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FlhDC DNA-binding transcriptional dual regulator

Synonyms: FlhDC
Summary:
The FlhD and FlhC proteins are transcriptional factors and can form homodimers independently (FlhD2 and FlhC2) [3], and the assembly of these homodimers results in the formation of heterotetramers (FlhD2C2) [1, 3, 10]. The complex transcription factor FlhD2C2 is the principal regulator of bacterial flagellum biogenesis and swarming migration [1, 10]. This heterotetrameric regulator activates class II genes involved in the flagellar basal body [1, 3, 4, 10], proteins of the export machinery, the flagellar σ subunit (FliA), and its anti-σ factor, FlgM [1, 10, 11]. Currently, no inducer for this regulator has been reported in the literature. A microarray analysis showed that the master regulator, FlhD2C2, regulates several nonflagellar genes, but the direct effect has not been determined.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
FlhDC     nd nd
Evolutionary Family: FlhC_like, FlhD_like
Connectivity class: Local Regulator
Gene name: flhC
  Genome position: 1977266-1977844
  Length: 579 bp / 192 aa
Operon name: flhDC
TU(s) encoding the TF:
Transcription unit        Promoter
flhDC
flhDp
flhDC
flhDp2
Gene name: flhD
  Genome position: 1977847-1978197
  Length: 351 bp / 116 aa
Operon name: flhDC
TU(s) encoding the TF:
Transcription unit        Promoter
flhDC
flhDp
flhDC
flhDp2


Regulon       
Regulated gene(s) ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH, flgA, flgB, flgC, flgD, flgE, flgF, flgG, flgH, flgI, flgJ, flgK, flgL, flgM, flgN, flhA, flhB, flhE, fliA, fliD, fliE, fliF, fliG, fliH, fliI, fliJ, fliK, fliL, fliM, fliN, fliO, fliP, fliQ, fliR, fliS, fliT, fliZ, glpA, glpB, glpC, gltI, gltJ, gltK, gltL, hydN, hypF, mdh, mglA, mglB, mglC, napA, napB, napC, napD, napF, napG, napH, nrfA,
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Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
flagella (34)
motility, chemotaxis, energytaxis (aerotaxis, redoxtaxis etc) (32)
flagellum (29)
anaerobic respiration (18)
membrane (17)
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Regulated operon(s) flgAMN, flgBCDEFGHIJ, flgKL, flhBAE, fliAZ-tcyJ, fliDST, fliE, fliFGHIJK, fliLMNOPQR, glpABC, gltI-sroC-gltJKL, hydN-hypF, mdh, mglBAC, napFDAGHBC-ccmABCDEFGH, nrfABCDEFG, pdeH, ppdAB-ygdB-ppdC-recC, ycgR, yecR, ygbJK
First gene in the operon(s) flgA, flgB, flgK, flhB, fliA, fliD, fliE, fliF, fliL, glpA, gltI, hydN, mdh, mglB, napF, napF, nrfA, pdeH, ppdA, ycgR, yecR, ygbK
Simple and complex regulons ArcA,CRP,DpiA,FlhDC
ArcA,CRP,FNR,Fis,FlhDC,GlpR
CRP,FlhDC,GalR,GalS
CsgD,FlhDC
CsgD,FlhDC,H-NS,MatA,NsrR,SutR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[FlhDC,+](10)


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
  FlhDC activator flgAp Sigma70 -68.0 -90.0 flgA, flgM, flgN
tacgcgcgcgTTATCGGCGGAATAAACgcaaaatggg
1130945 1130961 [GEA], [HIBSCS] [1]
  FlhDC activator flgAp Sigma70 -40.0 -62.0 flgA, flgM, flgN
caaaatgggtCGCTATTTATGCCGTTGatggtcattg
1130917 1130933 [GEA], [HIBSCS] [1]
  FlhDC activator flgBp Sigma70 -67.5 -93.0 flgB, flgC, flgD, flgE, flgF, flgG, flgH, flgI, flgJ
caatgaccatCAACGGCATAAATAGCGacccattttg
1130917 1130933 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator flgBp Sigma70 -41.5 -67.0 flgB, flgC, flgD, flgE, flgF, flgG, flgH, flgI, flgJ
gacccattttGCGTTTATTCCGCCGATaacgcgcgcg
1130943 1130959 [BPP], [GEA], [HIBSCS] [1]
  FlhDC activator flgKp Sigma28 nd nd flgK, flgL nd nd [BPP], [GEA] [2]
  FlhDC activator flhBp Sigma70 -67.5 -92.5 flhB, flhA, flhE
tgtgtggcagCAAAAGCCCTAAATCCCGcctgttttgc
1966275 1966292 [BPP], [GEA], [HIBSCS] [1], [3]
  FlhDC activator flhBp Sigma70 -39.0 -64.0 flhB, flhA, flhE
ctgttttgccCCTTACTCAAACCATTGaacgctttgc
1966247 1966263 [BPP], [GEA], [HIBSCS] [1], [3]
  FlhDC activator fliAp1 Sigma70 -67.0 -97.0 fliA, fliZ, tcyJ
gaatttacctGTAACCCCCAAATAACCcctcatttca
2001878 2001894 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [3], [4], [5]
  FlhDC activator fliAp1 Sigma70 -38.0 -68.0 fliA, fliZ, tcyJ
tcatttcaccCACTAATCGTCCGATTAaaaaccctgc
2001849 2001865 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [3], [4], [5], [6]
  FlhDC activator fliDp Sigma70 -69.0 -124.0 fliD, fliS, fliT
cattttttgtTAGTCGCCGAAATACTCttttctctgc
2003740 2003756 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator fliDp Sigma70 -41.0 -96.0 fliD, fliS, fliT
tttctctgccCCTTATTCCCGCTATTAaaaaaaacaa
2003768 2003784 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator fliEp1 Sigma70 -69.0 -91.0 fliE
tcgtttttttCTATCCGCCAATAAACCcgtttttttg
2013097 2013113 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator fliEp1 Sigma70 -40.5 -62.5 fliE
gtttttttgtTGCTATTTAGCGCCTTTGtcttattgac
2013068 2013085 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator fliFp1 Sigma70 -69.5 -152.5 fliF, fliG, fliH, fliI, fliJ, fliK
gtcaataagaCAAAGGCGCTAAATAGCAacaaaaaaac
2013068 2013085 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator fliFp1 Sigma70 -41.0 -124.0 fliF, fliG, fliH, fliI, fliJ, fliK
caaaaaaacgGGTTTATTGGCGGATAGaaaaaaacga
2013097 2013113 [BPP], [GEA], [HIBSCS] [1], [2]
  FlhDC activator fliLp1 Sigma70 -65.0 -99.0 fliL, fliM, fliN, fliO, fliP, fliQ, fliR
tattttcgccTAACGTCAGAGGTAGCAccgtaatccg
2019511 2019527 [BPP], [GEA], [HIBSCS] [1], [2], [3]
  FlhDC activator fliLp1 Sigma70 -37.0 -71.0 fliL, fliM, fliN, fliO, fliP, fliQ, fliR
cgtaatccgcGTCTTTTCCCCGCTTTGttgcgctcaa
2019539 2019555 [BPP], [GEA], [HIBSCS] [1], [2], [3], [6]
  FlhDC activator glpABCp Sigma70 nd nd glpA, glpB, glpC nd nd [GEA] [7]
  FlhDC activator gltIp1 Sigma70 -62.0 -211.0 gltI, sroC, gltJ, gltK, gltL
aatggcgaagAAACGGTCTAAATAGGCtgattcaagg
687950 687966 [BPP], [GEA], [HIBSCS] [1]
  FlhDC activator gltIp1 Sigma70 -47.5 -196.5 gltI, sroC, gltJ, gltK, gltL
ggtctaaataGGCTGATTCAAGGCATTTacgggagaaa
687935 687952 [BPP], [GEA], [HIBSCS] [1]
  FlhDC activator hydNp Sigma54 nd nd hydN, hypF nd nd [GEA] [7]
  FlhDC repressor mdhp1 Sigma70 nd nd mdh nd nd [GEA] [7]
  FlhDC repressor mglBp Sigma70 nd nd mglB, mglA, mglC nd nd [GEA] [7]
  FlhDC activator napFp1 Sigma70 nd nd napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH nd nd [GEA] [7]
  FlhDC activator napFp2 Sigma70 nd nd napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH nd nd [GEA] [7]
  FlhDC activator nrfAp Sigma70 nd nd nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG nd nd [GEA] [7]
  FlhDC activator ppdAp Sigma28 nd nd ppdA, ppdB, ygdB, ppdC, recC nd nd [GEA] [8]
  FlhDC activator ycgRp Sigma28 nd nd ycgR nd nd [GEA] [9]
  FlhDC activator yecRp nd -68.0 -90.0 yecR
gacacctacaGATGGCAAGAAATAGCGcctgccaggc
1988124 1988140 [BPP], [GEA], [HIBSCS] [1]
  FlhDC activator yecRp nd -41.0 -63.0 yecR
cctgccaggcGTCTTTTCCGGCCATTGtcgcagcact
1988151 1988167 [BPP], [GEA], [HIBSCS] [1]
  FlhDC activator ygbKp Sigma28 nd nd ygbK nd nd [GEA] [8]
  FlhDC activator yhjHp Sigma28 nd nd pdeH nd nd [GEA] [9]


Alignment and PSSM for FlhDC TFBSs    

Aligned TFBS of FlhDC   
  Sequence
 

Position weight matrix (PWM).   
A	0	2	0	0	11	5	0	1	7	3	2	1	0	4	4	0
C	10	4	8	3	0	2	1	3	7	4	5	8	12	4	1	0
G	4	10	3	2	0	0	0	0	1	5	8	7	4	6	0	0
T	2	0	5	11	5	9	15	12	1	4	1	0	0	2	11	16

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    

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [BPP] Binding of purified proteins

 [SM] Site mutation



Reference(s)    

 [1] Stafford GP., Ogi T., Hughes C., 2005, Binding and transcriptional activation of non-flagellar genes by the Escherichia coli flagellar master regulator FlhD2C2., Microbiology. 151(Pt 6):1779-88

 [2] Brandi A., Giangrossi M., Giuliodori AM., Falconi M., 2016, An Interplay among FIS, H-NS, and Guanosine Tetraphosphate Modulates Transcription of the Escherichia coli cspA Gene under Physiological Growth Conditions., Front Mol Biosci. 3:19

 [3] Liu X., Matsumura P., 1994, The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons., J Bacteriol. 176(23):7345-51

 [4] Ikebe T., Iyoda S., Kutsukake K., 1999, Promoter analysis of the class 2 flagellar operons of Salmonella., Genes Genet Syst. 74(4):179-83

 [5] Lee YY., Barker CS., Matsumura P., Belas R., 2011, Refining the Binding of the Escherichia coli Flagellar Master Regulator, FlhD4C2, on a Base-Specific Level., J Bacteriol. 193(16):4057-68

 [6] Liu X., Matsumura P., 1996, Differential regulation of multiple overlapping promoters in flagellar class II operons in Escherichia coli., Mol Microbiol. 21(3):613-20

 [7] Pruss BM., Liu X., Hendrickson W., Matsumura P., 2001, FlhD/FlhC-regulated promoters analyzed by gene array and lacZ gene fusions., FEMS Microbiol Lett. 197(1):91-7

 [8] Park K., Choi S., Ko M., Park C., 2001, Novel sigmaF-dependent genes of Escherichia coli found using a specified promoter consensus., FEMS Microbiol Lett. 202(2):243-50

 [9] Ko M., Park C., 2000, Two novel flagellar components and H-NS are involved in the motor function of Escherichia coli., J Mol Biol. 303(3):371-82

 [10] Claret L., Hughes C., 2002, Interaction of the atypical prokaryotic transcription activator FlhD2C2 with early promoters of the flagellar gene hierarchy., J Mol Biol. 321(2):185-99

 [11] Barker CS., Pruss BM., Matsumura P., 2004, Increased motility of Escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon., J Bacteriol. 186(22):7529-37

 [12] Bartlett DH., Frantz BB., Matsumura P., 1988, Flagellar transcriptional activators FlbB and FlaI: gene sequences and 5' consensus sequences of operons under FlbB and FlaI control., J Bacteriol. 170(4):1575-81

 [13] Shin S., Park C., 1995, Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR., J Bacteriol. 177(16):4696-702

 [14] Soutourina O., Kolb A., Krin E., Laurent-Winter C., Rimsky S., Danchin A., Bertin P., 1999, Multiple control of flagellum biosynthesis in Escherichia coli: role of H-NS protein and the cyclic AMP-catabolite activator protein complex in transcription of the flhDC master operon., J Bacteriol. 181(24):7500-8

 [15] Sperandio V., Torres AG., Kaper JB., 2002, Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli., Mol Microbiol. 43(3):809-21

 [16] Lehnen D., Blumer C., Polen T., Wackwitz B., Wendisch VF., Unden G., 2002, LrhA as a new transcriptional key regulator of flagella, motility and chemotaxis genes in Escherichia coli., Mol Microbiol. 45(2):521-32

 [17] Bertin P., Terao E., Lee EH., Lejeune P., Colson C., Danchin A., Collatz E., 1994, The H-NS protein is involved in the biogenesis of flagella in Escherichia coli., J Bacteriol. 176(17):5537-40

 [18] Wang S., Fleming RT., Westbrook EM., Matsumura P., McKay DB., 2006, Structure of the Escherichia coli FlhDC complex, a prokaryotic heteromeric regulator of transcription., J Mol Biol. 355(4):798-808

 [19] Campos A., Zhang RG., Alkire RW., Matsumura P., Westbrook EM., 2001, Crystal structure of the global regulator FlhD from Escherichia coli at 1.8 A resolution., Mol Microbiol. 39(3):567-80

 [20] Fitzgerald DM., Bonocora RP., Wade JT., 2014, Comprehensive mapping of the Escherichia coli flagellar regulatory network., PLoS Genet. 10(10):e1004649

 [21] Fitzgerald DM., Bonocora RP., Wade JT., 2015, Correction: Comprehensive Mapping of the Escherichia coli Flagellar Regulatory Network., PLoS Genet. 11(9):e1005456



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