PHOQ_SALT1
ID PHOQ_SALT1 Reviewed; 487 AA.
AC D0ZV89;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Virulence sensor histidine kinase PhoQ;
DE EC=2.7.13.3;
DE EC=3.1.3.-;
DE AltName: Full=Sensor histidine protein kinase/phosphatase PhoQ;
GN Name=phoQ; OrderedLocusNames=STM14_1408;
OS Salmonella typhimurium (strain 14028s / SGSC 2262).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=588858;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=14028s / SGSC 2262;
RX PubMed=19897643; DOI=10.1128/jb.01233-09;
RA Jarvik T., Smillie C., Groisman E.A., Ochman H.;
RT "Short-term signatures of evolutionary change in the Salmonella enterica
RT serovar typhimurium 14028 genome.";
RL J. Bacteriol. 192:560-567(2010).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, DIVALENT CATION-BINDING SITES, AND MUTAGENESIS OF
RP THR-48.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=8999810; DOI=10.1074/jbc.272.3.1440;
RA Garcia Vescovi E., Ayala Y.M., Di Cera E., Groisman E.A.;
RT "Characterization of the bacterial sensor protein PhoQ. Evidence for
RT distinct binding sites for Mg2+ and Ca2+.";
RL J. Biol. Chem. 272:1440-1443(1997).
RN [3]
RP FUNCTION.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=8392513; DOI=10.1128/jb.175.14.4475-4484.1993;
RA Behlau I., Miller S.I.;
RT "A PhoP-repressed gene promotes Salmonella typhimurium invasion of
RT epithelial cells.";
RL J. Bacteriol. 175:4475-4484(1993).
RN [4]
RP AUTOREGULATION.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=7543474; DOI=10.1128/jb.177.15.4364-4371.1995;
RA Soncini F.C., Garcia Vescovi E., Groisman E.A.;
RT "Transcriptional autoregulation of the Salmonella typhimurium phoPQ
RT operon.";
RL J. Bacteriol. 177:4364-4371(1995).
RN [5]
RP REGULATION BY MG(2+).
RC STRAIN=14028s / SGSC 2262;
RX PubMed=8548821; DOI=10.1016/s0092-8674(00)81003-x;
RA Garcia Vescovi E., Soncini F.C., Groisman E.A.;
RT "Mg2+ as an extracellular signal: environmental regulation of Salmonella
RT virulence.";
RL Cell 84:165-174(1996).
RN [6]
RP FUNCTION.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=10084994; DOI=10.1128/iai.67.4.1614-1622.1999;
RA van Velkinburgh J.C., Gunn J.S.;
RT "PhoP-PhoQ-regulated loci are required for enhanced bile resistance in
RT Salmonella spp.";
RL Infect. Immun. 67:1614-1622(1999).
RN [7]
RP FUNCTION.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=10775270; DOI=10.1093/emboj/19.8.1861;
RA Kox L.F.F., Woesten M.M.S.M., Groisman E.A.;
RT "A small protein that mediates the activation of a two-component system by
RT another two-component system.";
RL EMBO J. 19:1861-1872(2000).
RN [8]
RP PHOSPHORYLATION AT HIS-277, AND MUTAGENESIS OF THR-47; PRO-83; ILE-88;
RP TYR-89; GLY-93; LEU-96; TRP-97; HIS-120; ASP-149; ASP-150; ASP-151;
RP ASP-152; THR-156 AND HIS-277.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=12507481; DOI=10.1016/s0022-2836(02)01268-8;
RA Chamnongpol S., Cromie M., Groisman E.A.;
RT "Mg2+ sensing by the Mg2+ sensor PhoQ of Salmonella enterica.";
RL J. Mol. Biol. 325:795-807(2003).
RN [9]
RP FUNCTION, AND REGULATION BY CATIONIC ANTIMICROBIAL PEPTIDES (CAMP).
RC STRAIN=14028s / SGSC 2262;
RX PubMed=14507376; DOI=10.1046/j.1365-2958.2003.03675.x;
RA Bader M.W., Navarre W.W., Shiau W., Nikaido H., Frye J.G., McClelland M.,
RA Fang F.C., Miller S.I.;
RT "Regulation of Salmonella typhimurium virulence gene expression by cationic
RT antimicrobial peptides.";
RL Mol. Microbiol. 50:219-230(2003).
RN [10]
RP AUTOPHOSPHORYLATION, INDUCTION, TOPOLOGY, PROBABLE BINDING TO ANTIMICROBIAL
RP PEPTIDES, COFACTOR, AND MUTAGENESIS OF THR-156 AND GLU-184.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=16096064; DOI=10.1016/j.cell.2005.05.030;
RA Bader M.W., Sanowar S., Daley M.E., Schneider A.R., Cho U., Xu W.,
RA Klevit R.E., Le Moual H., Miller S.I.;
RT "Recognition of antimicrobial peptides by a bacterial sensor kinase.";
RL Cell 122:461-472(2005).
RN [11]
RP FUNCTION.
RC STRAIN=14028s / SGSC 2262;
RX PubMed=15948951; DOI=10.1111/j.1365-2958.2005.04668.x;
RA Bijlsma J.J.E., Groisman E.A.;
RT "The PhoP/PhoQ system controls the intramacrophage type three secretion
RT system of Salmonella enterica.";
RL Mol. Microbiol. 57:85-96(2005).
CC -!- FUNCTION: Member of the two-component regulatory system PhoP/PhoQ which
CC regulates the expression of genes involved in virulence, adaptation to
CC acidic and low Mg(2+) environments and resistance to host defense
CC antimicrobial peptides. Essential for intramacrophage survival of
CC S.typhimurium. In low periplasmic Mg(2+), PhoQ functions as a membrane-
CC associated protein kinase that undergoes autophosphorylation and
CC subsequently transfers the phosphate to PhoP, resulting in the
CC expression of PhoP-activated genes (PAG) and repression of PhoP-
CC repressed genes (PRG). In high periplasmic Mg(2+), acts as a protein
CC phosphatase that dephosphorylates phospho-PhoP, resulting in the
CC repression of PAG and may lead to expression of some PRG. Essential for
CC transcription of spiC inside macrophages by controlling the expression
CC of the two-component regulatory system SsrB/SpiR (SsrA) and Pir at
CC transcriptional and post-transcriptional levels respectively. Promotes
CC expression of the two-component regulatory system PmrA/PmrB via
CC activation of pmrD gene. Is required to attenuate bacterial growth
CC within fibroblast cells and to enhance bacterial resistance to bile in
CC intestinal cells. Negatively regulates prgH, which is required for
CC invasion of epithelial cells. Involved in acid tolerance.
CC {ECO:0000269|PubMed:10084994, ECO:0000269|PubMed:10775270,
CC ECO:0000269|PubMed:14507376, ECO:0000269|PubMed:15948951,
CC ECO:0000269|PubMed:8392513}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:16096064};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16096064};
CC Note=Binds up to 3 divalent cations (Ca(2+) or Mg(2+)); their binding
CC site probably overlaps with that of cationic antimicrobial peptides
CC that induce the operon. {ECO:0000269|PubMed:16096064};
CC -!- SUBUNIT: Homodimer; probably dimerizes via the cytoplasmic domain (By
CC similarity). Interacts with MgrB in the periplasm, altering its
CC activity and that of downstream effector PhoP (Probable). {ECO:0000250,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}.
CC -!- INDUCTION: The phoP/phoQ operon is positively autoregulated by both
CC PhoP and PhoQ in a Mg(2+)-dependent manner. Repressed by RcsB via sigma
CC factor RpoS (Probable). Induced by antimicrobial peptides (similar to
CC those in macrophages) and low Mg(2+) concentrations.
CC {ECO:0000269|PubMed:16096064, ECO:0000305}.
CC -!- MISCELLANEOUS: Substitutions experiments show that amino acid Thr-48
CC may be involved in the conformational changes responsible for the
CC balance between kinase-dominant state and phosphatase-dominant state.
CC -!- MISCELLANEOUS: The PhoP/PhoQ-signaling cascade, which activates
CC virulence membrane genes (pagC, pagO, pagD, pagK, pgtE and phoN), is
CC induced by cationic antimicrobial peptides (CAMP) (polymyxin, alpha-
CC helical peptide C18G and sheet peptide protegrin-1) at sublethal
CC concentrations.
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DR EMBL; CP001363; ACY87894.1; -; Genomic_DNA.
DR RefSeq; WP_001031687.1; NZ_CP043402.1.
DR AlphaFoldDB; D0ZV89; -.
DR BMRB; D0ZV89; -.
DR SMR; D0ZV89; -.
DR iPTMnet; D0ZV89; -.
DR PRIDE; D0ZV89; -.
DR EnsemblBacteria; ACY87894; ACY87894; STM14_1408.
DR KEGG; seo:STM14_1408; -.
DR PATRIC; fig|588858.6.peg.1378; -.
DR HOGENOM; CLU_000445_42_0_6; -.
DR OMA; TLVFIYD; -.
DR BioCyc; SENT588858:STM14_RS06660-MON; -.
DR PHI-base; PHI:4899; -.
DR PHI-base; PHI:6318; -.
DR PHI-base; PHI:7356; -.
DR Proteomes; UP000002695; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IEA:UniProtKB-KW.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IEA:InterPro.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR Gene3D; 3.30.450.140; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003660; HAMP_dom.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR036097; HisK_dim/P_sf.
DR InterPro; IPR015014; PhoQ_Sensor.
DR InterPro; IPR038429; PhoQ_Sensor_sf.
DR InterPro; IPR004358; Sig_transdc_His_kin-like_C.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF08918; PhoQ_Sensor; 1.
DR PRINTS; PR00344; BCTRLSENSOR.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF47384; SSF47384; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS50885; HAMP; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell inner membrane; Cell membrane; Direct protein sequencing;
KW Growth regulation; Hydrolase; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Protein phosphatase; Transferase;
KW Transmembrane; Transmembrane helix; Two-component regulatory system;
KW Virulence.
FT CHAIN 1..487
FT /note="Virulence sensor histidine kinase PhoQ"
FT /id="PRO_0000424541"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16096064"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..193
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:16096064"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16096064"
FT DOMAIN 215..266
FT /note="HAMP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00102"
FT DOMAIN 274..481
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT REGION 51..181
FT /note="Sensor domain, required for response to
FT antimicrobial peptides"
FT BINDING 123
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT BINDING 151
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT BINDING 386..394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 386
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 416..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 435..447
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 443
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 202
FT /note="Plays a critical role in the switching between
FT kinase and phosphatase states"
FT /evidence="ECO:0000250"
FT MOD_RES 277
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107,
FT ECO:0000269|PubMed:12507481"
FT MUTAGEN 47
FT /note="T->A: Retains a wild-type Mg(2+) response."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 48
FT /note="T->I: In pho-24; low affinity for Ca(2+). Confers to
FT cells a PhoP constitutively active phenotype. Affects
FT PhoP/PhoQ-signaling cascade and increase net
FT phosphorylation of PhoP. No effect on initial rate of
FT autophosphorylation and decreases phosphatase activity."
FT /evidence="ECO:0000269|PubMed:8999810"
FT MUTAGEN 83
FT /note="P->A: Retains a wild-type Mg(2+) response."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 88
FT /note="I->A: Retains a wild-type Mg(2+) response."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 89
FT /note="Y->A: Retains a wild-type Mg(2+) response."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 93
FT /note="G->A: Retains a wild-type Mg(2+) response. Less
FT sensitive to Mg(2+) response than wild-type and defective
FT in Mg(2+) binding; when associated with R-97."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 96
FT /note="L->A: Retains a wild-type Mg(2+) response."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 97
FT /note="W->A: Retains a wild-type Mg(2+) response."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 97
FT /note="W->R: Less sensitive to Mg(2+) response than wild-
FT type and defective in Mg(2+) binding; when associated with
FT A-93."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 120
FT /note="H->A: Less sensitive to Mg(2+)response and defective
FT in Mg(2+) binding than wild-type."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 149
FT /note="D->A: Less sensitive to Mg(2+) response than wild-
FT type. Retains a wild-type Mg(2+) response in strain PhoP*
FT PhoQ expressing mutant phoP N-93."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 150
FT /note="D->A: Less sensitive to Mg(2+) response than wild-
FT type in strain PhoP* PhoQ expressing mutant phoP N-93."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 151
FT /note="D->A: Less sensitive to Mg(2+) response than wild-
FT type in strain PhoP* PhoQ expressing mutant phoP N-93."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 152
FT /note="D->A: Less sensitive to Mg(2+) response than wild-
FT type in strain PhoP* PhoQ expressing mutant phoP N-93."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 156
FT /note="T->A: Less sensitive to Mg(2+) response and
FT defective binding than wild-type."
FT /evidence="ECO:0000269|PubMed:12507481,
FT ECO:0000269|PubMed:16096064"
FT MUTAGEN 156
FT /note="T->K: Defective in antimicrobial peptide response.
FT Further decrease; when associated with K-184."
FT /evidence="ECO:0000269|PubMed:12507481,
FT ECO:0000269|PubMed:16096064"
FT MUTAGEN 184
FT /note="E->K: Defective in antimicrobial peptide response.
FT Further decrease; when associated with K-156."
FT /evidence="ECO:0000269|PubMed:16096064"
FT MUTAGEN 277
FT /note="H->A: Retains a wild-type Mg(2+) response only at 10
FT mM."
FT /evidence="ECO:0000269|PubMed:12507481"
FT MUTAGEN 277
FT /note="H->V: Retains a wild-type Mg(2+) response only at 10
FT mM in strain PhoP* PhoQ expressing mutant phoP N-93. Loss
FT of autophosphorylation, irrespective of the presence of
FT Mg(2+). Unable to promote phoP dephosphorylation even in
FT presence of added Mg(2+)."
FT /evidence="ECO:0000269|PubMed:12507481"
SQ SEQUENCE 487 AA; 55467 MW; BDCFEFC56F4CA058 CRC64;
MNKFARHFLP LSLRVRFLLA TAGVVLVLSL AYGIVALVGY SVSFDKTTFR LLRGESNLFY
TLAKWENNKI SVELPENLDM QSPTMTLIYD ETGKLLWTQR NIPWLIKSIQ PEWLKTNGFH
EIETNVDATS TLLSEDHSAQ EKLKEVREDD DDAEMTHSVA VNIYPATARM PQLTIVVVDT
IPIELKRSYM VWSWFVYVLA ANLLLVIPLL WIAAWWSLRP IEALAREVRE LEDHHREMLN
PETTRELTSL VRNLNQLLKS ERERYNKYRT TLTDLTHSLK TPLAVLQSTL RSLRNEKMSV
SKAEPVMLEQ ISRISQQIGY YLHRASMRGS GVLLSRELHP VAPLLDNLIS ALNKVYQRKG
VNISMDISPE ISFVGEQNDF VEVMGNVLDN ACKYCLEFVE ISARQTDDHL HIFVEDDGPG
IPHSKRSLVF DRGQRADTLR PGQGVGLAVA REITEQYAGQ IIASDSLLGG ARMEVVFGRQ
HPTQKEE
