Member of the two-component regulatory system PhoP/PhoQ which regulates the expression of genes involved in virulence, adaptation to acidic and low Mg(2+) environments and resistance to host defense antimicrobial peptides. Essential for intramacrophage survival of S.typhimurium. In low periplasmic Mg(2+), 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 Mg(2+), 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. ATP + protein L-histidine = ADP + protein N-phospho-L-histidine. Binds up to 3 divalent cations (Ca(2+) or Mg(2+)); increasing concentrations of divalent cations allows better binding to phospholipids. Autokinase and kinase activities depend on low (uM range) Mg(2+) concentrations. Phosphatase activity is stimulated by high (mM range) Mg(2+) concentrations and ADP at 1 mM. Autokinase inhibited by radicicol. 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). The phoP/phoQ operon is positively autoregulated by both PhoP and PhoQ in a Mg(2+)-dependent manner. Repressed by RcsB via sigma factor RpoS. 10,000-fold reduction in virulence in male BALB/c mice (for strain ATCC 14028). Decreased tolerance to acid stress. 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.