ID   MAZE6_MYCTU             Reviewed;          82 AA.
AC   P9WJ87; F2GGA0; P0CL59; Q8VJS6;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 33.
DE   RecName: Full=Antitoxin MazE6 {ECO:0000305};
GN   Name=mazE6; Synonyms=mazE-mt3 {ECO:0000303|PubMed:16611633};
GN   OrderedLocusNames=Rv1991A;
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   IDENTIFICATION, AND POSSIBLE FUNCTION.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=15718296; DOI=10.1093/nar/gki201;
RA   Pandey D.P., Gerdes K.;
RT   "Toxin-antitoxin loci are highly abundant in free-living but lost from
RT   host-associated prokaryotes.";
RL   Nucleic Acids Res. 33:966-976(2005).
RN   [3]
RP   GENE NAME, AND POSSIBLE FUNCTION.
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   [4]
RP   FUNCTION AS AN ANTITOXIN.
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   [5]
RP   EXPRESSION IN E.COLI, EXPRESSION IN M.SMEGMATIS, SUBUNIT, FUNCTION AS AN
RP   ANTITOXIN, DNA-BINDING, POSSIBLE FUNCTION AS A TRANSCRIPTIONAL REGULATOR,
RP   AND MUTAGENESIS OF SER-25 AND ARG-26.
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   [6]
RP   EXPRESSION IN E.COLI, AND FUNCTION AS AN ANTITOXIN.
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 AN ANTITOXIN.
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 AN ANTITOXIN, AND INTERACTION WITH TOXINS MAZF6; VAPC27 AND
RP   VAPC40.
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   INTERACTION WITH MAZF6, AND INDUCTION.
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: Antitoxin component of a type II toxin-antitoxin (TA) system.
CC       Upon expression in E.coli and in M.smegmatis counteracts the
CC       ribonuclease activity of cognate toxin MazF6.
CC       {ECO:0000269|PubMed:17623030, ECO:0000269|PubMed:18258191,
CC       ECO:0000269|PubMed:19016878, ECO:0000269|PubMed:20011113,
CC       ECO:0000269|PubMed:20876537}.
CC   -!- SUBUNIT: Forms a complex with cognate toxin MazF6 which neutralizes the
CC       toxin. Interacts physically with non-cognate toxins VapC27 and VapC40.
CC       {ECO:0000269|PubMed:18258191, ECO:0000269|PubMed:20876537,
CC       ECO:0000269|PubMed:25608501}.
CC   -!- INDUCTION: Strongly induced (about 10-fold) by nitrosative stress.
CC       {ECO:0000269|PubMed:25608501}.
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DR   EMBL; AL123456; CCP44763.1; -; Genomic_DNA.
DR   RefSeq; WP_003410014.1; NZ_NVQJ01000043.1.
DR   RefSeq; YP_007410673.1; NC_000962.3.
DR   AlphaFoldDB; P9WJ87; -.
DR   SMR; P9WJ87; -.
DR   STRING; 83332.Rv1991A; -.
DR   GeneID; 14515890; -.
DR   GeneID; 45425970; -.
DR   KEGG; mtu:Rv1991A; -.
DR   TubercuList; Rv1991A; -.
DR   eggNOG; COG0864; Bacteria.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR   GO; GO:0097351; F:toxin sequestering activity; IPI:MTBBASE.
DR   GO; GO:0098754; P:detoxification; IMP:MTBBASE.
DR   GO; GO:0045926; P:negative regulation of growth; IMP:MTBBASE.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR   Gene3D; 1.10.1220.10; -; 1.
DR   InterPro; IPR013321; Arc_rbn_hlx_hlx.
DR   InterPro; IPR002145; CopG.
DR   InterPro; IPR010985; Ribbon_hlx_hlx.
DR   Pfam; PF01402; RHH_1; 1.
DR   SUPFAM; SSF47598; SSF47598; 1.
PE   1: Evidence at protein level;
KW   DNA-binding; Reference proteome; Toxin-antitoxin system.
FT   CHAIN           1..82
FT                   /note="Antitoxin MazE6"
FT                   /id="PRO_0000406300"
FT   MUTAGEN         25
FT                   /note="S->A: No DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:18258191"
FT   MUTAGEN         26
FT                   /note="R->A: No DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:18258191"
SQ   SEQUENCE   82 AA;  9290 MW;  AE34DE0F70F68114 CRC64;
     MKTAISLPDE TFDRVSRRAS ELGMSRSEFF TKAAQRYLHE LDAQLLTGQI DRALESIHGT
     DEAEALAVAN AYRVLETMDD EW