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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)DescriptionActionsGraphical viewLength
Metal bindingi151Divalent metal cationBy similarity1
Metal bindingi152Divalent metal cationBy similarity1
Sitei202Plays a critical role in the switching between kinase and phosphatase statesBy similarity1
Metal bindingi386MagnesiumBy similarity1
Metal bindingi443MagnesiumBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi386 – 394ATPBy similarity9
Nucleotide bindingi416 – 421ATPCurated6
Nucleotide bindingi435 – 447ATPBy similarityAdd BLAST13

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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeSalmonella
Proteomesi
  • UP000001014 Componenti: Chromosome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 16CytoplasmicSequence analysisAdd BLAST16
Transmembranei17 – 37HelicalSequence analysisAdd BLAST21
Topological domaini38 – 193PeriplasmicSequence analysisAdd BLAST156
Transmembranei194 – 214HelicalSequence analysisAdd BLAST21
Topological domaini215 – 487CytoplasmicSequence analysisAdd BLAST273

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)DescriptionActionsGraphical viewLength
Mutagenesisi48T → 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 Publication1
Mutagenesisi48T → 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 Publication1
Mutagenesisi48T → 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 Publication1
Mutagenesisi48T → 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 Publication1
Mutagenesisi48T → 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 Publication1
Mutagenesisi149 – 150DD → KK: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication2
Mutagenesisi155M → I: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication1
Mutagenesisi156T → K: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication1
Mutagenesisi157H → R: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication1
Mutagenesisi179D → L: Impaired PhoP repression by high concentrations of divalent cation. 1 Publication1
Mutagenesisi184E → K: Impaired PhoP repression by high concentrations of divalent cations. 1 Publication1
Mutagenesisi185L → A: Impaired PhoP repression by high concentrations of divalent cation. 1 Publication1
Mutagenesisi186K → A: Impaired PhoP repression by high concentrations of divalent cation. 1 Publication1
Mutagenesisi277H → N: Abolishes autophosphorylation activity. 2 Publications1
Mutagenesisi277H → 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 Publications1

Chemistry databases

ChEMBLiCHEMBL6096.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000748431 – 487Virulence sensor histidine kinase PhoQAdd BLAST487

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei277Phosphohistidine; by autocatalysisPROSITE-ProRule annotation1 Publication1

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

1487
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi49 – 62Combined sources14
Beta strandi63 – 66Combined sources4
Beta strandi69 – 72Combined sources4
Beta strandi83 – 90Combined sources8
Beta strandi95 – 100Combined sources6
Helixi103 – 108Combined sources6
Helixi112 – 115Combined sources4
Beta strandi118 – 125Combined sources8
Helixi126 – 132Combined sources7
Helixi137 – 149Combined sources13
Beta strandi154 – 164Combined sources11
Beta strandi173 – 181Combined sources9
Helixi183 – 185Combined sources3
Beta strandi333 – 335Combined sources3
Beta strandi338 – 340Combined sources3
Helixi341 – 355Combined sources15
Turni356 – 360Combined sources5
Beta strandi362 – 366Combined sources5
Beta strandi372 – 375Combined sources4
Helixi377 – 394Combined sources18
Beta strandi396 – 406Combined sources11
Beta strandi409 – 418Combined sources10
Helixi445 – 447Combined sources3
Helixi448 – 456Combined sources9
Beta strandi460 – 465Combined sources6
Beta strandi469 – 477Combined sources9
Beta strandi482 – 485Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini215 – 266HAMPPROSITE-ProRule annotationAdd BLAST52
Domaini274 – 481Histidine kinasePROSITE-ProRule annotationAdd BLAST208

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)DescriptionActionsGraphical viewLength
Natural varianti82 – 99Missing in strain: ATCC 10428. Add BLAST18
Natural varianti442 – 459Missing in strain: ATCC 10428. Add BLAST18

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi99287.STM1230.

Chemistry databases

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...

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: November 2, 2016
This is version 25 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.