Escherichia coli K-12 substr. MG1655 Protein: EnvZ sensory histidine kinase

Gene: envZ Accession Numbers: EG10269 (EcoCyc), b3404, ECK3391

Synonyms: tpo, perA, ompB

Regulation Summary Diagram: ?

Regulation summary diagram for envZ

Subunit composition of EnvZ sensory histidine kinase = [EnvZ]2

Alternative forms of EnvZ sensory histidine kinase: EnvZ sensory histidine kinase - phosphorylated

EnvZ is the sensory histidine kinase of the EnvZ/OmpR two-component system which regulates expression of the major outer membrane porin genes, ompF and ompC, in response to fluctuations in extracellular osmotic pressure.

EnvZ undergoes autophosphorylation by transferrring the gamma phosphate of ATP to histidine residue 243. The phosphate is then transferred to asp55 of the OmpR response regulator [Forst89]. Phosphorylated OmpR serves as a transcription factor, differentially modulating expression of the outer membrane porin genes [Matsuyama86, Mizuno87]. EnvZ also possesses an OmpR-phosphate phosphatase function [Forst89]. The specific mechanism by which EnvZ senses changes in osmolarity is not yet understood.

The envZ ompR genes are transcribed as a single polycistronic mRNA however the amount of EnvZ molecules per cell is significantly less than OmpR during exponential growth in medium with varying osmolarities [Cai02]. EnvZ is a dimeric, inner membrane protein [Yaku97, Forst87] containing two trans-membrane regions, a periplasmic domain and a cytoplasmic domain - the latter including a 228 residue kinase/phosphatase domain. NMR solution structures of the active portions of the cytoplasmic domain of EnvZ have been reported [Tomomori99, Tanaka98a].

Citations: [Mizuno90, Waukau92, Yoshida07]

Locations: inner membrane

Map Position: [3,532,538 <- 3,533,890] (76.14 centisomes, 274°)
Length: 1353 bp / 450 aa

Molecular Weight of Polypeptide: 50.334 kD (from nucleotide sequence)

Molecular Weight of Multimer: 50.0 kD (experimental) [Comeau85]

pI: 6.75

Unification Links: ASAP:ABE-0011108 , CGSC:807 , DIP:DIP-48357N , EchoBASE:EB0265 , EcoGene:EG10269 , EcoliWiki:b3404 , Mint:MINT-8398485 , ModBase:P0AEJ4 , OU-Microarray:b3404 , PortEco:envZ , PR:PRO_000022527 , Protein Model Portal:P0AEJ4 , RefSeq:NP_417863 , RegulonDB:EG10269 , SMR:P0AEJ4 , String:511145.b3404 , Swiss-Model:P0AEJ4 , UniProt:P0AEJ4

Relationship Links: InterPro:IN-FAMILY:IPR003594 , InterPro:IN-FAMILY:IPR003660 , InterPro:IN-FAMILY:IPR003661 , InterPro:IN-FAMILY:IPR004358 , InterPro:IN-FAMILY:IPR005467 , InterPro:IN-FAMILY:IPR009082 , PDB:Structure:1BXD , PDB:Structure:1JOY , PDB:Structure:1NJV , PDB:Structure:3ZCC , PDB:Structure:3ZRV , PDB:Structure:3ZRW , PDB:Structure:3ZRX , PDB:Structure:4CTI , PDB:Structure:4KP4 , Pfam:IN-FAMILY:PF00512 , Pfam:IN-FAMILY:PF00672 , Pfam:IN-FAMILY:PF02518 , Prints:IN-FAMILY:PR00344 , Prosite:IN-FAMILY:PS50109 , Prosite:IN-FAMILY:PS50885 , Smart:IN-FAMILY:SM00304 , Smart:IN-FAMILY:SM00387 , Smart:IN-FAMILY:SM00388

In Paralogous Gene Group: 122 (29 members)

Reactions known to consume the compound:

EnvZ Two-Component Signal Transduction System, osmotic responsive :
EnvZ sensory histidine kinase + ATP → ADP + EnvZ-Phis

Reactions known to produce the compound:

EnvZ Two-Component Signal Transduction System, osmotic responsive :
EnvZ-Phis + OmpR → EnvZ sensory histidine kinase + OmpR-P

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for envZ

GO Terms:

Biological Process: GO:0000160 - phosphorelay signal transduction system Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Igo89]
GO:0006470 - protein dephosphorylation Inferred from experiment [Igo89]
GO:0016048 - detection of temperature stimulus Inferred from experiment [Gerken09]
GO:0016310 - phosphorylation Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Igo89]
GO:0023014 - signal transduction by protein phosphorylation Inferred from experiment Inferred by computational analysis [GOA01a, Forst89]
GO:0046777 - protein autophosphorylation Inferred from experiment [Dutta00, Igo89]
GO:0047484 - regulation of response to osmotic stress Inferred from experiment [Matsuyama86]
GO:0007165 - signal transduction Inferred by computational analysis [GOA01a]
GO:0018106 - peptidyl-histidine phosphorylation Inferred by computational analysis [Gaudet10]
Molecular Function: GO:0000155 - phosphorelay sensor kinase activity Inferred from experiment Inferred by computational analysis [GOA01a, Forst89]
GO:0004721 - phosphoprotein phosphatase activity Inferred from experiment [Igo89]
GO:0005515 - protein binding Inferred from experiment [Gerken10a, Gerken09]
GO:0042803 - protein homodimerization activity Inferred from experiment [Yaku97]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0004673 - protein histidine kinase activity Inferred by computational analysis [GOA01]
GO:0004871 - signal transducer activity Inferred by computational analysis [GOA01a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016772 - transferase activity, transferring phosphorus-containing groups Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005622 - intracellular Inferred by computational analysis Inferred from experiment [Igo89, UniProtGOA11a]
GO:0005887 - integral component of plasma membrane Inferred from experiment [Forst87]
GO:0009898 - cytoplasmic side of plasma membrane Inferred from experiment [Forst87]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, DiazMejia09, Forst87]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]

MultiFun Terms: cell structure membrane
information transfer protein related posttranslational modification
regulation type of regulation posttranscriptional covalent modification, demodification, maturation
regulation type of regulation transcriptional level complex regulation two component regulatory systems (external signal)

Essentiality data for envZ knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Last-Curated ? 25-Nov-2010 by Mackie A , Macquarie University

Sequence Features

Protein sequence of EnvZ with features indicated

Feature Class Location Attached Group Citations Comment State
Transmembrane-Region 16 -> 35  
UniProt: Helical;; Non-Experimental Qualifier: probable;
Transmembrane-Region 159 -> 179  
UniProt: Helical;; Non-Experimental Qualifier: probable;
Conserved-Region 180 -> 232  
UniProt: HAMP;
Mutagenesis-Variant 193  
[Kishii07, UniProt11]
[Kishii07, UniProt11]
A → V: No effect.
A → L: Promotes the formation of alpha- helical secondary structure of the HAMP domain.
Conserved-Region 240 -> 440  
UniProt: Histidine kinase;
Phosphorylation-Modification 243  
[Roberts94, UniProt13]
UniProt: Phosphohistidine; by autocatalysis.
Amino-Acid-Sites-That-Bind 347  
UniProt: ATP.
Mutagenesis-Variant 347  
[Tanaka98a, UniProt11]
UniProt: Loss of ATP binding; loss of autophosphorylation.
Nucleotide-Phosphate-Binding-Region 373 -> 387 ATP
UniProt: ATP.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b3404 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10269; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Cai02: Cai SJ, Inouye M (2002). "EnvZ-OmpR interaction and osmoregulation in Escherichia coli." J Biol Chem 277(27);24155-61. PMID: 11973328

Comeau85: Comeau DE, Ikenaka K, Tsung KL, Inouye M (1985). "Primary characterization of the protein products of the Escherichia coli ompB locus: structure and regulation of synthesis of the OmpR and EnvZ proteins." J Bacteriol 1985;164(2);578-84. PMID: 2997120

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dutta00: Dutta R, Yoshida T, Inouye M (2000). "The critical role of the conserved Thr247 residue in the functioning of the osmosensor EnvZ, a histidine Kinase/Phosphatase, in Escherichia coli." J Biol Chem 275(49);38645-53. PMID: 10973966

Forst87: Forst S, Comeau D, Norioka S, Inouye M (1987). "Localization and membrane topology of EnvZ, a protein involved in osmoregulation of OmpF and OmpC in Escherichia coli." J Biol Chem 262(34);16433-8. PMID: 2824492

Forst89: Forst S, Delgado J, Inouye M (1989). "Phosphorylation of OmpR by the osmosensor EnvZ modulates expression of the ompF and ompC genes in Escherichia coli." Proc Natl Acad Sci U S A 86(16);6052-6. PMID: 2668953

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

Gerken09: Gerken H, Charlson ES, Cicirelli EM, Kenney LJ, Misra R (2009). "MzrA: a novel modulator of the EnvZ/OmpR two-component regulon." Mol Microbiol 72(6);1408-22. PMID: 19432797

Gerken10a: Gerken H, Misra R (2010). "MzrA-EnvZ interactions in the periplasm influence the EnvZ/OmpR two-component regulon." J Bacteriol 192(23);6271-8. PMID: 20889743

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Igo89: Igo MM, Ninfa AJ, Stock JB, Silhavy TJ (1989). "Phosphorylation and dephosphorylation of a bacterial transcriptional activator by a transmembrane receptor." Genes Dev 3(11);1725-34. PMID: 2558046

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kishii07: Kishii R, Falzon L, Yoshida T, Kobayashi H, Inouye M (2007). "Structural and functional studies of the HAMP domain of EnvZ, an osmosensing transmembrane histidine kinase in Escherichia coli." J Biol Chem 282(36);26401-8. PMID: 17635923

Matsuyama86: Matsuyama S, Mizuno T, Mizushima S (1986). "Interaction between two regulatory proteins in osmoregulatory expression of ompF and ompC genes in Escherichia coli: a novel ompR mutation suppresses pleiotropic defects caused by an envZ mutation." J Bacteriol 1986;168(3);1309-14. PMID: 3536870

Mizuno87: Mizuno T, Mizushima S (1987). "Isolation and characterization of deletion mutants of ompR and envZ, regulatory genes for expression of the outer membrane proteins OmpC and OmpF in Escherichia coli." J Biochem (Tokyo) 1987;101(2);387-96. PMID: 3294816

Mizuno90: Mizuno T, Mizushima S (1990). "Signal transduction and gene regulation through the phosphorylation of two regulatory components: the molecular basis for the osmotic regulation of the porin genes." Mol Microbiol 4(7);1077-82. PMID: 1700256

Roberts94: Roberts DL, Bennett DW, Forst SA (1994). "Identification of the site of phosphorylation on the osmosensor, EnvZ, of Escherichia coli." J Biol Chem 1994;269(12);8728-33. PMID: 8132603

Tanaka98a: Tanaka T, Saha SK, Tomomori C, Ishima R, Liu D, Tong KI, Park H, Dutta R, Qin L, Swindells MB, Yamazaki T, Ono AM, Kainosho M, Inouye M, Ikura M (1998). "NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ." Nature 396(6706);88-92. PMID: 9817206

Tomomori99: Tomomori C, Tanaka T, Dutta R, Park H, Saha SK, Zhu Y, Ishima R, Liu D, Tong KI, Kurokawa H, Qian H, Inouye M, Ikura M (1999). "Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ." Nat Struct Biol 6(8);729-34. PMID: 10426948

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Waukau92: Waukau J, Forst S (1992). "Molecular analysis of the signaling pathway between EnvZ and OmpR in Escherichia coli." J Bacteriol 174(5);1522-7. PMID: 1311295

Yaku97: Yaku H, Mizuno T (1997). "The membrane-located osmosensory kinase, EnvZ, that contains a leucine zipper-like motif functions as a dimer in Escherichia coli." FEBS Lett 1997;417(3);409-13. PMID: 9409762

Yoshida07: Yoshida T, Phadtare S, Inouye M (2007). "Functional and structural characterization of EnvZ, an osmosensing histidine kinase of E. coli." Methods Enzymol 423;184-202. PMID: 17609132

Other References Related to Gene Regulation

Huang92a: Huang L, Tsui P, Freundlich M (1992). "Positive and negative control of ompB transcription in Escherichia coli by cyclic AMP and the cyclic AMP receptor protein." J Bacteriol 1992;174(3);664-70. PMID: 1310090

Marzan13: Marzan LW, Hasan CM, Shimizu K (2013). "Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant." Arch Microbiol 195(3);161-71. PMID: 23274360

Tsui91: Tsui P, Huang L, Freundlich M (1991). "Integration host factor binds specifically to multiple sites in the ompB promoter of Escherichia coli and inhibits transcription." J Bacteriol 1991;173(18);5800-7. PMID: 1885551

Viveiros07: Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pages JM, Amaral L (2007). "Antibiotic stress, genetic response and altered permeability of E. coli." PLoS ONE 2;e365. PMID: 17426813

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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