ID   MEATP_MYCTU             Reviewed;         311 AA.
AC   O86311; F2GFX0; I6Y5Z4; L0T8R2;
DT   05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   03-AUG-2022, entry version 152.
DE   RecName: Full=Multidrug efflux system ATP-binding protein Rv1218c {ECO:0000305};
DE            EC=7.6.2.- {ECO:0000305};
GN   OrderedLocusNames=Rv1218c {ECO:0000312|EMBL:CCP43974.1};
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   SUBUNIT.
RX   PubMed=10978546; DOI=10.1111/j.1574-6976.2000.tb00550.x;
RA   Braibant M., Gilot P., Content J.;
RT   "The ATP binding cassette (ABC) transport systems of Mycobacterium
RT   tuberculosis.";
RL   FEMS Microbiol. Rev. 24:449-467(2000).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX   PubMed=20921309; DOI=10.1128/aac.00610-10;
RA   Balganesh M., Kuruppath S., Marcel N., Sharma S., Nair A., Sharma U.;
RT   "Rv1218c, an ABC transporter of Mycobacterium tuberculosis with
RT   implications in drug discovery.";
RL   Antimicrob. Agents Chemother. 54:5167-5172(2010).
RN   [4]
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   [5]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=23143285; DOI=10.1007/s00284-012-0215-3;
RA   Wang K., Pei H., Huang B., Zhu X., Zhang J., Zhou B., Zhu L., Zhang Y.,
RA   Zhou F.F.;
RT   "The expression of ABC efflux pump, Rv1217c-Rv1218c, and its association
RT   with multidrug resistance of Mycobacterium tuberculosis in China.";
RL   Curr. Microbiol. 66:222-226(2013).
RN   [6]
RP   INDUCTION.
RC   STRAIN=H37Rv;
RX   PubMed=24424575; DOI=10.1002/pro.2424;
RA   Kumar N., Radhakrishnan A., Wright C.C., Chou T.H., Lei H.T., Bolla J.R.,
RA   Tringides M.L., Rajashankar K.R., Su C.C., Purdy G.E., Yu E.W.;
RT   "Crystal structure of the transcriptional regulator Rv1219c of
RT   Mycobacterium tuberculosis.";
RL   Protein Sci. 23:423-432(2014).
CC   -!- FUNCTION: Probably part of the ABC transporter complex Rv1217c-Rv1218c
CC       involved in the resistance to a wide range of structurally unrelated
CC       drugs (PubMed:20921309, PubMed:23143285). Could be involved in the
CC       efflux of substrates belonging to the diverse chemical classes of
CC       novobiocins, biarylpiperazines, pyridines, bisanilinopyrimidines,
CC       pyrroles and, to a smaller extent, pyrazolones (PubMed:20921309).
CC       Probably responsible for energy coupling to the transport system
CC       (Probable). {ECO:0000269|PubMed:20921309, ECO:0000269|PubMed:23143285,
CC       ECO:0000305}.
CC   -!- SUBUNIT: The complex is probably composed of two ATP-binding proteins
CC       (Rv1218c) and a transmembrane protein (Rv1217c).
CC       {ECO:0000305|PubMed:10978546}.
CC   -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305}; Peripheral
CC       membrane protein {ECO:0000305}.
CC   -!- INDUCTION: Transcriptionally regulated by RaaS (Rv1219c)
CC       (PubMed:24424575). Expression increases in multidrug-resistant clinical
CC       strains (MDR-TB) compared to drug-susceptible strains
CC       (PubMed:23143285). {ECO:0000269|PubMed:23143285,
CC       ECO:0000269|PubMed:24424575}.
CC   -!- DISRUPTION PHENOTYPE: Inactivation of the gene leads to a 4- to 8-fold
CC       decrease in minimal inhibitory concentrations (MICs) for ethidium
CC       bromide, novobiocins, biarylpiperazines, bisanilopyrimidines, pyrroles
CC       and pyridones. {ECO:0000269|PubMed:20921309}.
CC   -!- SIMILARITY: Belongs to the ABC transporter superfamily. {ECO:0000305}.
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DR   EMBL; AL123456; CCP43974.1; -; Genomic_DNA.
DR   RefSeq; NP_215734.1; NC_000962.3.
DR   RefSeq; WP_003906541.1; NZ_NVQJ01000039.1.
DR   AlphaFoldDB; O86311; -.
DR   SMR; O86311; -.
DR   STRING; 83332.Rv1218c; -.
DR   PaxDb; O86311; -.
DR   PRIDE; O86311; -.
DR   DNASU; 888518; -.
DR   GeneID; 888518; -.
DR   KEGG; mtu:Rv1218c; -.
DR   PATRIC; fig|83332.111.peg.1361; -.
DR   TubercuList; Rv1218c; -.
DR   eggNOG; COG1131; Bacteria.
DR   OMA; NVFQQCV; -.
DR   PhylomeDB; O86311; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046677; P:response to antibiotic; IDA:MTBBASE.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR003593; AAA+_ATPase.
DR   InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR   InterPro; IPR017871; ABC_transporter-like_CS.
DR   InterPro; IPR025302; DUF4162.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   Pfam; PF00005; ABC_tran; 1.
DR   Pfam; PF13732; DUF4162; 1.
DR   SMART; SM00382; AAA; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR   PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE   1: Evidence at protein level;
KW   Antibiotic resistance; ATP-binding; Cell inner membrane; Cell membrane;
KW   Membrane; Nucleotide-binding; Reference proteome; Translocase; Transport.
FT   CHAIN           1..311
FT                   /note="Multidrug efflux system ATP-binding protein Rv1218c"
FT                   /id="PRO_0000447330"
FT   DOMAIN          10..235
FT                   /note="ABC transporter"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   BINDING         42..49
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
SQ   SEQUENCE   311 AA;  33448 MW;  C3A3F4E70FD10759 CRC64;
     MSADNHQVPI EIRGLTKHFG SVRALDGLDL TVREGEVHGF LGPNGAGKST TLRILLGLVK
     ADGGSVRLLG GDPWTDAVDL HRHIAYVPGD VTLWPSLTGG ETIDLLARMR GGIDNARRAE
     LIERFGLDPT KKARTYSKGN RQKVSLISAL SSHATLLLLD EPSSGLDPLM ENVFQQCIGE
     ARQRGVTVLL SSHILAETEA LCEKVTIIRA GKTVESGSLD ALRHLSRTSI KAEMIGDPGD
     LSQIKGVEDI SIEGTTVRAQ VDSESLRELI QVLGHAGVRS LVSQPPTLEE LFLRHYSLGP
     EVAAEQQVAT P