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PhoP DNA-binding transcriptional dual regulator

Synonyms: PhoP-Phosphorylated, PhoP
Summary:
PhoP is a dual transcriptional regulator that is activated in response to low extracellular levels of divalent cations, e.g., magnesium or calcium [10, 17, 18]. In Escherichia coli K-12, PhoP activates transcription of a large collection of genes involved in Mg2+ homeostasis, resistance to antimicrobial peptides, acid resistance, and LPS modification [3, 10, 19].
PhoP belongs to the OmpR/PhoB subfamily of response regulators characterized by a winged-helix DNA-binding domain. The structure of the N-terminal receiver domain has been solved in the absence and presence of the phosphoryl analog beryllofluoride [20]. PhoP is phosphorylated and thereby activated by its cognate sensor kinase PhoQ at a low extracellular concentration of magnesium. At high levels of magnesium the phospho-PhoP phosphatase activity of the sensor protein is induced [21].
Regulation of the PhoQ/PhoP system is connected to the EvgS/EvgA system through the small inner membrane protein B1500.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
PhoP Non-Functional   Apo [BPP], [IPI] [1]
PhoP-Phosphorylated Functional Covalent Holo [BPP], [IPI] [1]
Evolutionary Family: OmpR
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: phoP
  Genome position: 1189776-1190447
  Length: 672 bp / 223 aa
Operon name: phoPQ
TU(s) encoding the TF:
Transcription unit        Promoter
phoPQ
phoPp1
phoPQ
phoPp2
phoPQ
phoPp3


Regulon       
Regulated gene(s) acrA, acrB, argD, borD, cysB, dcuD, fadL, gadE, gadW, glgA, glgB, glgC, glgP, glgX, hdeA, hdeB, hdeD, hemL, iraM, malS, metB, metL, mgrB, mgrR, mgtA, mgtL, nagA, ompT, pagP, phoP, phoQ, purD, purH, rstA, rstB, rutA, rutB, rutC, rutD, rutE, rutF, rutG, safA, slyB, tolC, treR, ybjG, ydeO, ydeP, ygiA, ygiB, ygiC, yhiD, yneM, yrbL
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (10)
Transcription related (7)
pH (6)
nitrogen metabolism (6)
activator (5)
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Regulated operon(s) acrAB, argD, borD, cysB, dcuD, envY-ompT, fadL, gadAXW, gadE-mdtEF, glgBXCAP, hdeAB-yhiD, hdeD, hemL, iraM, malS, metBL, mgrB, mgrR, mgtLA, nagBAC-umpH, pagP, phoPQ, purHD, rstAB, rutABCDEFG, safA-ydeO, slyB, tolC-ygiABC, treR, ybjG, ydeP, yneM, yrbL
First gene in the operon(s) acrA, argD, borD, cysB, dcuD, fadL, gadE, gadW, glgA, glgB, hdeA, hdeD, hemL, iraM, iraM, malS, metB, mgrB, mgrR, mgtL, nagA, ompT, pagP, phoP, phoP, purH, rstA, rutA, safA, slyB, slyB, tolC, treR, treR, ybjG, ydeP, yneM, yrbL
Simple and complex regulons AcrR,EnvR,MarA,MprA,PhoP,Rob,SoxS
ArcA,CRP,FadR,OmpR,PhoP
ArcA,FNR,PhoP
ArcA,GadE,PhoP
ArcA,NtrC,PhoP,RutR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[PhoP,-](9)
[PhoP,+](28)


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
  PhoP-Phosphorylated repressor acrAp Sigma70 32.0 -48.0 acrA, acrB
cgcagcaatgGGTTTATTAACTTTTGAccattgacca
485659 485675 [GEA] [2]
  PhoP-Phosphorylated repressor argDp Sigma70 11.0 -31.0 argD
ttgtggttatAATTTCACATTTGTTTAtgcgtaacag
3490203 3490219 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated activator borDp nd -33.0 -61.0 borD
ttcaactcatTGTTTAGGGTTTGTTTAattttctaca
578946 578962 [BPP], [HIBSCS] [3]
  PhoP-Phosphorylated activator cysBp Sigma70 -43.0 -110.0 cysB
acctatacacTAAGGCTATAAATGATATAGTGGttatagttag
1333734 1333756 [AIBSCS], [HIBSCS] [4]
  PhoP-Phosphorylated repressor dcuDp Sigma70 56.5 -47.5 dcuD
ataacatcgtTGTTTTCAATCTGCCGTTTAtgggattgac
3374812 3374831 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated activator fadLp Sigma38 -191.5 -292.5 fadL
ttccggaaagTGCTGCTCCAGTTGTTAAttctgcaaaa
2461005 2461022 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated activator gadEp1 Sigma38 -85.0 -209.0 gadE
ttttgtttgcTATTTACAAGCTGATAAcaaccaggaa
3658149 3658165 [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator gadWp2 nd -28.0 -191.0 gadW
catttttttaTAAACATAAGCTATACGctgtgcgaaa
3664801 3664817 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator glgAp Sigma70 nd nd glgA, glgP nd nd [GEA] [6]
  PhoP-Phosphorylated activator glgBp Sigma70 -34.0 -189.0 glgB, glgX, glgC, glgA, glgP
gatgtttcatGATTTACCGGGAGTTAAatagagcatt
3573683 3573699 [AIBSCS], [GEA] [6]
  PhoP-Phosphorylated activator hdeAp Sigma38 -32.0 -83.0 hdeA, hdeB, yhiD
atattttccaTCAACATGACATATACAgaaaaccagg
3656815 3656831 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator hdeDp Sigma70 -137.0 -172.0 hdeD
cctggttttcTGTATATGTCATGTTGAtggaaaatat
3656815 3656831 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator hemLp Sigma28 -31.0 -70.0 hemL
agcagcctgaTGTTTGACGAGTATTTAacttgttatg
174944 174960 [BPP], [GEA], [HIBSCS] [3]
  PhoP-Phosphorylated activator iraMp nd -199.5 -286.5 iraM
ataatgtttaGCAAATTGGCACAAAGtagcataaag
1212282 1212297 [GEA], [HIBSCS] [7]
  PhoP-Phosphorylated activator iraMp nd -68.0 -155.0 iraM
aatctcatttTGTTTAACATCCATTGAgattccttgc
1212150 1212166 [BPP], [GEA], [HIBSCS] [7], [8]
  PhoP-Phosphorylated activator iraMp2 Sigma70 -35.0 -155.0 iraM
aatctcatttTGTTTAACATCCATTGAgattccttgc
1212150 1212166 [BPP], [GEA], [HIBSCS] [7], [8]
  PhoP-Phosphorylated activator malSp Sigma70 -161.0 -188.0 malS
caaatctgaaACTATGTCACGTGTTAAcgattcagat
3737301 3737317 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated activator metBp Sigma70 -20.0 -56.0 metB, metL
tattgacgtcCATTAACACAATGTTTActctggtgcc
4128608 4128624 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated activator mgrBp nd -33.0 -59.0 mgrB
aatatcgacaTAGTTAGGCGCTGTTTAactaacgcat
1908817 1908833 [BPP], [GEA], [HIBSCS] [3], [9], [10]
  PhoP-Phosphorylated activator mgrRp Sigma70 -44.0 -44.0 mgrR
tgattaaccgAGTTTAAGCTCCGTTTAacattcattg
1622950 1622966 [GEA], [HIBSCS] [11]
  PhoP-Phosphorylated activator mgtAp1 Sigma70 -34.0 -102.0 mgtL, mgtA
ggtaaagtctGGTTTATCGTTGGTTTAgttgtcagca
4467321 4467337 [BPP], [GEA], [HIBSCS], [SM] [3], [10], [12], [13]
  PhoP-Phosphorylated activator nagAp nd -31.0 -455.0 nagA
aaaattcatcTGTTTATGGGCGGTGTAggtaacgacg
703198 703214 [BPP], [GEA], [HIBSCS] [3]
  PhoP-Phosphorylated activator ompTp nd -49.0 -81.0 ompT
aaacaaaataTAAACAGTGGAGCAATAtgtaattgac
585706 585722 [GEA], [HIBSCS] [3], [5]
  PhoP-Phosphorylated activator pagPp nd -32.0 -63.0 pagP
atgttgggtcTATTAAGGTTATGTTAAttgtagcttt
656486 656502 [GEA], [HIBSCS] [9]
  PhoP-Phosphorylated repressor phoPp1 nd -33.0 -69.0 phoP, phoQ
cctccccgctGGTTTATTTAATGTTTAcccccataac
1190508 1190524 [AIBSCS], [BPP], [GEA], [HIBSCS] [2], [3], [9], [10]
  PhoP-Phosphorylated activator phoPp2 nd -8.0 -69.0 phoP, phoQ
cctccccgctGGTTTATTTAATGTTTAcccccataac
1190508 1190524 [AIBSCS], [BPP], [GEA], [HIBSCS] [2], [3], [9], [10]
  PhoP-Phosphorylated activator purHp Sigma70 -479.0 -574.0 purH, purD
taaacttcgtAATGAATTACGTGTTCActcttgagac
4208098 4208114 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated activator rstAp nd -44.0 -65.0 rstA, rstB
gatgaaaactTGTTTAGAAACGATTGAtagtaagtaa
1682086 1682102 [AIBSCS], [BPP], [GEA], [HIBSCS] [2], [3], [14]
  PhoP-Phosphorylated activator rutAp Sigma54 -106.0 -121.0 rutA, rutB, rutC, rutD, rutE, rutF, rutG
tatgtgcaacTGTTTTGACCGTTTAgtccactttt
1074125 1074139 [AIBSCS], [GEA] [2]
  PhoP-Phosphorylated repressor safAp Sigma70 33.0 -37.0 safA, ydeO
ttaagcatacTGATTAACGATTTTTAAcgttatccgc
1583988 1584004 [GEA], [HIBSCS], [SM] [15]
  PhoP-Phosphorylated repressor safAp Sigma70 53.0 -17.0 safA, ydeO
tttttaacgtTATCCGCTAAATAAACAtatttgaaat
1583968 1583984 [GEA], [HIBSCS], [SM] [15]
  PhoP-Phosphorylated activator slyBp1 nd -33.0 -132.0 slyB
atgaatgtttTGTTTATAATTGGTTGAtcctactttc
1719736 1719752 [BPP], [GEA], [HIBSCS] [3]
  PhoP-Phosphorylated repressor slyBp2 nd -4.0 -132.0 slyB
atgaatgtttTGTTTATAATTGGTTGAtcctactttc
1719736 1719752 [BPP], [GEA], [HIBSCS] [3]
  PhoP-Phosphorylated activator tolCp2 nd -46.0 -149.0 tolC, ygiA, ygiB, ygiC
atttcagcgaCGTTTGACTGCCGTTTGagcagtcatg
3177958 3177974 [GEA], [HIBSCS] [16]
  PhoP-Phosphorylated repressor treRp3 Sigma70 -50.0 -83.0 treR
tgctgacaacTAAACCAACGATAAACCagactttacc
4467321 4467337 [BPP], [GEA], [HIBSCS], [SM] [3], [10], [13]
  PhoP-Phosphorylated repressor treRp4 Sigma70 19.0 -83.0 treR
tgctgacaacTAAACCAACGATAAACCagactttacc
4467321 4467337 [BPP], [GEA], [HIBSCS], [SM] [3], [10], [13]
  PhoP-Phosphorylated activator ybjGp nd -32.0 -152.0 ybjG
agctacgcttTCTTTAAGTTTTATTTAacctatgccc
883532 883548 [GEA], [HIBSCS] [9]
  PhoP-Phosphorylated repressor ydePp Sigma70 34.5 -144.5 ydeP
taacttatcgTATTTAATCTATTGTTTAacgataatag
1586622 1586639 [GEA], [HIBSCS] [15]
  PhoP-Phosphorylated activator yneMp Sigma70 -35.0 -93.0 yneM
ataaagatttAATTCAGCCTTCGTTTAggttacctct
1622545 1622561 [GEA], [HIBSCS] [11]
  PhoP-Phosphorylated activator yrbLp nd -28.0 -59.0 yrbL
taagaggcatTGTTTAGGTTTTGTTTAagttaatcga
3348385 3348401 [AIBSCS], [BPP], [GEA], [HIBSCS] [2], [3]


Alignment and PSSM for PhoP TFBSs    

Aligned TFBS of PhoP   
  Sequence
 

Position weight matrix (PWM).   
A	9	8	0	5	5	25	8	5	11	10	4	1	4	1	1	7	32
C	2	5	0	1	2	2	4	15	5	4	12	9	0	0	1	1	0
G	4	16	2	4	1	4	8	8	5	6	5	4	27	3	2	5	1
T	18	4	31	23	25	2	13	5	12	13	12	19	2	29	29	20	0

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

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation



Reference(s)    

 [1] Yamamoto K., Hirao K., Oshima T., Aiba H., Utsumi R., Ishihama A., 2005, Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli., J Biol Chem. 280(2):1448-56

 [2] Monsieurs P., De Keersmaecker S., Navarre WW., Bader MW., De Smet F., McClelland M., Fang FC., De Moor B., Vanderleyden J., Marchal K., 2005, Comparison of the PhoPQ regulon in Escherichia coli and Salmonella typhimurium., J Mol Evol. 60(4):462-74

 [3] Minagawa S., Ogasawara H., Kato A., Yamamoto K., Eguchi Y., Oshima T., Mori H., Ishihama A., Utsumi R., 2003, Identification and molecular characterization of the Mg2+ stimulon of Escherichia coli., J Bacteriol. 185(13):3696-702

 [4] Kaleta C., Gohler A., Schuster S., Jahreis K., Guthke R., Nikolajewa S., 2010, Integrative inference of gene-regulatory networks in Escherichia coli using information theoretic concepts and sequence analysis., BMC Syst Biol. 4:116

 [5] Zwir I., Shin D., Kato A., Nishino K., Latifi T., Solomon F., Hare JM., Huang H., Groisman EA., 2005, Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica., Proc Natl Acad Sci U S A. 102(8):2862-7

 [6] Montero M., Almagro G., Eydallin G., Viale AM., Munoz FJ., Bahaji A., Li J., Rahimpour M., Baroja-Fernandez E., Pozueta-Romero J., 2011, Escherichia coli glycogen genes are organized in a single glgBXCAP transcriptional unit possessing an alternative suboperonic promoter within glgC that directs glgAP expression., Biochem J. 433(1):107-17

 [7] Bougdour A., Cunning C., Baptiste PJ., Elliott T., Gottesman S., 2008, Multiple pathways for regulation of sigmaS (RpoS) stability in Escherichia coli via the action of multiple anti-adaptors., Mol Microbiol. 68(2):298-313

 [8] Eguchi Y., Ishii E., Hata K., Utsumi R., 2011, Regulation of acid resistance by connectors of two-component signal transduction systems in Escherichia coli., J Bacteriol. 193(5):1222-8

 [9] Eguchi Y., Okada T., Minagawa S., Oshima T., Mori H., Yamamoto K., Ishihama A., Utsumi R., 2004, Signal transduction cascade between EvgA/EvgS and PhoP/PhoQ two-component systems of Escherichia coli., J Bacteriol. 186(10):3006-14

 [10] Kato A., Tanabe H., Utsumi R., 1999, Molecular characterization of the PhoP-PhoQ two-component system in Escherichia coli K-12: identification of extracellular Mg2+-responsive promoters., J Bacteriol. 181(17):5516-20

 [11] Moon K., Gottesman S., 2009, A PhoQ/P-Regulated small RNA Regulates Sensitivity of Escherichia coli to Antimicrobial Peptides., Mol Microbiol. 74(6):1314-30

 [12] Oshima T., Aiba H., Masuda Y., Kanaya S., Sugiura M., Wanner BL., Mori H., Mizuno T., 2002, Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12., Mol Microbiol. 46(1):281-91

 [13] Yamamoto K., Ogasawara H., Fujita N., Utsumi R., Ishihama A., 2002, Novel mode of transcription regulation of divergently overlapping promoters by PhoP, the regulator of two-component system sensing external magnesium availability., Mol Microbiol. 45(2):423-38

 [14] Ogasawara H., Hasegawa A., Kanda E., Miki T., Yamamoto K., Ishihama A., 2007, Genomic SELEX search for target promoters under the control of the PhoQP-RstBA signal relay cascade., J Bacteriol. 189(13):4791-9

 [15] Burton NA., Johnson MD., Antczak P., Robinson A., Lund PA., 2010, Novel aspects of the acid response network of E. coli K-12 are revealed by a study of transcriptional dynamics., J Mol Biol. 401(5):726-42

 [16] Eguchi Y., Oshima T., Mori H., Aono R., Yamamoto K., Ishihama A., Utsumi R., 2003, Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli., Microbiology. 149(Pt 10):2819-28

 [17] Groisman EA., Heffron F., Solomon F., 1992, Molecular genetic analysis of the Escherichia coli phoP locus., J Bacteriol. 174(2):486-91

 [18] Kasahara M., Nakata A., Shinagawa H., 1992, Molecular analysis of the Escherichia coli phoP-phoQ operon., J Bacteriol. 174(2):492-8

 [19] Miyashiro T., Goulian M., 2007, Stimulus-dependent differential regulation in the Escherichia coli PhoQ PhoP system., Proc Natl Acad Sci U S A. 104(41):16305-10

 [20] Bachhawat P., Stock AM., 2007, Crystal structures of the receiver domain of the response regulator PhoP from Escherichia coli in the absence and presence of the phosphoryl analog beryllofluoride., J Bacteriol. 189(16):5987-95

 [21] Castelli ME., Garcia Vescovi E., Soncini FC., 2000, The phosphatase activity is the target for Mg2+ regulation of the sensor protein PhoQ in Salmonella., J Biol Chem. 275(30):22948-54

 [22] Eguchi Y., Itou J., Yamane M., Demizu R., Yamato F., Okada A., Mori H., Kato A., Utsumi R., 2007, B1500, a small membrane protein, connects the two-component systems EvgS/EvgA and PhoQ/PhoP in Escherichia coli., Proc Natl Acad Sci U S A. 104(47):18712-7



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