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EvgA DNA-binding transcriptional activator

Synonyms: EvgA, EvgA-Phosphorylated
Summary:
The transcriptional activator EvgA initiates a complex activation cascade for gene products involved in acid resistance and multidrug resistance [3, 6, 7, 9, 10, 11]
It directly activates at least six operons, among which the b1500-ydeO operon encodes two additional activator proteins. B1500 is the connector protein for the PhoPQ two-component system, which is involved in acid resistance and Mg2+ homeostasis [8] YdeO is an AraC-like transcriptional activator for at least 12 operons, including the gadE-mdtE-mdtF operon [4, 12, 12, 13] mdtEF encodes a multidrug efflux pump, and gadE encodes the master regulator for glutamate-dependent acid resistance [14, 15] GadE activates transcription of two additional AraC-like transcriptional activators, GadX and GadW. The EvgA-YdeO-GadE circuit is very complex and involves feedback loops and autoactivation [6, 7, 16] It is activated during exponential growth in acidified minimal medium and enables the cell to survive gastric acidity.
EvgA belongs to the two-component system EvgS/EvgA [17] which is highly homologous to the virulence-related BvgAS system of Bordetella pertussis.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
EvgA Non-Functional   Apo [AIFS], [BPP], [SM] [1]
EvgA-Phosphorylated Functional Covalent Holo [AIFS], [BPP], [SM] [1]
Evolutionary Family: LuxR/UhpA
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: evgA
  Genome position: 2483755-2484369
  Length: 615 bp / 204 aa
Operon name: evgAS
TU(s) encoding the TF:
Transcription unit        Promoter
evgAS
evgAp1
evgAS
evgAp2


Regulon       
Regulated gene(s) acrD, emrK, emrY, evgA, evgS, frc, gadE, mdtE, mdtF, oxc, safA, ydeO, ydeP, yegR, yegZ, yfdE, yfdV, yfdX
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (5)
Porters (Uni-, Sym- and Antiporters) (4)
drug resistance/sensitivity (3)
Transcription related (3)
activator (3)
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Regulated operon(s) acrD, emrKY, evgAS, gadE-mdtEF, safA-ydeO, ydeP, yegRZ, yfdX-frc-oxc-yfdVE
First gene in the operon(s) acrD, emrK, evgA, evgA, frc, gadE, safA, ydeP, yegR, yfdX
Simple and complex regulons CRP,EvgA,FliZ,GadE,GadW,GadX,H-NS,YdeO
EvgA
EvgA,FNR
EvgA,H-NS
EvgA,H-NS,NagC,NarL,NarP,PhoP,RcsB,UvrY
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[EvgA,+](9)


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
  EvgA-Phosphorylated activator acrDp Sigma70 -31.5 -151.5 acrD
aatgtaatgcCTCCTACTGACCAAAGAAtacttgcact
2587435 2587452 [AIBSCS], [GEA] [2]
  EvgA-Phosphorylated activator emrKp nd -73.5 -182.5 emrK, emrY
cttcttactaATCCTACAGGCGTAAGAAttgtattgca
2483513 2483530 [AIBSCS], [BPP], [GEA], [HIBSCS] [1], [3], [4], [5]
  EvgA-Phosphorylated activator evgAp1 Sigma38 -119.5 -233.5 evgA, evgS
tgcaatacaaTTCTTACGCCTGTAGGATtagtaagaag
2483513 2483530 [AIBSCS], [BPP], [GEA], [HIBSCS] [3], [4], [5]
  EvgA-Phosphorylated activator evgAp2 Sigma70 -109.5 -233.5 evgA, evgS
tgcaatacaaTTCTTACGCCTGTAGGATtagtaagaag
2483513 2483530 [AIBSCS], [BPP], [GEA], [HIBSCS] [3], [4], [5]
  EvgA-Phosphorylated activator frcp Sigma70 -75.5 -260.5 frc
tcaccggcgcTTCTTACAGTTGTAAGAAtaacatcaca
2493506 2493523 [AIBSCS], [BPP], [GEA] [4], [6]
  EvgA-Phosphorylated activator gadEp Sigma38 nd nd gadE, mdtE, mdtF nd nd [BPP], [GEA] [7]
  EvgA-Phosphorylated activator safAp Sigma70 -51.5 -120.5 safA, ydeO
tataaacttcTGCCTACAGCTGTAAGAAactccgctca
1584071 1584088 [AIBSCS], [BPP], [GEA] [4], [6], [8]
  EvgA-Phosphorylated activator ydePp Sigma70 -74.5 -252.5 ydeP
gaaggctattAGCCTACACCTGTAAGAAaatccgcgca
1586730 1586747 [AIBSCS], [BPP], [GEA] [4], [6]
  EvgA-Phosphorylated activator yegRp Sigma70 -72.5 -115.5 yegR, yegZ
atgtccgtaaTTCCTACTTATGTAGGAAatgttgtaca
2168413 2168430 [AIBSCS], [BPP], [GEA] [4], [6]
  EvgA-Phosphorylated activator yfdXp Sigma70 -113.5 -144.5 yfdX, frc, oxc, yfdV, yfdE
aggaagcataTTCCTACAATTGTAAGACtaaaatactt
2494538 2494555 [AIBSCS], [BPP], [GEA] [4], [6]
  EvgA-Phosphorylated activator yfdXp Sigma70 -75.5 -106.5 yfdX, frc, oxc, yfdV, yfdE
cttgcgataaTAACTACAACTGTAAGATaaccctttca
2494500 2494517 [BPP], [GEA] [6]


Alignment and PSSM for EvgA TFBSs    

Aligned TFBS of EvgA   
  Sequence
 

Position weight matrix (PWM).   
A	0	0	0	0	8	0	6	1	2	0	0	1	8	3	0	5	7
C	0	8	3	0	0	8	0	0	1	2	1	0	0	0	0	2	0
G	0	0	0	0	0	0	0	6	2	0	7	0	0	5	7	0	0
T	8	0	5	8	0	0	2	1	3	6	0	7	0	0	1	1	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


Evidence    

 [AIFS] Automated inference of function from sequence

 [BPP] Binding of purified proteins

 [SM] Site mutation

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences



Reference(s)    

 [1] Kato A., Ohnishi H., Yamamoto K., Furuta E., Tanabe H., Utsumi R., 2000, Transcription of emrKY is regulated by the EvgA-EvgS two-component system in Escherichia coli K-12., Biosci Biotechnol Biochem. 64(6):1203-9

 [2] Hirakawa H., Nishino K., Yamada J., Hirata T., Yamaguchi A., 2003, Beta-lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli., J Antimicrob Chemother. 52(4):576-82

 [3] Eguchi Y., Oshima T., Mori H., Aono R., Yamamoto K., Ishihama A., Utsumi R., 2003, Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli., Microbiology. 149(Pt 10):2819-28

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

 [5] Tanabe H., Yamasaki K., Katoh A., Yoshioka S., Utsumi R., 1998, Identification of the promoter region and the transcriptional regulatory sequence of the evgAS operon of Escherichia coli., Biosci Biotechnol Biochem. 62(2):286-90

 [6] 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

 [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] Eguchi Y., Itou J., Yamane M., Demizu R., Yamato F., Okada A., Mori H., Kato A., Utsumi R., 2007, B1500, a small membrane protein, connects the two-component systems EvgS/EvgA and PhoQ/PhoP in Escherichia coli., Proc Natl Acad Sci U S A. 104(47):18712-7

 [9] Nishino K., Inazumi Y., Yamaguchi A., 2003, Global analysis of genes regulated by EvgA of the two-component regulatory system in Escherichia coli., J Bacteriol. 185(8):2667-72

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

 [11] Foster JW., 2004, Escherichia coli acid resistance: tales of an amateur acidophile., Nat Rev Microbiol. 2(11):898-907

 [12] Nishino K., Senda Y., Hayashi-Nishino M., Yamaguchi A., 2009, Role of the AraC-XylS family regulator YdeO in multi-drug resistance of Escherichia coli., J Antibiot (Tokyo). 62(5):251-7

 [13] Martin RG., Rosner JL., 2001, The AraC transcriptional activators., Curr Opin Microbiol. 4(2):132-7

 [14] 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

 [15] 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

 [16] 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

 [17] Utsumi R., Katayama S., Ikeda M., Igaki S., Nakagawa H., Miwa A., Taniguchi M., Noda M., 1992, Cloning and sequence analysis of the evgAS genes involved in signal transduction of Escherichia coli K-12., Nucleic Acids Symp Ser (27):149-50

 [18] Tanabe H., Masuda T., Yamasaki K., Katoh A., Yoshioka S., Utsumi R., 1998, Molecular interaction between proteins involved in EvgAS signal transduction of Escherichia coli., Biosci Biotechnol Biochem. 62(1):78-82

 [19] Bantscheff M., Perraud AL., Bock A., Rippe K., Weiss V., Glocker M., Gross R., 2000, Structure-function relationships in the Bvg and Evg two-component phosphorelay systems., Int J Med Microbiol. 290(4-5):317-23

 [20] Perraud AL., Kimmel B., Weiss V., Gross R., 1998, Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C-terminal HPt domains of the sensor proteins., Mol Microbiol. 27(5):875-87



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