MBCA_MYCTU
ID MBCA_MYCTU Reviewed; 113 AA.
AC P9WLP7; L0TB09; P64909; Q10868;
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=Mycobacterial cidal antitoxin MbcA {ECO:0000303|PubMed:30792174};
DE AltName: Full=Antitoxin Xre {ECO:0000303|PubMed:30315706};
DE AltName: Full=ucAT8 antitoxin {ECO:0000303|PubMed:28724903};
GN Name=mbcA {ECO:0000303|PubMed:30792174}; OrderedLocusNames=Rv1990c;
GN ORFNames=MTCY39.29;
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 INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=18231589; DOI=10.1371/journal.pone.0001502;
RA Rustad T.R., Harrell M.I., Liao R., Sherman D.R.;
RT "The enduring hypoxic response of Mycobacterium tuberculosis.";
RL PLoS ONE 3:E1502-E1502(2008).
RN [3]
RP INDUCTION IN MOUSE INFECTION MODEL.
RC STRAIN=H37Rv;
RX PubMed=20628579; DOI=10.1371/journal.ppat.1000988;
RA Homolka S., Niemann S., Russell D.G., Rohde K.H.;
RT "Functional genetic diversity among Mycobacterium tuberculosis complex
RT clinical isolates: delineation of conserved core and lineage-specific
RT transcriptomes during intracellular survival.";
RL PLoS Pathog. 6:E1000988-E1000988(2010).
RN [4]
RP INDUCTION BY HYPOXIA AND IN PERSISTER CELLS.
RC STRAIN=H37Rv;
RX PubMed=21673191; DOI=10.1128/mbio.00100-11;
RA Keren I., Minami S., Rubin E., Lewis K.;
RT "Characterization and transcriptome analysis of Mycobacterium tuberculosis
RT persisters.";
RL MBio 2:E00100-E00111(2011).
RN [5]
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 [6]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=28096490; DOI=10.1128/mbio.02133-16;
RA DeJesus M.A., Gerrick E.R., Xu W., Park S.W., Long J.E., Boutte C.C.,
RA Rubin E.J., Schnappinger D., Ehrt S., Fortune S.M., Sassetti C.M.,
RA Ioerger T.R.;
RT "Comprehensive essentiality analysis of the Mycobacterium tuberculosis
RT genome via saturating transposon mutagenesis.";
RL MBio 8:0-0(2017).
RN [7]
RP INDUCTION BY STRESS.
RC STRAIN=H37Rv;
RX PubMed=28724903; DOI=10.1038/s41598-017-06003-7;
RA Gupta A., Venkataraman B., Vasudevan M., Gopinath Bankar K.;
RT "Co-expression network analysis of toxin-antitoxin loci in Mycobacterium
RT tuberculosis reveals key modulators of cellular stress.";
RL Sci. Rep. 7:5868-5868(2017).
RN [8]
RP FUNCTION AS A TOXIN, AND EXPRESSION IN E.COLI.
RC STRAIN=H37Rv;
RX PubMed=30315706; DOI=10.1111/mmi.14150;
RA Skjerning R.B., Senissar M., Winther K.S., Gerdes K., Brodersen D.E.;
RT "The RES domain toxins of RES-Xre toxin-antitoxin modules induce cell
RT stasis by degrading NAD+.";
RL Mol. Microbiol. 111:221-236(2019).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH TOXIN, FUNCTION AS
RP AN ANTITOXIN, SUBUNIT, INDUCTION, BIOTECHNOLOGY, AND MUTAGENESIS OF
RP 104-ILE--VAL-113.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=30792174; DOI=10.1016/j.molcel.2019.01.028;
RA Freire D.M., Gutierrez C., Garza-Garcia A., Grabowska A.D., Sala A.J.,
RA Ariyachaokun K., Panikova T., Beckham K.S.H., Colom A., Pogenberg V.,
RA Cianci M., Tuukkanen A., Boudehen Y.M., Peixoto A., Botella L.,
RA Svergun D.I., Schnappinger D., Schneider T.R., Genevaux P.,
RA de Carvalho L.P.S., Wilmanns M., Parret A.H.A., Neyrolles O.;
RT "An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell
RT death.";
RL Mol. Cell 73:1282-1291(2019).
CC -!- FUNCTION: Antitoxin component of a type II toxin-antitoxin (TA) system
CC (PubMed:30315706, PubMed:30792174). Neutralizes the activity of cognate
CC toxin MbcT by blocking access to the toxin active site
CC (PubMed:30792174). {ECO:0000269|PubMed:30315706,
CC ECO:0000269|PubMed:30792174}.
CC -!- SUBUNIT: Heterotetramer with 2 subunits each of MbcT and MbcA; the
CC tetramers further assemble into trimers with 3-fold symmetry.
CC {ECO:0000269|PubMed:30792174}.
CC -!- INDUCTION: Induced by hypoxia (PubMed:18231589). Expression probably
CC induced in both active and resting C57BL/6 mouse macrophages
CC (PubMed:20628579). Induced in persister cells (PubMed:21673191).
CC Induced by Ethambutol, Isoniazid and streptomycin treatment and by
CC starvation, repressed by rifampicin treatment (PubMed:28724903).
CC Probably part of the mbcT-mbcA operon (PubMed:30792174).
CC {ECO:0000269|PubMed:18231589, ECO:0000269|PubMed:20628579,
CC ECO:0000269|PubMed:21673191, ECO:0000269|PubMed:28724903,
CC ECO:0000269|PubMed:30792174}.
CC -!- DISRUPTION PHENOTYPE: Essential, it cannot be deleted
CC (PubMed:28096490). Deletion of the mbcT-mbcA operon has no visible
CC phenotype (PubMed:30792174). {ECO:0000269|PubMed:28096490,
CC ECO:0000269|PubMed:30792174}.
CC -!- BIOTECHNOLOGY: Molecules that disrupt the MbcT-MbcA complex could be
CC candidates for anti-tuberculosis therapy.
CC {ECO:0000269|PubMed:30792174}.
CC -!- SIMILARITY: Belongs to the MbcA/ParS/Xre antitoxin family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44760.1; -; Genomic_DNA.
DR PIR; D70757; D70757.
DR RefSeq; NP_216506.1; NC_000962.3.
DR RefSeq; WP_003410003.1; NZ_NVQJ01000043.1.
DR PDB; 6FKG; X-ray; 1.80 A; C/D=1-113.
DR PDBsum; 6FKG; -.
DR AlphaFoldDB; P9WLP7; -.
DR SASBDB; P9WLP7; -.
DR SMR; P9WLP7; -.
DR STRING; 83332.Rv1990c; -.
DR PaxDb; P9WLP7; -.
DR DNASU; 885422; -.
DR GeneID; 885422; -.
DR KEGG; mtu:Rv1990c; -.
DR TubercuList; Rv1990c; -.
DR eggNOG; ENOG503154Z; Bacteria.
DR OMA; ETRLWLH; -.
DR PhylomeDB; P9WLP7; -.
DR Proteomes; UP000001584; Chromosome.
DR InterPro; IPR024467; Xre/MbcA/ParS-like_toxin-bd.
DR Pfam; PF09722; DUF2384; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Toxin-antitoxin system.
FT CHAIN 1..113
FT /note="Mycobacterial cidal antitoxin MbcA"
FT /id="PRO_0000014116"
FT MUTAGEN 104..113
FT /note="Missing: No longer neutralizes the toxic effect of
FT MbcT."
FT /evidence="ECO:0000269|PubMed:30792174"
FT HELIX 5..17
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 21..28
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 50..63
FT /evidence="ECO:0007829|PDB:6FKG"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 88..93
FT /evidence="ECO:0007829|PDB:6FKG"
FT HELIX 97..108
FT /evidence="ECO:0007829|PDB:6FKG"
SQ SEQUENCE 113 AA; 12488 MW; 41978D1BE45E74C9 CRC64;
MGVNVLASTV SGAIERLGLT YEEVGDIVDA SPRSVARWTA GQVVPQRLNK QRLIELAYVA
DALAEVLPRD QANVWMFSPN RLLEHRKPAD LVRDGEYQRV LALIDAMAEG VFV
