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PhoP DNA-binding transcriptional dual regulator

Synonyms: PhoP, PhoP-Phosphorylated
Summary:
Member of the two-component regulatory system phoQ/phoP involved in adaptation to low Mg2+ environments and the control of acid resistance genes. Mediates magnesium influx to the cytosol by activation of mgtA. Promotes expression of the two-component regulatory system rstA/rstB and transcription of the hemL, mgrB, nagA, slyB, vboR and yrbL genes.


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] [1]
PhoP-Phosphorylated Functional Covalent Holo [APPHINH], [BPP], [HIFS], [IMP], [IPI] [1], [2], [3], [4], [5], [6]
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, clpS, cysB, dcuD, fadL, gadE, gadF, gadW, glgA, glgB, glgC, glgP, glgX, hdeA, hdeB, hdeD, hemL, iraM, malS, metB, metL, mgrB, mgrR, mgtA, mgtL, mgtS, nagA, ompT, pagP, phoP, phoQ, purD, purH, rstA, rstB, rutA, rutB, rutC, rutD, rutE, rutF, rutG, safA, slyB, tolC, treR, ybjG, ydeO, ydeP, ygiB, ygiC, yhiD, yrbL
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (11)
Transcription related (7)
pH (6)
nitrogen metabolism (6)
activator (5)
Read more >
Regulated operon(s) acrAB, argD, borD, clpS, cysB, dcuD, envY-ompT, fadL, gadAXW, gadEF-mdtEF, glgBXCAP, hdeAB-yhiD, hdeD, hemL, iraM, malS, metBL, mgrB, mgrR, mgtLA, mgtS, nagBAC-umpH, pagP, phoPQ, purHD, rstAB, rutABCDEFG, safA-ydeO, slyB, tolC-ygiBC, treR, ybjG, ydeP, yrbL
First gene in the operon(s) acrA, argD, borD, clpS, cysB, dcuD, fadL, gadE, gadW, glgA, glgB, hdeA, hdeD, hemL, iraM, malS, metB, mgrB, mgrR, mgtL, nagA, ompT, pagP, phoP, phoP, purH, rstA, rutA, safA, slyB, slyB, tolC, treR, treR, ybjG, ydeP, yrbL, iraM, mgtS
Simple and complex regulons AcrR,EnvR,MarA,MprA,PhoP,Rob,SoxS
ArcA,CRP,FadR,OmpR,PhoP,ppGpp
ArcA,FNR,PhoP
ArcA,GadE,PhoP
ArcA,NtrC,PhoP,RutR
Read more >
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[PhoP,-](10)
[PhoP,+](29)


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
  PhoP-Phosphorylated repressor acrAp Sigma70 32.0 -48.0 acrA, acrB
cgcagcaatgGGTTTATTAACTTTTGAccattgacca
485659 485675 [GEA] [7]
  PhoP-Phosphorylated repressor argDp Sigma70 11.0 -31.0 argD
ttgtggttatAATTTCACATTTGTTTAtgcgtaacag
3490203 3490219 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated activator borDp nd -33.0 -61.0 borD
ttcaactcatTGTTTAGGGTTTGTTTAattttctaca
578946 578962 [BPP], [HIBSCS] [5]
  PhoP-Phosphorylated repressor clpSp nd -7.0 -169.0 clpS
gacaaggggcAGGTATGAATCAAAAATttgaagcagt
922736 922752 [BCE], [GEA], [IHBCE] [8]
  PhoP-Phosphorylated activator cysBp Sigma70 -43.0 -109.5 cysB
acctatacacTAAGGCTATAAATGATATAGTGGTtatagttagc
1333734 1333757 [AIBSCS], [HIBSCS] [9]
  PhoP-Phosphorylated repressor dcuDp Sigma70 56.5 -47.0 dcuD
ataacatcgtTGTTTTCAATCTGCCGTTTATgggattgacc
3374812 3374832 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated activator fadLp Sigma38 -191.5 -292.0 fadL
ttccggaaagTGCTGCTCCAGTTGTTAATtctgcaaaat
2461005 2461023 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated activator gadEp1 Sigma38 -85.0 -209.0 gadE, gadF
ttttgtttgcTATTTACAAGCTGATAAcaaccaggaa
3658149 3658165 [GEA], [HIBSCS] [6]
  PhoP-Phosphorylated activator gadWp2 nd -28.0 -191.0 gadW
catttttttaTAAACATAAGCTATACGctgtgcgaaa
3664801 3664817 [BPP], [GEA], [HIBSCS] [6]
  PhoP-Phosphorylated activator glgAp Sigma70 nd nd glgA, glgP nd nd [GEA] [10]
  PhoP-Phosphorylated activator glgBp Sigma70 -34.0 -189.0 glgB, glgX, glgC, glgA, glgP
gatgtttcatGATTTACCGGGAGTTAAatagagcatt
3573683 3573699 [AIBSCS], [GEA] [10]
  PhoP-Phosphorylated activator hdeAp Sigma38, Sigma70, Sigma70, Sigma38 -32.0 -83.0 hdeA, hdeB, yhiD
atattttccaTCAACATGACATATACAgaaaaccagg
3656815 3656831 [BPP], [GEA], [HIBSCS] [6]
  PhoP-Phosphorylated activator hdeDp Sigma38, Sigma70 -137.0 -172.0 hdeD
cctggttttcTGTATATGTCATGTTGAtggaaaatat
3656815 3656831 [BPP], [GEA], [HIBSCS] [6]
  PhoP-Phosphorylated activator hemLp Sigma28 -31.0 -70.0 hemL
agcagcctgaTGTTTGACGAGTATTTAacttgttatg
174944 174960 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator iraMp nd -199.5 -287.0 iraM
cataatgtttAGCAAATTGGCACAAAGtagcataaag
1212282 1212298 [GEA], [HIBSCS] [11]
  PhoP-Phosphorylated activator iraMp nd -68.0 -155.0 iraM
aatctcatttTGTTTAACATCCATTGAgattccttgc
1212150 1212166 [BPP], [GEA], [HIBSCS] [11], [12]
  PhoP-Phosphorylated activator iraMp2 Sigma70 -35.0 -155.0 iraM
aatctcatttTGTTTAACATCCATTGAgattccttgc
1212150 1212166 [BPP], [GEA], [HIBSCS] [11], [12]
  PhoP-Phosphorylated activator malSp Sigma70 -161.0 -188.0 malS
caaatctgaaACTATGTCACGTGTTAAcgattcagat
3737301 3737317 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated activator metBp Sigma70 -20.0 -56.0 metB, metL
tattgacgtcCATTAACACAATGTTTActctggtgcc
4128608 4128624 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated activator mgrBp nd -33.0 -59.0 mgrB
aatatcgacaTAGTTAGGCGCTGTTTAactaacgcat
1908817 1908833 [BPP], [GEA], [HIBSCS] [4], [5], [13]
  PhoP-Phosphorylated activator mgrRp Sigma70 -44.0 -44.0 mgrR
tgattaaccgAGTTTAAGCTCCGTTTAacattcattg
1622950 1622966 [GEA], [HIBSCS] [14]
  PhoP-Phosphorylated activator mgtAp1 Sigma70 -34.0 -102.0 mgtL, mgtA
ggtaaagtctGGTTTATCGTTGGTTTAgttgtcagca
4467321 4467337 [BPP], [GEA], [HIBSCS], [SM] [4], [5], [15], [16]
  PhoP-Phosphorylated activator mgtSp Sigma70 -35.0 -93.0 mgtS
ataaagatttAATTCAGCCTTCGTTTAggttacctct
1622545 1622561 [GEA], [HIBSCS] [14]
  PhoP-Phosphorylated activator nagAp nd -31.0 -455.0 nagA
aaaattcatcTGTTTATGGGCGGTGTAggtaacgacg
703198 703214 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator ompTp nd -49.0 -81.0 ompT
aaacaaaataTAAACAGTGGAGCAATAtgtaattgac
585706 585722 [GEA], [HIBSCS] [5], [6]
  PhoP-Phosphorylated activator pagPp nd -32.0 -63.0 pagP
atgttgggtcTATTAAGGTTATGTTAAttgtagcttt
656486 656502 [GEA], [HIBSCS] [13]
  PhoP-Phosphorylated repressor phoPp1 nd -33.0 -69.0 phoP, phoQ
cctccccgctGGTTTATTTAATGTTTAcccccataac
1190508 1190524 [AIBSCS], [BPP], [GEA], [HIBSCS] [4], [5], [7], [13]
  PhoP-Phosphorylated activator phoPp2 nd -8.0 -69.0 phoP, phoQ
cctccccgctGGTTTATTTAATGTTTAcccccataac
1190508 1190524 [AIBSCS], [BPP], [GEA], [HIBSCS] [4], [5], [7], [13]
  PhoP-Phosphorylated activator purHp Sigma70 -479.0 -574.0 purH, purD
taaacttcgtAATGAATTACGTGTTCActcttgagac
4208098 4208114 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated activator rstAp nd -44.0 -65.0 rstA, rstB
gatgaaaactTGTTTAGAAACGATTGAtagtaagtaa
1682086 1682102 [AIBSCS], [BPP], [GEA], [HIBSCS] [5], [7], [17]
  PhoP-Phosphorylated activator rutAp Sigma54 -106.0 -121.5 rutA, rutB, rutC, rutD, rutE, rutF, rutG
ttatgtgcaaCTGTTTTGACCGTTTAgtccactttt
1074125 1074140 [AIBSCS], [GEA] [7]
  PhoP-Phosphorylated repressor safAp Sigma70 33.0 -37.5 safA, ydeO
attaagcataCTGATTAACGATTTTTAAcgttatccgc
1583988 1584005 [GEA], [HIBSCS], [SM] [18]
  PhoP-Phosphorylated repressor safAp Sigma70 53.0 -17.5 safA, ydeO
atttttaacgTTATCCGCTAAATAAACAtatttgaaat
1583968 1583985 [GEA], [HIBSCS], [SM] [18]
  PhoP-Phosphorylated activator slyBp1 nd -33.0 -132.0 slyB
atgaatgtttTGTTTATAATTGGTTGAtcctactttc
1719736 1719752 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated repressor slyBp2 nd -4.0 -132.0 slyB
atgaatgtttTGTTTATAATTGGTTGAtcctactttc
1719736 1719752 [BPP], [GEA], [HIBSCS] [5]
  PhoP-Phosphorylated activator tolCp2 nd -46.0 -148.5 tolC, ygiB, ygiC
atttcagcgaCGTTTGACTGCCGTTTGAgcagtcatgt
3177958 3177975 [GEA], [HIBSCS] [19]
  PhoP-Phosphorylated repressor treRp3 Sigma70 -50.0 -83.0 treR
tgctgacaacTAAACCAACGATAAACCagactttacc
4467321 4467337 [BPP], [GEA], [HIBSCS], [SM] [4], [5], [16]
  PhoP-Phosphorylated repressor treRp4 Sigma70 19.0 -83.0 treR
tgctgacaacTAAACCAACGATAAACCagactttacc
4467321 4467337 [BPP], [GEA], [HIBSCS], [SM] [4], [5], [16]
  PhoP-Phosphorylated activator ybjGp nd -32.0 -152.0 ybjG
agctacgcttTCTTTAAGTTTTATTTAacctatgccc
883532 883548 [GEA], [HIBSCS] [13]
  PhoP-Phosphorylated repressor ydePp Sigma70 34.5 -145.0 ydeP
ttaacttatcGTATTTAATCTATTGTTTAacgataatag
1586622 1586640 [GEA], [HIBSCS] [18]
  PhoP-Phosphorylated activator yrbLp nd -28.0 -59.0 yrbL
taagaggcatTGTTTAGGTTTTGTTTAagttaatcga
3348385 3348401 [AIBSCS], [BPP], [GEA], [HIBSCS] [5], [7]



High-throughput Transcription factor binding sites (TFBSs)
      

  Functional conformation Function Object name Object type Distance to first Gene Sequence LeftPos RightPos Growth Condition Evidence (Confirmed, Strong, Weak) References
  PhoP-Phosphorylated activator queE nd nd nd nd nd [BPP], [GEA] [20]


Alignment and PSSM for PhoP TFBSs    

Aligned TFBS of PhoP   
  Sequence
  TTGTTTAGGTTTTGTTTA
  TTGTTTAGGGTTTGTTTA
  GAGTTTAAGCTCCGTTTA
  TGGTTTATCGTTGGTTTA
  TGGTTTATTTAATGTTTA
  TTGTTTAACATCCATTGA
  CTGTTTATGGGCGGTGTA
  TTGTTTATAATTGGTTGA
  TAATTTCACATTTGTTTA
  TATTTAATCTATTGTTTA
  GCGTATAGCTTATGTTTA
  CTGTATATGTCATGTTGA
  ATATTGCTCCACTGTTTA
  TTCTTTAAGTTTTATTTA
  ATAGTTAGGCGCTGTTTA
  ATGTTTGACGAGTATTTA
  CTATTAAGGTTATGTTAA
  CTATTTAACTCCCGGTAA
  TAATTCAGCCTTCGTTTA
  TTGTTTAGAAACGATTGA
  GGGTTTATTAACTTTTGA
  TTTTCAATCTGCCGTTTA
  ACGTTTGACTGCCGTTTG
  CCATTAACACAATGTTTA
  ATGTTTATTTAGCGGATA
  CTGATTAACGATTTTTAA
  ATTTATAGCCTTAGTGTA
  AACTGTTTTGACCGTTTA
  CTATTTACAAGCTGATAA
  AACTATGTCACGTGTTAA
  TAATGAATTACGTGTTCA
  GTATGAATCAAAAATTTG
  GTGCTGCTCCAGTTGTTA
  CTACTTTGTGCCAATTTG

Position weight matrix (PWM). PhoP matrix-quality result   
A	8	7	11	1	4	6	26	8	4	9	12	6	3	6	1	1	5	31
C	8	3	3	2	1	1	3	2	16	7	5	13	8	0	0	0	1	0
G	5	3	17	1	3	2	3	9	8	7	5	5	4	25	3	2	5	3
T	13	21	3	30	26	25	2	15	6	11	12	10	19	3	30	31	23	0

Consensus   
;	consensus.strict             	ttgTttatctactGTTtA
;	consensus.strict.rc          	TAAACAGTAGATAAACAA
;	consensus.IUPAC              	ytrTttakskwcyGTTtA
;	consensus.IUPAC.rc           	TAAACRGWMSMTAAAYAR
;	consensus.regexp             	[ct]t[ag]Ttta[gt][cg][gt][at]c[ct]GTTtA
;	consensus.regexp.rc          	TAAAC[AG]G[AT][AC][CG][AC]TAAA[CT]A[AG]

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

 [APPHINH] Assay of protein purified to homogeneity from its native host

 [HIFS] Human inference of function from sequence

 [IMP] Inferred from mutant phenotype

 [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

 [BCE] Binding of cellular extracts

 [IHBCE] Inferred by a human based on computational evidence

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

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

 [4] 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

 [5] 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

 [6] 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

 [7] 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

 [8] Yeom J., Gao X., Groisman EA., 2018, Reduction in adaptor amounts establishes degradation hierarchy among protease substrates., Proc Natl Acad Sci U S A 115(19):E4483-E4492

 [9] 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

 [10] 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

 [11] 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

 [12] 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

 [13] 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

 [14] 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

 [15] 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

 [16] 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

 [17] 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

 [18] 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

 [19] 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

 [20] Yadavalli SS., Carey JN., Leibman RS., Chen AI., Stern AM., Roggiani M., Lippa AM., Goulian M., 2016, Antimicrobial peptides trigger a division block in Escherichia coli through stimulation of a signalling system., Nat Commun 7:12340



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