URA8/YJR103W Summary Help

Standard Name URA8 1
Systematic Name YJR103W
Feature Type ORF, Verified
Description Minor CTP synthase isozyme (see also URA7); catalyzes the ATP-dependent transfer of the amide nitrogen from glutamine to UTP, forming CTP, the final step in de novo biosynthesis of pyrimidines; involved in phospholipid biosynthesis; capable of forming cytoplasmic filaments termed cytoophidium, especially during conditions of glucose depletion; URA8 has a paralog, URA7, that arose from the whole genome duplication (1, 2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description URAcil requiring 1
Chromosomal Location
ChrX:620754 to 622490 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All URA8 GO evidence and references
  View Computational GO annotations for URA8
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
Resources
53 total interaction(s) for 34 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 5
  • Affinity Capture-RNA: 3
  • Biochemical Activity: 2
  • Co-localization: 1
  • Co-purification: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 3

Genetic Interactions
  • Negative Genetic: 30
  • Positive Genetic: 3
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 578
Molecular Weight (Da) 64,510
Isoelectric Point (pI) 5.39
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrX:620754 to 622490 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 2011-02-03
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1737 620754..622490 2011-02-03 2011-02-03
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 SGDIDS000003864
SUMMARY PARAGRAPH for URA8

URA7 and URA8 encode CTP synthetase, the enzyme that catalyzes the ATP-dependent conversion of UTP to CTP (7, 1). This final step in the pathway of CTP biosynthesis, shown here, is important for balancing nucleotide pools and also for synthesizing membrane phospholipids (7, 1, 3). The two CTP synthetases, Ura7p and Ura8p, share 78% amino acid identity and are functionally overlapping (1). Null mutations in either gene decrease intracellular levels of CTP, leading to a reduced growth rate, while deletion of both gene products results in lethality (7, 1). While both URA7 and URA8 are maximally expressed during exponential growth, overall expression of URA7 is two-fold higher than that of URA8 (2). Ura7p is also responsible for the majority of CTP synthesis (78%; 1) and the difference in activity between the two isoforms is due to differential regulation in addition to their differential expression.

Both CTP synthetases are allosterically regulated by their substrates, ATP and UTP, and their product, CTP. The presence of UTP and ATP cause the inactive homodimer form of the CTP synthetase to oligomerize to an active tetrameric form. The Ura7p CTP synthetase exhibits positive cooperative kinetics with respect to UTP and ATP, but the Ura8p isoform requires the additional presence of CTP for positive substrate cooperativity. CTP is a negative regulator of CTP synthetase, inhibiting enzyme activity by increasing the positive cooperativity of the protein for UTP; Ura8p is more sensitive than Ura7p to CTP inhibition (8, 2).

Mammalian cell lines mutant in CTP synthetase have abnormally high intracellular levels of CTP and dCTP and an increased rate of spontaneous mutation (see 9 and references contained therein). Like S. cerevisiae, humans also have two CTP synthetases, CTPS1 (OMIM) and CTPS2 (OMIM), and increased enzyme activity has been found in several human tumor types (10 and references contained therein).

Last updated: 2006-01-24 Contact SGD

References cited on this page View Complete Literature Guide for URA8
1) Ozier-Kalogeropoulos O, et al.  (1994) Use of synthetic lethal mutants to clone and characterize a novel CTP synthetase gene in Saccharomyces cerevisiae. Mol Gen Genet 242(4):431-9
2) Nadkarni AK, et al.  (1995) Differential biochemical regulation of the URA7- and URA8-encoded CTP synthetases from Saccharomyces cerevisiae. J Biol Chem 270(42):24982-8
3) Ostrander DB, et al.  (1998) Effect of CTP synthetase regulation by CTP on phospholipid synthesis in Saccharomyces cerevisiae. J Biol Chem 273(30):18992-9001
4) McDonough VM, et al.  (1995) Regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by CTP. J Biol Chem 270(32):18774-80
5) 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
6) Noree C, et al.  (2010) Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster. J Cell Biol 190(4):541-51
7) Ozier-Kalogeropoulos O, et al.  (1991) Cloning, sequencing and characterization of the Saccharomyces cerevisiae URA7 gene encoding CTP synthetase. Mol Gen Genet 231(1):7-16
8) Yang WL, et al.  (1994) Purification and characterization of CTP synthetase, the product of the URA7 gene in Saccharomyces cerevisiae. Biochemistry 33(35):10785-93
9) Yang WL, et al.  (1996) Regulation of yeast CTP synthetase activity by protein kinase C. J Biol Chem 271(19):11113-9
10) Han GS, et al.  (2005) Expression of Human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A. J Biol Chem 280(46):38328-36