|Synonyms: AtoC, AtoC-phosphorylated|
AtoC, also known as antizyme protein (Az), is a protein that regulates processes at the transcriptional and posttranslational levels |CITS:|. It inhibits posttranslationally ornithine decarboxylase (ODC) |CITS:|, which is a key enzyme for biosynthesis of the polyamines which are essential components for cellular growth and proliferation |CITS:|. On the other hand, in the presence of acetoacetate, AtoC regulates the transcription of the atoDAEB operon |CITS:|, whose products are involved in catabolism of short-chain fatty acids |CITS:|. 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 |CITS:|. 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 |CITS:[ 12897016]|. AtoSC is involved in the flagellar regulon, controlling the motility and chemotaxis responses |CITS: |.
Through atoDAEB operon regulation, AtoC modules positively the biosynthesis and the intracellular distribution of poly-(R)-3-hydroxybutyrate (cPHB), a biopolymer with many physiological roles |CITS:|. The products of the catabolism of short-chain fatty acids appear to be the substrates in the biosynthesis of this polymer |CITS:|.
By an unknown mechanism, histamine and extracellular Ca2+ appear to be signals that modulate AtoS/AtoC-dependent cPHB production |CITS:[ 18235991][ 18855762]|.Read more >
AtoC is the response regulator in the two-component regulatory system AtoC/AtoS |CITS:[ 16153782]|. Autophosphorylation of AtoS appears to be stimulated by acetoacetate or one of its metabolic products |CITS:|. Then, the phosphate group is transferred from AtoS to the D55 residue of AtoC to activate this protein |CITS:|. It has also been suggested that the D55 residue could transfer the phosphate group to the H73 residue of AtoC |CITS:|.
AtoC belongs to the NtrC-NifA family of σ54-RNA polymerase transcriptional activators |CITS:| and, as for a number of members of this family, AtoC contains three domains: the N-terminal receiver domain to be phosphorylated, the central domain involved in ATP hydrolysis and interaction with σ54, and the DNA-binding C-terminal domain that contains a helix-turn-helix motif |CITS:|.
It was suggested that AtoC oligomerizes, but the stoichiometry is unknown |CITS:|. This protein recognizes and binds a sequence of 20 bp in DNA |CITS:|. In the atoDAEB regulatory region there are two of these sites arranged as inverted repeats separated by 1 bp |CITS:|. However, a BLAST analysis showed that although there are several regions with significant homology to the 20-bp AtoC-binding site, they are not arranged as palindromes |CITS:|. AtoC-dependent atoDAEB transcription requires the presence and binding of IHF |CITS:|.
Proteins with antizyme activity have been found in several organisms, from plants to eubacteria |CITS:|. A BLAST analysis showed AtoC is homologous in proteobacteria, enterobacteria, eubacteria, and spirochetes |CITS:|.
atoC, encoding the response regulator, and atoS, encoding the sensor kinase, are located in the genome upstream of the atoDAEB operon |CITS:|. The transcription of the gene atoC is induced by polyamines |CITS:| and histamine |CITS:[ 18235991]|; microarray analysis shows that OmpR may regulate the transcription of this gene |CITS:[ 12366850]|. On the other hand, it does not appear to be autoregulated |CITS:|.
AtoC: acetoacetate |CITS:|
|Sensing class:||External-Two-component systems|
|Connectivity class:||Local Regulator|
|Length:||1386 bp / 461 aa|
|TU(s) encoding the TF:||
|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)
atoA, atoB, atoD
Putative uncharacterized transport protein (1)
|First gene in the operon(s)||atoD|
|Simple and complex regulons|
|Simple and complex regulatory phrases||
Regulatory phrase (List of promoters regulated by the phrase)
|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]||, , , |
|AtoC-phosphorylated||activator||atoDp||Sigma54||-119.5||-154.5||atoD, atoA, atoE, atoB||
|2323283||2323302||[BPP], [GEA], [HIBSCS], [SM]||, , , |
|Evolutionary conservation of regulatory elements|
 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
 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
 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
 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