RegulonDB RegulonDB 9.4:Regulon Page

GadE DNA-binding transcriptional activator

Synonyms: GadE
The transcriptional activator GadE, for Glutamic acid decarboxylase, is positively autoregulated [1, 7]and controls the transcription of genes involved in the maintenance of pH homeostasis, including the principal acid resistance system [1, 4, 10, 11, 12, 13, 14, 15] glutamate dependent (GAD), also referred as the GAD system, and genes involved in multidrug efflux, among others [1, 5, 6, 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 [1, 4] GadE is encoded by the gadE-mdtEF operon, inducible by low pH [15] 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 [8] 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 [1, 8, 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     nd nd
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

Regulated gene(s) cyoA, cyoB, cyoC, cyoD, cyoE, fabZ, fliC, gadB, gadC, gadE, gadF, gadW, gadX, gltB, gltD, gltF, gnd, hdeA, hdeB, hdeD, lpxA, lpxD, lrp, mdtE, mdtF, purA, rcsA, skp, yhiD
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (7)
aerobic respiration (5)
pH (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
First gene in the operon(s) cyoA, fliC, gadB, gadE, gadE, gadX, gadX, gltB, gnd, hdeA, hdeD, lrp, purA, rcsA, skp
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 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 nd cyoA, cyoB, cyoC, cyoD, cyoE nd nd [GEA] [1]
  GadE activator fliCp Sigma28 nd nd fliC nd nd [GEA] [1]
  GadE activator gadBp Sigma38 -62.5 -89.5 gadB, gadC
1572125 1572144 [BPP], [GEA], [HIBSCS] [2], [3], [4], [5], [6]
  GadE activator gadEp Sigma38 -198.5 -219.5 gadE, gadF, mdtE, mdtF
3658137 3658156 [BPP], [GEA] [7]
  GadE activator gadEp Sigma38 -63.5 -84.5 gadE, gadF, mdtE, mdtF
3658272 3658291 [BPP], [GEA], [HIBSCS] [6], [7]
  GadE activator gadEp Sigma38 -30.5 -51.5 gadE, gadF, mdtE, mdtF
3658305 3658324 [BPP], [GEA] [7]
  GadE activator gadEp1 Sigma38 nd nd gadE, gadF nd nd [GEA] [8]
  GadE activator gadXp Sigma38 nd nd gadX, gadW nd nd [BPP], [GEA] [1]
  GadE activator gltBp Sigma70 nd nd gltB, gltD, gltF nd nd [BPP], [GEA] [1]
  GadE activator gndp Sigma70 nd nd gnd nd nd [GEA] [1]
  GadE activator hdeAp Sigma38 -117.5 -168.5 hdeA, hdeB, yhiD
3656899 3656918 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [3], [6], [9]
  GadE activator hdeDp Sigma70 -51.5 -86.5 hdeD
3656899 3656918 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [3], [6], [9]
  GadE activator hlpAp Sigma24 nd nd skp, lpxD, fabZ, lpxA nd nd [GEA] [1]
  GadE activator lrpp Sigma70 nd nd lrp nd nd [GEA] [1]
  GadE activator purAp Sigma70 nd nd purA nd nd [GEA] [1]
  GadE activator rcsAp Sigma70 nd nd rcsA nd nd [BPP], [GEA] [1]

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


 [GEA] Gene expression analysis

 [BPP] Binding of purified proteins

 [HIBSCS] Human inference based on similarity to consensus sequences

 [AIBSCS] Automated inference based on similarity to consensus sequences


 [1] 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

 [2] 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

 [3] 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

 [4] 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

 [5] 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

 [6] 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

 [7] 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

 [8] 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

 [9] 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

 [10] Tramonti A., De Canio M., Bossa F., De Biase D., 2003, Stability and oligomerization of recombinant GadX, a transcriptional activator of the Escherichia coli glutamate decarboxylase system., Biochim Biophys Acta. 1647(1-2):376-80

 [11] 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

 [12] Shin S., Castanie-Cornet MP., Foster JW., Crawford JA., Brinkley C., Kaper JB., 2001, An activator of glutamate decarboxylase genes regulates the expression of enteropathogenic Escherichia coli virulence genes through control of the plasmid-encoded regulator, Per., Mol Microbiol. 41(5):1133-50

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

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

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

 [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] Senda T., Ogawa N., 2005, [Structure function relationship of the LysR type transcriptional regulator], Tanpakushitsu Kakusan Koso. 50(12):1535-40

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