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DnaA DNA-binding transcriptional dual regulator

Synonyms: DnaA, DnaA-ATP
Summary:
DnaA plays an important role in initiating chromosomal replication to bind sequences in the chromosomal origin.
It belongs to the DnaA family of transcriptional regulators.
DnaA also binds to sites at the datA locus and this binding serves to limit excess DnaA activity, but other DnaA-binding sites are shown not to share this function [14].
Regulation has been described [1, 15, 16] Hda is a member of the AAA chaperone-like family of ATPases [15]that is required for the inhibition of the initiation of DNA synthesis via antagonism of DnaA activity by the DNA polymerase III beta subunit (sliding clamp) [1, 15]. Hda and the sliding clamp stimulate ATP hydrolysis within the DnaA-ATP complex, which renders it inactive, and DNA replication activity also contributes to this downregulation [1]
DnaA also can inhibit the gene expression of other genes such as guaA, dam, rpoH, ftsA, and mioC.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
DnaA Non-Functional   Apo [BPP], [IPI] [1]
DnaA-ATP Functional Allosteric Holo [BPP], [IPI] [1]
Evolutionary Family: DnaA
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: dnaA
  Genome position: 3882326-3883729
  Length: 1404 bp / 467 aa
Operon name: dnaAN-recF
TU(s) encoding the TF:
Transcription unit        Promoter
dnaAN-recF
dnaAp1
dnaAN-recF
dnaAp2


Regulon       
Regulated gene(s) aldA, dnaA, dnaN, guaA, guaB, nrdA, nrdB, polA, recF, rpoH, yfaE, yjeV
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
DNA replication (4)
nucleotide and nucleoside conversions (4)
Transcription related (2)
purine biosynthesis (2)
carbon compounds (1)
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Regulated operon(s) aldA, dnaAN-recF, guaBA, nrdAB-yfaE, polA, rpoH, yjeV
First gene in the operon(s) aldA, dnaA, dnaA, guaB, nrdA, polA, rpoH, rpoH, yjeV
Simple and complex regulons ArcA,CRP,DnaA,FNR
ArgP,CRP,DnaA,Fis,H-NS,NrdR
ArgP,DnaA
CRP,CytR,DnaA
CRP,DnaA,Fis,PurR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[DnaA,-](8)
[DnaA,+](2)
[DnaA,+-](1)


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
  DnaA-ATP repressor aldAp Sigma70 -7.5 -50.0 aldA
gatgattgatGTTAATTAAcaatgtattc
1488178 1488186 [BPP], [GEA] [2]
  DnaA-ATP repressor dnaAp1 nd 23.0 -210.0 dnaA, dnaN, recF
aagtcctgtgGATAAATCGggaaaatctg
3883935 3883943 [BPP], [GEA] [3], [4]
  DnaA-ATP dual dnaAp2 Sigma70 -73.0 -226.0 dnaA, dnaN, recF
cttagcgagtTCTGGAAAGtcctgtggat
3883951 3883959 [BPP] [5]
  DnaA-ATP dual dnaAp2 Sigma70 -61.0 -214.0 dnaA, dnaN, recF
tggaaagtccTGTGGATAAatcgggaaaa
3883939 3883947 [BPP], [SM] [5]
  DnaA-ATP repressor dnaAp2 Sigma70 -57.0 -210.0 dnaA, dnaN, recF
aagtcctgtgGATAAATCGggaaaatctg
3883935 3883943 [BPP], [GEA] [3], [4]
  DnaA-ATP dual dnaAp2 Sigma70 -51.0 -204.0 dnaA, dnaN, recF
tgtggataaaTCGGGAAAAtctgtgagaa
3883929 3883937 [BPP] [5]
  DnaA-ATP dual dnaAp2 Sigma70 -40.0 -193.0 dnaA, dnaN, recF
cgggaaaatcTGTGAGAAAcagaagatct
3883918 3883926 [BPP], [SM] [5]
  DnaA-ATP repressor guaBp Sigma70 248.0 210.0 guaB, guaA
gtatcggcttTATCCACAAaaacatgtcc
2633856 2633864 [BPP], [GEA], [HIBSCS] [6], [7]
  DnaA-ATP activator nrdAp Sigma70 -48.0 -158.0 nrdA, nrdB, yfaE
ccttcctgagTTATCCACAaagttatgca
2344703 2344711 [BPP], [HIBSCS], [SM] [8], [9]
  DnaA-ATP activator nrdAp Sigma70 -36.5 -147.0 nrdA, nrdB, yfaE
tatccacaaaGTTATGCACttgcaagagg
2344714 2344722 [BPP], [HIBSCS], [SM] [8], [9]
  DnaA-ATP repressor nrdAp Sigma70 -14.0 -124.0 nrdA, nrdB, yfaE
aagagggtcaTTTTCACACtatcttgcag
2344737 2344745 [HIBSCS] [10]
  DnaA-ATP activator polAp nd -101.0 -127.0 polA
tgcacaaagtTATCCACATgacgatttgc
4046835 4046843 [BPP], [GEA] [11]
  DnaA-ATP repressor rpoHp3 Sigma24 -48.0 -135.0 rpoH
tgtgcgtaatTTATTCACAagcttgcatt
3600914 3600922 [BCE], [HIBSCS] [12]
  DnaA-ATP repressor rpoHp4 Sigma70 -55.0 -135.0 rpoH
tgtgcgtaatTTATTCACAagcttgcatt
3600914 3600922 [BCE], [HIBSCS] [12]
  DnaA-ATP repressor rpoHp4 Sigma70 -31.0 -111.0 rpoH
gcattgaactTGTGGATAAaatcacggtc
3600890 3600898 [HIBSCS] [12]
  DnaA-ATP repressor yjeVp Sigma70 -55.0 -211.0 yjeV
tctcaataaaATATCCACAgcgacgcgat
4392677 4392685 [BPP], [GEA] [13]
  DnaA-ATP repressor yjeVp Sigma70 13.0 -144.0 yjeV
gtaaacagagTTATCCACAgcctcaggct
4392744 4392752 [BPP], [GEA] [13]


Alignment and PSSM for DnaA TFBSs    

Aligned TFBS of DnaA   
  Sequence
 

Position weight matrix (PWM).   
A	7	3	2	1	10	0	0	1	13	0	13
C	1	1	1	0	0	1	9	13	1	12	0
G	3	5	0	0	0	0	1	0	0	2	0
T	3	5	11	13	4	13	4	0	0	0	1

PWM logo   


 


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


Evidence    

 [BPP] Binding of purified proteins

 [IPI] Inferred from physical interaction

 [GEA] Gene expression analysis

 [SM] Site mutation

 [HIBSCS] Human inference based on similarity to consensus sequences

 [BCE] Binding of cellular extracts



Reference(s)    

 [1] Katayama T., Kubota T., Kurokawa K., Crooke E., Sekimizu K., 1998, The initiator function of DnaA protein is negatively regulated by the sliding clamp of the E. coli chromosomal replicase., Cell. 94(1):61-71

 [2] Ozaki T., Kumaki Y., Kitagawa R., Ogawa T., 2001, Anomalous DnaA protein binding to the regulatory region of the Escherichia coli aldA gene., Microbiology. 147(Pt 1):153-9

 [3] Lee Y., Lee H., Yim J., Hwang D., 1997, The binding of two dimers of IciA protein to the dnaA promoter 1P element enhances the binding of RNA polymerase to the dnaA promoter 1P., Nucleic Acids Res. 25(17):3486-9

 [4] Lee YS., Kim H., Hwang DS., 1996, Transcriptional activation of the dnaA gene encoding the initiator for oriC replication by IciA protein, an inhibitor of in vitro oriC replication in Escherichia coli., Mol Microbiol. 19(2):389-96

 [5] Saggioro C., Olliver A., Sclavi B., 2013, Temperature-dependence of the DnaA-DNA interaction and its effect on the autoregulation of dnaA expression., Biochem J. 449(2):333-41

 [6] Tesfa-Selase F., Drabble WT., 1992, Regulation of the gua operon of Escherichia coli by the DnaA protein., Mol Gen Genet. 231(2):256-64

 [7] Tesfa-Selase F., Drabble WT., 1996, Specific binding of DnaA protein to a DnaA box in the guaB gene of Escherichia coli K12., Eur J Biochem. 241(2):411-6

 [8] Augustin LB., Jacobson BA., Fuchs JA., 1994, Escherichia coli Fis and DnaA proteins bind specifically to the nrd promoter region and affect expression of an nrd-lac fusion., J Bacteriol. 176(2):378-87

 [9] Han JS., Kwon HS., Yim JB., Hwang DS., 1998, Effect of IciA protein on the expression of the nrd gene encoding ribonucleoside diphosphate reductase in E. coli., Mol Gen Genet. 259(6):610-4

 [10] Olliver A., Saggioro C., Herrick J., Sclavi B., 2010, DnaA-ATP acts as a molecular switch to control levels of ribonucleotide reductase expression in Escherichia coli., Mol Microbiol. 76(6):1555-71

 [11] Quinones A., Wandt G., Kleinstauber S., Messer W., 1997, DnaA protein stimulates polA gene expression in Escherichia coli., Mol Microbiol. 23(6):1193-202

 [12] Wang QP., Kaguni JM., 1989, dnaA protein regulates transcriptions of the rpoH gene of Escherichia coli., J Biol Chem. 264(13):7338-44

 [13] Kitagawa R., Mitsuki H., Okazaki T., Ogawa T., 1996, A novel DnaA protein-binding site at 94.7 min on the Escherichia coli chromosome., Mol Microbiol. 19(5):1137-47

 [14] Ogawa T., Yamada Y., Kuroda T., Kishi T., Moriya S., 2002, The datA locus predominantly contributes to the initiator titration mechanism in the control of replication initiation in Escherichia coli., Mol Microbiol. 44(5):1367-75

 [15] Kato J., Katayama T., 2001, Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli., EMBO J. 20(15):4253-62

 [16] Riber L., Lobner-Olesen A., 2005, Coordinated replication and sequestration of oriC and dnaA are required for maintaining controlled once-per-cell-cycle initiation in Escherichia coli., J Bacteriol. 187(16):5605-13



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