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AtoC DNA-binding transcriptional activator

Synonyms: AtoC, AtoC-phosphorylated
AtoC, also known as antizyme protein (Az), is a protein that regulates processes at the transcriptional and posttranslational levels [8] It inhibits posttranslationally ornithine decarboxylase (ODC) [8] which is a key enzyme for biosynthesis of the polyamines which are essential components for cellular growth and proliferation [9] On the other hand, in the presence of acetoacetate, AtoC regulates the transcription of the atoDAEB operon [5, 7] whose products are involved in catabolism of short-chain fatty acids [10] However, transcriptome analyses have shown that this protein not only regulates this operon but also upregulates or downregulates 11 and 32 genes, respectively, that are involved in flagellar synthesis [11] On the other hand, phenotypical analysis with an AtoS mutant showed reduced motility, sodium chloride sensitivity, and increased susceptibility to membrane-acting agents and an aminoglycoside antibiotic [12] AtoSC is involved in the flagellar regulon, controlling the motility and chemotaxis responses [13].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
AtoC Non-Functional   Apo [AIFS], [BPP], [GEA], [IPI], [SM] [1], [2], [3], [4]
AtoC-phosphorylated Functional Covalent Holo [AIFS], [BPP], [GEA], [IPI], [SM] [1], [2], [3], [4]
Evolutionary Family: EBP
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: atoC
  Genome position: 2321866-2323251
  Length: 1386 bp / 461 aa
Operon name: atoSC
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) atoA, atoB, atoD, atoE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
fatty acids (3)
membrane (1)
Putative uncharacterized transport protein (1)
Regulated operon(s) atoDAEB
First gene in the operon(s) atoD
Simple and complex regulons AtoC,IHF
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
  AtoC-phosphorylated activator atoDp Sigma54 -138.5 -173.5 atoD, atoA, atoE, atoB
2323264 2323283 [BPP], [GEA], [HIBSCS], [SM] [3], [5], [6], [7]
  AtoC-phosphorylated activator atoDp Sigma54 -119.5 -154.5 atoD, atoA, atoE, atoB
2323283 2323302 [BPP], [GEA], [HIBSCS], [SM] [3], [5], [6], [7]

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


 [AIFS] Automated inference of function from sequence

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [IPI] Inferred from physical interaction

 [SM] Site mutation

 [HIBSCS] Human inference based on similarity to consensus sequences


 [1] Filippou PS., Kasemian LD., Panagiotidis CA., Kyriakidis DA., 2008, Functional characterization of the histidine kinase of the E. coli two-component signal transduction system AtoS-AtoC., Biochim Biophys Acta. 1780(9):1023-31

 [2] Grigoroudis AI., Panagiotidis CA., Lioliou EE., Vlassi M., Kyriakidis DA., 2007, Molecular modeling and functional analysis of the AtoS-AtoC two-component signal transduction system of Escherichia coli., Biochim Biophys Acta. 1770(8):1248-58

 [3] Lioliou EE., Mimitou EP., Grigoroudis AI., Panagiotidis CH., Panagiotidis CA., Kyriakidis DA., 2005, Phosphorylation activity of the response regulator of the two-component signal transduction system AtoS-AtoC in E. coli., Biochim Biophys Acta. 1725(3):257-68

 [4] Papadopoulos G, Grigoroudis AI, Kyriakidis DA., 2010, Dimerization of the AtoC response regulator and modelling of its binding to DNA., J Mol Graph Model.

 [5] Jenkins LS., Nunn WD., 1987, Regulation of the ato operon by the atoC gene in Escherichia coli., J Bacteriol. 169(5):2096-102

 [6] Jenkins LS., Nunn WD., 1987, Genetic and molecular characterization of the genes involved in short-chain fatty acid degradation in Escherichia coli: the ato system., J Bacteriol. 169(1):42-52

 [7] Matta MK., Lioliou EE., Panagiotidis CH., Kyriakidis DA., Panagiotidis CA., 2007, Interactions of the AtoC/antizyme with regulatory elements of the Escherichia coli atoDAEB operon., J Bacteriol. 189(17):6324-32

 [8] Lioliou EE., Kyriakidis DA., 2004, The role of bacterial antizyme: From an inhibitory protein to AtoC transcriptional regulator., Microb Cell Fact. 3(1):8

 [9] Tabor CW., Tabor H., 1985, Polyamines in microorganisms., Microbiol Rev. 49(1):81-99

 [10] Pauli G., Overath P., 1972, ato Operon: a highly inducible system for acetoacetate and butyrate degradation in Escherichia coli., Eur J Biochem. 29(3):553-62

 [11] Oshima T., Aiba H., Masuda Y., Kanaya S., Sugiura M., Wanner BL., Mori H., Mizuno T., 2002, Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12., Mol Microbiol. 46(1):281-91

 [12] Zhou L., Lei XH., Bochner BR., Wanner BL., 2003, Phenotype microarray analysis of Escherichia coli K-12 mutants with deletions of all two-component systems., J Bacteriol. 185(16):4956-72

 [13] Theodorou MC., Theodorou EC., Kyriakidis DA., 2012, Involvement of AtoSC two-component system in Escherichia coli flagellar regulon., Amino Acids. 43(2):833-44

 [14] Theodorou MC., Panagiotidis CA., Panagiotidis CH., Pantazaki AA., Kyriakidis DA., 2006, Involvement of the AtoS-AtoC signal transduction system in poly-(R)-3-hydroxybutyrate biosynthesis in Escherichia coli., Biochim Biophys Acta. 1760(6):896-906

 [15] Kyriakidis DA., Theodorou MC., Filippou PS., Kyriakidis KD., Tiligada E., 2008, Effect of histamine on the signal transduction of the AtoS-AtoC two component system and involvement in poly-(R)-3-hydroxybutyrate biosynthesis in Escherichia coli., Amino Acids. 35(1):45-52

 [16] Theodorou MC., Tiligada E., Kyriakidis DA., 2008, Extracellular Ca2+ transients affect poly-(R)-3-hydroxybutyrate regulation by the AtoS-AtoC system in E. coli., Biochem J

 [17] Filippou PS., Lioliou EE., Panagiotidis CA., Athanassopoulos CM., Garnelis T., Papaioannou D., Kyriakidis DA., 2007, Effect of polyamines and synthetic polyamine-analogues on the expression of antizyme (AtoC) and its regulatory genes., BMC Biochem. 8:1