ADE4/YMR300C Summary Help

Standard Name ADE4 1
Systematic Name YMR300C
Feature Type ORF, Verified
Description Phosphoribosylpyrophosphate amidotransferase (PRPPAT; amidophosphoribosyltransferase), catalyzes first step of the 'de novo' purine nucleotide biosynthetic pathway (2, 3 and see Summary Paragraph)
Name Description ADEnine requiring
Chromosomal Location
ChrXIII:867091 to 865559 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 213 cM
Gene Ontology Annotations All ADE4 GO evidence and references
  View Computational GO annotations for ADE4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Pathways
Mutant phenotypes All ADE4 Phenotype evidence and references
Classical genetics
activation
null
overexpression
Large-scale survey
null
Resources
interactions All ADE4 Interaction evidence and references
43 total interaction(s) for 33 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 2
  • PCA: 4
  • Two-hybrid: 1
Genetic Interactions
  • Dosage Lethality: 3
  • Negative Genetic: 14
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 2
  • Positive Genetic: 2
  • Synthetic Growth Defect: 3
  • Synthetic Rescue: 2
Resources
Expression Summary
histogram
Resources
Protein Information All ADE4 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:867091 to 865559 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 213 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..1533 867091..865559 2011-02-03 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 SGDIDS000004915
SUMMARY PARAGRAPH for ADE4

ADE4 encodes 5-phosphoribosyl-1-pyrophosphate amidotransferase (EC 2.4.2.14), also known as amidophosphoribosyltransferase or PRPPAT (phosphoribosylpyrophosphate amidotransferase), which catalyzes the first step of the de novo purine nucleotide biosynthetic pathway (4, 5). Expression of ADE4, and of other genes in the yeast ADE regulon, is repressed by the presence of purine bases and derepressed in the absence of purines through the action of transcription factors such as Bas1p, Pho2p, and Gcn4p (6, 7). Bas1p binds several ADE promoters (ADE1, ADE2, ADE4, and ADE5,7) and DNA-bound Bas1p recruits Pho2p to activate ADE genes in S. cerevisiae (6). Gcn4p also regulates the expression of these genes (8). There are three Gcn4p responsive elements (GCREs) in the 5'-flanking region of ADE4 (9). Two GCREs are essential to synergistically activate ADE4 transcription by binding Gcn4p (9). The distal GCRE1 is also required for basal transcription of ADE4 (9). Ade4p forms cytoplasmic foci in the absence of adenine, and cycling between punctate and diffuse cellular distribution can be controlled by adenine subtraction and addition (10).

ade4 null mutants exhibit adenine auxotrophy, decreased resistance to ethanol, and slow growth (11, 12, 13). Cisplatin resistance is conferred either by an ADE4 activation mutation, which causes constitutive AMP synthesis and hypoxanthine excretion, or by overexpression of ADE4, which increases de novo synthesis of purine nucleotides (14). Mutations in ADE4 are epistatic with mutations in ADE2, which encodes encodes aminoimidazole ribonucleotide-carboxylase (AIR-carboxylase), an enzyme catalyzing the sixth step of purine nucleotide biosynthesis (15), and with mutations in ADE13, which encodes adenylosuccinate lyase, an enzyme catalyzing steps 8 and 12 of the de novo purine pathway (16).

Orthologs of Ade4p have been identified in Bacillus subtilis, Escherichia coli, Ashbya gossypii, Schizosaccharomyces pombe, Gallus gallus, Rattus rattus, and Homo sapiens (1, 7, 17, 18, 19). The human PRPPAT cDNA complements the S. cerevisiae ade4 null mutant (20).

Last updated: 2010-06-18

References cited on this page View Complete Literature Guide for ADE4
1) Mantsala P and Zalkin H  (1984) Glutamine nucleotide sequence of Saccharomyces cerevisiae ADE4 encoding phosphoribosylpyrophosphate amidotransferase. J Biol Chem 259(13):8478-84
2) Nieto DJ and Woods RA  (1983) Studies on mutants affecting amidophosphoribosyltransferase activity in Saccharomyces cerevisiae. Can J Microbiol 29(6):681-8
3) Jones EW and Fink GR  (1982) "Regulation of amino acid and nucleotide biosynthesis in yeast." Pp.181-299 in The Molecular Biology of the Yeast Saccharomyces: Metabolism and Gene Expression, edited by Strathern JN, Jones EW and Broach JR. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
4) Woods RA, et al.  (1983) Hypoxanthine: guanine phosphoribosyltransferase mutants in Saccharomyces cerevisiae. Mol Gen Genet 191(3):407-12
5) Smolina VS and Bekker ML  (1982) [Properties of 5-phosphoryl-1-pyrophosphate amidotransferase from the yeast Saccharomyces cerevisiae wild type and mutant with altered purine biosynthesis regulation] Biokhimiia 47(1):162-7
6) Som I, et al.  (2005) DNA-bound Bas1 recruits Pho2 to activate ADE genes in Saccharomyces cerevisiae. Eukaryot Cell 4(10):1725-35
7) Ludin KM, et al.  (1994) The ade4 gene of Schizosaccharomyces pombe: cloning, sequence and regulation. Curr Genet 25(5):465-8
8) Rolfes RJ and Hinnebusch AG  (1993) Translation of the yeast transcriptional activator GCN4 is stimulated by purine limitation: implications for activation of the protein kinase GCN2. Mol Cell Biol 13(8):5099-111
9) Mosch HU, et al.  (1991) Transcriptional activation of yeast nucleotide biosynthetic gene ADE4 by GCN4. J Biol Chem 266(30):20453-6
10) Narayanaswamy R, et al.  (2009) Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation. Proc Natl Acad Sci U S A 106(25):10147-52
11) Roberts RL, et al.  (2003) Purine synthesis and increased Agrobacterium tumefaciens transformation of yeast and plants. Proc Natl Acad Sci U S A 100(11):6634-9
12) Yoshikawa K, et al.  (2009) Comprehensive phenotypic analysis for identification of genes affecting growth under ethanol stress in Saccharomyces cerevisiae. FEMS Yeast Res 9(1):32-44
13) Li Z, et al.  (2009) Rational extension of the ribosome biogenesis pathway using network-guided genetics. PLoS Biol 7(10):e1000213
14) Kowalski D, et al.  (2008) Dysregulation of Purine Nucleotide Biosynthesis Pathways Modulates Cisplatin Cytotoxicity in Saccharomyces cerevisiae. Mol Pharmacol 74(4):1092-100
15) Zekhnov AM, et al.  (1998) [New phenotypic manifestation of the ad2 mutation in Saccharomyces cerevisiae yeast--the inability to grow on a synthetic medium with glycerol and hypoxanthine] Genetika 34(2):190-7
16) Zekhnov AM, et al.  (1995) [Mutation of ade13-1 of the yeast Saccharomyces cerevisiae leads to the absence of growth on a complete medium with glucose and epistatically interacts with mutations in other genes for purine biosynthesis] Genetika 31(1):15-23
17) Iwahana H, et al.  (1993) Molecular cloning of human amidophosphoribosyltransferase. Biochem Biophys Res Commun 190(1):192-200
18) Iwahana H, et al.  (1993) Molecular cloning of rat amidophosphoribosyltransferase. J Biol Chem 268(10):7225-37
19) Mateos L, et al.  (2006) Purine biosynthesis, riboflavin production, and trophic-phase span are controlled by a Myb-related transcription factor in the fungus Ashbya gossypii. Appl Environ Microbiol 72(7):5052-60
20) Barton JW, et al.  (1991) Isolation of a human cDNA encoding amidophosphoribosyltransferase and functional complementation of a CHO Ade-A mutant deficient in this activity. Somat Cell Mol Genet 17(3):311-22