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Protein

Virulence sensor histidine kinase PhoQ

Gene

phoQ

Organism
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Member of the two-component regulatory system PhoP/PhoQ which regulates the expression of genes involved in virulence, adaptation to acidic and low Mg2+ environments and resistance to host defense antimicrobial peptides. Essential for intramacrophage survival of S.typhimurium. In low periplasmic Mg2+, PhoQ functions as a membrane-associated protein kinase that undergoes autophosphorylation and subsequently transfers the phosphate to PhoP, resulting in the expression of PhoP-activated genes (PAG) and repression of PhoP-repressed genes (PRG). In high periplasmic Mg2+, acts as a protein phosphatase that dephosphorylates phospho-PhoP, resulting in the repression of PAG and may lead to expression of some PRG. Essential for transcription of spiC inside macrophages by controlling the expression of the two-component regulatory system SsrB/SpiR (SsrA) and Pir at transcriptional and post-transcriptional levels respectively. Promotes expression of the two-component regulatory system PmrA/PmrB via activation of pmrD gene. Is required to attenuate bacterial growth within fibroblast cells and to enhance bacterial resistance to bile in intestinal cells. Negatively regulates prgH, which is required for invasion of epithelial cells. Involved in acid tolerance.3 Publications

Catalytic activityi

ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.2 Publications

Cofactori

Ca2+1 Publication, Mg2+1 PublicationNote: Binds up to 3 divalent cations (Ca2+ or Mg2+); increasing concentrations of divalent cations allows better binding to phospholipids.1 Publication

Enzyme regulationi

Autokinase and kinase activities depend on low (µM range) Mg2+ concentrations. Phosphatase activity is stimulated by high (mM range) Mg2+ concentrations and ADP at 1 mM. Autokinase inhibited by radicicol.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi151 – 1511Divalent metal cationBy similarity
Metal bindingi152 – 1521Divalent metal cationBy similarity
Sitei202 – 2021Plays a critical role in the switching between kinase and phosphatase statesBy similarity
Metal bindingi386 – 3861MagnesiumBy similarity
Metal bindingi443 – 4431MagnesiumBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi386 – 3949ATPBy similarity
Nucleotide bindingi416 – 4216ATPCurated
Nucleotide bindingi435 – 44713ATPBy similarityAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Protein phosphatase, Transferase

Keywords - Biological processi

Growth regulation, Two-component regulatory system, Virulence

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Virulence sensor histidine kinase PhoQ (EC:2.7.13.3, EC:3.1.3.-)
Alternative name(s):
Sensor histidine protein kinase/phosphatase PhoQ
Gene namesi
Name:phoQ
Synonyms:phoZ
Ordered Locus Names:STM1230
OrganismiSalmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Taxonomic identifieri99287 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeSalmonella
Proteomesi
  • UP000001014 Componenti: Chromosome

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1616CytoplasmicSequence analysisAdd
BLAST
Transmembranei17 – 3721HelicalSequence analysisAdd
BLAST
Topological domaini38 – 193156PeriplasmicSequence analysisAdd
BLAST
Transmembranei194 – 21421HelicalSequence analysisAdd
BLAST
Topological domaini215 – 487273CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

10,000-fold reduction in virulence in male BALB/c mice (for strain ATCC 14028). Decreased tolerance to acid stress.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi48 – 481T → A: Confers to cells a PhoP wild-type phenotype. No effect on net phosphorylation of PhoP. Decreases 5-fold initial rate of autophosphorylation and increases phosphatase activity. 1 Publication
Mutagenesisi48 – 481T → I in pho-24; low affinity for Ca(2+). Confers to cells a PhoP constitutively active phenotype. Affects PhoP/PhoQ-signaling cascade and increase net phosphorylation of PhoP. No effect on initial rate of autophosphorylation and decreases phosphatase activity. 1 Publication
Mutagenesisi48 – 481T → L: Confers to cells a PhoP constitutively inactive phenotype. Affects PhoP/PhoQ-signaling cascade but no significantly effect on net phosphorylation of PhoP. Decreases 3-fold initial rate of autophosphorylation and increases phosphatase activity. 1 Publication
Mutagenesisi48 – 481T → S: Confers to cells a PhoP wild-type phenotype. No effect on net phosphorylation of PhoP. Decreases 5-fold initial rate of autophosphorylation and shows a wild-type phosphatase activity. 1 Publication
Mutagenesisi48 – 481T → V: Confers to cells a PhoP constitutively active phenotype. Affects PhoP/PhoQ-signaling cascade and increases net phosphorylation of PhoP. No effect on initial rate of autophosphorylation and decreases phosphatase activity. 1 Publication
Mutagenesisi149 – 1502DD → KK: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication
Mutagenesisi155 – 1551M → I: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication
Mutagenesisi156 – 1561T → K: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication
Mutagenesisi157 – 1571H → R: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication
Mutagenesisi179 – 1791D → L: Impaired PhoP repression by high concentrations of divalent cation. 1 Publication
Mutagenesisi184 – 1841E → K: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication
Mutagenesisi185 – 1851L → A: Impaired PhoP repression by high concentrations of divalent cation. 1 Publication
Mutagenesisi186 – 1861K → A: Impaired PhoP repression by high concentrations of divalent cation. 1 Publication
Mutagenesisi277 – 2771H → N: Abolishes autophosphorylation activity. 2 Publications
Mutagenesisi277 – 2771H → V: Retains a wild-type Mg(2+) response only at 10 mM in strain PhoP* PhoQ expressing mutant phoP N-93. Loss of autophosphorylation, irrespective of the presence of Mg(2+). Unable to promote phoP dephosphorylation even in presence of added Mg(2+). 2 Publications

Chemistry

ChEMBLiCHEMBL6096.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 487487Virulence sensor histidine kinase PhoQPRO_0000074843Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei277 – 2771Phosphohistidine; by autocatalysisPROSITE-ProRule annotation1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP0DM80.

PTM databases

iPTMnetiP0DM80.

Expressioni

Inductioni

The phoP/phoQ operon is positively autoregulated by both PhoP and PhoQ in a Mg2+-dependent manner. Repressed by RcsB via sigma factor RpoS.

Interactioni

Subunit structurei

Homodimer (Probable); probably dimerizes via the cytoplasmic domain. Interacts with MgrB in the periplasm, altering its activity and that of downstream effector PhoP (By similarity).By similarity

Protein-protein interaction databases

STRINGi99287.STM1230.

Structurei

Secondary structure

1
487
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi49 – 6214Combined sources
Beta strandi63 – 664Combined sources
Beta strandi69 – 724Combined sources
Beta strandi83 – 908Combined sources
Beta strandi95 – 1006Combined sources
Helixi103 – 1086Combined sources
Helixi112 – 1154Combined sources
Beta strandi118 – 1258Combined sources
Helixi126 – 1327Combined sources
Helixi137 – 14913Combined sources
Beta strandi154 – 16411Combined sources
Beta strandi173 – 1819Combined sources
Helixi183 – 1853Combined sources
Beta strandi333 – 3353Combined sources
Beta strandi338 – 3403Combined sources
Helixi341 – 35515Combined sources
Turni356 – 3605Combined sources
Beta strandi362 – 3665Combined sources
Beta strandi372 – 3754Combined sources
Helixi377 – 39418Combined sources
Beta strandi396 – 40611Combined sources
Beta strandi409 – 41810Combined sources
Helixi445 – 4473Combined sources
Helixi448 – 4569Combined sources
Beta strandi460 – 4656Combined sources
Beta strandi469 – 4779Combined sources
Beta strandi482 – 4854Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YAXX-ray2.40A/B/C/D45-190[»]
3CGYX-ray2.60A/B/C332-487[»]
3CGZX-ray1.90A/B/C332-487[»]
4UEYX-ray1.90A/B/C45-190[»]
ProteinModelPortaliP0DM80.
SMRiP0DM80. Positions 45-190, 332-487.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini215 – 26652HAMPPROSITE-ProRule annotationAdd
BLAST
Domaini274 – 481208Histidine kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 HAMP domain.PROSITE-ProRule annotation
Contains 1 histidine kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105IFJ. Bacteria.
COG0642. LUCA.
KOiK07637.
OMAiTLVFIYD.
PhylomeDBiP0DM80.

Family and domain databases

Gene3Di3.30.565.10. 1 hit.
InterProiIPR003660. HAMP_dom.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
IPR003661. HisK_dim/P.
IPR015014. PhoQ_Sensor.
IPR004358. Sig_transdc_His_kin-like_C.
[Graphical view]
PfamiPF00672. HAMP. 1 hit.
PF02518. HATPase_c. 1 hit.
PF08918. PhoQ_Sensor. 1 hit.
[Graphical view]
PRINTSiPR00344. BCTRLSENSOR.
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF47384. SSF47384. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiPS50885. HAMP. 1 hit.
PS50109. HIS_KIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0DM80-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNKFARHFLP LSLRVRFLLA TAGVVLVLSL AYGIVALVGY SVSFDKTTFR
60 70 80 90 100
LLRGESNLFY TLAKWENNKI SVELPENLDM QSPTMTLIYD ETGKLLWTQR
110 120 130 140 150
NIPWLIKSIQ PEWLKTNGFH EIETNVDATS TLLSEDHSAQ EKLKEVREDD
160 170 180 190 200
DDAEMTHSVA VNIYPATARM PQLTIVVVDT IPIELKRSYM VWSWFVYVLA
210 220 230 240 250
ANLLLVIPLL WIAAWWSLRP IEALAREVRE LEDHHREMLN PETTRELTSL
260 270 280 290 300
VRNLNQLLKS ERERYNKYRT TLTDLTHSLK TPLAVLQSTL RSLRNEKMSV
310 320 330 340 350
SKAEPVMLEQ ISRISQQIGY YLHRASMRGS GVLLSRELHP VAPLLDNLIS
360 370 380 390 400
ALNKVYQRKG VNISMDISPE ISFVGEQNDF VEVMGNVLDN ACKYCLEFVE
410 420 430 440 450
ISARQTDDHL HIFVEDDGPG IPHSKRSLVF DRGQRADTLR PGQGVGLAVA
460 470 480
REITEQYAGQ IIASDSLLGG ARMEVVFGRQ HPTQKEE
Length:487
Mass (Da):55,467
Last modified:November 13, 2013 - v1
Checksum:iBDCFEFC56F4CA058
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti82 – 9918Missing in strain: ATCC 10428.
Add
BLAST
Natural varianti442 – 45918Missing in strain: ATCC 10428.
Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24424 Genomic DNA. Translation: AAA27189.1.
AE006468 Genomic DNA. Translation: AAL20159.1.
PIRiB32932. VZEBPT.
RefSeqiNP_460200.1. NC_003197.1.
WP_001031687.1. NC_003197.1.

Genome annotation databases

EnsemblBacteriaiAAL20159; AAL20159; STM1230.
GeneIDi1252748.
KEGGistm:STM1230.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24424 Genomic DNA. Translation: AAA27189.1.
AE006468 Genomic DNA. Translation: AAL20159.1.
PIRiB32932. VZEBPT.
RefSeqiNP_460200.1. NC_003197.1.
WP_001031687.1. NC_003197.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YAXX-ray2.40A/B/C/D45-190[»]
3CGYX-ray2.60A/B/C332-487[»]
3CGZX-ray1.90A/B/C332-487[»]
4UEYX-ray1.90A/B/C45-190[»]
ProteinModelPortaliP0DM80.
SMRiP0DM80. Positions 45-190, 332-487.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi99287.STM1230.

Chemistry

ChEMBLiCHEMBL6096.

PTM databases

iPTMnetiP0DM80.

Proteomic databases

PaxDbiP0DM80.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAL20159; AAL20159; STM1230.
GeneIDi1252748.
KEGGistm:STM1230.

Phylogenomic databases

eggNOGiENOG4105IFJ. Bacteria.
COG0642. LUCA.
KOiK07637.
OMAiTLVFIYD.
PhylomeDBiP0DM80.

Family and domain databases

Gene3Di3.30.565.10. 1 hit.
InterProiIPR003660. HAMP_dom.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
IPR003661. HisK_dim/P.
IPR015014. PhoQ_Sensor.
IPR004358. Sig_transdc_His_kin-like_C.
[Graphical view]
PfamiPF00672. HAMP. 1 hit.
PF02518. HATPase_c. 1 hit.
PF08918. PhoQ_Sensor. 1 hit.
[Graphical view]
PRINTSiPR00344. BCTRLSENSOR.
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF47384. SSF47384. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiPS50885. HAMP. 1 hit.
PS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence."
    Miller S.I., Kukral A.M., Mekalanos J.J.
    Proc. Natl. Acad. Sci. U.S.A. 86:5054-5058(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN VIRULENCE, DISRUPTION PHENOTYPE.
    Strain: ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023 and LT2 / SGSC1412 / ATCC 700720.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: LT2 / SGSC1412 / ATCC 700720.
  3. "A low pH-inducible, PhoPQ-dependent acid tolerance response protects Salmonella typhimurium against inorganic acid stress."
    Bearson B.L., Wilson L., Foster J.W.
    J. Bacteriol. 180:2409-2417(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ACID TOLERANCE, DISRUPTION PHENOTYPE.
    Strain: LT2 / SGSC1412 / ATCC 700720.
  4. "The phosphatase activity is the target for Mg2+ regulation of the sensor protein PhoQ in Salmonella."
    Castelli M.E., Garcia Vescovi E., Soncini F.C.
    J. Biol. Chem. 275:22948-22954(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHATASE ACTIVITY, ENZYME REGULATION, MUTAGENESIS OF HIS-277.
    Strain: EG5172.
  5. "Characterization of the catalytic activities of the PhoQ histidine protein kinase of Salmonella enterica serovar Typhimurium."
    Montagne M., Martel A., Le Moual H.
    J. Bacteriol. 183:1787-1791(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, PHOSPHORYLATION AT HIS-277, MUTAGENESIS OF HIS-277.
  6. "Mutational analysis of the residue at position 48 in the Salmonella enterica Serovar Typhimurium PhoQ sensor kinase."
    Sanowar S., Martel A., Le Moual H.
    J. Bacteriol. 185:1935-1941(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF THR-48.
  7. "Functional reconstitution of the Salmonella typhimurium PhoQ histidine kinase sensor in proteoliposomes."
    Sanowar S., Le Moual H.
    Biochem. J. 390:769-776(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION.
  8. "Metal bridges between the PhoQ sensor domain and the membrane regulate transmembrane signaling."
    Cho U.S., Bader M.W., Amaya M.F., Daley M.E., Klevit R.E., Miller S.I., Xu W.
    J. Mol. Biol. 356:1193-1206(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 45-190 BOUND TO CA(2+), COFACTOR, SUBUNIT, MUTAGENESIS OF 149-ASP-ASP-150; MET-155; THR-156; HIS-157; ASP-179; GLU-184; LEU-185 AND LYS-186.
  9. "The Hsp90 inhibitor radicicol interacts with the ATP-binding pocket of bacterial sensor kinase PhoQ."
    Guarnieri M.T., Zhang L., Shen J., Zhao R.
    J. Mol. Biol. 379:82-93(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 332-487 IN THE PRESENCE AND ABSENCE OF INHIBITOR, ENZYME REGULATION, AUTOPHOSPHORYLATION.

Entry informationi

Entry nameiPHOQ_SALTY
AccessioniPrimary (citable) accession number: P0DM80
Secondary accession number(s): P14147, Q9L3L1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2013
Last sequence update: November 13, 2013
Last modified: May 11, 2016
This is version 23 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Substitutions experiments show that amino acid Thr-48 may be involved in the conformational changes responsible for the balance between kinase-dominant state and phosphatase-dominant state.
The PhoP/PhoQ-signaling cascade, which activates virulence membrane genes (pagC, pagO, pagD, pagK, pgtE and phoN), is induced by cationic antimicrobial peptides (CAMP) (polymyxin, alpha-helical peptide C18G and sheet peptide protegrin-1) at sublethal concentrations.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.