ZWF1/YNL241C Summary Help

Standard Name ZWF1 1
Systematic Name YNL241C
Alias MET19 2 , POS10
Feature Type ORF, Verified
Description Glucose-6-phosphate dehydrogenase (G6PD); catalyzes the first step of the pentose phosphate pathway; involved in adapting to oxidative stress; homolog of the human G6PD which is deficient in patients with hemolytic anemia; protein abundance increases in response to DNA replication stress (1, 3, 4, 5, 6 and see Summary Paragraph)
Name Description ZWischenFerment 1
Chromosomal Location
ChrXIV:197943 to 196426 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: -153 cM
Gene Ontology Annotations All ZWF1 GO evidence and references
  View Computational GO annotations for ZWF1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 16 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
Resources
53 total interaction(s) for 41 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 5
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 1
  • Co-fractionation: 1
  • Co-purification: 1

Genetic Interactions
  • Dosage Rescue: 2
  • Negative Genetic: 8
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 2
  • Positive Genetic: 2
  • Synthetic Growth Defect: 11
  • Synthetic Lethality: 13
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 505
Molecular Weight (Da) 57,521
Isoelectric Point (pI) 6.24
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIV:197943 to 196426 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: -153 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1518 197943..196426 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 SGDIDS000005185
SUMMARY PARAGRAPH for ZWF1

Zwf1p is a cytoplasmic glucose-6-phosphate dehydrogenase (EC 1.1.1.49) that catalyzes the first step, which is irreversible and rate-limiting, of the pentose phosphate pathway (7, 8, 1, 9), which regenerates NADPH from NADP+ through an oxidation/reduction reaction. Zwf1p is important for maintaining cytosolic levels of NADPH but has little effect on mitochondrial levels (5, 10). Zwf1p is also involved in protecting yeast against oxidative stress (11, 12). Although Zwf1p expression in yeast is essentially constitutive (13), Zwf1p activity is inhibited by NADPH such that processes that decrease the cytosolic levels of NADPH stimulate the oxidative branch of the pentose phosphate pathway (14).

Null mutants in zwf1 are viable (1), but display decreased sporulation (15), reduced aerobic growth on medium lacking lysine (16), increased sensitivity to oxidative stress (hydrogen peroxide) (17, 18, 12, 19), and increased sensitivity to the fermentation inhibitor furfural (20). Null mutants require an organic sulfur source (methionine, S-adenosylmethionine, cysteine, glutathione or homocysteine) (21) and display methionine auxotrophy when grown on glucose (17, 22, 23, 19). Double null mutants in ald6 and zwf1 are inviable under standard conditions (glucose-containing medium; 22) but may be isolated and propagated on nonfermentable carbon sources (13), and idp2 zwf1 double nulls exhibit a rapid loss of viability when transferred to medium containing oleate as the carbon source (23).

Zwf1p is of industrial interest because its deletion from recombinant Saccharomyces cerevisiae strains engineered to ferment xylose to ethanol (24) results in increased ethanol production and decreased xylitol production (25, 26). Zwf1p also influences sensitivity to furfural, which is an inhibitory byproduct of xylose fermentation (20). Zwf1p is of medical interest because of its homology to human glucose-6-phosphate dehydrogenase (G6PD), which is highly polymorphic with over 130 mutations identified thus far. Complete loss of G6PD in humans is fatal, while partial loss of function can result in neonatal jaundice and hemolytic anemia (4, 27). Zwf1p also displays similarity to the glucose-6-phosphate dehydrogenase proteins in Drosophila and rats (1, 28, 4).

Last updated: 2007-11-07 Contact SGD

References cited on this page View Complete Literature Guide for ZWF1
1) Nogae I and Johnston M  (1990) Isolation and characterization of the ZWF1 gene of Saccharomyces cerevisiae, encoding glucose-6-phosphate dehydrogenase. Gene 96(2):161-9
2) Masselot M and De Robichon-Szulmajster H  (1975) Methionine biosynthesis in Saccharomyces cerevisiae. I. Genetical analysis of auxotrophic mutants. Mol Gen Genet 139(2):121-32
3) Izawa S, et al.  (1998) Importance of glucose-6-phosphate dehydrogenase in the adaptive response to hydrogen peroxide in Saccharomyces cerevisiae. Biochem J 330 ( Pt 2)():811-7
4) Grabowska D, et al.  (2004) A novel mutation in the glucose-6-phosphate dehydrogenase gene in a subject with chronic nonspherocytic hemolytic anemia--characterization of enzyme using yeast expression system and molecular modeling. Blood Cells Mol Dis 32(1):124-30
5) Blank LM, et al.  (2005) Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast. Genome Biol 6(6):R49
6) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
7) Kumar A, et al.  (2002) Subcellular localization of the yeast proteome. Genes Dev 16(6):707-19
8) Huh WK, et al.  (2003) Global analysis of protein localization in budding yeast. Nature 425(6959):686-91
9) Jarori GK and Maitra PK  (1991) Nature of primary product(s) of D-glucose 6-phosphate dehydrogenase reaction. 13C and 31P NMR study. FEBS Lett 278(2):247-51
10) Outten CE and Culotta VC  (2003) A novel NADH kinase is the mitochondrial source of NADPH in Saccharomyces cerevisiae. EMBO J 22(9):2015-24
11) Juhnke H, et al.  (1996) Mutants that show increased sensitivity to hydrogen peroxide reveal an important role for the pentose phosphate pathway in protection of yeast against oxidative stress. Mol Gen Genet 252(4):456-64
12) Lee J, et al.  (1999) Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem 274(23):16040-6
13) Minard KI and McAlister-Henn L  (2005) Sources of NADPH in yeast vary with carbon source. J Biol Chem 280(48):39890-6
14) Llobell A, et al.  (1988) Glutathione reductase directly mediates the stimulation of yeast glucose-6-phosphate dehydrogenase by GSSG. Biochem J 249(1):293-6
15) Dickinson JR and Williams AS  (1986) A genetic and biochemical analysis of the role of gluconeogenesis in sporulation of Saccharomyces cerevisiae. J Gen Microbiol 132(9):2605-10
16) Jensen LT, et al.  (2004) Mutations in Saccharomyces cerevisiae iron-sulfur cluster assembly genes and oxidative stress relevant to Cu,Zn superoxide dismutase. J Biol Chem 279(29):29938-43
17) Minard KI, et al.  (1998) Sources of NADPH and expression of mammalian NADP+-specific isocitrate dehydrogenases in Saccharomyces cerevisiae. J Biol Chem 273(47):31486-93
18) Krems B, et al.  (1995) Mutants of Saccharomyces cerevisiae sensitive to oxidative and osmotic stress. Curr Genet 27(5):427-34
19) Slekar KH, et al.  (1996) The yeast copper/zinc superoxide dismutase and the pentose phosphate pathway play overlapping roles in oxidative stress protection. J Biol Chem 271(46):28831-6
20) Gorsich SW, et al.  (2006) Tolerance to furfural-induced stress is associated with pentose phosphate pathway genes ZWF1, GND1, RPE1, and TKL1 in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 71(3):339-49
21) Thomas D, et al.  (1991) Identification of the structural gene for glucose-6-phosphate dehydrogenase in yeast. Inactivation leads to a nutritional requirement for organic sulfur. EMBO J 10(3):547-53
22) Grabowska D and Chelstowska A  (2003) The ALD6 gene product is indispensable for providing NADPH in yeast cells lacking glucose-6-phosphate dehydrogenase activity. J Biol Chem 278(16):13984-8
23) Minard KI and McAlister-Henn L  (1999) Dependence of peroxisomal beta-oxidation on cytosolic sources of NADPH. J Biol Chem 274(6):3402-6
24) Walfridsson M, et al.  (1995) Xylose-metabolizing Saccharomyces cerevisiae strains overexpressing the TKL1 and TAL1 genes encoding the pentose phosphate pathway enzymes transketolase and transaldolase. Appl Environ Microbiol 61(12):4184-90
25) Jeppsson M, et al.  (2002) Reduced oxidative pentose phosphate pathway flux in recombinant xylose-utilizing Saccharomyces cerevisiae strains improves the ethanol yield from xylose. Appl Environ Microbiol 68(4):1604-9
26) Jeppsson M, et al.  (2003) Effect of enhanced xylose reductase activity on xylose consumption and product distribution in xylose-fermenting recombinant Saccharomyces cerevisiae. FEMS Yeast Res 3(2):167-75
27) Merritt J, et al.  (2005) Parallel analysis of mutant human glucose 6-phosphate dehydrogenase in yeast using PCR colonies. Biotechnol Bioeng 92(5):519-31
28) Persson B, et al.  (1991) Functionally important regions of glucose-6-phosphate dehydrogenase defined by the Saccharomyces cerevisiae enzyme and its differences from the mammalian and insect forms. Eur J Biochem 198(2):485-91