Disease relevance of URA2

• Alignment of the enzyme sequence derived from URA2 with sequences from Escherichia coli carA carB and yeast arginine-specific CP A1 CP A2 indicates that monofunctional and bifunctional carbamoyl phosphate synthetases are probably homologous [1].

High impact information on URA2

• In a ura2 strain transformed by nonintegrated pFL1 plasmids bearing the URA2-ATCase activity encoding gene, the lead phosphate precipitate was observed predominantly in the cytoplasm [2].
• We have constructed viable Saccharomyces cerevisiae strains containing a reciprocal translocation between the URA2 site of chromosome X and the HIS3 site of chromosome XV [3].
• Third, after several generations of growth on uracil-supplemented medium, ura2+ colonies were selected which resulted from mitotic recombination between the nonoverlapping deletions of URA2 located on chromosomes X and XV [3].
• The first two steps of the de novo pyrimidine biosynthetic pathway in Saccharomyces cerevisiae are catalyzed by a 240-kDa bifunctional protein encoded by the ura2 locus [4].
• However, the pyrABCN gene apparently contains an evolutionary remnant of a DHOase-encoding sequence, similarly to the Ura2 gene of Saccharomyces cerevisiae [5].

Biological context of URA2

• Second, part of the coding sequence of the wild-type URA2 gene (without promotor) was inserted at the HIS3 locus of the ura2- strain [3].
• The sequence encodes the 5' coding region of the URA2 gene and 18 open reading frames of at least 100 amino acids [6].
• Expression is initiated by a sequence located in the delta element of the Tyl and not by a sequence of the URA2 gene itself [7].
• This unusual type of Ty-mediated gene activation is possible as the URA2 gene product is a multifunctional protein containing the carbamoyl phosphate synthetase (CPSase), the ATCase and a cryptic dihydroorotase (DHOase) domain [7].
• 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 [8].

Anatomical context of URA2

• All three approaches localize the bulk of Ura2 to the cytoplasm, whereas the signals associated with the nucleus, mitochondria or vacuoles are close to or at the background level [9].
• Enzymatic activities of Ura2 and Ura1 proteins (aspartate carbamoyltransferase and dihydro-orotate dehydrogenase) are present in both isolated membranes and cytoplasm of Saccharomyces cerevisiae [10].

Associations of URA2 with chemical compounds

• Gene ura2 codes for a multifunctional protein that carries the first two enzymatic activities of the pathway, i.e., carbamylphosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase) [8].
• Proteolytically induced changes in the molecular form of the carbamyl phosphate synthetase-uracil-aspartate transcarbamylase complex coded for by the URA2 locus in Saccharomyces cerevisiae [11].
• An excess of the final product, the intracellular UTP (uridine triphosphate), inhibits both the transcription of the URA2 gene and the enzymatic activities [12].
• We also enlarged the collection of ura2 point mutations by using a positive selection method based on resistance to the toxic accumulation of ureidosuccinic acid (USA) [13].
• Computational analysis predicted three potential hydrophobic transmembrane alpha-helices within the Ura2 multidomain protein of Saccharomyces cerevisiae, the C-terminal subdomain of which catalyses the second step of uridine-monophosphate biosynthesis by its L-aspartate carbamoyltransferase activity (EC 2.1.3.2) [10].

Other interactions of URA2

• Its organization and regulation indicate that the S. pombe URA1 gene product appears very similar to the S. cerevisiae URA2 gene product [14].
• Genetic mapping confirms that the MRS3 gene is 2 cM distal to the URA2 gene on the right arm of chromosome X [15].

Analytical, diagnostic and therapeutic context of URA2

• 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 [9].

References