URA5/YML106W Summary Help

Standard Name URA5 1
Systematic Name YML106W
Alias PYR5
Feature Type ORF, Verified
Description Major orotate phosphoribosyltransferase (OPRTase) isozyme; catalyzes the fifth enzymatic step in de novo biosynthesis of pyrimidines, converting orotate into orotidine-5'-phosphate; URA5 has a paralog, URA10, that arose from the whole genome duplication (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description URAcil requiring 1, 3
Chromosomal Location
ChrXIII:56773 to 57453 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All URA5 GO evidence and references
  View Computational GO annotations for URA5
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 2 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
80 total interaction(s) for 70 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 14
  • Affinity Capture-RNA: 3
  • PCA: 1
  • Two-hybrid: 2

Genetic Interactions
  • Negative Genetic: 46
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Positive Genetic: 8
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 226
Molecular Weight (Da) 24,664
Isoelectric Point (pI) 5.92
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:56773 to 57453 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..681 56773..57453 1996-07-31 1996-07-31
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 SGDIDS000004574
SUMMARY PARAGRAPH for URA5

The fifth step in the pathway of de novo synthesis of pyrimidine ribonucleotides (shown here; 7) is the conversion of orotate to orotidine- 5'-monophosphate (OMP), which is catalyzed by orotate phosphoribosyl transferase (OPRTase). S. cerevisiae has two genes that encode for OPRTase, URA5 and URA10 (3, 2). These two gene products share greater than 75% amino acid similarity (2). Ura5p contributes most of the OPRTase activity found in yeast cells and is not regulated by any product or intermediate of the pyrimidine biosynthesis pathway. (2, 3). In contrast, Ura10p is responsible for 20% of the total OPRTase activity and URA10 expression is upregulated by the pyrimidine intermediate dihydoorotic acid (DHO) via Ppr1p (2, reviewed in 8). Ppr1p is a transcriptional activator that binds to the UASURA motif CGGN6CCG in gene promoters (9). DNA-bound Ppr1p is transcriptionally inactive, but the addition of DHO converts Ppr1p to an active state that interacts with RNA polymerase II, leading to increased expression of Ppr1p-regulated genes (9).

Unrelated to pathway intermediates, URA5 transcription is downregulated by DMSO, but URA10 expression is upregulated under the same conditions (10). URA10 is also upregulated by zinc depletion through Zap1p activity(11), downregulated by inositol and choline in a Opi1p-dependent manner (12), and upregulated by the presence of lithium (13).

In higher eukaryotes, orotate conversion to OMP is mediated by a bifunctional enzyme that catalyzes both this and the following step in the pyrimidine biosynthesis pathway (14, 15). S. cerevisiae OPRTase shares ~30% sequence similarity with the OPRTase domain of the homologous Arabidopsis thaliana protein (15). Mutations in the human homolog, UMP synthase, lead to the only known human disease of the de novo pyrimidine biosynthetic pathway, orotic aciduria (OMIM I and II; 14 and references contained therein).

Last updated: 2005-12-15 Contact SGD

References cited on this page View Complete Literature Guide for URA5
1) Jund R and Lacroute F  (1972) Regulation of orotidylic acid pyrophosphorylase in Saccharomyces cerevisiae. J Bacteriol 109(1):196-202
2) de Montigny J, et al.  (1990) Cloning and sequencing of URA10, a second gene encoding orotate phosphoribosyl transferase in Saccharomyces cerevisiae. Curr Genet 17(2):105-11
3) de Montigny J, et al.  (1989) Structure and expression of the URA5 gene of Saccharomyces cerevisiae. Mol Gen Genet 215(3):455-62
4) Schmidt R, et al.  (1979) Purification and characterization of the hypoxanthine-guanine phosphoribosyltransferase from Saccharomyces cerevisiae. Eur J Biochem 93(2):355-61
5) Umezu K, et al.  (1971) Purification and properties of orotidine-5'-phosphate pyrophosphorylase and orotidine-5'-phosphate decarboxylase from baker's yeast. J Biochem 70(2):249-62
6) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
7) Roy A  (1992) Nucleotide sequence of the URA1 gene of Saccharomyces cerevisiae. Gene 118(1):149-50
8) Denis-Duphil M  (1989) Pyrimidine biosynthesis in Saccharomyces cerevisiae: the ura2 cluster gene, its multifunctional enzyme product, and other structural or regulatory genes involved in de novo UMP synthesis. Biochem Cell Biol 67(9):612-31
9) Flynn PJ and Reece RJ  (1999) Activation of transcription by metabolic intermediates of the pyrimidine biosynthetic pathway. Mol Cell Biol 19(1):882-8
10) Zhang W, et al.  (2003) Microarray analyses of the metabolic responses of Saccharomyces cerevisiae to organic solvent dimethyl sulfoxide. J Ind Microbiol Biotechnol 30(1):57-69
11) Lyons TJ, et al.  (2000) Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc Natl Acad Sci U S A 97(14):7957-62
12) Santiago TC and Mamoun CB  (2003) Genome expression analysis in yeast reveals novel transcriptional regulation by inositol and choline and new regulatory functions for Opi1p, Ino2p, and Ino4p. J Biol Chem 278(40):38723-30
13) Bro C, et al.  (2003) Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells. J Biol Chem 278(34):32141-9
14) Suchi M, et al.  (1997) Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet 60(3):525-39
15) Nasr F, et al.  (1994) Heterospecific cloning of Arabidopsis thaliana cDNAs by direct complementation of pyrimidine auxotrophic mutants of Saccharomyces cerevisiae. I. Cloning and sequence analysis of two cDNAs catalysing the second, fifth and sixth steps of the de novo pyrimidine biosynthesis pathway. Mol Gen Genet 244(1):23-32