Member of the two-component regulatory system EnvZ/OmpR involved in osmoregulation (particularly of genes ompF and ompC) as well as other genes (PubMed:2997120, PubMed:3536870). EnvZ functions as a membrane-associated protein kinase that phosphorylates OmpR in response to environmental signals; at low osmolarity OmpR activates ompF transcription, while at high osmolarity it represses ompF and activates ompC transcription (PubMed:2656684, PubMed:2668281, PubMed:2668953, PubMed:2674113, PubMed:2558046, PubMed:2277041, PubMed:1323560). Also dephosphorylates OmpR in the presence of ATP (PubMed:2668281, PubMed:2558046, PubMed:2277041, PubMed:1323560). The cytoplasmic dimerization domain (CDD) forms an osmosensitive core; increasing osmolarity stabilizes this segment (possibly by its contraction), enhancing the autophosphorylation rate and consequently, downstream phosphotransfer to OmpR and signaling (PubMed:22543870, PubMed:28256224). Autophosphorylation is greater when full-length EnvZ is reconstituted in a lipid environment, lipid-mediated allostery impacts the kinase function of EnvZ (PubMed:28256224). Involved in acid stress response; this requires EnvZ but not OmpR phosphorylation, and suggests that EnvZ senses cytoplasmic acidic pH (PubMed:29138484). ATP + protein L-histidine = ADP + protein N-phospho-L-histidine. Activity is modulated by MzrA (PubMed:19432797, PubMed:20889743). In the presence of 0.2 M NaCl, 2.0 mM sodium cholate (bile salts) decreases expression from the ompC promoter; how this is mediated is unknown (PubMed:28423182). Autophosphorylation is inhibited by the angucycline antibiotic waldiomycin in a non-competitive manner; waldiomycin prevents dimerization of the cytoplasmic domain and autophosphorylation (PubMed:27999439). Homodimer (PubMed:10426948, PubMed:15357641, PubMed:9817206, PubMed:28256224, PubMed:29953503, PubMed:27999439). Interacts with MzrA (PubMed:19432797, PubMed:20889743, PubMed:29953503). Part of the ompR-envZ operon. The periplasmic domain interacts with MzrA (PubMed:20889743) (Probable). The periplasmic domain assumes a PDC sensor fold (PubMed:28423182). The HAMP domain by itself is intrinsically disordered (PubMed:17635923). The cytoplasmic dimerization domain (CDD, residues 223-289) forms an osmosensitive core; increasing osmolarity stabilizes this segment, enhancing its autophosphorylation rate and consequently, downstream phosphotransfer to OmpR and signaling (PubMed:17635923, PubMed:28256224). The autophosphorylation activity of the CDD is inhibited by the angucycline antibiotic waldiomycin which probably binds to it (PubMed:27999439). The soluble EnvZ C-terminal fragment (residues 180-450) is capable of conferring osmolarity-sensitive expression of OmpC in the absence of the membrane anchor (PubMed:17635923). Autophosphorylated (PubMed:3056929, PubMed:2656684, PubMed:2668281, PubMed:2668953, PubMed:8132603, PubMed:2277041). Incubation of isolated EnvZ C-terminal fragment (residues 180-450) with increasing levels of NaCl or sucrose increases its autophosphorylation (PubMed:17635923). No expression of OmpC or OmpF during growth at 0% sucrose, low expression of OmpF at 15% sucrose (PubMed:3056929). Single deletion of envZ has no OmpC or OmpF at 0% sucrose, low levels of OmpC and very low levels of OmpF at 15% sucrose. Deletion of both ompR and envZ leads to loss of both OmpC and OmpF expression at 0% and 15% sucrose (PubMed:2277041). Cross talk between this and the Che and Ntr two-component systems can occur at least in vitro. Two or more proline residues often cause ribosome stalling and decreased protein translation; the cytoplasmic strong stop motif IPPPL does not have this effect and instead is involved in homodimerization, while the weaker periplasmic stop motif VVPPA motif is involved in MzrA interaction.