ID   MMPL5_MYCTU             Reviewed;         964 AA.
AC   P9WJV1; L0T659; O53784;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 30.
DE   RecName: Full=Siderophore exporter MmpL5 {ECO:0000305};
GN   Name=mmpL5; OrderedLocusNames=Rv0676c; ORFNames=MTV040.04c;
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.
RC   STRAIN=H37Rv;
RX   PubMed=12065475; DOI=10.1128/iai.70.7.3371-3381.2002;
RA   Rodriguez G.M., Voskuil M.I., Gold B., Schoolnik G.K., Smith I.;
RT   "IdeR, an essential gene in Mycobacterium tuberculosis: role of IdeR in
RT   iron-dependent gene expression, iron metabolism, and oxidative stress
RT   response.";
RL   Infect. Immun. 70:3371-3381(2002).
RN   [3]
RP   FUNCTION IN AZOLE RESISTANCE.
RC   STRAIN=H37Rv;
RX   PubMed=18851927; DOI=10.1016/j.tube.2008.08.003;
RA   Milano A., Pasca M.R., Provvedi R., Lucarelli A.P., Manina G.,
RA   Ribeiro A.L., Manganelli R., Riccardi G.;
RT   "Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-
RT   MmpL5 efflux system.";
RL   Tuberculosis 89:84-90(2009).
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 INTERACTION WITH MMPS4 AND MMPS5.
RC   STRAIN=H37Rv;
RX   PubMed=23431276; DOI=10.1371/journal.ppat.1003120;
RA   Wells R.M., Jones C.M., Xi Z., Speer A., Danilchanka O., Doornbos K.S.,
RA   Sun P., Wu F., Tian C., Niederweis M.;
RT   "Discovery of a siderophore export system essential for virulence of
RT   Mycobacterium tuberculosis.";
RL   PLoS Pathog. 9:E1003120-E1003120(2013).
RN   [6]
RP   FUNCTION IN ANTIBIOTIC RESISTANCE, AND INDUCTION.
RC   STRAIN=H37Rv;
RX   PubMed=24590481; DOI=10.1128/aac.00037-14;
RA   Hartkoorn R.C., Uplekar S., Cole S.T.;
RT   "Cross-resistance between clofazimine and bedaquiline through upregulation
RT   of MmpL5 in Mycobacterium tuberculosis.";
RL   Antimicrob. Agents Chemother. 58:2979-2981(2014).
RN   [7]
RP   INDUCTION.
RC   STRAIN=H37Rv;
RX   PubMed=24737322; DOI=10.1074/jbc.m113.538959;
RA   Radhakrishnan A., Kumar N., Wright C.C., Chou T.H., Tringides M.L.,
RA   Bolla J.R., Lei H.T., Rajashankar K.R., Su C.C., Purdy G.E., Yu E.W.;
RT   "Crystal structure of the transcriptional regulator Rv0678 of Mycobacterium
RT   tuberculosis.";
RL   J. Biol. Chem. 289:16526-16540(2014).
RN   [8]
RP   FUNCTION IN ANTIBIOTIC RESISTANCE.
RC   STRAIN=H37Rv;
RX   PubMed=25010492; DOI=10.1371/journal.pone.0102135;
RA   Andries K., Villellas C., Coeck N., Thys K., Gevers T., Vranckx L.,
RA   Lounis N., de Jong B.C., Koul A.;
RT   "Acquired resistance of Mycobacterium tuberculosis to bedaquiline.";
RL   PLoS ONE 9:E102135-E102135(2014).
CC   -!- FUNCTION: Part of an export system, which is required for biosynthesis
CC       and secretion of siderophores. {ECO:0000269|PubMed:23431276}.
CC   -!- FUNCTION: Overexpression of the system confers non-target based
CC       resistance to azoles, clofazimine and bedaquiline, via an efflux
CC       mechanism. {ECO:0000269|PubMed:18851927, ECO:0000269|PubMed:24590481,
CC       ECO:0000269|PubMed:25010492}.
CC   -!- SUBUNIT: Interacts with MmpS5. Can also interact with MmpS4.
CC       {ECO:0000269|PubMed:23431276}.
CC   -!- SUBCELLULAR LOCATION: Cell inner membrane
CC       {ECO:0000305|PubMed:23431276}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- INDUCTION: Repressed by MmpR5 (PubMed:24590481, PubMed:24737322).
CC       Repressed by iron (PubMed:12065475). Regulation is IdeR-independent
CC       (PubMed:12065475). {ECO:0000269|PubMed:12065475,
CC       ECO:0000269|PubMed:24590481, ECO:0000269|PubMed:24737322}.
CC   -!- SIMILARITY: Belongs to the resistance-nodulation-cell division (RND)
CC       (TC 2.A.6) family. MmpL subfamily. {ECO:0000305}.
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DR   EMBL; AL123456; CCP43419.1; -; Genomic_DNA.
DR   PIR; E70826; E70826.
DR   RefSeq; NP_215190.1; NC_000962.3.
DR   RefSeq; WP_009935604.1; NZ_NVQJ01000007.1.
DR   AlphaFoldDB; P9WJV1; -.
DR   STRING; 83332.Rv0676c; -.
DR   PaxDb; P9WJV1; -.
DR   DNASU; 888219; -.
DR   GeneID; 888219; -.
DR   KEGG; mtu:Rv0676c; -.
DR   TubercuList; Rv0676c; -.
DR   eggNOG; COG1033; Bacteria.
DR   eggNOG; COG2409; Bacteria.
DR   OMA; MVALMPE; -.
DR   PhylomeDB; P9WJV1; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR   GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR   GO; GO:0005887; C:integral component of plasma membrane; HDA:MTBBASE.
DR   InterPro; IPR004869; MMPL_dom.
DR   InterPro; IPR004707; MmpL_fam.
DR   Pfam; PF03176; MMPL; 2.
DR   TIGRFAMs; TIGR00833; actII; 1.
PE   1: Evidence at protein level;
KW   Cell inner membrane; Cell membrane; Membrane; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..964
FT                   /note="Siderophore exporter MmpL5"
FT                   /id="PRO_0000103568"
FT   TRANSMEM        31..51
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        203..223
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        230..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        255..275
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        302..322
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        340..360
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        389..409
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        773..793
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        803..823
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        826..846
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        880..900
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        923..943
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   964 AA;  104785 MW;  B7C945940A1176BD CRC64;
     MIVQRTAAPT GSVPPDRHAA RPFIPRMIRT FAVPIILGWL VTIAVLNVTV PQLETVGQIQ
     AVSMSPDAAP SMISMKHIGK VFEEGDSDSA AMIVLEGQRP LGDAAHAFYD QMIGRLQADT
     THVQSLQDFW GDPLTATGAQ SSDGKAAYVQ VKLAGNQGES LANESVEAVK TIVERLAPPP
     GVKVYVTGSA ALVADQQQAG DRSLQVIEAV TFTVIIVMLL LVYRSIITSA IMLTMVVLGL
     LATRGGVAFL GFHRIIGLST FATNLLVVLA IAAATDYAIF LIGRYQEARG LGQDRESAYY
     TMFGGTAHVV LGSGLTIAGA TFCLSFTRLP YFQTLGVPLA IGMVIVVAAA LTLGPAIIAV
     TSRFGKLLEP KRMARVRGWR KVGAAIVRWP GPILVGAVAL ALVGLLTLPG YRTNYNDRNY
     LPADLPANEG YAAAERHFSQ ARMNPEVLMV ESDHDMRNSA DFLVINKIAK AIFAVEGISR
     VQAITRPDGK PIEHTSIPFL ISMQGTSQKL TEKYNQDLTA RMLEQVNDIQ SNIDQMERMH
     SLTQQMADVT HEMVIQMTGM VVDVEELRNH IADFDDFFRP IRSYFYWEKH CYDIPVCWSL
     RSVFDTLDGI DVMTEDINNL LPLMQRLDTL MPQLTAMMPE MIQTMKSMKA QMLSMHSTQE
     GLQDQMAAMQ EDSAAMGEAF DASRNDDSFY LPPEVFDNPD FQRGLEQFLS PDGHAVRFII
     SHEGDPMSQA GIARIAKIKT AAKEAIKGTP LEGSAIYLGG TAAMFKDLSD GNTYDLMIAG
     ISALCLIFII MLITTRSVVA AAVIVGTVVL SLGASFGLSV LIWQHILGIE LHWLVLAMAV
     IILLAVGADY NLLLVARLKE EIHAGINTGI IRAMGGSGSV VTAAGLVFAF TMMSFAVSEL
     TVMAQVGTTI GMGLLFDTLI VRSFMTPSIA ALLGKWFWWP QVVRQRPIPQ PWPSPASART
     FALV