LFRR_MYCS2
ID LFRR_MYCS2 Reviewed; 189 AA.
AC A0R5K4; I7FUD9;
DT 05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=HTH-type transcriptional repressor LfrR {ECO:0000305};
GN Name=lfrR {ECO:0000303|PubMed:15215089};
GN OrderedLocusNames=MSMEG_6223 {ECO:0000312|EMBL:ABK72312.1},
GN MSMEI_6062 {ECO:0000312|EMBL:AFP42493.1};
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 [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 [2]
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 [3]
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 [4]
RP FUNCTION, 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 [5]
RP FUNCTION, DNA-BINDING, ACTIVITY REGULATION, AND 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 [6]
RP 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).
RN [7] {ECO:0007744|PDB:2V57, ECO:0007744|PDB:2WGB}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOPROTEIN AND IN COMPLEX WITH
RP PROFLAVINE, ACTIVITY REGULATION, SUBUNIT, AND DOMAIN.
RX PubMed=19820093; DOI=10.1128/jb.00631-09;
RA Bellinzoni M., Buroni S., Schaeffer F., Riccardi G., De Rossi E.,
RA Alzari P.M.;
RT "Structural plasticity and distinct drug-binding modes of LfrR, a
RT mycobacterial efflux pump regulator.";
RL J. Bacteriol. 191:7531-7537(2009).
CC -!- FUNCTION: Represses the transcription of the lfrRA operon by binding
CC directly to the promoter region of lfrR-lfrA (PubMed:15215089,
CC PubMed:17043130). Binds specifically to a 143-bp region upstream of the
CC lfrR gene (PubMed:17043130). {ECO:0000269|PubMed:15215089,
CC ECO:0000269|PubMed:17043130}.
CC -!- ACTIVITY REGULATION: Repressor activity is regulated by binding of
CC different substrates of the LfrA multidrug efflux pump, such as
CC acriflavine, proflavine, ethidium bromide and rhodamine 123. Binding of
CC these ligands causes the dissociation of LfrR from the promoter,
CC inducing lfrA expression. {ECO:0000269|PubMed:17043130,
CC ECO:0000269|PubMed:19820093}.
CC -!- SUBUNIT: Homodimer. Forms a structurally asymmetric homodimer
CC exhibiting local unfolding and a blocked drug-binding site.
CC {ECO:0000269|PubMed:19820093}.
CC -!- INDUCTION: Negatively autoregulated. {ECO:0000269|PubMed:17043130}.
CC -!- DOMAIN: Binding of ligands causes significant conformational changes.
CC {ECO:0000269|PubMed:19820093}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene increases the expression of
CC lfrA and produces higher resistance to multiple drugs.
CC {ECO:0000269|PubMed:15215089, ECO:0000269|PubMed:21332993}.
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DR EMBL; CP000480; ABK72312.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42493.1; -; Genomic_DNA.
DR RefSeq; WP_003897643.1; NZ_SIJM01000027.1.
DR RefSeq; YP_890442.1; NC_008596.1.
DR PDB; 2V57; X-ray; 1.90 A; A/B/C/D=1-189.
DR PDB; 2WGB; X-ray; 2.00 A; A/B=1-189.
DR PDBsum; 2V57; -.
DR PDBsum; 2WGB; -.
DR AlphaFoldDB; A0R5K4; -.
DR SMR; A0R5K4; -.
DR STRING; 246196.MSMEI_6062; -.
DR EnsemblBacteria; ABK72312; ABK72312; MSMEG_6223.
DR EnsemblBacteria; AFP42493; AFP42493; MSMEI_6062.
DR GeneID; 66737506; -.
DR KEGG; msg:MSMEI_6062; -.
DR KEGG; msm:MSMEG_6223; -.
DR PATRIC; fig|246196.56.peg.6185; -.
DR eggNOG; COG1309; Bacteria.
DR OMA; LHRYFPE; -.
DR OrthoDB; 2047542at2; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0010468; P:regulation of gene expression; IEA:UniProt.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001647; HTH_TetR.
DR Pfam; PF00440; TetR_N; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50977; HTH_TETR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..189
FT /note="HTH-type transcriptional repressor LfrR"
FT /id="PRO_0000447321"
FT DOMAIN 12..70
FT /note="HTH tetR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT DNA_BIND 33..52
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT REGION 70..71
FT /note="Proflavine binding"
FT /evidence="ECO:0000269|PubMed:19820093"
SQ SEQUENCE 189 AA; 20618 MW; C6BA0B92B0C36F4F CRC64;
MTSPSIESGA RERTRRAILD AAMLVLADHP TAALGDIAAA AGVGRSTVHR YYPERTDLLR
ALARHVHDLS NAAIERADPT SGPVDAALRR VVESQLDLGP IVLFVYYEPS ILADPELAAY
FDIGDEAIVE VLNRASTERP EYPPGWARRV FWALMQAGYE AAKDGMPRHQ IVDAIMTSLT
SGIITLPRT
