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GadE DNA-binding transcriptional activator

Synonyms: GadE
Summary:
The transcriptional activator GadE, for "Glutamic acid decarboxylase," is positively autoregulated [1, 9]and controls the transcription of genes involved in the maintenance of pH homeostasis, including the principal acid resistance system [1, 4, 11, 12, 13, 14, 15, 16] glutamate dependent (GAD), also referred as the GAD system, and genes involved in multidrug efflux, among others [1, 6, 7, 17, 18, 19] 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 [16] which is located in the region called the acid fitness island [18] 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, 20] Ma et al.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
GadE Functional   nd nd nd
Evolutionary Family: LuxR/UhpA
TFBs length: 20
TFBs symmetry: asymmetric
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
gadE-mdtEF
gadEp4
gadEF
gadEp1
gadEF
gadEp3
gadEF-mdtEF
gadEp2


Regulon       
Regulated gene(s) cyoA, cyoB, cyoC, cyoD, cyoE, fabZ, fliC, fliX, 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 (6)
aerobic respiration (5)
Transcription related (5)
electron acceptors (4)
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Regulated operon(s) bamA-skp-lpxD-fabZ-lpxAB-rnhB-dnaE, cyoABCDE, fliCX, gadAXW, gadBC, gadEF-mdtEF, gltBDF, gnd, hdeAB-yhiD, hdeD, lrp, purA, rcsA, yhiM, yjbQR
First gene in the operon(s) cyoA, fliC, gadB, gadE, gadX, gltB, gnd, hdeA, hdeD, skp, lrp, purA, rcsA, yhiM, yjbQ
Simple and complex regulons AdiY,ArgR,CRP,FNR,Fur,GadE,HdfR,IHF,Lrp,Nac
AdiY,CRP,Fis,FliZ,GadE,GadW,GadX,RcsB
ArcA,CRP,Cra,CusR,FNR,Fis,Fur,GadE,HprR,PdhR
ArcA,GadE,PhoP
CRP,EvgA,FliZ,GadE,GadW,GadX,H-NS,YdeO
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[GadE,+](26)


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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  GadE activator cyoAp Sigma70 nd nd cyoA, cyoB, cyoC, cyoD, cyoE
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [1]
  GadE activator fliCp Sigma28 nd nd fliC, fliX
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [1], [1]
  GadE activator gadBp Sigma70 -62.5 -89.5 gadB, gadC
ataaataacaTTAGGATTTTGTTATTTAAAcacgagtcct
 1572125 1572144 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [2], [3], [3], [4], [4], [5], [5], [6], [7]
  GadE activator gadBp2 Sigma38 -62.5 -89.5 gadB, gadC
ataaataacaTTAGGATTTTGTTATTTAAAcacgagtcct
 1572125 1572144 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [2], [3], [3], [4], [4], [5], [5], [6], [7]
  GadE activator gadEp1 Sigma38 nd nd gadE, gadF
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [8]
  GadE activator gadEp2 Sigma38 -198.5 -219.5 gadE, gadF, mdtE, mdtF
caaacgttaaCTTTTTGTTTGCTATTTACAagctgataac
 3658137 3658156 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [9], [9]
  GadE activator gadEp2 Sigma38 -63.5 -84.5 gadE, gadF, mdtE, mdtF
taaagttcttATAGGCGTTTACTATATTGAacaacgattc
 3658272 3658291 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [7], [9], [9]
  GadE activator gadEp2 Sigma38 -30.5 -51.5 gadE, gadF, mdtE, mdtF
acgattcggaCAAGGATGTAAATAATGAAAaggatgacat
 3658305 3658324 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [9], [9]
  GadE activator gadXp Sigma38 nd nd gadX, gadW
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  GadE activator gltBp Sigma70 -284.0 -500.0 gltB, gltD, gltF
gcttatcttgTGTCAGATTTTTTTATCTCCtgatggattt
 3354215 3354234 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-HINF], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [5], [5]
  GadE activator gltBp2 Sigma38 -284.0 -500.0 gltB, gltD, gltF
gcttatcttgTGTCAGATTTTTTTATCTCCtgatggattt
 3354215 3354234 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-HINF], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [5], [5]
  GadE activator gndp Sigma70 nd nd gnd
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [1]
  GadE activator hdeAp Sigma70 -117.5 -168.5 hdeA, hdeB, yhiD
aatgcagtcgATTTAATAAAAATTTCCTAAttgcagtatc
 3656899 3656918 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [3], [5], [5], [7], [10], [10]
  GadE activator hdeAp Sigma70 9.5 -42.5 hdeA, hdeB, yhiD
ataacctcagTGTCGAAATTGATTCGTGACggctctttca
 3656773 3656792 [EXP-IEP-RNA-SEQ], [COMP-HINF], [EXP-CHIP-EXO-MANUAL] S [5], [5]
  GadE activator hdeAp2 Sigma38 -117.5 -168.5 hdeA, hdeB, yhiD
aatgcagtcgATTTAATAAAAATTTCCTAAttgcagtatc
 3656899 3656918 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [3], [5], [5], [7], [10], [10]
  GadE activator hdeAp2 Sigma38 9.5 -42.5 hdeA, hdeB, yhiD
ataacctcagTGTCGAAATTGATTCGTGACggctctttca
 3656773 3656792 [EXP-IEP-RNA-SEQ], [COMP-HINF], [EXP-CHIP-EXO-MANUAL] S [5], [5]
  GadE activator hdeDp Sigma70 -51.5 -86.5 hdeD
gatactgcaaTTAGGAAATTTTTATTAAATcgactgcatt
 3656899 3656918 [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [3], [5], [5], [7], [10], [10]
  GadE activator hdeDp2 Sigma38 -51.5 -86.5 hdeD
gatactgcaaTTAGGAAATTTTTATTAAATcgactgcatt
 3656899 3656918 [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IEP-RNA-SEQ], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO-MANUAL], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [3], [5], [5], [7], [10], [10]
  GadE activator hlpAp Sigma24 nd nd skp, lpxD, fabZ, lpxA
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [1]
  GadE activator lrpp Sigma70 nd nd lrp
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [1], [1]
  GadE activator purAp Sigma70 nd nd purA
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [1]
  GadE activator rcsAp Sigma70 nd nd rcsA
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  GadE activator yhiMp Sigma38 -78.5 -176.5 yhiM
gcataagaatTAATCTTAGGATAAATTTTTatttatcatg
 3634655 3634674 [EXP-IEP-RNA-SEQ], [COMP-HINF], [EXP-CHIP-EXO-MANUAL] S [5], [5]
  GadE activator yjbQp nd -40.0 -64.0 yjbQ, yjbR
cgaatgctgtTTTTTTAATCACACCTTTATcctttcgctg
 4270164 4270183 [EXP-IEP-RNA-SEQ], [COMP-HINF], [EXP-CHIP-EXO-MANUAL] S [5], [5]


Alignment and PSSM for GadE TFBSs    

Aligned TFBS of GadE   
  Sequence
  TTTAAATAACAAAATCCTAAGC
  TTTAAATAACAAAATCCTAATG
  ATTTAATAAAAATTTCCTAATT
  TTTCATTATTTACATCCTTGTC
  AGGAGATAAAAAAATCTGACAC
  TTTTTTTAATCACACCTTTATC
  TCAATATAGTAAACGCCTATAA
  CGTCACGAATCAATTTCGACAC
  TAAATAAAAATTTATCCTAAGA
  TGTAAATAGCAAACAAAAAGTT

Position weight matrix (PWM). GadE matrix-quality result    
A	2	1	2	6	6	7	1	10	7	3	6	9	6	6	1	1	1	1	8	5	3	2
C	1	1	0	2	0	1	0	0	0	3	2	0	2	2	1	8	7	0	0	2	0	5
G	0	3	1	0	1	0	1	0	2	0	0	0	0	0	1	0	0	2	0	2	2	1
T	7	5	7	2	3	2	8	0	1	4	2	1	2	2	7	1	2	7	2	1	5	2

Consensus    
;	consensus.strict             	tttaaatAacaAaatCCtaatc
;	consensus.strict.rc          	GATTAGGATTTTGTTATTTAAA
;	consensus.IUPAC              	tktawatAahaAaatCCtaawc
;	consensus.IUPAC.rc           	GWTTAGGATTTTDTTATWTAMA
;	consensus.regexp             	t[gt]ta[at]atAa[act]aAaatCCtaa[at]c
;	consensus.regexp.rc          	G[AT]TTAGGATTTT[AGT]TTAT[AT]TA[AC]A

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


Evidence    

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-IEP-RNA-SEQ] high throughput RNA-seq evidence

 [COMP-HINF] Inferred by a human based on computational evidence

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-CHIP-EXO-MANUAL] ChIP-exo evidence used in manual assertion

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences


Reference(s)    

 [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] Seo SW., Kim D., O'Brien EJ., Szubin R., Palsson BO., 2015, Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli., Nat Commun 6:7970

 [6] 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

 [7] 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

 [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] 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

 [10] 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

 [11] 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 10.1016/s1570-9639(03)00098-0

 [12] 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

 [13] 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 10.1046/j.1365-2958.2001.02570.x

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

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

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

 [17] 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

 [18] 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

 [19] 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

 [20] 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

 [21] Senda T, Ogawa N, 2005, [Structure function relationship of the LysR type transcriptional regulator]., Tanpakushitsu Kakusan Koso, 50(12):1535 None

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

 [23] Gregorchuk BSJ, Reimer SL, Green KAC, Cartwright NH, Beniac DR, Hiebert SL, Booth TF, Chong PM, Westmacott GR, Zhanel GG, Bay DC, 2021, Phenotypic and Multi-Omics Characterization of Escherichia coli K-12 Adapted to Chlorhexidine Identifies the Role of MlaA and Other Cell Envelope Alterations Regulated by Stress Inducible Pathways in CHX Resistance., Front Mol Biosci, 8(None):659058 10.3389/fmolb.2021.659058

 [24] Brombacher E., Dorel C., Zehnder AJ., Landini P., 2003, The curli biosynthesis regulator CsgD co-ordinates the expression of both positive and negative determinants for biofilm formation in Escherichia coli., Microbiology 149(Pt 10):2847-57


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