PHOQ_SALTY
ID PHOQ_SALTY Reviewed; 487 AA.
AC P0DM80; P14147; Q9L3L1;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 1.
DT 03-AUG-2022, entry version 51.
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; Synonyms=phoZ; OrderedLocusNames=STM1230;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN VIRULENCE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023, and
RC LT2 / SGSC1412 / ATCC 700720;
RX PubMed=2544889; DOI=10.1073/pnas.86.13.5054;
RA Miller S.I., Kukral A.M., Mekalanos J.J.;
RT "A two-component regulatory system (phoP phoQ) controls Salmonella
RT typhimurium virulence.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5054-5058(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP FUNCTION IN ACID TOLERANCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=9573193; DOI=10.1128/jb.180.9.2409-2417.1998;
RA Bearson B.L., Wilson L., Foster J.W.;
RT "A low pH-inducible, PhoPQ-dependent acid tolerance response protects
RT Salmonella typhimurium against inorganic acid stress.";
RL J. Bacteriol. 180:2409-2417(1998).
RN [4]
RP PHOSPHATASE ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-277.
RC STRAIN=EG5172;
RX PubMed=10807931; DOI=10.1074/jbc.m909335199;
RA Castelli M.E., Garcia Vescovi E., Soncini F.C.;
RT "The phosphatase activity is the target for Mg2+ regulation of the sensor
RT protein PhoQ in Salmonella.";
RL J. Biol. Chem. 275:22948-22954(2000).
RN [5]
RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT HIS-277, AND MUTAGENESIS OF HIS-277.
RX PubMed=11160113; DOI=10.1128/jb.183.5.1787-1791.2001;
RA Montagne M., Martel A., Le Moual H.;
RT "Characterization of the catalytic activities of the PhoQ histidine protein
RT kinase of Salmonella enterica serovar Typhimurium.";
RL J. Bacteriol. 183:1787-1791(2001).
RN [6]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF THR-48.
RX PubMed=12618457; DOI=10.1128/jb.185.6.1935-1941.2003;
RA Sanowar S., Martel A., Le Moual H.;
RT "Mutational analysis of the residue at position 48 in the Salmonella
RT enterica Serovar Typhimurium PhoQ sensor kinase.";
RL J. Bacteriol. 185:1935-1941(2003).
RN [7]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=15910283; DOI=10.1042/bj20050060;
RA Sanowar S., Le Moual H.;
RT "Functional reconstitution of the Salmonella typhimurium PhoQ histidine
RT kinase sensor in proteoliposomes.";
RL Biochem. J. 390:769-776(2005).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 45-190 BOUND TO CA(2+), COFACTOR,
RP SUBUNIT, AND MUTAGENESIS OF 149-ASP-ASP-150; MET-155; THR-156; HIS-157;
RP ASP-179; GLU-184; LEU-185 AND LYS-186.
RX PubMed=16406409; DOI=10.1016/j.jmb.2005.12.032;
RA Cho U.S., Bader M.W., Amaya M.F., Daley M.E., Klevit R.E., Miller S.I.,
RA Xu W.;
RT "Metal bridges between the PhoQ sensor domain and the membrane regulate
RT transmembrane signaling.";
RL J. Mol. Biol. 356:1193-1206(2006).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 332-487 IN THE PRESENCE AND
RP ABSENCE OF INHIBITOR, ACTIVITY REGULATION, AND AUTOPHOSPHORYLATION.
RX PubMed=18440021; DOI=10.1016/j.jmb.2008.03.036;
RA Guarnieri M.T., Zhang L., Shen J., Zhao R.;
RT "The Hsp90 inhibitor radicicol interacts with the ATP-binding pocket of
RT bacterial sensor kinase PhoQ.";
RL J. Mol. Biol. 379:82-93(2008).
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:15910283, ECO:0000269|PubMed:2544889,
CC ECO:0000269|PubMed:9573193}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:11160113,
CC ECO:0000269|PubMed:12618457};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:16406409};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16406409};
CC Note=Binds up to 3 divalent cations (Ca(2+) or Mg(2+)); increasing
CC concentrations of divalent cations allows better binding to
CC phospholipids. {ECO:0000269|PubMed:16406409};
CC -!- ACTIVITY REGULATION: Autokinase and kinase activities depend on low (uM
CC range) Mg(2+) concentrations. Phosphatase activity is stimulated by
CC high (mM range) Mg(2+) concentrations and ADP at 1 mM. Autokinase
CC inhibited by radicicol. {ECO:0000269|PubMed:10807931,
CC ECO:0000269|PubMed:15910283, ECO:0000269|PubMed:18440021}.
CC -!- SUBUNIT: Homodimer (Probable); probably dimerizes via the cytoplasmic
CC domain. Interacts with MgrB in the periplasm, altering its activity and
CC that of downstream effector PhoP (By similarity). {ECO:0000250}.
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.
CC -!- DISRUPTION PHENOTYPE: 10,000-fold reduction in virulence in male BALB/c
CC mice (for strain ATCC 14028). Decreased tolerance to acid stress.
CC {ECO:0000269|PubMed:2544889, ECO:0000269|PubMed:9573193}.
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. {ECO:0000305}.
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DR EMBL; M24424; AAA27189.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL20159.1; -; Genomic_DNA.
DR PIR; B32932; VZEBPT.
DR RefSeq; NP_460200.1; NC_003197.2.
DR RefSeq; WP_001031687.1; NC_003197.2.
DR PDB; 1YAX; X-ray; 2.40 A; A/B/C/D=45-190.
DR PDB; 3CGY; X-ray; 2.60 A; A/B/C=332-487.
DR PDB; 3CGZ; X-ray; 1.90 A; A/B/C=332-487.
DR PDB; 4UEY; X-ray; 1.90 A; A/B/C=45-190.
DR PDBsum; 1YAX; -.
DR PDBsum; 3CGY; -.
DR PDBsum; 3CGZ; -.
DR PDBsum; 4UEY; -.
DR AlphaFoldDB; P0DM80; -.
DR SMR; P0DM80; -.
DR STRING; 99287.STM1230; -.
DR BindingDB; P0DM80; -.
DR ChEMBL; CHEMBL6096; -.
DR DrugBank; DB03758; Radicicol.
DR iPTMnet; P0DM80; -.
DR PaxDb; P0DM80; -.
DR EnsemblBacteria; AAL20159; AAL20159; STM1230.
DR GeneID; 1252748; -.
DR KEGG; stm:STM1230; -.
DR PATRIC; fig|99287.12.peg.1301; -.
DR HOGENOM; CLU_000445_42_0_6; -.
DR OMA; TLVFIYD; -.
DR PhylomeDB; P0DM80; -.
DR BioCyc; SENT99287:STM1230-MON; -.
DR BRENDA; 2.7.13.3; 5542.
DR PHI-base; PHI:2675; -.
DR PHI-base; PHI:6592; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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:0000160; P:phosphorelay signal transduction system; IBA:GO_Central.
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 3D-structure; ATP-binding; Cell inner membrane; Cell membrane;
KW Growth regulation; Hydrolase; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Two-component regulatory system; Virulence.
FT CHAIN 1..487
FT /note="Virulence sensor histidine kinase PhoQ"
FT /id="PRO_0000074843"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..193
FT /note="Periplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
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 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 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:0000305"
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:11160113"
FT VARIANT 82..99
FT /note="Missing (in strain: ATCC 10428)"
FT VARIANT 442..459
FT /note="Missing (in strain: ATCC 10428)"
FT MUTAGEN 48
FT /note="T->A: Confers to cells a PhoP wild-type phenotype.
FT No effect on net phosphorylation of PhoP. Decreases 5-fold
FT initial rate of autophosphorylation and increases
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12618457"
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:12618457"
FT MUTAGEN 48
FT /note="T->L: Confers to cells a PhoP constitutively
FT inactive phenotype. Affects PhoP/PhoQ-signaling cascade but
FT no significantly effect on net phosphorylation of PhoP.
FT Decreases 3-fold initial rate of autophosphorylation and
FT increases phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12618457"
FT MUTAGEN 48
FT /note="T->S: Confers to cells a PhoP wild-type phenotype.
FT No effect on net phosphorylation of PhoP. Decreases 5-fold
FT initial rate of autophosphorylation and shows a wild-type
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12618457"
FT MUTAGEN 48
FT /note="T->V: Confers to cells a PhoP constitutively active
FT phenotype. Affects PhoP/PhoQ-signaling cascade and
FT increases net phosphorylation of PhoP. No effect on initial
FT rate of autophosphorylation and decreases phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:12618457"
FT MUTAGEN 149..150
FT /note="DD->KK: Impaired PhoP repression by high
FT concentrations of divalent cations."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 155
FT /note="M->I: Impaired PhoP repression by high
FT concentrations of divalent cations."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 156
FT /note="T->K: Impaired PhoP repression by high
FT concentrations of divalent cations."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 157
FT /note="H->R: Impaired PhoP repression by high
FT concentrations of divalent cations."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 179
FT /note="D->L: Impaired PhoP repression by high
FT concentrations of divalent cation."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 184
FT /note="E->K: Impaired PhoP repression by high
FT concentrations of divalent cations."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 185
FT /note="L->A: Impaired PhoP repression by high
FT concentrations of divalent cation."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 186
FT /note="K->A: Impaired PhoP repression by high
FT concentrations of divalent cation."
FT /evidence="ECO:0000269|PubMed:16406409"
FT MUTAGEN 277
FT /note="H->N: Abolishes autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:10807931,
FT ECO:0000269|PubMed:11160113"
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:10807931,
FT ECO:0000269|PubMed:11160113"
FT HELIX 49..62
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 83..90
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:4UEY"
FT HELIX 103..108
FT /evidence="ECO:0007829|PDB:4UEY"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 118..125
FT /evidence="ECO:0007829|PDB:4UEY"
FT HELIX 126..132
FT /evidence="ECO:0007829|PDB:4UEY"
FT HELIX 137..149
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 154..164
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:4UEY"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:4UEY"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:3CGZ"
FT HELIX 341..355
FT /evidence="ECO:0007829|PDB:3CGZ"
FT TURN 356..360
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 362..366
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 372..375
FT /evidence="ECO:0007829|PDB:3CGZ"
FT HELIX 377..394
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 396..406
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 409..418
FT /evidence="ECO:0007829|PDB:3CGZ"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:3CGZ"
FT HELIX 448..456
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 460..465
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 469..477
FT /evidence="ECO:0007829|PDB:3CGZ"
FT STRAND 482..485
FT /evidence="ECO:0007829|PDB:3CGZ"
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
