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UhpA DNA-binding transcriptional activator

Synonyms: UhpA-Phosphorylated, UhpA
Summary:
The regulatory protein for "uptake of hexose phosphates," UhpA [], activates the transcription of a gene that codes for UhpT, a protein that transports many phosphorylated sugars into the cell []. UhpA is the response regulator in the unusual two-component regulatory system comprised of three proteins, UhpA/UhpB/UhpC, and is a member of the NarL subfamily of response regulators. The signal that triggers this signaling pathway is glucose 6-phosphate external. This sugar is sensed by UhpC, which interacts with UhpB to stimulate its autophosphorylation. Then, phosphorylated UhpB transfers the phosphate group to UhpA in Asp-54 to activate it [14]. UhpB unphosphorylated is able to dephosphorylate to UhpA [14, 15]. UhpA has two modules: the receiver module, which contains the putative site of phosphorylation in the N-terminal domain [6], and the activation module, which contains a helix-turn-helix motif for DNA binding in the C-terminal domain[6, 16].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
UhpA Non-Functional   Apo [BPP] [1]
UhpA-Phosphorylated Functional Covalent Holo [AIFS], [BPP], [IEP], [IPI] [1], [2], [3], [4], [5], [6]
Evolutionary Family: LuxR/UhpA
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: uhpA
  Genome position: 3850136-3850726
  Length: 591 bp / 196 aa
Operon name: ivbL-ilvBN-uhpABC
TU(s) encoding the TF:
Transcription unit        Promoter
ivbL-ilvBN-uhpABC
null
uhpABC
null


Regulon       
Regulated gene(s) uhpT
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (1)
Porters (Uni-, Sym- and Antiporters) (1)
membrane (1)
Regulated operon(s) uhpT
First gene in the operon(s) uhpT
Simple and complex regulons CRP,UhpA,UvrY
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[UhpA,+](1)


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
  UhpA-Phosphorylated activator uhpTp Sigma70 -64.5 -95.5 uhpT
tccaggcaaaACCTGGAAAATTTCTTAGTTttgccggata
3847253 3847272 [BPP], [GEA], [SM] [2], [3], [4], [7], [8], [9]
  UhpA-Phosphorylated activator uhpTp Sigma70 -41.5 -72.5 uhpT
agcaaatcagGCCTGAGATAGCGTCCAGGCaaaacctgga
3847230 3847249 [BCE], [BPP], [GEA], [SM] [2], [3], [4], [7], [8], [9], [10], [11], [12], [13]


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


Evidence    

 [BPP] Binding of purified proteins

 [AIFS] Automated inference of function from sequence

 [IEP] Inferred from expression pattern

 [IPI] Inferred from physical interaction

 [GEA] Gene expression analysis

 [SM] Site mutation

 [BCE] Binding of cellular extracts



Reference(s)    

 [1] Yamamoto K., Hirao K., Oshima T., Aiba H., Utsumi R., Ishihama A., 2005, Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli., J Biol Chem 280(2):1448-56

 [2] Dahl JL., Wei BY., Kadner RJ., 1997, Protein phosphorylation affects binding of the Escherichia coli transcription activator UhpA to the uhpT promoter., J Biol Chem 272(3):1910-9

 [3] Olekhnovich IN., Dahl JL., Kadner RJ., 1999, Separate contributions of UhpA and CAP to activation of transcription of the uhpT promoter of Escherichia coli., J Mol Biol 292(5):973-86

 [4] Olekhnovich IN., Kadner RJ., 2002, Mutational scanning and affinity cleavage analysis of UhpA-binding sites in the Escherichia coli uhpT promoter., J Bacteriol 184(10):2682-91

 [5] Stock AM., Robinson VL., Goudreau PN., 2000, Two-component signal transduction., Annu Rev Biochem 69:183-215

 [6] Webber CA., Kadner RJ., 1995, Action of receiver and activator modules of UhpA in transcriptional control of the Escherichia coli sugar phosphate transport system., Mol Microbiol 15(5):883-93

 [7] Chen Q., Kadner RJ., 2000, Effect of altered spacing between uhpT promoter elements on transcription activation., J Bacteriol 182(16):4430-6

 [8] Verhamme DT., Postma PW., Crielaard W., Hellingwerf KJ., 2002, Cooperativity in signal transfer through the Uhp system of Escherichia coli., J Bacteriol 184(15):4205-10

 [9] Wright JS., Olekhnovich IN., Touchie G., Kadner RJ., 2000, The histidine kinase domain of UhpB inhibits UhpA action at the Escherichia coli uhpT promoter., J Bacteriol 182(22):6279-86

 [10] Merkel TJ., Dahl JL., Ebright RH., Kadner RJ., 1995, Transcription activation at the Escherichia coli uhpT promoter by the catabolite gene activator protein., J Bacteriol 177(7):1712-8

 [11] Merkel TJ., Nelson DM., Brauer CL., Kadner RJ., 1992, Promoter elements required for positive control of transcription of the Escherichia coli uhpT gene., J Bacteriol 174(9):2763-70

 [12] Olekhnovich IN., Kadner RJ., 1999, RNA polymerase alpha and sigma(70) subunits participate in transcription of the Escherichia coli uhpT promoter., J Bacteriol 181(23):7266-73

 [13] Webber CA., Kadner RJ., 1997, Involvement of the amino-terminal phosphorylation module of UhpA in activation of uhpT transcription in Escherichia coli., Mol Microbiol 24(5):1039-48

 [14] Verhamme DT., Arents JC., Postma PW., Crielaard W., Hellingwerf KJ., 2001, Glucose-6-phosphate-dependent phosphoryl flow through the Uhp two-component regulatory system., Microbiology 147(Pt 12):3345-52

 [15] Wright JS., Kadner RJ., 2001, The phosphoryl transfer domain of UhpB interacts with the response regulator UhpA., J Bacteriol 183(10):3149-59

 [16] Weston LA., Kadner RJ., 1988, Role of uhp genes in expression of the Escherichia coli sugar-phosphate transport system., J Bacteriol 170(8):3375-83

 [17] Weston LA., Kadner RJ., 1987, Identification of uhp polypeptides and evidence for their role in exogenous induction of the sugar phosphate transport system of Escherichia coli K-12., J Bacteriol 169(8):3546-55



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