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DpiA DNA-binding transcriptional dual regulator

Synonyms: DpiA, DpiA-phosphorylated
Summary:
CitB/DpiA is a dual transcriptional regulator involved in anaerobic citrate catabolism. In the presence of citrate and under anaerobic conditions it activates genes for citrate fermentation, the citCDEFXGT operon, the citAB operon, and mdh, as well as the exuTR operon for dissimilation of hexuronate [3] Due to the ability of CitB/DpiA to bind to A/T-rich sequences, multiple other roles have been assigned to CitB. When overexpressed in E. coli, it destabilizes plasmid inheritance, represses transcription of appY, encoding a regulator of anaerobic metabolism, and induces the SOS response by competing with DnaA and DnaB in binding to A/T-rich sequences at the replication origin [1, 6]. Moreover, inactivation of penicillin-binding protein 3, FtsI, either chemically or genetically, induces SOS in E. coli. This induction requires dpiBA [7] CitB/DpiA belongs to the two-component system DpiB/DpiA, or CitBA. The operon containing both genes, citB (dpiA), encoding the response regulator, and citA (dpiB), encoding the sensor kinase, is transcribed divergently to the citCDEFXGT operon.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
DpiA Non-Functional   Apo [EXP-IEP], [EXP-IMP-SITE-MUTATION] S [1]
DpiA-phosphorylated Functional Covalent Holo [EXP-IEP], [EXP-IMP-SITE-MUTATION] S [1]
Evolutionary Family: HTH_11
TFBs length: 23
TFBs symmetry: inverted-repeat
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: dpiA
  Genome position: 653862-654542
  Length: 681 bp / 226 aa
Operon name: dpiBA
TU(s) encoding the TF:
Transcription unit        Promoter
dpiBA
dpiBp1
dpiBA
dpiBp2


Regulon       
Regulated gene(s) appY, citC, citD, citE, citF, citG, citX, dpiA, dpiB, exuT, mdh
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
posttranslational modification (4)
unassigned reversible reactions (3)
Transcription related (2)
activator (2)
two component regulatory systems (external signal) (2)
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Regulated operon(s) appY, citCDEFXG, dpiBA, exuT, mdh
First gene in the operon(s) appY, citC, dpiB, exuT, mdh
Simple and complex regulons ArcA,BtsR,CRP,DpiA,FlhDC
ArcA,CRP,DpiA,FNR,NarL
ArcA,DpiA
CRP,DpiA,ExuR
CRP,DpiA,FNR,NarL
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[DpiA,+](7)
[DpiA,-](1)


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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  DpiA-phosphorylated repressor appYp1 Sigma70 nd nd appY
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [1], [1]
  DpiA-phosphorylated activator citCp1 nd -177.0 -273.0 citC, citD, citE, citF, citX, citG
cgtggcaaatTTTATTCATTAAATCAATTAAATCacttaaacct
 652118 652141 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4]
  DpiA-phosphorylated activator citCp1 nd -135.0 -231.0 citC, citD, citE, citF, citX, citG
ctgcgagtcaTTTCGTAATTACATTAATTAAAAAacttaaaatc
 652076 652099 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5]
  DpiA-phosphorylated activator citCp1 nd -108.0 -204.0 citC, citD, citE, citF, citX, citG
ttaaaaaactTAAAATCATTAAATAAATAAAAAAccactaactc
 652049 652072 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5]
  DpiA-phosphorylated activator citCp2 nd -90.0 -273.0 citC, citD, citE, citF, citX, citG
cgtggcaaatTTTATTCATTAAATCAATTAAATCacttaaacct
 652118 652141 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4]
  DpiA-phosphorylated activator citCp2 nd -48.0 -231.0 citC, citD, citE, citF, citX, citG
ctgcgagtcaTTTCGTAATTACATTAATTAAAAAacttaaaatc
 652076 652099 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5]
  DpiA-phosphorylated activator citCp2 nd -21.0 -204.0 citC, citD, citE, citF, citX, citG
ttaaaaaactTAAAATCATTAAATAAATAAAAAAccactaactc
 652049 652072 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5]
  DpiA-phosphorylated activator dpiBp1 nd 77.0 -175.0 dpiB, dpiA
gagttagtggTTTTTTATTTATTTAATGATTTTAagttttttaa
 652049 652072 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5]
  DpiA-phosphorylated activator dpiBp1 nd 104.0 -148.0 dpiB, dpiA
gattttaagtTTTTTAATTAATGTAATTACGAAAtgactcgcag
 652076 652099 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4], [5]
  DpiA-phosphorylated activator dpiBp1 nd 146.0 -106.0 dpiB, dpiA
aggtttaagtGATTTAATTGATTTAATGAATAAAatttgccacg
 652118 652141 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [3], [4]
  DpiA-phosphorylated activator exuTp1 nd nd nd exuT
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [3], [3]
  DpiA-phosphorylated activator exuTp2 nd nd nd exuT
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [3], [3]
  DpiA-phosphorylated activator mdhp1 Sigma70 nd nd mdh
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [3], [3]
  DpiA-phosphorylated activator mdhp2 nd nd nd mdh
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [3], [3]


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


Evidence    

 [EXP-IEP] Inferred from expression pattern

 [EXP-IMP-SITE-MUTATION] Site mutation

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-GSELEX] high throughput Genomic SELEX-chip evidence

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing


Reference(s)    

 [1] Ingmer H., Miller CA., Cohen SN., 1998, Destabilized inheritance of pSC101 and other Escherichia coli plasmids by DpiA, a novel two-component system regulator., Mol Microbiol 29(1):49-59

 [2] Scheu PD., Witan J., Rauschmeier M., Graf S., Liao YF., Ebert-Jung A., Basche T., Erker W., Unden G., 2012, CitA/CitB two-component system regulating citrate fermentation in Escherichia coli and its relation to the DcuS/DcuR system in vivo., J Bacteriol 194(3):636-45

 [3] Yamamoto K., Matsumoto F., Oshima T., Fujita N., Ogasawara N., Ishihama A., 2008, Anaerobic regulation of citrate fermentation by CitAB in Escherichia coli., Biosci Biotechnol Biochem 72(11):3011-4

 [4] Ishihama A, Shimada T, Yamazaki Y, 2016, Transcription profile of Escherichia coli: genomic SELEX search for regulatory targets of transcription factors., Nucleic Acids Res, 44(5):2058 10.1093/nar/gkw051

 [5] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [6] Miller C, Ingmer H, Thomsen LE, Skarstad K, Cohen SN, 2003, DpiA binding to the replication origin of Escherichia coli plasmids and chromosomes destabilizes plasmid inheritance and induces the bacterial SOS response., J Bacteriol, 185(20):6025 10.1128/JB.185.20.6025-6031.2003

 [7] Miller C., Thomsen LE., Gaggero C., Mosseri R., Ingmer H., Cohen SN., 2004, SOS response induction by beta-lactams and bacterial defense against antibiotic lethality., Science 305(5690):1629-31

 [8] Kaspar S, Bott M, 2002, The sensor kinase CitA (DpiB) of Escherichia coli functions as a high-affinity citrate receptor., Arch Microbiol, 177(4):313 10.1007/s00203-001-0393-z

 [9] Yamamoto K, Matsumoto F, Minagawa S, Oshima T, Fujita N, Ogasawara N, Ishihama A, 2009, Characterization of CitA-CitB signal transduction activating genes involved in anaerobic citrate catabolism in Escherichia coli., Biosci Biotechnol Biochem, 73(2):346 10.1271/bbb.80586

 [10] Meyer M, Dimroth P, Bott M, 1997, In vitro binding of the response regulator CitB and of its carboxy-terminal domain to A + T-rich DNA target sequences in the control region of the divergent citC and citS operons of Klebsiella pneumoniae., J Mol Biol, 269(5):719 10.1006/jmbi.1997.1076


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