Escherichia coli K-12 substr. MG1655 Polypeptide: GadW DNA-binding transcriptional dual regulator

Gene: gadW Accession Numbers: EG12242 (EcoCyc), b3515, ECK3499

Synonyms: yhiW

Regulation Summary Diagram: ?

Regulation summary diagram for gadW

The transcription factor GadW, for "Glutamic acid decarboxylase," is negatively autoregulated and controls the transcription of the genes involved in the principal acid resistance system, is glutamate dependent (GAD), and is also referred to as the GAD system [Ma02, Tramonti08, Tucker03, Tramonti06, Sayed07]. In addition, GadW also activates the transcription of the central activator involved in the acid response [Sayed07]. The physiological inducer is unknown. Richard et al. proposed that GadW can sense intracellular Na+ concentrations, but the mechanism is not known [Richard07].

GadW is one of the regulators in the acid resistance system and is encoded by the unusual gadXW operon, which is located in the region called the acid fitness island [Tramonti08]. This operon encodes two transcriptional regulators, GadX and GadW, both of which are members of the AraC/XylS family of transcriptional regulators [Gallegos97, Martin01, Tramonti08].

The activities of GadW and GadX are indispensable upon entry into the stationary phase in response to acid pH [Tramonti02, Ma02]. In addition, Tramonti et al. provided evidence that the transcription of the gadXW operon is regulated to a posttranscriptional level by a gadY small RNA [Tramonti08, Opdyke04].

GadW is highly homologous to GadX (42%), and apparently both are capable of cross talk to regulate expression of the genes of this system [Tramonti08]. Although little is known about the regulating mechanism of GadW, Tucker et al. proposed that this regulator and GadX have distinct molecular mechanisms [Tucker03, Tramonti06]. These regulators form homodimers [Gallegos97] and heterodimers [Ma02] in vivo.

Currently, the GadW/GadX-dependent circuit, involved in the GAD system, is under discussion and study. Tramonti et al. showed that GadX alone activates gadA and gadB promoters [Tramonti02]; Ma et al. added to this regulatory interaction with the GadW protein, showing that it inhibits GadX and that in some cases it activates in the absence of GadX [Ma02]. Trucker et al. gave evidence that GadW can work as a coactivator of GadX or it can inhibit the GadX-dependent activation; they also provided evidence of more target genes for GadX/GadW regulation [Tucker03]. Regarding these interactions, Tramonti et al. showed the direct GadX binding at promoters of the gadB (two sites) and gadA (four sites) operons [Tramonti02]; also, Ma et al. showed that GadW forms a homodimer and that it also binds to the DNA of the gadA and gadB promoters [Ma02].

As a member of the AraC/XylS family, this transcription factor is composed of two domains: the C-terminal domain (60% homologous to the C terminal of GadX), which contains two potential helix-turn-helix DNA-binding motifs in the DNA-binding region, and the amino-terminal domain (30% homologous to the N terminal of GadX), which is responsible for dimerization [Gallegos97, Gallegos93, Ma02].

Tramonti et al. speculated that GadW binds in tandem to two directed repeat sequences, in the same orientation, in the intergenic regions to activate or repress the transcription of the genes regulated [Tramonti08]. The binding targets for GadW consist of 21-nucleotide-long directed repeat sequences that possess conserved motifs, called the GAD box, which is proposed to be the binding site for GadW and GadX [Tucker03, Tucker03, Tramonti08]. This proposal was not unexpected, because the identity and similarity of the C-terminal domains are 41% and 66%, respectively [Tramonti08]. Each monomer of GadW binds to one of these conserved sequences [Tramonti08].
ArcA appears to activate gadW gene expression under anaerobiosis. A putative ArcA binding site was identified 131 bp upstream of this gene [Salmon05], but no promoter upstream of it has been identified.

Locations: cytosol

Map Position: [3,661,913 <- 3,662,641] (78.93 centisomes, 284°)
Length: 729 bp / 242 aa

Molecular Weight of Polypeptide: 28.028 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0011482 , EchoBASE:EB2153 , EcoGene:EG12242 , EcoliWiki:b3515 , ModBase:P63201 , OU-Microarray:b3515 , PortEco:gadW , PR:PRO_000022744 , Protein Model Portal:P63201 , RefSeq:NP_417972 , RegulonDB:EG12242 , SMR:P63201 , String:511145.b3515 , UniProt:P63201

Relationship Links: InterPro:IN-FAMILY:IPR009057 , InterPro:IN-FAMILY:IPR018060 , InterPro:IN-FAMILY:IPR018062 , InterPro:IN-FAMILY:IPR020449 , Pfam:IN-FAMILY:PF00165 , Prints:IN-FAMILY:PR00032 , Prosite:IN-FAMILY:PS00041 , Prosite:IN-FAMILY:PS01124 , Smart:IN-FAMILY:SM00342

In Paralogous Gene Group: 22 (29 members)

Genetic Regulation Schematic: ?

Genetic regulation schematic for gadW

GO Terms:

Biological Process: GO:0006351 - transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Sayed07]
GO:0006355 - regulation of transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Ma02]
GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Khil02]
Molecular Function: GO:0003677 - DNA binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Ma02]
GO:0003700 - sequence-specific DNA binding transcription factor activity Inferred from experiment Inferred by computational analysis [GOA01a, Ma02]
GO:0043565 - sequence-specific DNA binding Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: information transfer RNA related Transcription related
regulation type of regulation transcriptional level repressor

DNA binding site length: 20 base-pairs

Symmetry: Asymmetric

Consensus DNA Binding Sequence: atgtctgatntttatattat

Regulated Transcription Units (9 total): ?


Transcription-unit diagram

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Transcription-unit diagram

Essentiality data for gadW knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Sequence Features

Protein sequence of GadW DNA-binding transcriptional dual regulator with features indicated

Feature Class Location Citations Comment
DNA-Binding-Region 155 -> 174
UniProt: H-T-H motif; Non-Experimental Qualifier: by similarity;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

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Transcription-unit diagram


1/26/1998 (pkarp) Merged genes G7770/b3515 and EG12242/yhiW


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Gallegos93: Gallegos MT, Michan C, Ramos JL (1993). "The XylS/AraC family of regulators." Nucleic Acids Res 21(4);807-10. PMID: 8451183

Gallegos97: Gallegos MT, Schleif R, Bairoch A, Hofmann K, Ramos JL (1997). "Arac/XylS family of transcriptional regulators." Microbiol Mol Biol Rev 61(4);393-410. PMID: 9409145

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Ma02: Ma Z, Richard H, Tucker DL, Conway T, Foster JW (2002). "Collaborative regulation of Escherichia coli glutamate-dependent acid resistance by two AraC-like regulators, GadX and GadW (YhiW)." J Bacteriol 2002;184(24);7001-12. PMID: 12446650

Martin01: Martin RG, Rosner JL (2001). "The AraC transcriptional activators." Curr Opin Microbiol 4(2);132-7. PMID: 11282467

Opdyke04: Opdyke JA, Kang JG, Storz G (2004). "GadY, a small-RNA regulator of acid response genes in Escherichia coli." J Bacteriol 186(20);6698-705. PMID: 15466020

Richard07: Richard H, Foster JW (2007). "Sodium regulates Escherichia coli acid resistance, and influences GadX- and GadW-dependent activation of gadE." Microbiology 153(Pt 9);3154-61. PMID: 17768258

Salmon05: Salmon KA, Hung SP, Steffen NR, Krupp R, Baldi P, Hatfield GW, Gunsalus RP (2005). "Global gene expression profiling in Escherichia coli K12: effects of oxygen availability and ArcA." J Biol Chem 280(15);15084-96. PMID: 15699038

Sayed07: Sayed AK, Odom C, Foster JW (2007). "The Escherichia coli AraC-family regulators GadX and GadW activate gadE, the central activator of glutamate-dependent acid resistance." Microbiology 153(Pt 8);2584-92. PMID: 17660422

Tramonti02: Tramonti A, Visca P, De Canio M, Falconi M, De Biase D (2002). "Functional characterization and regulation of gadX, a gene encoding an AraC/XylS-like transcriptional activator of the Escherichia coli glutamic acid decarboxylase system." J Bacteriol 2002;184(10);2603-13. PMID: 11976288

Tramonti06: Tramonti A, De Canio M, Delany I, Scarlato V, De Biase D (2006). "Mechanisms of transcription activation exerted by GadX and GadW at the gadA and gadBC gene promoters of the glutamate-based acid resistance system in Escherichia coli." J Bacteriol 188(23);8118-27. PMID: 16980449

Tramonti08: Tramonti A, De Canio M, De Biase D (2008). "GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites." Mol Microbiol 70(4);965-82. PMID: 18808381

Tucker03: Tucker DL, Tucker N, Ma Z, Foster JW, Miranda RL, Cohen PS, Conway T (2003). "Genes of the GadX-GadW regulon in Escherichia coli." J Bacteriol 185(10);3190-201. PMID: 12730179

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Other References Related to Gene Regulation

Constantinidou06: Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW, Cole JA, Overton TW (2006). "A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth." J Biol Chem 281(8);4802-15. PMID: 16377617

Dyszel10: Dyszel JL, Soares JA, Swearingen MC, Lindsay A, Smith JN, Ahmer BM (2010). "E. coli K-12 and EHEC genes regulated by SdiA." PLoS One 5(1);e8946. PMID: 20126629

Giangrossi05: Giangrossi M, Zattoni S, Tramonti A, De Biase D, Falconi M (2005). "Antagonistic role of H-NS and GadX in the regulation of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli." J Biol Chem 280(22);21498-505. PMID: 15795232

Hommais01: Hommais F, Krin E, Laurent-Winter C, Soutourina O, Malpertuy A, Le Caer JP, Danchin A, Bertin P (2001). "Large-scale monitoring of pleiotropic regulation of gene expression by the prokaryotic nucleoid-associated protein, H-NS." Mol Microbiol 40(1);20-36. PMID: 11298273

Hommais04: Hommais F, Krin E, Coppee JY, Lacroix C, Yeramian E, Danchin A, Bertin P (2004). "GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli." Microbiology 150(Pt 1);61-72. PMID: 14702398

Johnson11: Johnson MD, Burton NA, Gutierrez B, Painter K, Lund PA (2011). "RcsB Is Required for Inducible Acid Resistance in Escherichia coli and Acts at gadE-Dependent and -Independent Promoters." J Bacteriol 193(14);3653-6. PMID: 21571995

Krin10: Krin E, Danchin A, Soutourina O (2010). "Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli." BMC Microbiol 10;273. PMID: 21034467

Marzan13: Marzan LW, Hasan CM, Shimizu K (2013). "Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant." Arch Microbiol 195(3);161-71. PMID: 23274360

Moen09: Moen B, Janbu AO, Langsrud S, Langsrud O, Hobman JL, Constantinidou C, Kohler A, Rudi K (2009). "Global responses of Escherichia coli to adverse conditions determined by microarrays and FT-IR spectroscopy." Can J Microbiol 55(6);714-28. PMID: 19767843

Opdyke11: Opdyke JA, Fozo EM, Hemm MR, Storz G (2011). "RNase III participates in GadY-dependent cleavage of the gadX-gadW mRNA." J Mol Biol 406(1);29-43. PMID: 21147125

Shimada07: Shimada T, Hirao K, Kori A, Yamamoto K, Ishihama A (2007). "RutR is the uracil/thymine-sensing master regulator of a set of genes for synthesis and degradation of pyrimidines." Mol Microbiol 66(3);744-57. PMID: 17919280

Yamanaka14: Yamanaka Y, Oshima T, Ishihama A, Yamamoto K (2014). "Characterization of the YdeO regulon in Escherichia coli." PLoS One 9(11);e111962. PMID: 25375160

Zwir05: Zwir I, Shin D, Kato A, Nishino K, Latifi T, Solomon F, Hare JM, Huang H, Groisman EA (2005). "Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica." Proc Natl Acad Sci U S A 102(8);2862-7. PMID: 15703297

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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