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UhpA DNA-binding transcriptional activator

Synonyms: UhpA-Phosphorylated, UhpA
The regulatory protein for uptake of hexose phosphates, UhpA [12] activates the transcription of a gene that codes for UhpT, a protein that transports many phosphorylated sugars into the cell [13]
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 [16] and the activation module, which contains a helix-turn-helix motif for DNA binding in the C-terminal domain[16, 17] UhpA shows 30% identity with DctD [17]
The RNA polymerase RpoA and RpoD subunits are necessary for the transcriptional activation by UhpA [10] which induces open complex formation, but the stabilization of this complex is CRP dependent [4] These two regulatory proteins appear to stimulate the DNA binding of each other to the uhpT promoter [4]
Two UhpA dimers bind to two sites with different affinities upstream of uhpT.
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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], [IPI] [1]
UhpA-Phosphorylated Functional Covalent Holo [BPP], [IPI] [1]
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

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)

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
3847253 3847272 [BPP], [GEA], [SM] [2], [3], [4], [5], [6], [7]
  UhpA-Phosphorylated activator uhpTp Sigma70 -41.5 -72.5 uhpT
3847230 3847249 [BCE], [BPP], [GEA], [SM] [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]

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


 [BPP] Binding of purified proteins

 [IPI] Inferred from physical interaction

 [GEA] Gene expression analysis

 [SM] Site mutation

 [BCE] Binding of cellular extracts


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

 [3] 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

 [4] 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

 [5] 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

 [6] 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

 [7] 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

 [8] 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

 [9] 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

 [10] 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

 [11] 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

 [12] Kornberg HL., Smith J., 1969, Genetic control of hexose phosphate uptake by Escherichia coli., Nature. 224(5226):1261-2

 [13] Kadner RJ., Shattuck-Eidens DM., 1983, Genetic control of the hexose phosphate transport system of Escherichia coli: mapping of deletion and insertion mutations in the uhp region., J Bacteriol. 155(3):1052-61

 [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] 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

 [17] 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

 [18] 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