URA2/YJL130C Summary Help

Standard Name URA2 1
Systematic Name YJL130C
Feature Type ORF, Verified
Description Bifunctional carbamoylphosphate synthetase/aspartate transcarbamylase; catalyzes the first two enzymatic steps in the de novo biosynthesis of pyrimidines; both activities are subject to feedback inhibition by UTP (1, 2, 3, 4, 5 and see Summary Paragraph)
Name Description URAcil requiring 6, 7
Chromosomal Location
ChrX:172367 to 165723 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -89 cM
Gene Ontology Annotations All URA2 GO evidence and references
  View Computational GO annotations for URA2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Classical genetics
Large-scale survey
137 total interaction(s) for 124 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 76
  • Affinity Capture-RNA: 6
  • Co-purification: 1
  • PCA: 1

Genetic Interactions
  • Negative Genetic: 35
  • Positive Genetic: 13
  • Synthetic Growth Defect: 2
  • Synthetic Rescue: 3

Expression Summary
Length (a.a.) 2,214
Molecular Weight (Da) 245,040
Isoelectric Point (pI) 5.6
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrX:172367 to 165723 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -89 cM
Last Update Coordinates: 2011-02-03 | Sequence: 2011-02-03
Subfeature details
Most Recent Updates
Coordinates Sequence
5' UTR intron -385..-66 172752..172433 2011-02-03 2007-04-04
CDS 1..6645 172367..165723 2011-02-03 2011-02-03
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003666

URA2 encodes a bifunctional protein, comprised of an N-terminal carbamoyl phosphate synthetase domain (CPSase) and a C-terminal aspartate transcarbamoylase (ATCase) domain, that catalyzes the first two steps of de novo synthesis of pyrimidine ribonucleotides (shown here; 6, reviewed in 4). The Ura2p CPSase domain converts glutamine to carbamoyl-phosphate, then this intermediate is sequestered and channeled to the ATCase active site where it is synthesized into carbamoyl-aspartate (ureidosuccinate) (2). Linking these two domains is a region with similarity to dihydroorotase (DHOase), the enzyme that catalyzes the third reaction of the pyrimidine biosynthesis pathway (8). In S. cerevisiae this DHOase-like domain is non-functional, but in the mammalian homolog of Ura2p, CAD (OMIM), this domain is enzymatically active (8, reviewed in 4). Because Ura2p is integral in regulating the de novo synthesis of pyrimidine nucleotides and this process important in cancer cell metabolism, the regulation and function of CAD has been studied in the context of improving chemotheraputic strategies (9 and references contained therein).

The final product of this pathway, UTP, represses URA2 transcription and also inhibits Ura2p enzymatic activities (1, reviewed in 4). UTP-mediated repression of URA2 transcription has been shown to have less of an effect on pathway regulation than feedback inhibition of Ura2p (10). During protein regulation, UTP binds to a site in the CPSase domain, directly inhibiting CPSase activity. In contrast, the ATCase domain contains no UTP binding site and repression of ATCase is dependent upon the presence of the CPSase domain, suggesting that the mechanism of regulation is different for the two domains (3).

Last updated: 2005-12-16 Contact SGD

References cited on this page View Complete Literature Guide for URA2
1) Lacroute F  (1968) Regulation of pyrimidine biosynthesis in Saccharomyces cerevisiae. J Bacteriol 95(3):824-32
2) Serre V, et al.  (1999) Half of Saccharomyces cerevisiae carbamoyl phosphate synthetase produces and channels carbamoyl phosphate to the fused aspartate transcarbamoylase domain. J Biol Chem 274(34):23794-801
3) Antonelli R, et al.  (1998) Carbamyl-phosphate synthetase domain of the yeast multifunctional protein Ura2 is necessary for aspartate transcarbamylase inhibition by UTP. FEBS Lett 422(2):170-4
4) 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
5) Lue PF and Kaplan JG  (1969) The aspartate transcarbamylase and carbamoyl phosphate synthetase of yeast: a multi-functional enzyme complex. Biochem Biophys Res Commun 34(4):426-33
6) Souciet JL, et al.  (1982) Cloning and restriction mapping of the yeast URA2 gene coding for the carbamyl phosphate synthetase aspartate-transcarbamylase complex. Mol Gen Genet 186(3):385-90
7) Souciet JL, et al.  (1987) Nucleotide sequence of the pyrimidine specific carbamoyl phosphate synthetase, a part of the yeast multifunctional protein encoded by the URA2 gene. Mol Gen Genet 207(2-3):314-9
8) Souciet JL, et al.  (1989) Organization of the yeast URA2 gene: identification of a defective dihydroorotase-like domain in the multifunctional carbamoylphosphate synthetase-aspartate transcarbamylase complex. Gene 79(1):59-70
9) Benoist P, et al.  (2000) The yeast Ura2 protein that catalyses the first two steps of pyrimidines biosynthesis accumulates not in the nucleus but in the cytoplasm, as shown by immunocytochemistry and Ura2-green fluorescent protein mapping. Yeast 16(14):1299-312
10) Potier S, et al.  (1990) Studies on transcription of the yeast URA2 gene. FEMS Microbiol Lett 60(1-2):215-9