

5-fluorouracil (5-FU)
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Biomarkers

UPRT gene/protein expression may be used as a biomarker in gene therapy and cell-specific mRNA labeling strategies

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