MAZF6_MYCTU
ID MAZF6_MYCTU Reviewed; 114 AA.
AC P9WII3; L0T8B0; P64911; Q10867;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 38.
DE RecName: Full=Endoribonuclease MazF6 {ECO:0000305};
DE EC=3.1.27.- {ECO:0000305};
DE AltName: Full=Toxin MazF6 {ECO:0000303|PubMed:16611633};
DE AltName: Full=mRNA interferase MazF-mt3 {ECO:0000303|PubMed:18485066};
GN Name=mazF6; Synonyms=mazF-mt3 {ECO:0000303|PubMed:16611633};
GN OrderedLocusNames=Rv1991c; ORFNames=MTCY39.28;
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.
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 FUNCTION AS A TOXIN.
RX PubMed=17623030; DOI=10.1111/j.1574-6968.2007.00842.x;
RA Carroll P., Brown A.C., Hartridge A.R., Parish T.;
RT "Expression of Mycobacterium tuberculosis Rv1991c using an arabinose-
RT inducible promoter demonstrates its role as a toxin.";
RL FEMS Microbiol. Lett. 274:73-82(2007).
RN [4]
RP EXPRESSION IN E.COLI, EXPRESSION IN M.SMEGMATIS, SUBUNIT, AND FUNCTION AS
RP AN RNASE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18258191; DOI=10.1016/j.febslet.2008.01.045;
RA Zhao L., Zhang J.;
RT "Biochemical characterization of a chromosomal toxin-antitoxin system in
RT Mycobacterium tuberculosis.";
RL FEBS Lett. 582:710-714(2008).
RN [5]
RP FUNCTION AS AN MRNA INTERFERASE, AND SUBSTRATE SPECIFICITY.
RX PubMed=18485066; DOI=10.1111/j.1365-2958.2008.06284.x;
RA Zhu L., Phadtare S., Nariya H., Ouyang M., Husson R.N., Inouye M.;
RT "The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium
RT tuberculosis target unique pentad sequences in single-stranded RNA.";
RL Mol. Microbiol. 69:559-569(2008).
RN [6]
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 [7]
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 [8]
RP FUNCTION AS A TOXIN, AND INTERACTION WITH ANTITOXINS MAZE6; VAPB27 AND
RP VAPB40.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20876537; DOI=10.1074/jbc.m110.163105;
RA Zhu L., Sharp J.D., Kobayashi H., Woychik N.A., Inouye M.;
RT "Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and
RT functionally interact.";
RL J. Biol. Chem. 285:39732-39738(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=23345537; DOI=10.1074/mcp.m112.018846;
RA Albrethsen J., Agner J., Piersma S.R., Hoejrup P., Pham T.V., Weldingh K.,
RA Jimenez C.R., Andersen P., Rosenkrands I.;
RT "Proteomic profiling of Mycobacterium tuberculosis identifies nutrient-
RT starvation-responsive toxin-antitoxin systems.";
RL Mol. Cell. Proteomics 12:1180-1191(2013).
RN [11]
RP FUNCTION, SUBSTRATE SPECIFICITY, AND EXPRESSION IN E.COLI.
RC STRAIN=H37Rv;
RX PubMed=24709835; DOI=10.1038/ncomms4538;
RA Schifano J.M., Vvedenskaya I.O., Knoblauch J.G., Ouyang M., Nickels B.E.,
RA Woychik N.A.;
RT "An RNA-seq method for defining endoribonuclease cleavage specificity
RT identifies dual rRNA substrates for toxin MazF-mt3.";
RL Nat. Commun. 5:3538-3538(2014).
RN [12]
RP FUNCTION, INTERACTION WITH MAZE6, 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 Upon expression in E.coli and in M.smegmatis partially inhibits cell
CC growth and colony formation; its toxic effect is neutralized by
CC coexpression with cognate antitoxin MazE6. Acts as an mRNA interferase
CC on ssRNA, cleaving between the second and third bases in the sequences
CC CUCCU and UUCCU (PubMed:18485066). Further experiments demonstrate that
CC it digests between the first and second bases of UCCUU, yielding a 5'-
CC hydroxyl end; digests M.tuberculosis mRNA (in coding as well as the
CC 5'- and 3'-UTR regions) and 23S rRNA, digests E.coli 16S rRNA both
CC alone and in the 70S ribosome but no data for M.tuberculosis 16S rRNA
CC cleavage was presented. 23S and 16S rRNA digestion occurs in predicted
CC single-stranded regions, the 16S rRNA UCCUU site is in the anti-Shine-
CC Dalgarno site and would cleave off the last 7 nucleotides
CC (PubMed:24709835). Non-cognate antitoxins VapB27 and VapB40 partially
CC neutralize toxicity in vivo (PubMed:20876537).
CC {ECO:0000269|PubMed:17623030, ECO:0000269|PubMed:18258191,
CC ECO:0000269|PubMed:18485066, ECO:0000269|PubMed:19016878,
CC ECO:0000269|PubMed:20011113, ECO:0000269|PubMed:20876537,
CC ECO:0000269|PubMed:24709835, ECO:0000269|PubMed:25608501}.
CC -!- SUBUNIT: Forms a complex with cognate toxin MazE6, which neutralizes
CC the toxin. Interacts physically with non-cognate antitoxins VapB27 and
CC VapB40 which neutralize the toxin. {ECO:0000269|PubMed:18258191,
CC ECO:0000269|PubMed:20876537, ECO:0000269|PubMed:25608501}.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Following 6 weeks of nutrient
CC starvation. {ECO:0000269|PubMed:23345537}.
CC -!- INDUCTION: Strongly induced (17 to 25-fold) by nitrosative stress,
CC starvation, when grown in a non-replicating state, in the presence of
CC gentamycin or 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; CCP44762.1; -; Genomic_DNA.
DR PIR; E70757; E70757.
DR RefSeq; NP_216507.1; NC_000962.3.
DR RefSeq; WP_003410010.1; NZ_NVQJ01000043.1.
DR PDB; 5HK0; X-ray; 2.25 A; A/B/C/D=1-114.
DR PDB; 5HK3; X-ray; 1.56 A; A/B=1-114.
DR PDB; 5HKC; X-ray; 1.68 A; A/B=1-114.
DR PDBsum; 5HK0; -.
DR PDBsum; 5HK3; -.
DR PDBsum; 5HKC; -.
DR AlphaFoldDB; P9WII3; -.
DR SMR; P9WII3; -.
DR STRING; 83332.Rv1991c; -.
DR PaxDb; P9WII3; -.
DR DNASU; 885634; -.
DR GeneID; 45425969; -.
DR GeneID; 885634; -.
DR KEGG; mtu:Rv1991c; -.
DR TubercuList; Rv1991c; -.
DR eggNOG; COG2337; Bacteria.
DR OMA; VFNHSRI; -.
DR PhylomeDB; P9WII3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0004521; F:endoribonuclease activity; IBA:GO_Central.
DR GO; GO:0004540; F:ribonuclease activity; IDA:MTBBASE.
DR GO; GO:0044003; P:modulation by symbiont of host process; IMP:MTBBASE.
DR GO; GO:0006402; P:mRNA catabolic process; IMP:MTBBASE.
DR GO; GO:0045926; P:negative regulation of growth; IMP:MTBBASE.
DR GO; GO:0045927; P:positive regulation of growth; IMP:MTBBASE.
DR GO; GO:0016075; P:rRNA catabolic process; IMP: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.
DR PIRSF; PIRSF033490; MazF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endonuclease; Hydrolase; Nuclease; Reference proteome;
KW Secreted; Toxin-antitoxin system.
FT CHAIN 1..114
FT /note="Endoribonuclease MazF6"
FT /id="PRO_0000201904"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:5HK3"
FT STRAND 23..29
FT /evidence="ECO:0007829|PDB:5HK3"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:5HK3"
FT STRAND 42..50
FT /evidence="ECO:0007829|PDB:5HK3"
FT HELIX 52..56
FT /evidence="ECO:0007829|PDB:5HKC"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5HK3"
FT HELIX 65..68
FT /evidence="ECO:0007829|PDB:5HK3"
FT STRAND 74..85
FT /evidence="ECO:0007829|PDB:5HK3"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:5HK3"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:5HK3"
FT HELIX 98..112
FT /evidence="ECO:0007829|PDB:5HK3"
SQ SEQUENCE 114 AA; 12262 MW; 59A18C54B9EDDBCE CRC64;
MVISRAEIYW ADLGPPSGSQ PAKRRPVLVI QSDPYNASRL ATVIAAVITS NTALAAMPGN
VFLPATTTRL PRDSVVNVTA IVTLNKTDLT DRVGEVPASL MHEVDRGLRR VLDL
