LFRA_MYCS2
ID LFRA_MYCS2 Reviewed; 504 AA.
AC A0R5K5; I7GG83; Q50392;
DT 05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 25-MAY-2022, entry version 101.
DE RecName: Full=Multidrug efflux pump LfrA {ECO:0000305};
DE AltName: Full=Low-level fluoroquinolone resistance protein {ECO:0000303|PubMed:8552639};
GN Name=lfrA {ECO:0000303|PubMed:8552639};
GN OrderedLocusNames=MSMEG_6225 {ECO:0000312|EMBL:ABK70581.1},
GN MSMEI_6063 {ECO:0000312|EMBL:AFP42494.1};
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND OVEREXPRESSION.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=8552639; DOI=10.1073/pnas.93.1.362;
RA Takiff H.E., Cimino M., Musso M.C., Weisbrod T., Martinez R., Delgado M.B.,
RA Salazar L., Bloom B.R., Jacobs W.R. Jr.;
RT "Efflux pump of the proton antiporter family confers low-level
RT fluoroquinolone resistance in Mycobacterium smegmatis.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:362-366(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=8682782; DOI=10.1128/jb.178.13.3791-3795.1996;
RA Liu J., Takiff H.E., Nikaido H.;
RT "Active efflux of fluoroquinolones in Mycobacterium smegmatis mediated by
RT LfrA, a multidrug efflux pump.";
RL J. Bacteriol. 178:3791-3795(1996).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=11094273; DOI=10.1111/j.1574-6968.2000.tb09396.x;
RA Sander P., De Rossi E., Boeddinghaus B., Cantoni R., Branzoni M.,
RA Boettger E.C., Takiff H., Rodriquez R., Lopez G., Riccardi G.;
RT "Contribution of the multidrug efflux pump LfrA to innate mycobacterial
RT drug resistance.";
RL FEMS Microbiol. Lett. 193:19-23(2000).
RN [7]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=15215089; DOI=10.1128/aac.48.7.2415-2423.2004;
RA Li X.Z., Zhang L., Nikaido H.;
RT "Efflux pump-mediated intrinsic drug resistance in Mycobacterium
RT smegmatis.";
RL Antimicrob. Agents Chemother. 48:2415-2423(2004).
RN [8]
RP INDUCTION.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17043130; DOI=10.1128/aac.00656-06;
RA Buroni S., Manina G., Guglierame P., Pasca M.R., Riccardi G., De Rossi E.;
RT "LfrR is a repressor that regulates expression of the efflux pump LfrA in
RT Mycobacterium smegmatis.";
RL Antimicrob. Agents Chemother. 50:4044-4052(2006).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=21332993; DOI=10.1186/1471-2180-11-35;
RA Rodrigues L., Ramos J., Couto I., Amaral L., Viveiros M.;
RT "Ethidium bromide transport across Mycobacterium smegmatis cell-wall:
RT correlation with antibiotic resistance.";
RL BMC Microbiol. 11:35-35(2011).
CC -!- FUNCTION: Energy-dependent efflux pump that contributes to drug
CC resistance (PubMed:8682782, PubMed:11094273, PubMed:15215089,
CC PubMed:21332993). Catalyzes the efflux of norfloxacin and several
CC related fluoroquinolones (FQ) (PubMed:8682782). Contributes
CC significantly to the intrinsic MICs for ethidium bromide and
CC acriflavine (PubMed:11094273, PubMed:21332993). Overexpression confers
CC low-level resistance to hydrophilic FQ such as ciprofloxacin, ofloxacin
CC and levofloxacin, and to ethidium bromide, acridine, acriflavine,
CC rhodamine 123 and some quaternary ammonium compounds (PubMed:8552639,
CC PubMed:11094273). May contribute to resistance to certain beta-lactams
CC (PubMed:15215089). Probably uses the proton motive force
CC (PubMed:8682782). {ECO:0000269|PubMed:11094273,
CC ECO:0000269|PubMed:15215089, ECO:0000269|PubMed:21332993,
CC ECO:0000269|PubMed:8552639, ECO:0000269|PubMed:8682782}.
CC -!- ACTIVITY REGULATION: Inhibited by the protonophore carbonyl cyanide m-
CC chorophenylhydrazone (CCCP) (PubMed:8682782). Ethidium bromide efflux
CC is inhibited by chlorpromazine, thioridazine and verapamil
CC (PubMed:21332993). {ECO:0000269|PubMed:21332993,
CC ECO:0000269|PubMed:8682782}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:8682782};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is repressed by LfrR (PubMed:15215089,
CC PubMed:17043130). Induced by ethidium bromide, acriflavine or rhodamine
CC 123, via inhibition of LfrR binding (PubMed:17043130).
CC {ECO:0000269|PubMed:15215089, ECO:0000269|PubMed:17043130}.
CC -!- DISRUPTION PHENOTYPE: Disruption or deletion of the gene decreases
CC resistance to ethidium bromide and acriflavine and results in a small
CC decrease in minimal inhibitory concentrations (MICs) for ciprofloxacin,
CC doxorubicin, rhodamine, norfloxacin, isoniazid, tetracycline,
CC ethambutol and rifampicin. {ECO:0000269|PubMed:11094273,
CC ECO:0000269|PubMed:15215089, ECO:0000269|PubMed:21332993}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; U40487; AAC43550.1; -; Genomic_DNA.
DR EMBL; CP000480; ABK70581.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42494.1; -; Genomic_DNA.
DR RefSeq; WP_011731134.1; NZ_SIJM01000027.1.
DR RefSeq; YP_890443.1; NC_008596.1.
DR AlphaFoldDB; A0R5K5; -.
DR SMR; A0R5K5; -.
DR STRING; 246196.MSMEI_6063; -.
DR ChEMBL; CHEMBL4295530; -.
DR TCDB; 2.A.1.3.3; the major facilitator superfamily (mfs).
DR EnsemblBacteria; ABK70581; ABK70581; MSMEG_6225.
DR EnsemblBacteria; AFP42494; AFP42494; MSMEI_6063.
DR GeneID; 66737507; -.
DR KEGG; msg:MSMEI_6063; -.
DR KEGG; msm:MSMEG_6225; -.
DR PATRIC; fig|246196.19.peg.6062; -.
DR eggNOG; COG0477; Bacteria.
DR OMA; NLPVMAV; -.
DR OrthoDB; 626204at2; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Antibiotic resistance; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..504
FT /note="Multidrug efflux pump LfrA"
FT /id="PRO_0000447320"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CONFLICT 87
FT /note="L -> V (in Ref. 1; AAC43550)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="A -> T (in Ref. 1; AAC43550)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 51524 MW; 7CBFF4468811FE75 CRC64;
MSTCIEGTPS TTRTPTRAWV ALAVLALPVL LIAIDNTVLA FALPLIAEDF RPSATTQLWI
VDVYSLVLAA LLVAMGSLGD RLGRRRLLLI GGAGFAVVSA LAAFAPSAEL LVGARALLGV
FGAMLMPSTL SLIRNIFTDA SARRLAIAIW ASCFTAGSAL GPIVGGALLE HFHWGAVFLV
AVPILLPLLV LGPRLVPESR DPNPGPFDPV SIVLSFTTML PIVWAVKTAA HDGLSAAAAA
AFAVGIVSGA LFVRRQNRSA TPMLDIGLFK VMPFTSSILA NFLSIIGLIG FIFFISQHLQ
LVLGLSPLTA GLVTLPGAVV SMIAGLAVVK AAKRFAPDTL MVTGLVFVAV GFLMILLFRH
NLTVAAIIAS FVVLELGVGV SQTVSNDTIV ASVPAAKSGA ASAVSETAYE LGAVVGTATL
GTIFTAFYRS NVDVPAGLTP EQTGAAAESI GGAAAVAADL PAATATQLLD SARAAFDSGI
APTAVIAAML VLAAAAVVGV AFRR
