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P0AE70

- MAZF_ECOLI

UniProt

P0AE70 - MAZF_ECOLI

Protein

mRNA interferase MazF

Gene

mazF

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

    Toxic component of a toxin-antitoxin (TA) module. MazF is a sequence-specific mRNA endoribonuclease that inhibits protein synthesis and induces bacterial stasis. It is very stable, single-strand specific and cleavage is independent of the ribosome, although translation enhances cleavage for some mRNAs. Cleavage usually occurs between the first A and C of ACA sequences, yielding a 2',3'-cyclic phosphate and a free 5'-OH. The endoribonuclease activity (a toxin) is inhibited by the labile cognate antitoxin MazE. 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 overexpression of MazF leads to programmed cell death. MazF-mediated cell death occurs following a number of stress conditions in a relA-dependent fashion and only when cells are in log phase. Cell growth and viability are not affected when MazF and MazE are coexpressed. Programmed cell death occurs when cells are at high density and depends on the presence of MazE-MazF and a quorum sensing pentapeptide, the extracellular death factor (EDF) with sequence NNWNN, probably produced from the zwg gene product glucose-6-phosphate 1-dehydrogenase. Both MazE and MazE-MazF bind to the promoter region of the mazE-mazF operon to inhibit their transcription.
    Might also serve to protect cells against bacteriophage; in the presence of MazE-MazF fewer P1 phage are produced than in a disruption 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.
    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.

    Enzyme regulationi

    Inhibited by Mg2+.1 Publication

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. endoribonuclease activity Source: UniProtKB
    3. protein binding Source: EcoCyc
    4. RNA binding Source: UniProtKB-KW

    GO - Biological processi

    1. negative regulation of cell growth Source: UniProtKB
    2. quorum sensing Source: UniProtKB-KW
    3. regulation of mRNA stability Source: UniProtKB
    4. regulation of transcription, DNA-templated Source: UniProtKB-KW
    5. response to stress Source: UniProtKB-KW
    6. RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
    7. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Endonuclease, Hydrolase, Nuclease, Repressor, Toxin

    Keywords - Biological processi

    Quorum sensing, Stress response, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, RNA-binding

    Enzyme and pathway databases

    BioCyciEcoCyc:EG11249-MONOMER.
    ECOL316407:JW2753-MONOMER.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    mRNA interferase MazF (EC:3.1.-.-)
    Alternative name(s):
    Endoribonuclease MazF
    Toxin MazF
    Gene namesi
    Name:mazF
    Synonyms:chpA, chpAK
    Ordered Locus Names:b2782, JW2753
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318: Chromosome, UP000000625: Chromosome

    Organism-specific databases

    EcoGeneiEG11249. mazF.

    Pathology & Biotechi

    Biotechnological usei

    Can be used to produce large quantities of a single protein if the gene coding for the protein does not contain any ACA codons. Up to 90% of bacterial cellular protein can be the target, which can be produced for up to 4 days. The system also works in eukaryotic cells.1 Publication

    Disruption phenotypei

    Decreased sensitivity to dramatic intracellular increases of ppGpp. Cells missing mazE-mazF survive high temperature, various DNA-damaging agents and H2O2 exposure better than wild-type cells. Cells missing mazE-mazF produce more P1 phage than wild-type cells, while introduction of lysogens into a growing non-lysogenic deletion culture is lethal. Cells missing mazE-mazF show reduced biofilm formation, and survive antibiotic treatment in log phase better than wild-type cells.5 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi24 – 241E → A: Greatly reduces toxicity, about 10-fold less RNA cleavage activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 111111mRNA interferase MazFPRO_0000201897Add
    BLAST

    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.3 Publications

    Gene expression databases

    GenevestigatoriP0AE70.

    Interactioni

    Subunit structurei

    Probably a dimer. Forms a heterohexamer composed of alternating toxin and antitoxin homodimers MazF(2)-MazE(2)-MazF2. The binding site of MazE and ssRNA or ssDNA are largely overlapping; the presence of only 1 MazE molecule inhibits mRNA endoribonuclease activity.2 Publications

    Protein-protein interaction databases

    IntActiP0AE70. 2 interactions.
    STRINGi511145.b2782.

    Structurei

    Secondary structure

    1
    111
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi11 – 166
    Beta strandi28 – 336
    Helixi37 – 437
    Beta strandi46 – 538
    Beta strandi61 – 644
    Beta strandi66 – 694
    Beta strandi71 – 744
    Helixi75 – 773
    Beta strandi79 – 813
    Helixi83 – 864
    Beta strandi89 – 935
    Helixi96 – 11015

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1UB4X-ray1.70A/B2-111[»]
    3NFCX-ray2.00A/B/C/D/E/F1-111[»]
    DisProtiDP00299.
    ProteinModelPortaliP0AE70.
    SMRiP0AE70. Positions 2-111.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0AE70.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the PemK/MazF family.Curated

    Phylogenomic databases

    eggNOGiCOG2337.
    HOGENOMiHOG000290185.
    KOiK07171.
    OMAiQAGREQS.
    OrthoDBiEOG67X204.
    PhylomeDBiP0AE70.

    Family and domain databases

    Gene3Di2.30.30.110. 1 hit.
    InterProiIPR003477. PemK-like.
    IPR011067. Plasmid_toxin/cell-grow_inhib.
    [Graphical view]
    PfamiPF02452. PemK. 1 hit.
    [Graphical view]
    SUPFAMiSSF50118. SSF50118. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P0AE70-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVSRYVPDMG DLIWVDFDPT KGSEQAGHRP AVVLSPFMYN NKTGMCLCVP    50
    CTTQSKGYPF EVVLSGQERD GVALADQVKS IAWRARGATK KGTVAPEELQ 100
    LIKAKINVLI G 111
    Length:111
    Mass (Da):12,098
    Last modified:December 6, 2005 - v1
    Checksum:i1579C867DD6B96AC
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D16450 Genomic DNA. Translation: BAA03918.1.
    J04039 Unassigned DNA. Translation: AAA03239.1.
    U29580 Genomic DNA. Translation: AAA69292.1.
    U00096 Genomic DNA. Translation: AAC75824.1.
    AP009048 Genomic DNA. Translation: BAE76856.1.
    PIRiB49339.
    RefSeqiNP_417262.1. NC_000913.3.
    YP_490990.1. NC_007779.1.

    Genome annotation databases

    EnsemblBacteriaiAAC75824; AAC75824; b2782.
    BAE76856; BAE76856; BAE76856.
    GeneIDi12933306.
    947252.
    KEGGiecj:Y75_p2719.
    eco:b2782.
    PATRICi32120980. VBIEscCol129921_2882.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D16450 Genomic DNA. Translation: BAA03918.1 .
    J04039 Unassigned DNA. Translation: AAA03239.1 .
    U29580 Genomic DNA. Translation: AAA69292.1 .
    U00096 Genomic DNA. Translation: AAC75824.1 .
    AP009048 Genomic DNA. Translation: BAE76856.1 .
    PIRi B49339.
    RefSeqi NP_417262.1. NC_000913.3.
    YP_490990.1. NC_007779.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1UB4 X-ray 1.70 A/B 2-111 [» ]
    3NFC X-ray 2.00 A/B/C/D/E/F 1-111 [» ]
    DisProti DP00299.
    ProteinModelPortali P0AE70.
    SMRi P0AE70. Positions 2-111.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P0AE70. 2 interactions.
    STRINGi 511145.b2782.

    Chemistry

    BindingDBi P0AE70.
    ChEMBLi CHEMBL1795096.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai AAC75824 ; AAC75824 ; b2782 .
    BAE76856 ; BAE76856 ; BAE76856 .
    GeneIDi 12933306.
    947252.
    KEGGi ecj:Y75_p2719.
    eco:b2782.
    PATRICi 32120980. VBIEscCol129921_2882.

    Organism-specific databases

    EchoBASEi EB1229.
    EcoGenei EG11249. mazF.

    Phylogenomic databases

    eggNOGi COG2337.
    HOGENOMi HOG000290185.
    KOi K07171.
    OMAi QAGREQS.
    OrthoDBi EOG67X204.
    PhylomeDBi P0AE70.

    Enzyme and pathway databases

    BioCyci EcoCyc:EG11249-MONOMER.
    ECOL316407:JW2753-MONOMER.

    Miscellaneous databases

    EvolutionaryTracei P0AE70.
    PROi P0AE70.

    Gene expression databases

    Genevestigatori P0AE70.

    Family and domain databases

    Gene3Di 2.30.30.110. 1 hit.
    InterProi IPR003477. PemK-like.
    IPR011067. Plasmid_toxin/cell-grow_inhib.
    [Graphical view ]
    Pfami PF02452. PemK. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50118. SSF50118. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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 IN PROGRAMMED CELL DEATH, INTERACTION WITH MAZE, INDUCTION, DISRUPTION PHENOTYPE, 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, 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 A TOXIN.
      Strain: K12.
    8. "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: RNA CLEAVAGE, INDUCTION, DISRUPTION PHENOTYPE.
      Strain: K12 / MG1655 / ATCC 47076.
    9. "Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions."
      Hazan R., Sat B., Engelberg-Kulka H.
      J. Bacteriol. 186:3663-3669(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION IN STRESS RESPONSE, DEPENDENCE ON RELA.
      Strain: K12 / K38 / S26 and K12 / MC4100 / ATCC 35695 / DSM 6574.
    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: FUNCTION 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. "Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase."
      Zhang Y., Zhang J., Hara H., Kato I., Inouye M.
      J. Biol. Chem. 280:3143-3150(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS AN ENDONUCLEASE, ENZYME REGULATION, SUBSTRATE SPECIFICITY, RNA-BINDING.
    13. "Single protein production in living cells facilitated by an mRNA interferase."
      Suzuki M., Zhang J., Liu M., Woychik N.A., Inouye M.
      Mol. Cell 18:253-261(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOTECHNOLOGY.
    14. "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.
    15. "A linear pentapeptide is a quorum-sensing factor required for mazEF-mediated cell death in Escherichia coli."
      Kolodkin-Gal I., Hazan R., Gaathon A., Carmeli S., Engelberg-Kulka H.
      Science 318:652-655(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REQUIREMENT FOR EXTRACELLULAR DEATH FACTOR (EDF).
      Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
    16. "The extracellular death factor: physiological and genetic factors influencing its production and response in Escherichia coli."
      Kolodkin-Gal I., Engelberg-Kulka H.
      J. Bacteriol. 190:3169-3175(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: EDF PRODUCTION, STRAIN DIFFERENCES IN ABILITY TO MAKE AND RESPOND TO EDF.
      Strain: K12 / K38 / S26, K12 / MC4100 / ATCC 35695 / DSM 6574, K12 / MG1655 / ATCC 47076 and K12 / W3110 / ATCC 27325 / DSM 5911.
    17. "Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms."
      Christensen-Dalsgaard M., Gerdes K.
      Nucleic Acids Res. 36:6472-6481(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: TRANSLATION IMPROVES CLEAVAGE EFFICIENCY.
      Strain: K12.
    18. "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.
    19. "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.
    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) OF 2-111, POSSIBLE DNA-BINDING, SUBUNIT.
    21. "Characterization of dual substrate binding sites in the homodimeric structure of Escherichia coli mRNA interferase MazF."
      Li G.Y., Zhang Y., Chan M.C., Mal T.K., Hoeflich K.P., Inouye M., Ikura M.
      J. Mol. Biol. 357:139-150(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR, MUTAGENESIS OF GLU-24.

    Entry informationi

    Entry nameiMAZF_ECOLI
    AccessioniPrimary (citable) accession number: P0AE70
    Secondary accession number(s): P33645, Q2MA50
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 6, 2005
    Last sequence update: December 6, 2005
    Last modified: October 1, 2014
    This is version 73 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Caution

    Strain K12 / MG1655 is deficient in both production and response to EDF, unlike strains K12 / MC4100, K12 / W3110 and K12 / K38, all of which make and respond to EDF.Curated

    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