Transcription Factor

Accessions: ECK120006602 (RegulonDB 7.5)
Names: GadX, GadX DNA-binding transcriptional dual regulator
Organisms: ECK12
Libraries: RegulonDB 7.5 1
1 Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muniz-Rascado L, Garcia-Sotelo JS, Weiss V, Solano-Lira H, Martinez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernandez S, Alquicira-Hernandez K, Lopez-Fuentes A, Porron-Sotelo L, Huerta AM, Bonavides-Martinez C, Balderas-Martinez YI, Pannier L, Olvera M, Labastida A, Jimenez-Jacinto V, Vega-Alvarado L, Del Moral-Chavez V, Hernandez-Alvarez A, Morett E, Collado-Vides J. RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more. Nucleic Acids Res. 2013 Jan 1;41(D1):D203-D213. [Pubmed]
Notes: The transcriptional activator GadX, for Glutamic acid decarboxylase, is positively autoregulated and controls the transcription of pH-inducible genes, including the principal acid resistance system Tramonti A,2003; Tramonti A,2002; Shin S,2001 is glutamate dependent (GAD), is also referred to as the GAD system, and its genes are involved in multidrug efflux Ma Z,2002; Tramonti A,2008; Tucker DL,2003; Tramonti A,2006; Nishino K,2008 In addition GadX also activates the transcription of the central activator involved in the acid response Sayed AK,2007 The physiological inducer is unknown; Richard et al; proposed that GadX can sense intracellular Na+ concentrations, but the mechanism is not known Richard H,2007GadX is one of the regulators of the acid resistance system and is encoded by the unusual gadXW operon, which is located in the region called the acid fitness island Tramonti A,2008 This operon encodes two transcriptional regulators, GadX and GadW, both of which are members of the AraC/XylS family of transcriptional regulators Gallegos MT,1997; Martin RG,2001; Tramonti A,2008 The activities of GadX and GadW are indispensable upon entry into the stationary phase in response to acid pH Tramonti A,2002; Ma Z,2002 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 Tramonti A,2008; Opdyke JA,2004GadX is highly homologous to GadW (42%), and apparently both are capable of cross talk to regulate expression of the genes of this system Tramonti A,2008 Although little is known about the regulating mechanism of GadX, Tucker et al; proposed that this regulator and GadW have distinct molecular mechanisms Tucker DL,2003; Tramonti A,2006 These regulators form homodimers Gallegos MT,1997 and heterodimers Ma Z,2002in 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 the gadA and gadB promoters Tramonti A,2002 Ma et al; added to this regulatory interaction the GadW protein, showing that it inhibits GadX and that in some cases it activates in the absence of GadX Ma Z,2002 Trucker et al; provided evidence that GadW can work as a coactivator of GadX or it can inhibit the GadX-dependent activation, along with evidence of more target genes for GadX/GadW regulation Tucker DL,2003 About their interactions, Tramonti et al; showed the direct GadX binding at the promoters of the gadB (two sites) and gadA (four sites) operons Tramonti A,2002 also, Ma et al; showed that GadW forms a homodimer and that it also binds to the DNA of the gadA and gadB promoters Ma Z,2002 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 GadW), 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 GadW), which is responsible for dimerization Gallegos MT,1997; Gallegos MT,1993; Ma Z,2002 Tramonti et al; speculated that GadX binds in tandem to two directed repeat sequences, in the same orientation, in the intergenic regions to activate or represses the transcription of the genes regulated Tramonti A,2008 The binding targets for GadX 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 GadX and GadW Tucker DL,2003; Tramonti A,2008 This proposal was not unexpected, because the identity and similarity of the C-terminal domains are 41% and 66%, respectively Tramonti A,2008 Each monomer of GadX binds to one of these conserved sequences Tramonti A,2008; activator; Transcription related; regulation of transcription, DNA-dependent; sequence-specific DNA binding; sequence-specific DNA binding transcription factor activity; transcription activator activity; transcription, DNA-dependent; DNA binding; intracellular
Length: 275
Pfam Domains: 151-190 Bacterial regulatory helix-turn-helix proteins, AraC family
164-242 Helix-turn-helix domain
205-240 Bacterial regulatory helix-turn-helix proteins, AraC family
Sequence: MQSLHGNCLIAYARHKYILTMVNGEYRYFNGGDLVFADASQIRVDKCVENFVFVSRDTLS
LFLPMLKEEALNLHAHKKVSSLLVHHCSRDIPVFQEVAQLSQNKNLRYAEMLRKRALIFA
LLSVFLEDEHFIPLLLNVLQPNMRTRVCTVINNNIAHEWTLARIASELLMSPSLLKKKLR
EEETSYSQLLTECRMQRALQLIVIHGFSIKRVAVSCGYHSVSYFIYVFRNYYGMTPTEYQ
ERSAQRLSNRDSAASIVAQGNFYGTDRSAEGIRL*
Binding Motifs: GadX wAAwGtmtkATwTtwmyaw
Binding Sites: ECK120018550
ECK120018556
ECK125135092
ECK125135110
ECK125135113
ECK125135115
ECK125135117
Publications: Gallegos MT., Michan C., Ramos JL. The XylS/AraC family of regulators. Nucleic Acids Res. 21(4):807-10 (1993). [Pubmed]

Gallegos MT., Schleif R., Bairoch A., Hofmann K., Ramos JL. Arac/XylS family of transcriptional regulators. Microbiol Mol Biol Rev. 61(4):393-410 (1997). [Pubmed]

Ma Z., Richard H., Tucker DL., Conway T., Foster JW. Collaborative regulation of Escherichia coli glutamate-dependent acid resistance by two AraC-like regulators, GadX and GadW (YhiW). J Bacteriol. 184(24):7001-12 (2002). [Pubmed]

Tramonti A., Visca P., De Canio M., Falconi M., De Biase D. 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 (2002). [Pubmed]

Shin S., Castanie-Cornet MP., Foster JW., Crawford JA., Brinkley C., Kaper JB. 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 (2001). [Pubmed]

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

Nishino K., Senda Y., Yamaguchi A. 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 (2008). [Pubmed]

Sayed AK., Odom C., Foster JW. 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 (2007). [Pubmed]

Tramonti A., De Canio M., Delany I., Scarlato V., De Biase D. 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 (2006). [Pubmed]

Tucker DL., Tucker N., Ma Z., Foster JW., Miranda RL., Cohen PS., Conway T. Genes of the GadX-GadW regulon in Escherichia coli. J Bacteriol. 185(10):3190-201 (2003). [Pubmed]

Tramonti A., De Canio M., De Biase D. 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 (2008). [Pubmed]

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

Richard H., Foster JW. Sodium regulates Escherichia coli acid resistance, and influences GadX- and GadW-dependent activation of gadE. Microbiology. 153(Pt 9):3154-61 (2007). [Pubmed]

Opdyke JA., Kang JG., Storz G. GadY, a small-RNA regulator of acid response genes in Escherichia coli. J Bacteriol. 186(20):6698-705 (2004). [Pubmed]
Related annotations: PaperBLAST

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