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GadE DNA-binding transcriptional activator

Synonyms: GadE
The transcriptional activator GadE, for "Glutamic acid decarboxylase," is positively autoregulated [2, 12]and controls the transcription of genes involved in the maintenance of pH homeostasis, including the principal acid resistance system [2, 3, 4, 5, 7, 15] glutamate dependent (GAD), also referred as the GAD system, and genes involved in multidrug efflux, among others [2, 10, 11, 16, 17, 18] GadE also controls the expression of two transcription factors related to acid resistance, GadW and GadX, and for this reason it is considered the central activator of the acid response system [2, 3] GadE is encoded by the gadE-mdtEF operon, inducible by low pH [7] which is located in the region called the acid fitness island [17] Expression of gadE is controlled by an unusually large 798-bp upstream intergenic region, termed the sensory integration locus [13] At least six regulators related to the acid resistance system, GadE, GadX, GadW, EvgA, YdeO, and MnmE, are involved in the direct regulation of gadE [2, 13, 19] Ma et al.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
GadE Functional   [IE] [1], [2], [3], [4], [5], [6], [7]
Evolutionary Family: LuxR/UhpA
Connectivity class: Local Regulator
Gene name: gadE
  Genome position: 3658366-3658893
  Length: 528 bp / 175 aa
Operon name: gadEF-mdtEF
TU(s) encoding the TF:
Transcription unit        Promoter
Gene name: rcsB
  Genome position: 2316177-2316827
  Length: 651 bp / 216 aa
Operon name: rcsDB
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) cyoA, cyoB, cyoC, cyoD, cyoE, fabZ, fliC, gadA, gadB, gadC, gadE, gadF, gadW, gadX, gltB, gltD, gltF, gnd, hdeA, hdeB, hdeD, lpxA, lpxD, lrp, mdtE, mdtF, purA, rcsA, skp, yhiD, yhiM, yjbQ, yjbR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (7)
pH (7)
aerobic respiration (5)
Transcription related (5)
electron acceptors (4)
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Regulated operon(s) bamA-skp-lpxD-fabZ-lpxAB-rnhB-dnaE, cyoABCDE, fliC, gadAXW, gadBC, gadEF-mdtEF, gltBDF, gnd, hdeAB-yhiD, hdeD, lrp, purA, rcsA, yhiM, yjbQR
First gene in the operon(s) cyoA, fliC, gadA, gadB, gadE, gadE, gadX, gadX, gltB, gnd, hdeA, hdeD, lrp, purA, rcsA, skp, yhiM, yjbQ
Simple and complex regulons AdiY,ArgR,CRP,FNR,Fur,GadE,HdfR,IHF,Lrp,Nac
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

Transcription factor regulation    

Transcription factor binding sites (TFBSs) arrangements

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence
LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  GadE activator cyoAp Sigma70 nd 451610.0 cyoA, cyoB, cyoC, cyoD, cyoE nd nd [GEA] [2]
  GadE activator fliCp Sigma28 nd 2003606.0 fliC nd nd [GEA] [2]
  GadE activator gadAp Sigma38, Sigma70, Sigma38, Sigma70 -64.0 nd gadA, gadX 3667530 3667539 [CHIP-SV], [MSI] nd
  GadE activator gadBp Sigma38, Sigma70, Sigma38, Sigma70 -62.5 nd gadB, gadC 1572000 1572020 [CHIP-SV], [MSI] nd
  GadE activator gadBp Sigma38, Sigma70, Sigma38, Sigma70 -62.5 -89.5 gadB, gadC
1572125 1572144 [BPP], [GEA], [HIBSCS] [3], [8], [9], [10], [11]
  GadE activator gadEp Sigma38 -198.5 -219.5 gadE, gadF, mdtE, mdtF
3658137 3658156 [BPP], [GEA] [12]
  GadE activator gadEp Sigma38 -63.5 -84.5 gadE, gadF, mdtE, mdtF
3658272 3658291 [BPP], [GEA], [HIBSCS] [11], [12]
  GadE activator gadEp Sigma38 -30.5 -51.5 gadE, gadF, mdtE, mdtF
3658305 3658324 [BPP], [GEA] [12]
  GadE activator gadEp1 Sigma38 nd -3658366.0 gadE, gadF nd nd [GEA] [13]
  GadE activator gadXp Sigma38 nd 3665810.0 gadX, gadW nd nd [BPP], [GEA] [2]
  GadE activator gltBp Sigma70 -284.0 nd gltB, gltD, gltF 3354215 3354235 [CHIP-SV], [MSI] nd
  GadE activator gltBp Sigma70 nd -3354725.0 gltB, gltD, gltF nd nd [BPP], [GEA] [2]
  GadE activator gndp Sigma70 nd 2101268.0 gnd nd nd [GEA] [2]
  GadE activator hdeAp Sigma38, Sigma70, Sigma70, Sigma38 -117.5 -168.5 hdeA, hdeB, yhiD
3656899 3656918 [AIBSCS], [BPP], [GEA], [HIBSCS] [2], [9], [11], [14]
  GadE activator hdeAp Sigma38, Sigma70, Sigma70, Sigma38 9.5 nd hdeA, hdeB, yhiD 3656802 3656817 [CHIP-SV], [MSI] nd
  GadE activator hdeDp Sigma70 -54.0 nd hdeD 3656902 3656916 [CHIP-SV], [MSI] nd
  GadE activator hdeDp Sigma70 -51.5 -86.5 hdeD
3656899 3656918 [AIBSCS], [BPP], [GEA], [HIBSCS] [2], [9], [11], [14]
  GadE activator hlpAp Sigma24 nd -200482.0 skp, lpxD, fabZ, lpxA nd nd [GEA] [2]
  GadE activator lrpp Sigma70 nd -932595.0 lrp nd nd [GEA] [2]
  GadE activator purAp Sigma70 nd -4404687.0 purA nd nd [GEA] [2]
  GadE activator rcsAp Sigma70 nd -2023968.0 rcsA nd nd [BPP], [GEA] [2]
  GadE activator yhiMp Sigma38 -78.5 nd yhiM 3634655 3634675 [CHIP-SV], [MSI] nd
  GadE activator yjbQp nd -40.0 nd yjbQ, yjbR 4270164 4270184 [CHIP-SV], [MSI] nd

Alignment and PSSM for GadE TFBSs    

Position weight matrix (PWM).   
A	4	0	0	3	1	1	1	2	2	3	0	5	1	0	2	5	5	2
C	0	1	1	0	0	0	0	1	0	0	0	0	0	1	0	0	0	2
G	1	4	4	0	0	2	0	0	1	0	0	0	1	0	2	0	0	0
T	0	0	0	2	4	2	4	2	2	2	5	0	3	4	1	0	0	1

PWM logo   


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


 [IE] Inferred from experiment

 [GEA] Gene expression analysis

 [CHIP-SV] ChIP analysis and statistical validation of TFBSs

 [MSI] Mapping of signal intensities

 [BPP] Binding of purified proteins

 [HIBSCS] Human inference based on similarity to consensus sequences

 [AIBSCS] Automated inference based on similarity to consensus sequences


 [1] Bordi C., Theraulaz L., Mejean V., Jourlin-Castelli C., 2003, Anticipating an alkaline stress through the Tor phosphorelay system in Escherichia coli., Mol Microbiol 48(1):211-23

 [2] 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

 [3] Ma Z., Gong S., Richard H., Tucker DL., Conway T., Foster JW., 2003, GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12., Mol Microbiol 49(5):1309-20

 [4] Masuda N., Church GM., 2002, Escherichia coli gene expression responsive to levels of the response regulator EvgA., J Bacteriol 184(22):6225-34

 [5] Masuda N., Church GM., 2003, Regulatory network of acid resistance genes in Escherichia coli., Mol Microbiol 48(3):699-712

 [6] Tatsuno I., Nagano K., Taguchi K., Rong L., Mori H., Sasakawa C., 2003, Increased adherence to Caco-2 cells caused by disruption of the yhiE and yhiF genes in enterohemorrhagic Escherichia coli O157:H7., Infect Immun 71(5):2598-606

 [7] Tucker DL., Tucker N., Conway T., 2002, Gene expression profiling of the pH response in Escherichia coli., J Bacteriol 184(23):6551-8

 [8] Castanie-Cornet MP., Foster JW., 2001, Escherichia coli acid resistance: cAMP receptor protein and a 20 bp cis-acting sequence control pH and stationary phase expression of the gadA and gadBC glutamate decarboxylase genes., Microbiology 147(Pt 3):709-15

 [9] Itou J., Eguchi Y., Utsumi R., 2009, Molecular mechanism of transcriptional cascade initiated by the EvgS/EvgA system in Escherichia coli K-12., Biosci Biotechnol Biochem 73(4):870-8

 [10] 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

 [11] 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

 [12] Ma Z., Masuda N., Foster JW., 2004, Characterization of EvgAS-YdeO-GadE branched regulatory circuit governing glutamate-dependent acid resistance in Escherichia coli., J Bacteriol 186(21):7378-89

 [13] Sayed AK., Foster JW., 2009, A 750 bp sensory integration region directs global control of the Escherichia coli GadE acid resistance regulator., Mol Microbiol 71(6):1435-50

 [14] Ruiz C., McMurry LM., Levy SB., 2008, Role of the multidrug resistance regulator MarA in global regulation of the hdeAB acid resistance operon in Escherichia coli., J Bacteriol 190(4):1290-7

 [15] 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 184(10):2603-13

 [16] 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 184(24):7001-12

 [17] 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

 [18] Nishino K., Senda Y., Yamaguchi A., 2008, The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes., J Infect Chemother 14(1):23-9

 [19] 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

 [20] Schell MA., 1993, Molecular biology of the LysR family of transcriptional regulators., Annu Rev Microbiol 47:597-626