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DnaA DNA-binding transcriptional dual regulator

Synonyms: DnaA-ATP, DnaA
Summary:
DnaA is the linchpin element in the initiation of DNA replication in E. coli. It initiates the process of replication by binding to the origin of replication (oriC). This opens the origin to provide access to single-stranded DNA for the replicative helicase DnaB and its associated loading protein, DnaC, creating the two replication forks that will move outward as DNA polymerase synthesizes new DNA. DnaA is a central focus for regulation of this initiation process, maintaining the critical ratio of one initiation of DNA replication per cell division. As a consequence, a number of factors feed into the regulation of both DnaA abundance and activity, yielding an integrated control over this core cellular process. Recent reviews: |CITS: [24747048][29312202][29357054]| DnaA interacts with oriC via binding at short DNA sequences known as "DnaA boxes" |CITS: [7615570][2542031][6091903][6310593][9297181]|. Prior to the start of the replication initiation process, DnaA monomers are bound to three high-affinity sites within oriC. As the replication initiation process begins, DnaA oligomerizes, apparently "spidering out" from these high-affinity sites to facilitate binding of the low-affinity DnaA boxes |CITS: [19833870][10234818][9351837]|. IHF binds at the same time as this shift from high- to low-affinity sites occurs, enhancing binding by DnaA to these low-affinity boxes |CITS: [10692160][12366835]|. DnaA-ATP binds with somewhat greater affinity to the general oriC region than DnaA-ADP |CITS: [11250912]|.
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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 nd nd
DnaA-ATP Functional Allosteric Holo [APPH], [IEP], [IPI] [1], [2], [3], [4]
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,MarA,Rob,SoxS
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,+-](1)
[DnaA,-](8)
[DnaA,+](2)


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
  DnaA-ATP repressor aldAp Sigma70 -7.5 -50.0 aldA
gatgattgatGTTAATTAAcaatgtattc
1488178 1488186 [BPP], [GEA] [3]
  DnaA-ATP repressor dnaAp1 nd 23.0 -210.0 dnaA, dnaN, recF
cagattttccCGATTTATCcacaggactt
3883935 3883943 [BPP], [GEA] [1], [5]
  DnaA-ATP dual dnaAp2 Sigma70 -73.0 -226.5 dnaA, dnaN, recF
atccacaggaCTTTCCAGAactcgctaag
3883951 3883960 [BPP] [6]
  DnaA-ATP dual dnaAp2 Sigma70 -61.0 -214.5 dnaA, dnaN, recF
ttttcccgatTTATCCACAggactttcca
3883939 3883948 [BPP], [SM] [6]
  DnaA-ATP repressor dnaAp2 Sigma70 -57.0 -210.0 dnaA, dnaN, recF
cagattttccCGATTTATCcacaggactt
3883935 3883943 [BPP], [GEA] [1], [5]
  DnaA-ATP dual dnaAp2 Sigma70 -51.0 -204.5 dnaA, dnaN, recF
ttctcacagaTTTTCCCGAtttatccaca
3883929 3883938 [BPP] [6]
  DnaA-ATP dual dnaAp2 Sigma70 -40.0 -193.5 dnaA, dnaN, recF
agatcttctgTTTCTCACAgattttcccg
3883918 3883927 [BPP], [SM] [6]
  DnaA-ATP repressor guaBp Sigma70 248.0 210.0 guaB, guaA
ggacatgtttTTGTGGATAaagccgatac
2633856 2633864 [BPP], [GEA], [HIBSCS] [7], [8]
  DnaA-ATP activator nrdAp Sigma70 -48.0 -158.0 nrdA, nrdB, yfaE
ccttcctgagTTATCCACAaagttatgca
2344703 2344711 [BPP], [HIBSCS], [SM] [9], [10]
  DnaA-ATP activator nrdAp Sigma70 -36.5 -147.0 nrdA, nrdB, yfaE
tatccacaaaGTTATGCACttgcaagagg
2344714 2344722 [BPP], [HIBSCS], [SM] [9], [10]
  DnaA-ATP repressor nrdAp Sigma70 -14.0 -124.0 nrdA, nrdB, yfaE
aagagggtcaTTTTCACACtatcttgcag
2344737 2344745 [HIBSCS] [2]
  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
aatgcaagctTGTGAATAAattacgcaca
3600914 3600922 [BCE], [HIBSCS] [4]
  DnaA-ATP repressor rpoHp4 Sigma70 -55.0 -135.0 rpoH
aatgcaagctTGTGAATAAattacgcaca
3600914 3600922 [BCE], [HIBSCS] [4]
  DnaA-ATP repressor rpoHp4 Sigma70 -31.0 -111.0 rpoH
gaccgtgattTTATCCACAagttcaatgc
3600890 3600898 [HIBSCS] [4]
  DnaA-ATP repressor yjeVp Sigma70 -55.0 -211.0 yjeV
tctcaataaaATATCCACAgcgacgcgat
4392677 4392685 [BPP], [GEA] [12]
  DnaA-ATP repressor yjeVp Sigma70 13.0 -144.0 yjeV
gtaaacagagTTATCCACAgcctcaggct
4392744 4392752 [BPP], [GEA] [12]


Alignment and PSSM for DnaA TFBSs    

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    

 [APPH] Assay of protein purified to homogeneity

 [IEP] Inferred from expression pattern

 [IPI] Inferred from physical interaction

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [SM] Site mutation

 [HIBSCS] Human inference based on similarity to consensus sequences

 [BCE] Binding of cellular extracts



Reference(s)    

 [1] 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

 [2] 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

 [3] 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

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

 [5] 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

 [6] 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

 [7] 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

 [8] 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

 [9] 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

 [10] 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

 [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] 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



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