MFS55_MYCTU
ID MFS55_MYCTU Reviewed; 518 AA.
AC P9WJY3; L0T9B4; P71678; Q7D8H0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=Probable triacylglyceride transporter Rv1410c {ECO:0000303|PubMed:26751071};
DE AltName: Full=MFS-type drug efflux transporter P55;
GN OrderedLocusNames=Rv1410c;
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 DISRUPTION PHENOTYPE, AND VIRULENCE.
RC STRAIN=H37Rv;
RX PubMed=14998516; DOI=10.1016/j.micinf.2003.10.010;
RA Bigi F., Gioffre A., Klepp L., Santangelo M.P., Alito A., Caimi K.,
RA Meikle V., Zumarraga M., Taboga O., Romano M.I., Cataldi A.;
RT "The knockout of the lprG-Rv1410 operon produces strong attenuation of
RT Mycobacterium tuberculosis.";
RL Microbes Infect. 6:182-187(2004).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-22.
RC STRAIN=H37Rv;
RX PubMed=18156250; DOI=10.1128/jb.01046-07;
RA Farrow M.F., Rubin E.J.;
RT "Function of a mycobacterial major facilitator superfamily pump requires a
RT membrane-associated lipoprotein.";
RL J. Bacteriol. 190:1783-1791(2008).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=21762531; DOI=10.1186/1471-2334-11-195;
RA Bianco M.V., Blanco F.C., Imperiale B., Forrellad M.A., Rocha R.V.,
RA Klepp L.I., Cataldi A.A., Morcillo N., Bigi F.;
RT "Role of P27 -P55 operon from Mycobacterium tuberculosis in the resistance
RT to toxic compounds.";
RL BMC Infect. Dis. 11:195-195(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 FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=25232742; DOI=10.1371/journal.ppat.1004376;
RA Gaur R.L., Ren K., Blumenthal A., Bhamidi S., Gibbs S., Jackson M.,
RA Zare R.N., Ehrt S., Ernst J.D., Banaei N.;
RT "LprG-mediated surface expression of lipoarabinomannan is essential for
RT virulence of Mycobacterium tuberculosis.";
RL PLoS Pathog. 10:E1004376-E1004376(2014).
RN [7]
RP ERRATUM OF PUBMED:25232742.
RX PubMed=26650245; DOI=10.1371/journal.ppat.1005336;
RA Gaur R.L., Ren K., Blumenthal A., Bhamidi S., Gibbs S., Jackson M.,
RA Zare R.N., Ehrt S., Ernst J.D., Banaei N.;
RT "Correction: LprG-mediated surface expression of lipoarabinomannan is
RT essential for virulence of Mycobacterium tuberculosis.";
RL PLoS Pathog. 11:E1005336-E1005336(2015).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25356793; DOI=10.1371/journal.ppat.1004471;
RA Shukla S., Richardson E.T., Athman J.J., Shi L., Wearsch P.A., McDonald D.,
RA Banaei N., Boom W.H., Jackson M., Harding C.V.;
RT "Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and
RT determines its cell envelope localization to control phagolysosomal
RT fusion.";
RL PLoS Pathog. 10:E1004471-E1004471(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=26751071; DOI=10.1371/journal.ppat.1005351;
RA Martinot A.J., Farrow M., Bai L., Layre E., Cheng T.Y., Tsai J.H.,
RA Iqbal J., Annand J.W., Sullivan Z.A., Hussain M.M., Sacchettini J.,
RA Moody D.B., Seeliger J.C., Rubin E.J.;
RT "Mycobacterial metabolic syndrome: LprG and Rv1410 regulate
RT triacylglyceride levels, growth rate and virulence in Mycobacterium
RT tuberculosis.";
RL PLoS Pathog. 12:E1005351-E1005351(2016).
CC -!- FUNCTION: In association with lipoprotein LprG probably transports
CC triacylglycerides (TAG) across the inner cell membrane into the
CC periplasm; TAG probably regulates lipid metabolism and growth
CC regulation (PubMed:26751071). Confers resistance to ethidium bromide,
CC possibly acting as an efflux pump, requires LprG lipoprotein for normal
CC function (PubMed:18156250). With LprG maintains cell wall permeability
CC (PubMed:21762531). Probably required with LprG for normal surface
CC localization of LAM (PubMed:25232742, PubMed:25356793). Overexpression
CC of LprG and Rv1410c leads to increased levels of TAG in the culture
CC medium (PubMed:26751071). {ECO:0000269|PubMed:18156250,
CC ECO:0000269|PubMed:21762531, ECO:0000269|PubMed:26751071,
CC ECO:0000305|PubMed:25232742, ECO:0000305|PubMed:25356793}.
CC -!- ACTIVITY REGULATION: Inhibited by reserpine (PubMed:18156250).
CC {ECO:0000269|PubMed:18156250}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:26751071}; Multi-pass membrane protein
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Disruption of only this gene, or of the lrpG-
CC Rv1410c operon leads to increased levels of many triacylglyceride
CC alkylforms; up to 100-fold increase depending on the exact form
CC (PubMed:26751071). Cells grow more slowly on lipid carbon sources,
CC conditions thought to mimic infection, and grow more slowly in infected
CC mice (PubMed:26751071). Disruption of the preceeding gene lprG leads to
CC loss of expression of Rv1410c due to polar effects; in infected BALB/c
CC mice 1.5 and 2.5 log decrease in bacterial load 15 and 35 days after
CC infection (PubMed:14998516). The single lprG mutant increases
CC sensitivity to malachite green, sodium dodecyl sulfate (SDS),
CC isoniazid, ethambutal and ethidium bromide, alters the permeability of
CC the cell wall; both genes are required to fully restore the phenotypes
CC (PubMed:21762531). Single lprG deletion mutant (probably without
CC Rv1410c) has decreased surface-exposed glycolipid lipoarabinomannan
CC (LAM), although cellular LAM content is normal (PubMed:25232742,
CC PubMed:25356793). It also forms smaller colonies on agar
CC (PubMed:25232742). Loss of surface LAM has several consequences;
CC bacteria enter mouse macrophages with reduced efficiency and block
CC mouse macrophage phagosome-lysosome fusion less efficiently than wild-
CC type (PubMed:25232742). Reduced efficiency of mouse macrophage
CC phagosome-lysosome fusion was seen in another study (PubMed:25356793).
CC C57BL/6 mice infected with mutant bacteria have 10-fold less bacterial
CC burden after 10 days and about 2700-fold less burden after 70 days;
CC attenuation of mutant is not rescued in macrophages or mice impaired
CC for reactive oxygen or nitrogen generation (disruption of Ncf1 or iNOS)
CC (PubMed:25232742, PubMed:26751071). {ECO:0000269|PubMed:14998516,
CC ECO:0000269|PubMed:21762531, ECO:0000269|PubMed:26751071,
CC ECO:0000305|PubMed:25232742, ECO:0000305|PubMed:25356793}.
CC -!- MISCELLANEOUS: Bacterial LAM blocks host cell phagosome-lysosome fusion
CC and is one way in which M.tuberculosis evades the host immune system.
CC {ECO:0000305|PubMed:25232742, ECO:0000305|PubMed:25356793}.
CC -!- MISCELLANEOUS: Triacylglycerides accumulate in lipid droplets in the
CC cytoplasm of M.tuberculosis stationary phase and dormant bacteria, and
CC are used as an energy source during starvation (PubMed:26751071).
CC {ECO:0000305|PubMed:26751071}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44169.1; -; Genomic_DNA.
DR PIR; G70901; G70901.
DR RefSeq; NP_215926.1; NC_000962.3.
DR RefSeq; WP_003407310.1; NZ_NVQJ01000038.1.
DR AlphaFoldDB; P9WJY3; -.
DR SMR; P9WJY3; -.
DR STRING; 83332.Rv1410c; -.
DR PaxDb; P9WJY3; -.
DR DNASU; 886709; -.
DR GeneID; 45425388; -.
DR GeneID; 886709; -.
DR KEGG; mtu:Rv1410c; -.
DR PATRIC; fig|83332.111.peg.1569; -.
DR TubercuList; Rv1410c; -.
DR eggNOG; COG0477; Bacteria.
DR OMA; AGYWMTP; -.
DR PhylomeDB; P9WJY3; -.
DR Reactome; R-HSA-9636383; Prevention of phagosomal-lysosomal fusion.
DR PHI-base; PHI:5578; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MTBBASE.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IDA:MTBBASE.
DR GO; GO:0017089; F:glycolipid transfer activity; TAS:Reactome.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0052170; P:suppression by symbiont of host innate immune response; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; IDA:MTBBASE.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Virulence.
FT CHAIN 1..518
FT /note="Probable triacylglyceride transporter Rv1410c"
FT /id="PRO_0000391006"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 379..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 475..495
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MUTAGEN 22
FT /note="D->A: Susceptible to ethidium bromide, tested in
FT M.smegmatis."
FT /evidence="ECO:0000269|PubMed:18156250"
FT MUTAGEN 22
FT /note="D->E: Decreases resistance to ethidium bromide,
FT tested in M.smegmatis."
FT /evidence="ECO:0000269|PubMed:18156250"
SQ SEQUENCE 518 AA; 54689 MW; 3D211E3F5A3F77D0 CRC64;
MRAGRRVAIS AGSLAVLLGA LDTYVVVTIM RDIMNSVGIP INQLHRITWI VTMYLLGYIA
AMPLLGRASD RFGRKLMLQV SLAGFIIGSV VTALAGHFGD FHMLIAGRTI QGVASGALLP
ITLALGADLW SQRNRAGVLG GIGAAQELGS VLGPLYGIFI VWLLHDWRDV FWINVPLTAI
AMVMIHFSLP SHDRSTEPER VDLVGGLLLA LALGLAVIGL YNPNPDGKHV LPDYGAPLLV
GALVAAVAFF GWERFARTRL IDPAGVHFRP FLSALGASVA AGAALMVTLV DVELFGQGVL
QMDQAQAAGM LLWFLIALPI GAVTGGWIAT RAGDRAVAFA GLLIAAYGYW LISHWPVDLL
ADRHNILGLF TVPAMHTDLV VAGLGLGLVI GPLSSATLRV VPSAQHGIAS AAVVVARMTG
MLIGVAALSA WGLYRFNQIL AGLSAAIPPN ASLLERAAAI GARYQQAFAL MYGEIFTITA
IVCVFGAVLG LLISGRKEHA DEPEVQEQPT LAPQVEPL
