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Protein

Antitoxin MazE

Gene

mazE

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Antitoxin component of a type II toxin-antitoxin (TA) module. Labile antitoxin that binds to the MazF endoribonuclease toxin and neutralizes its endoribonuclease activity. Is considered to be an 'addiction' molecule as the cell dies in its absence. Toxicity results when the levels of MazE decrease in the cell, leading to mRNA degradation. This effect can be rescued by expression of MazE, but after 6 hours in rich medium the overexpression of MazF leads to programmed cell death. Cell growth and viability are not affected when MazF and MazE are coexpressed. Both MazE and MazE-MazF bind to the promoter region of the mazE-mazF operon to inhibit their own transcription (PubMed:8650219). There are 3 operators to which MazE binds (PubMed:12533537). MazE has higher affinity for promoter DNA in the presence of MazF (PubMed:25564525).7 Publications
Cell death governed by the MazE-MazF and DinJ-YafQ TA modules seems to play a role in biofilm formation, while MazE-MazF is also implicated in cell death in liquid media.2 Publications
Might also serve to protect cells against bacteriophage; in the presence of MazE-MazF fewer P1 phage are produced than in a disrupted strain. For strain K38 most wild-type cells are killed but not by phage lysis; it was suggested that MazE-MazF causes P1 phage exclusion from the bacterial population. This phenomenon is strain dependent.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciEcoCyc:EG10571-MONOMER.
ECOL316407:JW2754-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Antitoxin MazE
Gene namesi
Name:mazE
Synonyms:chpAI, chpR
Ordered Locus Names:b2783, JW2754
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10571. mazE.

Pathology & Biotechi

Disruption phenotypei

Decreased sensitivity to dramatic intracellular increases of ppGpp. Double mazE-mazF disruptions survive high temperature, various DNA-damaging agents and H2O2 exposure better than wild-type cells. They produce more P1 phage than wild-type cells, while introduction of lysogens into a growing non-lysogenic disruption culture is lethal (PubMed:15316771). Double mazE-mazF disruptions show reduced biofilm formation, and survive antibiotic treatment in log phase better than wild-type cells. Cells missing mazE-mazF survive hydroxyurea treatment better than wild-type; further disruption of relE-relB and tonB yields even better survival (PubMed:20005847).4 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi8 – 81R → A: Binds poorly to DNA. 1 Publication
Mutagenesisi16 – 161R → A: Does not bind to DNA. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 8282Antitoxin MazEPRO_0000089649Add
BLAST

Post-translational modificationi

Degraded by the ClpPA and Lon proteases.3 Publications

Expressioni

Inductioni

Expressed in exponentially growing cells. Induction has been reported to occur after amino acid starvation in a ppGpp-independent fashion and to be Lon protease-dependent (PubMed:12972253), but also to not occur after amino acid starvation and to be regulated by ppGpp (PubMed:8650219). MazE alone and in combination with MazF, represses transcription of the mazE-mazF operon. Fis activates transcription. Part of the relA-mazE-mazF-mazG operon, there is also a second mazE-mazF specific promoter which is negatively autoregulated. This operon induced by ectopic expression of toxin RelE; induction of this operon by amino acid starvation requires the relBEF operon (PubMed:23432955).5 Publications

Interactioni

Subunit structurei

Probably forms a homodimer in the absence of MazF; binds DNA as a homodimer (PubMed:25564525, PubMed:12533537). Forms a heterohexamer composed of alternating toxin and antitoxin homodimers MazF(2)-MazE(2)-MazF2.6 Publications

Protein-protein interaction databases

IntActiP0AE72. 10 interactions.
STRINGi511145.b2783.

Structurei

Secondary structure

1
82
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 94Combined sources
Beta strandi12 – 154Combined sources
Helixi19 – 246Combined sources
Beta strandi33 – 386Combined sources
Beta strandi41 – 466Combined sources
Helixi55 – 606Combined sources
Turni64 – 663Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MVFX-ray1.65D/E1-82[»]
1UB4X-ray1.70C1-82[»]
2MRNNMR-A/B2-50[»]
2MRUNMR-A/B2-50[»]
ProteinModelPortaliP0AE72.
SMRiP0AE72. Positions 2-76.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0AE72.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 4946SpoVT-AbrBPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the PemI family.Curated
Contains 1 SpoVT-AbrB domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG2336.
HOGENOMiHOG000289070.
InParanoidiP0AE72.
KOiK07172.
OMAiISQITPE.
OrthoDBiEOG6Z3KS9.
PhylomeDBiP0AE72.

Family and domain databases

InterProiIPR007159. SpoVT-AbrB_dom.
[Graphical view]
PfamiPF04014. Antitoxin-MazE. 1 hit.
[Graphical view]
SMARTiSM00966. SpoVT_AbrB. 1 hit.
[Graphical view]
PROSITEiPS51740. SPOVT_ABRB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0AE72-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIHSSVKRWG NSPAVRIPAT LMQALNLNID DEVKIDLVDG KLIIEPVRKE
60 70 80
PVFTLAELVN DITPENLHEN IDWGEPKDKE VW
Length:82
Mass (Da):9,356
Last modified:December 6, 2005 - v1
Checksum:iCD452A9AA4FB362E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16450 Genomic DNA. Translation: BAA41177.1.
J04039 Unassigned DNA. Translation: AAA03238.1.
U29580 Genomic DNA. Translation: AAA69293.1.
U00096 Genomic DNA. Translation: AAC75825.1.
AP009048 Genomic DNA. Translation: BAE76857.1.
PIRiB31996. BVECZE.
RefSeqiNP_417263.1. NC_000913.3.

Genome annotation databases

EnsemblBacteriaiAAC75825; AAC75825; b2783.
BAE76857; BAE76857; BAE76857.
GeneIDi947245.
KEGGiecj:Y75_p2720.
eco:b2783.
PATRICi32120982. VBIEscCol129921_2883.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16450 Genomic DNA. Translation: BAA41177.1.
J04039 Unassigned DNA. Translation: AAA03238.1.
U29580 Genomic DNA. Translation: AAA69293.1.
U00096 Genomic DNA. Translation: AAC75825.1.
AP009048 Genomic DNA. Translation: BAE76857.1.
PIRiB31996. BVECZE.
RefSeqiNP_417263.1. NC_000913.3.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MVFX-ray1.65D/E1-82[»]
1UB4X-ray1.70C1-82[»]
2MRNNMR-A/B2-50[»]
2MRUNMR-A/B2-50[»]
ProteinModelPortaliP0AE72.
SMRiP0AE72. Positions 2-76.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP0AE72. 10 interactions.
STRINGi511145.b2783.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC75825; AAC75825; b2783.
BAE76857; BAE76857; BAE76857.
GeneIDi947245.
KEGGiecj:Y75_p2720.
eco:b2783.
PATRICi32120982. VBIEscCol129921_2883.

Organism-specific databases

EchoBASEiEB0566.
EcoGeneiEG10571. mazE.

Phylogenomic databases

eggNOGiCOG2336.
HOGENOMiHOG000289070.
InParanoidiP0AE72.
KOiK07172.
OMAiISQITPE.
OrthoDBiEOG6Z3KS9.
PhylomeDBiP0AE72.

Enzyme and pathway databases

BioCyciEcoCyc:EG10571-MONOMER.
ECOL316407:JW2754-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP0AE72.
PROiP0AE72.

Family and domain databases

InterProiIPR007159. SpoVT-AbrB_dom.
[Graphical view]
PfamiPF04014. Antitoxin-MazE. 1 hit.
[Graphical view]
SMARTiSM00966. SpoVT_AbrB. 1 hit.
[Graphical view]
PROSITEiPS51740. SPOVT_ABRB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The nucleotide sequence and characterization of the relA gene of Escherichia coli."
    Metzger S., Dror I.B., Aizenman E., Schreiber G., Toone M., Friesen J.D., Cashel M., Glaser G.
    J. Biol. Chem. 263:15699-15704(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], OPERON STRUCTURE.
    Strain: K12.
  2. "chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100."
    Masuda Y., Miyakawa K., Nishimura Y., Ohtsubo E.
    J. Bacteriol. 175:6850-6856(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 / MC1000 / ATCC 39531.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  5. "An Escherichia coli chromosomal 'addiction module' regulated by guanosine 3',5'-bispyrophosphate: a model for programmed bacterial cell death."
    Aizenman E., Engelberg-Kulka H., Glaser G.
    Proc. Natl. Acad. Sci. U.S.A. 93:6059-6063(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CLEAVAGE BY THE CLPPA PROTEASE, INTERACTION WITH MAZF, INDUCTION, OPERON STRUCTURE.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  6. "The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome."
    Marianovsky I., Aizenman E., Engelberg-Kulka H., Glaser G.
    J. Biol. Chem. 276:5975-5984(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TRANSCRIPTION REGULATION, DNA-BINDING, SUBUNIT.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  7. "Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins."
    Pedersen K., Christensen S.K., Gerdes K.
    Mol. Microbiol. 45:501-510(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ANTITOXIN.
    Strain: K12.
  8. "Recognition of the intrinsically flexible addiction antidote MazE by a dromedary single domain antibody fragment. Structure, thermodynamics of binding, stability, and influence on interactions with DNA."
    Lah J., Marianovsky I., Glaser G., Engelberg-Kulka H., Kinne J., Wyns L., Loris R.
    J. Biol. Chem. 278:14101-14111(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, DNA-BINDING.
  9. "Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA."
    Christensen S.K., Pedersen K., Hansen F.G., Gerdes K.
    J. Mol. Biol. 332:809-819(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, POSSIBLE CLEAVAGE BY THE LON PROTEASE, DISRUPTION PHENOTYPE.
    Strain: K12 / MG1655 / ATCC 47076.
  10. "MazF-mediated cell death in Escherichia coli: a point of no return."
    Amitai S., Yassin Y., Engelberg-Kulka H.
    J. Bacteriol. 186:8295-8300(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN PROGRAMMED CELL DEATH.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  11. "Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1."
    Hazan R., Engelberg-Kulka H.
    Mol. Genet. Genomics 272:227-234(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHAGE IMMUNITY, DISRUPTION PHENOTYPE.
    Strain: K12 / JM109 / ATCC 53323, K12 / K38 / S26 and K12 / MC4100 / ATCC 35695 / DSM 6574.
  12. "MazG -- a regulator of programmed cell death in Escherichia coli."
    Gross M., Marianovsky I., Glaser G.
    Mol. Microbiol. 59:590-601(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, OPERON STRUCTURE.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574 and K12 / W3110 / ATCC 27325 / DSM 5911.
  13. "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli."
    Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J., Walker G.C.
    Mol. Cell 36:845-860(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  14. "A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation."
    Kolodkin-Gal I., Verdiger R., Shlosberg-Fedida A., Engelberg-Kulka H.
    PLoS ONE 4:E6785-E6785(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL DEATH, FUNCTION IN BIOFILM FORMATION, DISRUPTION PHENOTYPE.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  15. "The Escherichia coli extracellular death factor EDF induces the endoribonucleolytic activities of the toxins MazF and ChpBK."
    Belitsky M., Avshalom H., Erental A., Yelin I., Kumar S., London N., Sperber M., Schueler-Furman O., Engelberg-Kulka H.
    Mol. Cell 41:625-635(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  16. "Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli."
    Kasari V., Mets T., Tenson T., Kaldalu N.
    BMC Microbiol. 13:45-45(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY OTHER TA SYSTEMS.
    Strain: K12 / BW25113.
  17. "MazF-induced growth inhibition and persister generation in Escherichia coli."
    Tripathi A., Dewan P.C., Siddique S.A., Varadarajan R.
    J. Biol. Chem. 289:4191-4205(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY LON AND CLPP.
    Strain: K12 / BW25113 and K12 / MC4100 / ATCC 35695 / DSM 6574.
  18. "mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems."
    Yamaguchi Y., Inouye M.
    Prog. Mol. Biol. Transl. Sci. 85:467-500(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  19. Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH AN ANTIBODY FRAGMENT, DNA-BINDING, MUTAGENESIS OF ARG-8 AND ARG-16.
  20. "Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition."
    Kamada K., Hanaoka F., Burley S.K.
    Mol. Cell 11:875-884(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), SUBUNIT.
  21. "Escherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA binding."
    Zorzini V., Buts L., Schrank E., Sterckx Y.G., Respondek M., Engelberg-Kulka H., Loris R., Zangger K., van Nuland N.A.
    Nucleic Acids Res. 43:1241-1256(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 2-50 IN COMPLEX WITH DNA, FUNCTION, SUBUNIT, DNA-BINDING.

Entry informationi

Entry nameiMAZE_ECOLI
AccessioniPrimary (citable) accession number: P0AE72
Secondary accession number(s): P18534, Q2MA49
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: June 24, 2015
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.