MAZF3_MYCTU
ID MAZF3_MYCTU Reviewed; 103 AA.
AC P9WIH9; L0T5Q4; O53450; Q7D8U7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=Endoribonuclease MazF3 {ECO:0000305};
DE EC=3.1.-.-;
DE AltName: Full=23S rRNA endonuclease MazF3;
DE AltName: Full=Toxin MazF3 {ECO:0000303|PubMed:20011113};
DE AltName: Full=mRNA interferase MazF-mt6 {ECO:0000303|PubMed:16611633};
GN Name=mazF3; Synonyms=mazF-mt6 {ECO:0000303|PubMed:16611633};
GN OrderedLocusNames=Rv1102c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP EXPRESSION IN E.COLI, AND FUNCTION AS AN MRNA INTERFERASE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16611633; DOI=10.1074/jbc.m512693200;
RA Zhu L., Zhang Y., Teh J.S., Zhang J., Connell N., Rubin H., Inouye M.;
RT "Characterization of mRNA interferases from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 281:18638-18643(2006).
RN [3]
RP EXPRESSION IN E.COLI, AND FUNCTION AS A TOXIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19016878; DOI=10.1111/j.1574-6968.2008.01400.x;
RA Gupta A.;
RT "Killing activity and rescue function of genome-wide toxin-antitoxin loci
RT of Mycobacterium tuberculosis.";
RL FEMS Microbiol. Lett. 290:45-53(2009).
RN [4]
RP EXPRESSION IN M.SMEGMATIS, AND FUNCTION AS A TOXIN.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=20011113; DOI=10.1371/journal.pgen.1000767;
RA Ramage H.R., Connolly L.E., Cox J.S.;
RT "Comprehensive functional analysis of Mycobacterium tuberculosis toxin-
RT antitoxin systems: implications for pathogenesis, stress responses, and
RT evolution.";
RL PLoS Genet. 5:E1000767-E1000767(2009).
RN [5]
RP EXPRESSION IN E.COLI, EXPRESSION IN M.SMEGMATIS, FUNCTION AS A TOXIN,
RP SUBUNIT, AND ROLE IN PERSISTER CELL FORMATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20705052; DOI=10.1016/j.bbrc.2010.08.023;
RA Han J.S., Lee J.J., Anandan T., Zeng M., Sripathi S., Jahng W.J., Lee S.H.,
RA Suh J.W., Kang C.M.;
RT "Characterization of a chromosomal toxin-antitoxin, Rv1102c-Rv1103c system
RT in Mycobacterium tuberculosis.";
RL Biochem. Biophys. Res. Commun. 400:293-298(2010).
RN [6]
RP FUNCTION, SUBSTRATE SPECIFICITY, COFACTOR, EXPRESSION IN E.COLI, AND
RP EXPRESSION IN M.SMEGMATIS.
RC STRAIN=H37Rv;
RX PubMed=23650345; DOI=10.1073/pnas.1222031110;
RA Schifano J.M., Edifor R., Sharp J.D., Ouyang M., Konkimalla A.,
RA Husson R.N., Woychik N.A.;
RT "Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S
RT rRNA at the ribosomal A site.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:8501-8506(2013).
RN [7]
RP FUNCTION, INTERACTION WITH MAZE3, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=25608501; DOI=10.1038/ncomms7059;
RA Tiwari P., Arora G., Singh M., Kidwai S., Narayan O.P., Singh R.;
RT "MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and
RT virulence in guinea pigs.";
RL Nat. Commun. 6:6059-6059(2015).
CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system.
CC Acts as an mRNA and 23S rRNA interferase, cleaving predominantly after
CC the first 2 Us in the sequence 5'-UUCCU-3'; in 23S rRNA only cleaves
CC once in the ribosomal A site in dissociated but not intact ribosomes.
CC Cleavage of 23S rRNA inhibits protein translation; the 23S rRNA region
CC cleaved is involved in tRNA-binding in the A site, 30S and 50S subunit
CC interaction and ribosome recycling factor association
CC (PubMed:23650345). Upon expression in E.coli and M.smegmatis inhibits
CC cell growth and colony formation. It dramatically increases persister
CC cell formation in M.smegmatis upon challenge with gentamicin or
CC kanamycin. Overexpression leads to bacteriostasis rather than
CC bacteriocide. Its toxic effect is neutralized by coexpression with
CC cognate antitoxin MazE3. {ECO:0000269|PubMed:16611633,
CC ECO:0000269|PubMed:19016878, ECO:0000269|PubMed:20011113,
CC ECO:0000269|PubMed:20705052, ECO:0000269|PubMed:23650345,
CC ECO:0000269|PubMed:25608501}.
CC -!- COFACTOR:
CC Note=Digests 23S rRNA in the absence of Mg(2+), increasing Mg(2+)
CC concentrations decrease its efficiency. {ECO:0000269|PubMed:23650345};
CC -!- SUBUNIT: Forms a complex with cognate antitoxin MazE3, possibly with
CC 1:1 stoichiometry. {ECO:0000269|PubMed:20705052,
CC ECO:0000269|PubMed:25608501}.
CC -!- INDUCTION: Mildly induced (5 to 9-fold) by starvation, when grown in a
CC non-replicating state, in the presence of isoniazid, gentamycin or
CC rifampicin. {ECO:0000269|PubMed:25608501}.
CC -!- DISRUPTION PHENOTYPE: Individual deletion of mazF3, mazF6 and mazF9
CC have little to no phenotype, but a triple mutant shows increased
CC sensitivity to oxidative and antibiotic stress and starvation,
CC decreased formation of persisters cells, and a decreased bacterial load
CC and pathogenic damage in infected guinea pigs.
CC {ECO:0000269|PubMed:25608501}.
CC -!- SIMILARITY: Belongs to the PemK/MazF family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43855.1; -; Genomic_DNA.
DR PIR; D70897; D70897.
DR RefSeq; NP_215618.1; NC_000962.3.
DR RefSeq; WP_003898728.1; NZ_NVQJ01000021.1.
DR PDB; 5CCA; X-ray; 3.20 A; A/B=1-103.
DR PDB; 5UCT; X-ray; 2.70 A; A/B=1-103.
DR PDBsum; 5CCA; -.
DR PDBsum; 5UCT; -.
DR AlphaFoldDB; P9WIH9; -.
DR SMR; P9WIH9; -.
DR STRING; 83332.Rv1102c; -.
DR PaxDb; P9WIH9; -.
DR DNASU; 886001; -.
DR GeneID; 886001; -.
DR KEGG; mtu:Rv1102c; -.
DR TubercuList; Rv1102c; -.
DR eggNOG; COG2337; Bacteria.
DR OMA; HECAVAL; -.
DR PhylomeDB; P9WIH9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:MTBBASE.
DR GO; GO:0044003; P:modulation by symbiont of host process; IMP:MTBBASE.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:MTBBASE.
DR GO; GO:0045926; P:negative regulation of growth; IDA:MTBBASE.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0017148; P:negative regulation of translation; IDA:MTBBASE.
DR GO; GO:0045927; P:positive regulation of growth; IMP:MTBBASE.
DR GO; GO:0016075; P:rRNA catabolic process; IDA:UniProtKB.
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; Endonuclease; Hydrolase; Nuclease; Reference proteome;
KW Toxin-antitoxin system.
FT CHAIN 1..103
FT /note="Endoribonuclease MazF3"
FT /id="PRO_0000406306"
FT STRAND 3..17
FT /evidence="ECO:0007829|PDB:5UCT"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:5UCT"
FT STRAND 28..37
FT /evidence="ECO:0007829|PDB:5UCT"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:5UCT"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:5UCT"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:5UCT"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:5UCT"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:5UCT"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:5UCT"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:5UCT"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:5UCT"
FT HELIX 85..96
FT /evidence="ECO:0007829|PDB:5UCT"
SQ SEQUENCE 103 AA; 11050 MW; 5785AF38C1C1E19D CRC64;
MRPIHIAQLD KARPVLILTR EVVRPHLTNV TVAPITTTVR GLATEVPVDA VNGLNQPSVV
SCDNTQTIPV CDLGRQIGYL LASQEPALAE AIGNAFDLDW VVA
