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 24-JAN-2024, entry version 131. 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; Pseudomonadota; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 511145-b2782; -. DR EnsemblBacteria; AAC75824; AAC75824; b2782. DR GeneID; 75203827; -. 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 OrthoDB; 9808744at2; -. DR PhylomeDB; P0AE70; -. DR BioCyc; EcoCyc:EG11249-MONOMER; -. DR BioCyc; MetaCyc:EG11249-MONOMER; -. 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:0140677; F:molecular function activator activity; EXP:DisProt. 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:0004521; F:RNA endonuclease activity; IDA:UniProtKB. 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:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal. DR GO; GO:0040008; P:regulation of growth; 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; ENDORIBONUCLEASE MAZF-RELATED; 1. DR PANTHER; PTHR33988:SF3; ENDORIBONUCLEASE TOXIN CHPB-RELATED; 1. DR Pfam; PF02452; PemK_toxin; 1. DR SUPFAM; SSF50118; Cell growth inhibitor/plasmid maintenance toxic component; 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 //