ID MMPL7_MYCTU Reviewed; 920 AA.
AC P9WJU7; L0TB36; P65370; P96289;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 27-MAR-2024, entry version 39.
DE RecName: Full=Phthiocerol dimycocerosate exporter MmpL7 {ECO:0000305};
GN Name=mmpL7; OrderedLocusNames=Rv2942; ORFNames=MTCY24G1.07c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; 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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10573420; DOI=10.1038/47042;
RA Cox J.S., Chen B., McNeil M., Jacobs W.R. Jr.;
RT "Complex lipid determines tissue-specific replication of Mycobacterium
RT tuberculosis in mice.";
RL Nature 402:79-83(1999).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Mt103;
RX PubMed=11279114; DOI=10.1074/jbc.m100662200;
RA Camacho L.R., Constant P., Raynaud C., Laneelle M.A., Triccas J.A.,
RA Gicquel B., Daffe M., Guilhot C.;
RT "Analysis of the phthiocerol dimycocerosate locus of Mycobacterium
RT tuberculosis. Evidence that this lipid is involved in the cell wall
RT permeability barrier.";
RL J. Biol. Chem. 276:19845-19854(2001).
RN [4]
RP INTERACTION WITH PPSE, AND MUTAGENESIS OF ILE-611.
RX PubMed=16201014; DOI=10.1371/journal.ppat.0010002;
RA Jain M., Cox J.S.;
RT "Interaction between polyketide synthase and transporter suggests coupled
RT synthesis and export of virulence lipid in M. tuberculosis.";
RL PLoS Pathog. 1:e2-e2(2005).
RN [5]
RP FUNCTION IN M.SMEGMATIS.
RX PubMed=16251328; DOI=10.1128/aac.49.11.4775-4777.2005;
RA Pasca M.R., Guglierame P., De Rossi E., Zara F., Riccardi G.;
RT "mmpL7 gene of Mycobacterium tuberculosis is responsible for isoniazid
RT efflux in Mycobacterium smegmatis.";
RL Antimicrob. Agents Chemother. 49:4775-4777(2005).
RN [6]
RP FUNCTION IN VIRULENCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15908378; DOI=10.1128/iai.73.6.3492-3501.2005;
RA Domenech P., Reed M.B., Barry C.E. III;
RT "Contribution of the Mycobacterium tuberculosis MmpL protein family to
RT virulence and drug resistance.";
RL Infect. Immun. 73:3492-3501(2005).
RN [7]
RP PHOSPHORYLATION BY PKND.
RX PubMed=16879801; DOI=10.1016/j.bbrc.2006.06.164;
RA Perez J., Garcia R., Bach H., de Waard J.H., Jacobs W.R. Jr., Av-Gay Y.,
RA Bubis J., Takiff H.E.;
RT "Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for
RT kinase PknD.";
RL Biochem. Biophys. Res. Commun. 348:6-12(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
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).
CC -!- FUNCTION: Required for export of phthiocerol dimycocerosate (PDIM) to
CC the cell wall (PubMed:10573420, PubMed:11279114). Essential for normal
CC replication during the active-growth phase of the murine tuberculosis
CC model (PubMed:15908378). {ECO:0000269|PubMed:10573420,
CC ECO:0000269|PubMed:11279114, ECO:0000269|PubMed:15908378}.
CC -!- FUNCTION: Confers a high level of resistance to isoniazid (INH) when
CC overexpressed in M.smegmatis. {ECO:0000269|PubMed:16251328}.
CC -!- SUBUNIT: Interacts with PpsE. {ECO:0000269|PubMed:16201014}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:10573420}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- PTM: Phosphorylated by PknD in vitro. Phosphorylation could regulate
CC the formation of the cell wall. {ECO:0000269|PubMed:16879801}.
CC -!- DISRUPTION PHENOTYPE: Disruption causes altered colony morphology
CC (PubMed:10573420). Inactivation increases mouse survival
CC (PubMed:15908378). Mutants are unable to liberate PDIM into the culture
CC medium and are compromised for growth in mouse lungs, but not in the
CC liver or spleen (PubMed:10573420). DIM are found mostly in the cytosol
CC and plasma membrane, and mutants exhibit higher cell wall permeability
CC and are more sensitive to detergent (PubMed:11279114).
CC {ECO:0000269|PubMed:10573420, ECO:0000269|PubMed:11279114,
CC ECO:0000269|PubMed:15908378}.
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; CCP45745.1; -; Genomic_DNA.
DR PIR; C70668; C70668.
DR RefSeq; NP_217458.1; NC_000962.3.
DR RefSeq; WP_003414861.1; NZ_NVQJ01000015.1.
DR AlphaFoldDB; P9WJU7; -.
DR STRING; 83332.Rv2942; -.
DR PaxDb; 83332-Rv2942; -.
DR GeneID; 887548; -.
DR KEGG; mtu:Rv2942; -.
DR TubercuList; Rv2942; -.
DR eggNOG; COG2409; Bacteria.
DR InParanoid; P9WJU7; -.
DR OrthoDB; 4673837at2; -.
DR PhylomeDB; P9WJU7; -.
DR Reactome; R-MTU-9635470; Dimycocersyl phthiocerol biosynthesis.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0015245; F:fatty acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0008610; P:lipid biosynthetic process; TAS:Reactome.
DR GO; GO:0006869; P:lipid transport; IMP:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IMP:MTBBASE.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; IMP:MTBBASE.
DR InterPro; IPR004869; MMPL_dom.
DR PANTHER; PTHR33406; MEMBRANE PROTEIN MJ1562-RELATED; 1.
DR PANTHER; PTHR33406:SF6; MEMBRANE PROTEIN SCO0839-RELATED; 1.
DR Pfam; PF03176; MMPL; 2.
DR SUPFAM; SSF82866; Multidrug efflux transporter AcrB transmembrane domain; 1.
PE 1: Evidence at protein level;
KW Cell inner membrane; Cell membrane; Cell wall biogenesis/degradation;
KW Lipid transport; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Virulence.
FT CHAIN 1..920
FT /note="Phthiocerol dimycocerosate exporter MmpL7"
FT /id="PRO_0000103570"
FT TRANSMEM 44..64
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 761..781
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 790..810
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 822..842
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 864..884
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 888..908
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MUTAGEN 611
FT /note="I->S: Leads to decreased interaction with PpsE, but
FT does not decrease MmpL7 activity in vivo."
FT /evidence="ECO:0000269|PubMed:16201014"
SQ SEQUENCE 920 AA; 95122 MW; 019FCA9294A854D2 CRC64;
MPSPAGRLHR IRYIRLKKSS PDCRATITSG SADGQRRSPR LTNLLVVAAW VAAAVIANLL
LTFTQAEPHD TSPALLPQDA KTAAATSRIA QAFPGTGSNA IAYLVVEGGS TLEPQDQPYY
DAAVGALRAD TRHVGSVLDW WSDPVTAPLG TSPDGRSATA MVWLRGEAGT TQAAESLDAV
RSVLRQLPPS EGLRASIVVP AITNDMPMQI TAWQSATIVT VAAVIAVLLL LRARLSVRAA
AIVLLTADLS LAVAWPLAAV VRGHDWGTDS VFSWTLAAVL TIGTITAATM LAARLGSDAG
HSAAPTYRDS LPAFALPGAC VAIFTGPLLL ARTPALHGVG TAGLGVFVAL AASLTVLPAL
IALAGASRQL PAPTTGAGWT GRLSLPVSSA SALGTAAVLA ICMLPIIGMR WGVAENPTRQ
GGAQVLPGNA LPDVVVIKSA RDLRDPAALI AINQVSHRLV EVPGVRKVES AAWPAGVPWT
DASLSSAAGR LADQLGQQAG SFVPAVTAIK SMKSIIEQMS GAVDQLDSTV NVTLAGARQA
QQYLDPMLAA ARNLKNKTTE LSEYLETIHT WIVGFTNCPD DVLCTAMRKV IEPYDIVVTG
MNELSTGADR ISAISTQTMS ALSSAPRMVA QMRSALAQVR SFVPKLETTI QDAMPQIAQA
SAMLKNLSAD FADTGEGGFH LSRKDLADPS YRHVRESMFS SDGTATRLFL YSDGQLDLAA
AARAQQLEIA AGKAMKYGSL VDSQVTVGGA AQIAAAVRDA LIHDAVLLAV ILLTVVALAS
MWRGAVHGAA VGVGVLASYL AALGVSIALW QHLLDRELNA LVPLVSFAVL ASCGVPYLVA
GIKAGRIADE ATGARSKGAV SGRGAVAPLA ALGGVFGAGL VLVSGGSFSV LSQIGTVVVL
GLGVLITVQR AWLPTTPGRR
//
