FUR1/YHR128W Summary Help

Standard Name FUR1 1
Systematic Name YHR128W
Feature Type ORF, Verified
Description Uracil phosphoribosyltransferase; synthesizes UMP from uracil; involved in the pyrimidine salvage pathway (1 and see Summary Paragraph)
Name Description 5-FluoroURidine resistant 1
Chromosomal Location
ChrVIII:362115 to 362765 | ORF Map | GBrowse
Gbrowse
Genetic position: 91 cM
Gene Ontology Annotations All FUR1 GO evidence and references
  View Computational GO annotations for FUR1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 10 genes
Resources
Pathways
Classical genetics
null
unspecified
Large-scale survey
null
Resources
26 total interaction(s) for 21 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 16
  • Affinity Capture-RNA: 1
  • Biochemical Activity: 1
  • Protein-RNA: 1
  • Two-hybrid: 5

Genetic Interactions
  • Phenotypic Enhancement: 1
  • Synthetic Lethality: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 216
Molecular Weight (Da) 24,594
Isoelectric Point (pI) 5.53
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:362115 to 362765 | ORF Map | GBrowse
SGD ORF map
Genetic position: 91 cM
Last Update Coordinates: 2011-02-03 | Sequence: 2003-09-22
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..651 362115..362765 2011-02-03 2003-09-22
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001170
SUMMARY PARAGRAPH for FUR1

Fur1p is a uracil phosphoribosyltransferase (UPRTase) that catalyzes the conversion of uracil into uridine 5'-monophosphate (UMP) in the pyrimidine salvage pathway (1, 2). Uracil induces FUR1 and represses genes encoding the de novo pyrimidine biosynthetic enzymes (3), resulting in increased uracil phosphoribosyltransferase activity and decreased de novo biosynthesis of pyrimidines. FUR1 is repressed in response to lithium chloride during growth on galactose (4). FUR1 and ARP1 are convergently transcribed with the predicted polyadenylation signal of FUR1 residing in the C-terminal coding region of ARP1 (5).

fur1 null mutants are typically inviable unless supplemented with uracil and uridine, and because fur1 nulls cannot convert 5-fluorouracil (5-FU) to 5-fluoroUMP, which is toxic, the mutants are also resistant to 5-fluorocytidine, 5-fluorouridine, and 5-FU (2, 6, 1, 7). Disruption of FUR1 results in doubling times three-fold longer than wild type (8), and is synthetically lethal in ura3 null mutants (9). FUR1 is similar to Candida albicans FUR1 (10) and the Streptococcus salivarius uracil phosphoribosyltransferase gene (11).

Fur1p is of biomedical interest for use in cancer therapies because it can catalyze the conversion of 5-FU to 5-fluorouridine-5'-monophosphate, which can then be converted by mammalian enzymes into the toxic compounds 5-FUTP and 5-fluoro-dUMP (12). 5-FUTP can be incorporated into RNA in place of UTP, resulting in the inhibition of the nuclear processing of ribosomal and mRNAs, and 5-FdUMP irreversibly inhibits thymidylate synthase, preventing DNA synthesis (12). Expression of Fur1p increases tumor cell sensitivity to 5-FU, and expression of cytosine deaminase Fcy1p in tumor cells increases their sensitivity to 5-fluorocytosine (5-FC) (12). Tumor cells expressing a chimeric "suicide" protein, produced from a synthetic gene containing the FCY1 and FUR1 coding sequences fused in frame, display increased sensitivity to 5-FU, and significantly increased sensitivity to 5-FC (12). In a mouse model of tumor progression, injection of the fusion gene into tumors, in conjunction with the systemic administration of 5-FC, led to substantial delays in tumor growth, suggesting that the synthetic suicide gene may constitute a potent candidate for therapeutic cancer gene therapy (12).

Last updated: 2005-11-25 Contact SGD

References cited on this page View Complete Literature Guide for FUR1
1) Kern L, et al.  (1990) The FUR1 gene of Saccharomyces cerevisiae: cloning, structure and expression of wild-type and mutant alleles. Gene 88(2):149-57
2) Kurtz JE, et al.  (1999) New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism. Curr Genet 36(3):130-6
3) Kurtz JE, et al.  (2002) The URH1 uridine ribohydrolase of Saccharomyces cerevisiae. Curr Genet 41(3):132-41
4) Bro C, et al.  (2003) Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells. J Biol Chem 278(34):32141-9
5) Clark SW and Meyer DI  (1994) ACT3: a putative centractin homologue in S. cerevisiae is required for proper orientation of the mitotic spindle. J Cell Biol 127(1):129-38
6) Kern L, et al.  (1991) Regulation of the pyrimidine salvage pathway by the FUR1 gene product of Saccharomyces cerevisiae. Curr Genet 19(5):333-7
7) Paluszynski JP, et al.  (2008) Genetic prerequisites for additive or synergistic actions of 5-fluorocytosine and fluconazole in baker's yeast. Microbiology 154(Pt 10):3154-64
8) Karpova TS, et al.  (1998) Depolarization of the actin cytoskeleton is a specific phenotype in Saccharomyces cerevisiae. J Cell Sci 111 ( Pt 17)():2689-96
9) Koren A, et al.  (2003) Pitfalls of the synthetic lethality screen in Saccharomyces cerevisiae: an improved design. Curr Genet 43(1):62-9
10) Hope WW, et al.  (2004) Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob Agents Chemother 48(11):4377-86
11) Giffard PM, et al.  (1993) The ftf gene encoding the cell-bound fructosyltransferase of Streptococcus salivarius ATCC 25975 is preceded by an insertion sequence and followed by FUR1 and clpP homologues. J Gen Microbiol 139(5):913-20
12) Erbs P, et al.  (2000) In vivo cancer gene therapy by adenovirus-mediated transfer of a bifunctional yeast cytosine deaminase/uracil phosphoribosyltransferase fusion gene. Cancer Res 60(14):3813-22