MAZF_ECOLI
ID MAZF_ECOLI Reviewed; 111 AA.
AC P0AE70; P33645; Q2MA50;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Endoribonuclease toxin MazF;
DE EC=3.1.27.- {ECO:0000269|PubMed:15537630};
DE AltName: Full=Toxin MazF;
DE AltName: Full=mRNA interferase MazF {ECO:0000303|PubMed:15537630};
GN Name=mazF; Synonyms=chpA, chpAK; OrderedLocusNames=b2782, JW2753;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND OPERON STRUCTURE.
RC STRAIN=K12;
RX PubMed=2844820; DOI=10.1016/s0021-9258(19)37644-6;
RA Metzger S., Dror I.B., Aizenman E., Schreiber G., Toone M., Friesen J.D.,
RA Cashel M., Glaser G.;
RT "The nucleotide sequence and characterization of the relA gene of
RT Escherichia coli.";
RL J. Biol. Chem. 263:15699-15704(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / MC1000 / ATCC 39531;
RX PubMed=8226627; DOI=10.1128/jb.175.21.6850-6856.1993;
RA Masuda Y., Miyakawa K., Nishimura Y., Ohtsubo E.;
RT "chpA and chpB, Escherichia coli chromosomal homologs of the pem locus
RT responsible for stable maintenance of plasmid R100.";
RL J. Bacteriol. 175:6850-6856(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP FUNCTION IN PROGRAMMED CELL DEATH, INTERACTION WITH MAZE, INDUCTION,
RP DISRUPTION PHENOTYPE, AND OPERON STRUCTURE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=8650219; DOI=10.1073/pnas.93.12.6059;
RA Aizenman E., Engelberg-Kulka H., Glaser G.;
RT "An Escherichia coli chromosomal 'addiction module' regulated by guanosine
RT 3',5'-bispyrophosphate: a model for programmed bacterial cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6059-6063(1996).
RN [6]
RP TRANSCRIPTION REGULATION, AND SUBUNIT.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=11071896; DOI=10.1074/jbc.m008832200;
RA Marianovsky I., Aizenman E., Engelberg-Kulka H., Glaser G.;
RT "The regulation of the Escherichia coli mazEF promoter involves an unusual
RT alternating palindrome.";
RL J. Biol. Chem. 276:5975-5984(2001).
RN [7]
RP FUNCTION IN CELL DEATH, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=11222603; DOI=10.1128/jb.183.6.2041-2045.2001;
RA Sat B., Hazan R., Fisher T., Khaner H., Glaser G., Engelberg-Kulka H.;
RT "Programmed cell death in Escherichia coli: some antibiotics can trigger
RT mazEF lethality.";
RL J. Bacteriol. 183:2041-2045(2001).
RN [8]
RP FUNCTION AS A TOXIN.
RC STRAIN=K12;
RX PubMed=12123459; DOI=10.1046/j.1365-2958.2002.03027.x;
RA Pedersen K., Christensen S.K., Gerdes K.;
RT "Rapid induction and reversal of a bacteriostatic condition by controlled
RT expression of toxins and antitoxins.";
RL Mol. Microbiol. 45:501-510(2002).
RN [9]
RP RNA CLEAVAGE, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=12972253; DOI=10.1016/s0022-2836(03)00922-7;
RA Christensen S.K., Pedersen K., Hansen F.G., Gerdes K.;
RT "Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK
RT cleave translated RNAs and are counteracted by tmRNA.";
RL J. Mol. Biol. 332:809-819(2003).
RN [10]
RP DISRUPTION PHENOTYPE, FUNCTION IN STRESS RESPONSE, AND DEPENDENCE ON RELA.
RC STRAIN=K12 / K38 / S26, and K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=15150257; DOI=10.1128/jb.186.11.3663-3669.2004;
RA Hazan R., Sat B., Engelberg-Kulka H.;
RT "Escherichia coli mazEF-mediated cell death is triggered by various
RT stressful conditions.";
RL J. Bacteriol. 186:3663-3669(2004).
RN [11]
RP FUNCTION IN PROGRAMMED CELL DEATH.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=15576778; DOI=10.1128/jb.186.24.8295-8300.2004;
RA Amitai S., Yassin Y., Engelberg-Kulka H.;
RT "MazF-mediated cell death in Escherichia coli: a point of no return.";
RL J. Bacteriol. 186:8295-8300(2004).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / JM109 / ATCC 53323, K12 / K38 / S26, and
RC K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=15316771; DOI=10.1007/s00438-004-1048-y;
RA Hazan R., Engelberg-Kulka H.;
RT "Escherichia coli mazEF-mediated cell death as a defense mechanism that
RT inhibits the spread of phage P1.";
RL Mol. Genet. Genomics 272:227-234(2004).
RN [13]
RP FUNCTION AS AN ENDONUCLEASE, ACTIVITY REGULATION, SUBSTRATE SPECIFICITY,
RP AND RNA-BINDING.
RX PubMed=15537630; DOI=10.1074/jbc.m411811200;
RA Zhang Y., Zhang J., Hara H., Kato I., Inouye M.;
RT "Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase.";
RL J. Biol. Chem. 280:3143-3150(2005).
RN [14]
RP BIOTECHNOLOGY.
RX PubMed=15837428; DOI=10.1016/j.molcel.2005.03.011;
RA Suzuki M., Zhang J., Liu M., Woychik N.A., Inouye M.;
RT "Single protein production in living cells facilitated by an mRNA
RT interferase.";
RL Mol. Cell 18:253-261(2005).
RN [15]
RP INDUCTION, AND OPERON STRUCTURE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574, and
RC K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16390452; DOI=10.1111/j.1365-2958.2005.04956.x;
RA Gross M., Marianovsky I., Glaser G.;
RT "MazG -- a regulator of programmed cell death in Escherichia coli.";
RL Mol. Microbiol. 59:590-601(2006).
RN [16]
RP REQUIREMENT FOR EXTRACELLULAR DEATH FACTOR (EDF).
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=17962566; DOI=10.1126/science.1147248;
RA Kolodkin-Gal I., Hazan R., Gaathon A., Carmeli S., Engelberg-Kulka H.;
RT "A linear pentapeptide is a quorum-sensing factor required for mazEF-
RT mediated cell death in Escherichia coli.";
RL Science 318:652-655(2007).
RN [17]
RP EDF PRODUCTION, AND STRAIN DIFFERENCES IN ABILITY TO MAKE AND RESPOND TO
RP EDF.
RC STRAIN=K12 / K38 / S26, K12 / MC4100 / ATCC 35695 / DSM 6574,
RC K12 / MG1655 / ATCC 47076, and K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=18310334; DOI=10.1128/jb.01918-07;
RA Kolodkin-Gal I., Engelberg-Kulka H.;
RT "The extracellular death factor: physiological and genetic factors
RT influencing its production and response in Escherichia coli.";
RL J. Bacteriol. 190:3169-3175(2008).
RN [18]
RP TRANSLATION IMPROVES CLEAVAGE EFFICIENCY.
RC STRAIN=K12;
RX PubMed=18854355; DOI=10.1093/nar/gkn667;
RA Christensen-Dalsgaard M., Gerdes K.;
RT "Translation affects YoeB and MazF messenger RNA interferase activities by
RT different mechanisms.";
RL Nucleic Acids Res. 36:6472-6481(2008).
RN [19]
RP FUNCTION.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=19251848; DOI=10.1128/jb.00011-09;
RA Kolodkin-Gal I., Engelberg-Kulka H.;
RT "The stationary-phase sigma factor sigma(S) is responsible for the
RT resistance of Escherichia coli stationary-phase cells to mazEF-mediated
RT cell death.";
RL J. Bacteriol. 191:3177-3182(2009).
RN [20]
RP FUNCTION IN CELL DEATH, FUNCTION IN BIOFILM FORMATION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=19707553; DOI=10.1371/journal.pone.0006785;
RA Kolodkin-Gal I., Verdiger R., Shlosberg-Fedida A., Engelberg-Kulka H.;
RT "A differential effect of E. coli toxin-antitoxin systems on cell death in
RT liquid media and biofilm formation.";
RL PLoS ONE 4:E6785-E6785(2009).
RN [21]
RP FUNCTION, SUBSTRATE SPECIFICITY, AND TRANSLATION REGULATION.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=21944167; DOI=10.1016/j.cell.2011.07.047;
RA Vesper O., Amitai S., Belitsky M., Byrgazov K., Kaberdina A.C.,
RA Engelberg-Kulka H., Moll I.;
RT "Selective translation of leaderless mRNAs by specialized ribosomes
RT generated by MazF in Escherichia coli.";
RL Cell 147:147-157(2011).
RN [22]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH EDF, AND SUBUNIT.
RX PubMed=21419338; DOI=10.1016/j.molcel.2011.02.023;
RA Belitsky M., Avshalom H., Erental A., Yelin I., Kumar S., London N.,
RA Sperber M., Schueler-Furman O., Engelberg-Kulka H.;
RT "The Escherichia coli extracellular death factor EDF induces the
RT endoribonucleolytic activities of the toxins MazF and ChpBK.";
RL Mol. Cell 41:625-635(2011).
RN [23]
RP RETRACTED PAPER.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=21788497; DOI=10.1073/pnas.1100186108;
RA Maisonneuve E., Shakespeare L.J., Joergensen M.G., Gerdes K.;
RT "Bacterial persistence by RNA endonucleases.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:13206-13211(2011).
RN [24]
RP RETRACTION NOTICE OF PUBMED:21788497.
RX PubMed=29531044; DOI=10.1073/pnas.1803278115;
RA Maisonneuve E., Shakespeare L.J., Joergensen M.G., Gerdes K.;
RL Proc. Natl. Acad. Sci. U.S.A. 115:E2901-E2901(2018).
RN [25]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=20005847; DOI=10.1016/j.molcel.2009.11.024;
RA Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J.,
RA Walker G.C.;
RT "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia
RT coli.";
RL Mol. Cell 36:845-860(2009).
RN [26]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=22412352; DOI=10.1371/journal.pbio.1001281;
RA Erental A., Sharon I., Engelberg-Kulka H.;
RT "Two programmed cell death systems in Escherichia coli: an apoptotic-like
RT death is inhibited by the mazEF-mediated death pathway.";
RL PLoS Biol. 10:E1001281-E1001281(2012).
RN [27]
RP FUNCTION, AND INDUCTION BY OTHER TA SYSTEMS.
RC STRAIN=K12 / BW25113;
RX PubMed=23432955; DOI=10.1186/1471-2180-13-45;
RA Kasari V., Mets T., Tenson T., Kaldalu N.;
RT "Transcriptional cross-activation between toxin-antitoxin systems of
RT Escherichia coli.";
RL BMC Microbiol. 13:45-45(2013).
RN [28]
RP FUNCTION, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=23416055; DOI=10.1016/j.celrep.2013.01.026;
RA Dorsey-Oresto A., Lu T., Mosel M., Wang X., Salz T., Drlica K., Zhao X.;
RT "YihE kinase is a central regulator of programmed cell death in bacteria.";
RL Cell Rep. 3:528-537(2013).
RN [29]
RP FUNCTION, SUBSTRATE SPECIFICITY, DOMAIN, AND MUTAGENESIS OF 17-PHE--HIS-28
RP AND 53-THR--GLU-61.
RC STRAIN=K12 / BW25113;
RX PubMed=23280569; DOI=10.1002/prot.24246;
RA Park J.H., Yoshizumi S., Yamaguchi Y., Wu K.P., Inouye M.;
RT "ACA-specific RNA sequence recognition is acquired via the loop 2 region of
RT MazF mRNA interferase.";
RL Proteins 81:874-883(2013).
RN [30]
RP FUNCTION IN PERSISTENCE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-24
RP AND HIS-28.
RC STRAIN=K12 / BW25113, and K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=24375411; DOI=10.1074/jbc.m113.510511;
RA Tripathi A., Dewan P.C., Siddique S.A., Varadarajan R.;
RT "MazF-induced growth inhibition and persister generation in Escherichia
RT coli.";
RL J. Biol. Chem. 289:4191-4205(2014).
RN [31]
RP FUNCTION IN TRANSCRIPTION, AND SUBUNIT.
RX PubMed=25564525; DOI=10.1093/nar/gku1352;
RA Zorzini V., Buts L., Schrank E., Sterckx Y.G., Respondek M.,
RA Engelberg-Kulka H., Loris R., Zangger K., van Nuland N.A.;
RT "Escherichia coli antitoxin MazE as transcription factor: insights into
RT MazE-DNA binding.";
RL Nucleic Acids Res. 43:1241-1256(2015).
RN [32]
RP REVIEW.
RX PubMed=19215780; DOI=10.1016/s0079-6603(08)00812-x;
RA Yamaguchi Y., Inouye M.;
RT "mRNA interferases, sequence-specific endoribonucleases from the toxin-
RT antitoxin systems.";
RL Prog. Mol. Biol. Transl. Sci. 85:467-500(2009).
RN [33]
RP ACTIVITY REGULATION (MICROBIAL INFECTION), AND ADP-RIBOSYLATION AT ARG-4
RP (MICROBIAL INFECTION).
RX PubMed=26395283; DOI=10.1111/mmi.13225;
RA Alawneh A.M., Qi D., Yonesaki T., Otsuka Y.;
RT "An ADP-ribosyltransferase Alt of bacteriophage T4 negatively regulates the
RT Escherichia coli MazF toxin of a toxin-antitoxin module.";
RL Mol. Microbiol. 99:188-198(2016).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-111, POSSIBLE DNA-BINDING, AND
RP SUBUNIT.
RX PubMed=12718874; DOI=10.1016/s1097-2765(03)00097-2;
RA Kamada K., Hanaoka F., Burley S.K.;
RT "Crystal structure of the MazE/MazF complex: molecular bases of antidote-
RT toxin recognition.";
RL Mol. Cell 11:875-884(2003).
RN [35]
RP STRUCTURE BY NMR, AND MUTAGENESIS OF GLU-24.
RX PubMed=16413577; DOI=10.1016/j.jmb.2005.12.035;
RA Li G.Y., Zhang Y., Chan M.C., Mal T.K., Hoeflich K.P., Inouye M., Ikura M.;
RT "Characterization of dual substrate binding sites in the homodimeric
RT structure of Escherichia coli mRNA interferase MazF.";
RL J. Mol. Biol. 357:139-150(2006).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS).
RA Wang X., Wang K., Gao X., Zhang X., Li L., Su X., Zhang J.;
RT "Biochemical and structural analysis of E. coli MazF toxin.";
RL Submitted (JUN-2010) to the PDB data bank.
CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system. A
CC sequence-specific endoribonuclease it inhibits protein synthesis by
CC cleaving mRNA and inducing bacterial stasis. It is stable, single-
CC strand specific with mRNA cleavage independent of the ribosome,
CC although translation enhances cleavage for some mRNAs
CC (PubMed:18854355). Cleavage occurs at the 5'-end of ACA sequences,
CC yielding a 2',3'-cyclic phosphate and a free 5'-OH, although cleavage
CC can also occur on the 3'-end of the first A (PubMed:15537630,
CC PubMed:23280569). Digests 16S rRNA in vivo 43 nts upstream of the C-
CC terminus; this removes the anti-Shine-Dalgarno sequence forming a mixed
CC population of wild-type and 'stress ribosomes'. Stress ribosomes do not
CC translate leader-containing mRNA but are proficient in translation of
CC leaderless mRNA, which alters the protein expression profile of the
CC cell; MazF produces some leaderless mRNA (PubMed:21944167). The toxic
CC endoribonuclease activity is inhibited by its labile cognate antitoxin
CC MazE. Toxicity results when the levels of MazE decrease in the cell,
CC leading to mRNA degradation. This effect can be rescued by expression
CC of MazE, but after 6 hours in rich medium overexpression of MazF leads
CC to programmed cell death (PubMed:8650219, PubMed:11222603). MazF-
CC mediated cell death occurs following a number of stress conditions in a
CC relA-dependent fashion and only when cells are in log phase; sigma
CC factor S (rpoS) protects stationary phase cells from MazF-killing
CC (PubMed:15150257, PubMed:19251848). Cell growth and viability are not
CC affected when MazF and MazE are coexpressed. Both MazE and MazE-MazF
CC bind to the promoter region of the mazE-mazF operon to inhibit their
CC own transcription. MazE has higher affinity for promoter DNA in the
CC presence of MazF (PubMed:25564525). Cross-talk can occur between
CC different TA systems, ectopic expression of this toxin induces
CC transcription of the relBEF TA system operon with specific cleavage of
CC the mRNA produced (PubMed:23432955). {ECO:0000269|PubMed:11071896,
CC ECO:0000269|PubMed:11222603, ECO:0000269|PubMed:15150257,
CC ECO:0000269|PubMed:15537630, ECO:0000269|PubMed:18854355,
CC ECO:0000269|PubMed:19251848, ECO:0000269|PubMed:21944167,
CC ECO:0000269|PubMed:23280569, ECO:0000269|PubMed:23432955,
CC ECO:0000269|PubMed:25564525, ECO:0000269|PubMed:8650219}.
CC -!- FUNCTION: Might also serve to protect cells against bacteriophage; in
CC the presence of MazE-MazF fewer P1 phages are produced than in a
CC disrupted strain. For strain K38 most wild-type cells are killed but
CC not by phage lysis; it was suggested that MazE-MazF causes P1 phage
CC exclusion from the bacterial population. This phenomenon is strain
CC dependent. {ECO:0000269|PubMed:15316771}.
CC -!- FUNCTION: The physiological role of this TA system is debated.
CC Programmed cell death (PCD) occurs when cells are at high density and
CC depends on the presence of MazE-MazF and a quorum sensing pentapeptide,
CC the extracellular death factor (EDF) with sequence Asn-Asn-Trp-Asn-Asn
CC (NNWNN), probably produced from the zwf gene product glucose-6-
CC phosphate 1-dehydrogenase (PubMed:17962566, PubMed:18310334). Cell
CC death governed by the MazE-MazF and DinJ-YafQ TA systems seems to play
CC a role in biofilm formation, while MazE-MazF is also implicated in cell
CC death in liquid media (PubMed:19707553). Implicated in hydroxy radical-
CC mediated cell death induced by hydroxyurea treatment (PubMed:20005847,
CC PubMed:23416055). In conjunction with EDF prevents apoptotic-like death
CC (ALD) in the presence of DNA damaging agents, probably by reducing recA
CC mRNA levels in a non-endonuclease-mediated manner (PubMed:22412352).
CC Other studies (in strains BW25113 and MC4100, the latter makes EDF)
CC demonstrate MazF does not cause PCD but instead bacteriostasis and
CC possibly a dormant state as well as persister cell generation
CC (PubMed:24375411). {ECO:0000269|PubMed:17962566,
CC ECO:0000269|PubMed:18310334, ECO:0000269|PubMed:19707553,
CC ECO:0000269|PubMed:20005847, ECO:0000269|PubMed:21419338,
CC ECO:0000269|PubMed:22412352, ECO:0000269|PubMed:23416055,
CC ECO:0000269|PubMed:24375411, ECO:0000269|PubMed:8650219}.
CC -!- ACTIVITY REGULATION: (Microbial infection) RNA cleavage activity is
CC reduced when ADP-ribosylated. {ECO:0000269|PubMed:26395283}.
CC -!- ACTIVITY REGULATION: Inhibited by Mg(2+) (PubMed:15537630). Stimulated
CC in vitro in a concentration-dependent fashion by EDF, which is able to
CC overcome inhibition by cognate antitoxin MazE (PubMed:21419338). The TA
CC system is antagonized by stress response kinase SrkA, but probably not
CC by phosphorylation of MazF (PubMed:23416055).
CC {ECO:0000269|PubMed:15537630, ECO:0000269|PubMed:21419338,
CC ECO:0000269|PubMed:23416055}.
CC -!- SUBUNIT: Probably a dimer. Forms a heterohexamer composed of
CC alternating toxin and antitoxin homodimers MazF(2)-MazE(2)-MazF(2). The
CC binding site of MazE and ssRNA or ssDNA are largely overlapping; the
CC presence of only 1 MazE molecule inhibits mRNA endoribonuclease
CC activity. Binds to EDF but not a mutated EDF (NNGNN) (PubMed:21419338).
CC {ECO:0000269|PubMed:11071896, ECO:0000269|PubMed:12718874,
CC ECO:0000269|PubMed:21419338, ECO:0000269|PubMed:25564525,
CC ECO:0000269|PubMed:8650219}.
CC -!- INDUCTION: Expressed in exponentially growing cells. Induction has been
CC reported to occur after amino acid starvation in a ppGpp-independent
CC fashion and to be Lon protease-dependent (PubMed:12972253), but also to
CC not occur after amino acid starvation and to be regulated by ppGpp
CC (PubMed:8650219). Also induced in M9 minimal medium and by
CC chloramphenicol treatment (PubMed:21944167). MazE alone and in
CC combination with MazF, represses transcription of the mazE-mazF operon.
CC Fis activates transcription. Part of the relA-mazE-mazF-mazG operon,
CC there is also a second mazE-mazF specific promoter which is negatively
CC autoregulated (PubMed:2844820, PubMed:8650219). Operon induced by
CC ectopic expression of toxin RelE; operon induction by amino acid
CC starvation requires the relBEF operon (PubMed:23432955).
CC {ECO:0000269|PubMed:11071896, ECO:0000269|PubMed:12972253,
CC ECO:0000269|PubMed:16390452, ECO:0000269|PubMed:21944167,
CC ECO:0000269|PubMed:23432955, ECO:0000269|PubMed:2844820,
CC ECO:0000269|PubMed:8650219}.
CC -!- DOMAIN: Loop 1 (residues 17-28) effects catalytic activity while
CC recognition of the ACA cleavage site is influenced by loop 2 (residues
CC 53-61). Alterations of loop 2 generate new cleavage sites in addition
CC to retaining the original cleavage site. {ECO:0000305|PubMed:23280569}.
CC -!- PTM: (Microbial infection) ADP-ribosylated by enterobacteria phage T4.
CC {ECO:0000269|PubMed:26395283}.
CC -!- DISRUPTION PHENOTYPE: Decreased sensitivity to dramatic intracellular
CC increases of ppGpp. Cells missing mazE-mazF survive high temperature,
CC various DNA-damaging agents and H(2)O(2) exposure better than wild-type
CC cells. Cells missing mazE-mazF produce more P1 phage than wild-type
CC cells, while introduction of lysogens into a growing non-lysogenic
CC disruption culture is lethal (PubMed:15316771). Cells missing mazE-mazF
CC show reduced biofilm formation, and survive antibiotic treatment in log
CC phase better than wild-type cells (PubMed:11222603, PubMed:19707553).
CC However lag phase cells disrupted only for mazF had a lower survival
CC rate than wild-type cells (PubMed:24375411). Cells missing mazE-mazF
CC survive hydroxyurea treatment better than wild-type; further disruption
CC of relE-relB and tonB yields even better survival (PubMed:20005847).
CC Cells missing mazE-mazF undergo an apoptotic-like death (ALD) upon DNA
CC damage characterized by membrane depolarization and DNA fragmentation;
CC further disruption of recA prevents membrane depolarization
CC (PubMed:22412352). Unlike the single srkA disruption mutant, a triple
CC srkA-mazE-mazF disruption mutant shows no hyperlethality in the
CC presence of nalidixic acid or UV light, suggesting SrkA has a negative
CC effect on MazF (PubMed:23416055). {ECO:0000269|PubMed:11222603,
CC ECO:0000269|PubMed:12972253, ECO:0000269|PubMed:15150257,
CC ECO:0000269|PubMed:15316771, ECO:0000269|PubMed:19707553,
CC ECO:0000269|PubMed:20005847, ECO:0000269|PubMed:22412352,
CC ECO:0000269|PubMed:23416055, ECO:0000269|PubMed:24375411,
CC ECO:0000269|PubMed:8650219}.
CC -!- BIOTECHNOLOGY: Can be used to produce large quantities of a single
CC protein if the gene coding for the protein does not contain any ACA
CC codons. Up to 90% of expressed bacterial cellular protein can be the
CC target, which can be produced for up to 4 days. The system also works
CC in eukaryotic cells. {ECO:0000269|PubMed:15837428}.
CC -!- SIMILARITY: Belongs to the PemK/MazF family. {ECO:0000305}.
CC -!- CAUTION: Strain K12 / MG1655 is deficient in both production and
CC response to EDF, unlike strains K12 / MC4100, K12 / W3110 and K12 /
CC K38, all of which make and respond to EDF.
CC {ECO:0000269|PubMed:18310334}.
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DR EMBL; D16450; BAA03918.1; -; Genomic_DNA.
DR EMBL; J04039; AAA03239.1; -; Unassigned_DNA.
DR EMBL; U29580; AAA69292.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75824.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76856.1; -; Genomic_DNA.
DR PIR; B49339; B49339.
DR RefSeq; NP_417262.1; NC_000913.3.
DR RefSeq; WP_000254738.1; NZ_STEB01000030.1.
DR PDB; 1UB4; X-ray; 1.70 A; A/B=2-111.
DR PDB; 3NFC; X-ray; 2.00 A; A/B/C/D/E/F=1-111.
DR PDB; 5CK9; X-ray; 1.90 A; A/B=1-111.
DR PDB; 5CKB; X-ray; 2.80 A; A/B=1-111.
DR PDB; 5CKD; X-ray; 1.70 A; A/B=1-111.
DR PDB; 5CKE; X-ray; 2.31 A; A/B=1-111.
DR PDB; 5CKF; X-ray; 2.80 A; A/B=1-111.
DR PDB; 5CKH; X-ray; 2.45 A; A/B=1-111.
DR PDB; 5CO7; X-ray; 3.49 A; A/B/C/D/E/F=1-111.
DR PDB; 5CQX; X-ray; 1.63 A; A/B=1-111.
DR PDB; 5CQY; X-ray; 2.48 A; A/B=1-111.
DR PDB; 5CR2; X-ray; 2.90 A; A/B/C=1-111.
DR PDBsum; 1UB4; -.
DR PDBsum; 3NFC; -.
DR PDBsum; 5CK9; -.
DR PDBsum; 5CKB; -.
DR PDBsum; 5CKD; -.
DR PDBsum; 5CKE; -.
DR PDBsum; 5CKF; -.
DR PDBsum; 5CKH; -.
DR PDBsum; 5CO7; -.
DR PDBsum; 5CQX; -.
DR PDBsum; 5CQY; -.
DR PDBsum; 5CR2; -.
DR AlphaFoldDB; P0AE70; -.
DR BMRB; P0AE70; -.
DR SMR; P0AE70; -.
DR BioGRID; 4262300; 13.
DR ComplexPortal; CPX-1086; MazEF toxin-antitoxin complex.
DR IntAct; P0AE70; 2.
DR STRING; 511145.b2782; -.
DR BindingDB; P0AE70; -.
DR ChEMBL; CHEMBL1795096; -.
DR jPOST; P0AE70; -.
DR PaxDb; P0AE70; -.
DR PRIDE; P0AE70; -.
DR EnsemblBacteria; AAC75824; AAC75824; b2782.
DR EnsemblBacteria; BAE76856; BAE76856; BAE76856.
DR GeneID; 58459985; -.
DR GeneID; 947252; -.
DR KEGG; ecj:JW2753; -.
DR KEGG; eco:b2782; -.
DR PATRIC; fig|1411691.4.peg.3953; -.
DR EchoBASE; EB1229; -.
DR eggNOG; COG2337; Bacteria.
DR HOGENOM; CLU_121823_2_3_6; -.
DR InParanoid; P0AE70; -.
DR OMA; QIKGYPF; -.
DR PhylomeDB; P0AE70; -.
DR BioCyc; EcoCyc:EG11249-MON; -.
DR BioCyc; MetaCyc:EG11249-MON; -.
DR EvolutionaryTrace; P0AE70; -.
DR PRO; PR:P0AE70; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0110001; C:toxin-antitoxin complex; IPI:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:CAFA.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IMP:CACAO.
DR GO; GO:0009372; P:quorum sensing; IEA:UniProtKB-KW.
DR GO; GO:0040008; P:regulation of growth; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:ComplexPortal.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0016075; P:rRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0044010; P:single-species biofilm formation; IDA:ComplexPortal.
DR DisProt; DP00299; -.
DR Gene3D; 2.30.30.110; -; 1.
DR InterPro; IPR003477; PemK-like.
DR InterPro; IPR011067; Plasmid_toxin/cell-grow_inhib.
DR PANTHER; PTHR33988; PTHR33988; 1.
DR Pfam; PF02452; PemK_toxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Antiviral defense; DNA-binding;
KW Endonuclease; Hydrolase; Nuclease; Quorum sensing; Reference proteome;
KW Repressor; RNA-binding; Stress response; Toxin-antitoxin system;
KW Transcription; Transcription regulation; Translation regulation.
FT CHAIN 1..111
FT /note="Endoribonuclease toxin MazF"
FT /id="PRO_0000201897"
FT REGION 17..28
FT /note="Loop 1, participates in catalytic activity"
FT /evidence="ECO:0000305|PubMed:23280569"
FT REGION 53..61
FT /note="Loop 2, involved in substrate recognition"
FT /evidence="ECO:0000305|PubMed:23280569"
FT MOD_RES 4
FT /note="ADP-ribosylarginine"
FT /evidence="ECO:0000269|PubMed:26395283"
FT MUTAGEN 17..28
FT /note="FDPTKGSEQAGH->GGGGGGGGGGG: Changes loop 1 to poly-G;
FT loss of endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:23280569"
FT MUTAGEN 17..28
FT /note="FDPTKGSEQAGH->LGPPSGSQPAKR: Changes loop 1 to MazF6
FT M.tuberculosis sequence; loss of endoribonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:23280569"
FT MUTAGEN 17..28
FT /note="FDPTKGSEQAGH->PDDSRGPVPSYS: Changes loop 1 to MazF
FT M.xanthus sequence; loss of endoribonuclease activity."
FT /evidence="ECO:0000269|PubMed:23280569"
FT MUTAGEN 24
FT /note="E->A: Greatly reduces toxicity, about 10-fold less
FT RNA cleavage activity. Expression in the presence of wt
FT MazF has a dominant-negative phenotype, causing cell death
FT as it titrates out the MazE antitoxin; still activates
FT operon transcription."
FT /evidence="ECO:0000269|PubMed:16413577,
FT ECO:0000269|PubMed:24375411"
FT MUTAGEN 28
FT /note="H->A: No changes in toxicity."
FT /evidence="ECO:0000269|PubMed:24375411"
FT MUTAGEN 53..61
FT /note="TQSKGYPFE->GGGGGGGG,GGGGGGGGGGG: Changes loop 2 to
FT poly-G; reduces endoribonuclease activity, alters cleavage
FT sites."
FT /evidence="ECO:0000269|PubMed:23280569"
FT MUTAGEN 53..61
FT /note="TQSKGYPFE->SNLHRASEPGN: Changes loop 2 to MazF
FT M.xanthus sequence; reduces endoribonuclease activity,
FT alters cleavage sites."
FT /evidence="ECO:0000269|PubMed:23280569"
FT MUTAGEN 53..61
FT /note="TQSKGYPFE->SNTALAAMPGN: Changes loop 2 to MazF6
FT M.tuberculosis sequence; reduces endoribonuclease activity,
FT alters cleavage sites."
FT /evidence="ECO:0000269|PubMed:23280569"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:5CQX"
FT TURN 19..22
FT /evidence="ECO:0007829|PDB:5CQX"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:5CQX"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:5CQX"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:5CQX"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5CQX"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:5CKD"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:5CQX"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:5CQX"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:5CQX"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:5CQX"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:5CQX"
FT HELIX 96..110
FT /evidence="ECO:0007829|PDB:5CQX"
SQ SEQUENCE 111 AA; 12098 MW; 1579C867DD6B96AC CRC64;
MVSRYVPDMG DLIWVDFDPT KGSEQAGHRP AVVLSPFMYN NKTGMCLCVP CTTQSKGYPF
EVVLSGQERD GVALADQVKS IAWRARGATK KGTVAPEELQ LIKAKINVLI G
