UniProtKB - P0AEJ4 (ENVZ_ECOLI)
Protein
Sensor histidine kinase EnvZ
Gene
envZ
Organism
Escherichia coli (strain K12)
Status
Functioni
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).12 Publications
Miscellaneous
Cross talk between this and the Che and Ntr two-component systems can occur at least in vitro.1 Publication
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.1 Publication
Catalytic activityi
- ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.3 Publications1 Publication EC:2.7.13.3
Activity regulationi
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).4 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 243 | ATPCombined sources | 1 | |
Binding sitei | 373 | ATPCombined sources | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 347 – 351 | ATPCombined sources | 5 | |
Nucleotide bindingi | 392 – 393 | ATPCombined sources | 2 | |
Nucleotide bindingi | 402 – 406 | ATPCombined sources | 5 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- phosphoprotein phosphatase activity Source: EcoCyc
- phosphorelay sensor kinase activity Source: EcoCyc
GO - Biological processi
- peptidyl-histidine phosphorylation Source: EcoCyc
- phosphorelay signal transduction system Source: EcoliWiki
- phosphorylation Source: EcoliWiki
- protein autophosphorylation Source: EcoliWiki
- protein dephosphorylation Source: EcoliWiki
- response to osmotic stress Source: EcoCyc
- signal transduction Source: EcoCyc
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Stress response, Two-component regulatory system |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | EcoCyc:ENVZ-MONOMER MetaCyc:ENVZ-MONOMER |
BRENDAi | 2.7.13.3, 2026 |
Names & Taxonomyi
Protein namesi | Recommended name: Sensor histidine kinase EnvZCurated (EC:2.7.13.31 Publication)Alternative name(s): Osmolarity sensor protein EnvZCurated |
Gene namesi | Name:envZ Synonyms:ompB, perA, tpo Ordered Locus Names:b3404, JW3367 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell inner membrane 3 Publications; Multi-pass membrane protein 3 Publications
Cytosol
- cytosol Source: EcoCyc
Plasma Membrane
- integral component of plasma membrane Source: EcoCyc
Other locations
- outer membrane-bounded periplasmic space Source: EcoCyc
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 15 | Cytoplasmic1 PublicationAdd BLAST | 15 | |
Transmembranei | 16 – 35 | Helical1 PublicationAdd BLAST | 20 | |
Topological domaini | 36 – 158 | Periplasmic1 PublicationAdd BLAST | 123 | |
Transmembranei | 159 – 179 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 180 – 450 | Cytoplasmic3 PublicationsAdd BLAST | 271 |
Keywords - Cellular componenti
Cell inner membrane, Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
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).2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 38 | MRRLR…VLNFA → MTMITDSL in envZ115; low constitutive expression of OmpC or OmpF at low and high osmolarity. Phosphorylates and dephosphorylates OmpR. 2 PublicationsAdd BLAST | 38 | |
Mutagenesisi | 18 | L → F: No OmpC, constitutive OmpF, with or without sucrose. No change in phosphorylation or dephosphorylation of OmpR. 1 Publication | 1 | |
Mutagenesisi | 41 | P → L or S: Constitutive OmpC, no OmpF, with or without sucrose. Phosphorylates but does not dephosphorylate OmpR. 1 Publication | 1 | |
Mutagenesisi | 73 – 74 | PP → AA: Decreased interaction with MzrA. 1 Publication | 2 | |
Mutagenesisi | 180 | R → C: No OmpC, constitutive OmpF, with or without sucrose. Weakly phosphorylates OmpR, dephosphorylates normally. 1 Publication | 1 | |
Mutagenesisi | 185 | P → L: Constitutive OmpC, no OmpF, with or without sucrose. Weakly phosphorylates but does not dephosphorylate OmpR. 1 Publication | 1 | |
Mutagenesisi | 193 | A → L: Promotes the formation of alpha-helical secondary structure of the HAMP domain. 1 Publication | 1 | |
Mutagenesisi | 193 | A → V: No effect. 1 Publication | 1 | |
Mutagenesisi | 202 – 204 | PPP → AAA: Decreased protein homodimerization, constitutive OmpC, little to no OmpF with or without salt, no interaction with MzrA. 1 Publication | 3 | |
Mutagenesisi | 234 | R → A: Autophosphorylation by cytoplasmic dimerization domain (CDD) is resistant to waldiomycin. 1 Publication | 1 | |
Mutagenesisi | 242 | S → A: Autophosphorylation by CDD is resistant to waldiomycin, CDD peptide probably no longer binds waldiomycin. 1 Publication | 1 | |
Mutagenesisi | 243 | H → R: Does not autophosphorylate, does not dephosphorylate OmpR in vitro, no OmpC or OmpF at 0% sucrose, low levels of OmpC and very low levels of OmpF at 15% sucrose. 1 Publication | 1 | |
Mutagenesisi | 243 | H → V: Does not autophosphorylate, does not transfer phosphate to OmpR, increased expression of ompC, decreased expression of OmpF. 1 Publication | 1 | |
Mutagenesisi | 244 | D → A: Autophosphorylation by CDD is resistant to waldiomycin, CDD peptide probably no longer binds waldiomycin. 1 Publication | 1 | |
Mutagenesisi | 247 | T → A: Autophosphorylation by CDD is somewhat resistant to waldiomycin. 1 Publication | 1 | |
Mutagenesisi | 247 | T → R in envZ11/MH1461; OmpF- OmpC constitutive. Also prevents expression of PhoA and LamB. Phosphorylates OmpR but does not dephosphorylate it. 3 Publications | 1 | |
Mutagenesisi | 248 | P → A: Autophosphorylation by CDD is resistant to waldiomycin, CDD peptide probably no longer binds waldiomycin, alters structure. 1 Publication | 1 | |
Mutagenesisi | 347 | N → D: Loss of ATP binding; loss of autophosphorylation. 1 Publication | 1 |
Chemistry databases
DrugBanki | DB04395, Phosphoaminophosphonic Acid-Adenylate Ester |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000074759 | 1 – 450 | Sensor histidine kinase EnvZAdd BLAST | 450 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 243 | Phosphohistidine; by autocatalysisPROSITE-ProRule annotation1 Publication | 1 |
Post-translational modificationi
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).1 Publication6 Publications
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | P0AEJ4 |
PaxDbi | P0AEJ4 |
PRIDEi | P0AEJ4 |
PTM databases
iPTMneti | P0AEJ4 |
Expressioni
Inductioni
Part of the ompR-envZ operon.2 Publications
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsP0AEJ4
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-1121750,EBI-1121750 |
mzrA [P42615] | 3 | EBI-1121750,EBI-6412632 |
ompR [P0AA16] | 2 | EBI-1121750,EBI-369514 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 4261266, 47 interactors |
DIPi | DIP-48357N |
IntActi | P0AEJ4, 5 interactors |
MINTi | P0AEJ4 |
STRINGi | 511145.b3404 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P0AEJ4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P0AEJ4 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 180 – 232 | HAMPPROSITE-ProRule annotationAdd BLAST | 53 | |
Domaini | 240 – 440 | Histidine kinasePROSITE-ProRule annotationAdd BLAST | 201 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 223 – 289 | Cytoplasmic dimerization domain (CDD), when dimerized forms osmosensitive core1 PublicationAdd BLAST | 67 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 71 – 75 | polyP-periplasmic motif1 Publication | 5 | |
Motifi | 201 – 205 | polyP-cytoplasmic motif1 Publication | 5 |
Domaini
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).1 Publication5 Publications
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | COG2205, Bacteria |
HOGENOMi | CLU_000445_89_27_6 |
InParanoidi | P0AEJ4 |
PhylomeDBi | P0AEJ4 |
Family and domain databases
CDDi | cd00082, HisKA, 1 hit |
Gene3Di | 3.30.565.10, 1 hit |
InterProi | View protein in InterPro IPR003660, HAMP_dom IPR003594, HATPase_C IPR036890, HATPase_C_sf IPR005467, His_kinase_dom IPR003661, HisK_dim/P IPR036097, HisK_dim/P_sf IPR004358, Sig_transdc_His_kin-like_C |
Pfami | View protein in Pfam PF00672, HAMP, 1 hit PF02518, HATPase_c, 1 hit PF00512, HisKA, 1 hit |
PRINTSi | PR00344, BCTRLSENSOR |
SMARTi | View protein in SMART SM00304, HAMP, 1 hit SM00387, HATPase_c, 1 hit SM00388, HisKA, 1 hit |
SUPFAMi | SSF47384, SSF47384, 1 hit SSF55874, SSF55874, 1 hit |
PROSITEi | View protein in PROSITE PS50885, HAMP, 1 hit PS50109, HIS_KIN, 1 hit |
i Sequence
Sequence statusi: Complete.
P0AEJ4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRRLRFSPRS SFARTLLLIV TLLFASLVTT YLVVLNFAIL PSLQQFNKVL
60 70 80 90 100
AYEVRMLMTD KLQLEDGTQL VVPPAFRREI YRELGISLYS NEAAEEAGLR
110 120 130 140 150
WAQHYEFLSH QMAQQLGGPT EVRVEVNKSS PVVWLKTWLS PNIWVRVPLT
160 170 180 190 200
EIHQGDFSPL FRYTLAIMLL AIGGAWLFIR IQNRPLVDLE HAALQVGKGI
210 220 230 240 250
IPPPLREYGA SEVRSVTRAF NHMAAGVKQL ADDRTLLMAG VSHDLRTPLT
260 270 280 290 300
RIRLATEMMS EQDGYLAESI NKDIEECNAI IEQFIDYLRT GQEMPMEMAD
310 320 330 340 350
LNAVLGEVIA AESGYEREIE TALYPGSIEV KMHPLSIKRA VANMVVNAAR
360 370 380 390 400
YGNGWIKVSS GTEPNRAWFQ VEDDGPGIAP EQRKHLFQPF VRGDSARTIS
410 420 430 440 450
GTGLGLAIVQ RIVDNHNGML ELGTSERGGL SIRAWLPVPV TRAQGTTKEG
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J01656 Unassigned RNA Translation: AAA16242.1 U18997 Genomic DNA Translation: AAA58201.1 U00096 Genomic DNA Translation: AAC76429.1 AP009048 Genomic DNA Translation: BAE77887.1 |
PIRi | B25024, MMECZB |
RefSeqi | NP_417863.1, NC_000913.3 WP_001253696.1, NZ_STEB01000004.1 |
Genome annotation databases
EnsemblBacteriai | AAC76429; AAC76429; b3404 BAE77887; BAE77887; BAE77887 |
GeneIDi | 58460223 947272 |
KEGGi | ecj:JW3367 eco:b3404 |
PATRICi | fig|1411691.4.peg.3325 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J01656 Unassigned RNA Translation: AAA16242.1 U18997 Genomic DNA Translation: AAA58201.1 U00096 Genomic DNA Translation: AAC76429.1 AP009048 Genomic DNA Translation: BAE77887.1 |
PIRi | B25024, MMECZB |
RefSeqi | NP_417863.1, NC_000913.3 WP_001253696.1, NZ_STEB01000004.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BXD | NMR | - | A | 290-450 | [»] | |
1JOY | NMR | - | A/B | 223-289 | [»] | |
1NJV | model | - | A/B | 223-450 | [»] | |
3ZCC | X-ray | 1.25 | A/B | 229-288 | [»] | |
3ZRV | X-ray | 1.65 | A/B | 229-290 | [»] | |
3ZRW | X-ray | 2.25 | A/C/D | 229-289 | [»] | |
B | 231-289 | [»] | ||||
3ZRX | X-ray | 1.25 | A/B | 229-289 | [»] | |
4CTI | X-ray | 2.85 | A/B/C/D | 228-450 | [»] | |
4KP4 | X-ray | 3.00 | A/B | 223-253 | [»] | |
A/B | 266-450 | [»] | ||||
5B1N | X-ray | 1.33 | A | 223-289 | [»] | |
5B1O | X-ray | 2.30 | A/B | 223-289 | [»] | |
5XGA | X-ray | 1.95 | A | 36-158 | [»] | |
SMRi | P0AEJ4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4261266, 47 interactors |
DIPi | DIP-48357N |
IntActi | P0AEJ4, 5 interactors |
MINTi | P0AEJ4 |
STRINGi | 511145.b3404 |
Chemistry databases
DrugBanki | DB04395, Phosphoaminophosphonic Acid-Adenylate Ester |
PTM databases
iPTMneti | P0AEJ4 |
Proteomic databases
jPOSTi | P0AEJ4 |
PaxDbi | P0AEJ4 |
PRIDEi | P0AEJ4 |
Genome annotation databases
EnsemblBacteriai | AAC76429; AAC76429; b3404 BAE77887; BAE77887; BAE77887 |
GeneIDi | 58460223 947272 |
KEGGi | ecj:JW3367 eco:b3404 |
PATRICi | fig|1411691.4.peg.3325 |
Organism-specific databases
EchoBASEi | EB0265 |
Phylogenomic databases
eggNOGi | COG2205, Bacteria |
HOGENOMi | CLU_000445_89_27_6 |
InParanoidi | P0AEJ4 |
PhylomeDBi | P0AEJ4 |
Enzyme and pathway databases
BioCyci | EcoCyc:ENVZ-MONOMER MetaCyc:ENVZ-MONOMER |
BRENDAi | 2.7.13.3, 2026 |
Miscellaneous databases
EvolutionaryTracei | P0AEJ4 |
PROi | PR:P0AEJ4 |
Family and domain databases
CDDi | cd00082, HisKA, 1 hit |
Gene3Di | 3.30.565.10, 1 hit |
InterProi | View protein in InterPro IPR003660, HAMP_dom IPR003594, HATPase_C IPR036890, HATPase_C_sf IPR005467, His_kinase_dom IPR003661, HisK_dim/P IPR036097, HisK_dim/P_sf IPR004358, Sig_transdc_His_kin-like_C |
Pfami | View protein in Pfam PF00672, HAMP, 1 hit PF02518, HATPase_c, 1 hit PF00512, HisKA, 1 hit |
PRINTSi | PR00344, BCTRLSENSOR |
SMARTi | View protein in SMART SM00304, HAMP, 1 hit SM00387, HATPase_c, 1 hit SM00388, HisKA, 1 hit |
SUPFAMi | SSF47384, SSF47384, 1 hit SSF55874, SSF55874, 1 hit |
PROSITEi | View protein in PROSITE PS50885, HAMP, 1 hit PS50109, HIS_KIN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ENVZ_ECOLI | |
Accessioni | P0AEJ4Primary (citable) accession number: P0AEJ4 Secondary accession number(s): P02933, Q2M769 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | December 20, 2005 | |
Last modified: | April 7, 2021 | |
This is version 138 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references