|Gene:||gadW||Accession Numbers: EG12242 (EcoCyc), b3515, ECK3499|
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.
|Map Position: [3,661,913 <- 3,662,641] (78.93 centisomes)||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)
|Biological Process:||GO:0006351 - transcription, DNA-templated
GO:0006355 - regulation of transcription, DNA-templated [UniProtGOA11, GOA01, Ma02]
GO:0006974 - cellular response to DNA damage stimulus [Khil02]
|Molecular Function:||GO:0003677 - DNA binding
[UniProtGOA11, GOA01, Ma02]
GO:0003700 - sequence-specific DNA binding transcription factor activity [GOA01, Ma02]
GO:0043565 - sequence-specific DNA binding [GOA01]
|Cellular Component:||GO:0032993 - protein-DNA complex
GO:0005829 - cytosol [DiazMejia09]
|MultiFun Terms:||information transfer → RNA related → Transcription related|
|regulation → type of regulation → transcriptional level → repressor|
DNA binding site length: 20 base-pairs
Consensus DNA Binding Sequence: atgtctgatntttatattat
|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]|
|DNA-Binding-Region||155 -> 174|
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
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
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
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
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
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
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
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
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
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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