MMPR5_MYCTU
ID MMPR5_MYCTU Reviewed; 165 AA.
AC I6Y8F7;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=HTH-type transcriptional regulator MmpR5 {ECO:0000305};
GN Name=mmpR5 {ECO:0000303|PubMed:24590481};
GN OrderedLocusNames=Rv0678 {ECO:0000312|EMBL:CCP43421.1},
GN RVBD_0678 {ECO:0000312|EMBL:AFN48550.1};
GN ORFNames=LH57_03665 {ECO:0000312|EMBL:AIR13406.1},
GN P425_00707 {ECO:0000312|EMBL:KBJ39304.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genome Sequencing Platform;
RA Galagan J., Kreiswirth B., Dobos K., Fortune S., Fitzgerald M., Young S.K.,
RA Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Berlin A.M., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Gnerre S., Griggs A., Gujja S., Hansen M.,
RA Howarth C., Imamovic A., Larimer J., McCowan C., Murphy C., Pearson M.,
RA Poon T., Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J.,
RA Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Kreiswirth B., Gomez J., Victor T., Desjardins C., Abeel T.,
RA Young S., Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Griggs A., Gujja S., Hansen M., Howarth C.,
RA Imamovic A., Larimer J., Murphy C., Naylor J., Pearson M., Poon T.W.,
RA Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J., Nusbaum C.,
RA Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
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 [6]
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 [7]
RP FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, GENE NAME, AND VARIANT CFZ-R1
RP ARG-63.
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 [8]
RP DISRUPTION PHENOTYPE.
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 2-165, FUNCTION, DNA-BINDING,
RP SUBUNIT, AND MUTAGENESIS OF ASP-88 AND ARG-90.
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).
CC -!- FUNCTION: Controls the expression level of the Mmps2-MmpL2, MmpS4-
CC MmpL4, and MmpS5-MmpL5 transport systems. Also controls its own
CC expression. Acts by binding directly to the promoter regions.
CC {ECO:0000269|PubMed:18851927, ECO:0000269|PubMed:24590481,
CC ECO:0000269|PubMed:24737322}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24737322}.
CC -!- INDUCTION: Negatively autoregulated. {ECO:0000269|PubMed:18851927,
CC ECO:0000269|PubMed:24590481}.
CC -!- DISRUPTION PHENOTYPE: Mutations or insertions/deletions that inactivate
CC MmpR5, or decrease its activity, lead to increased levels of MmpL5 and
CC MmpS5, and to non-target based resistance to azoles, clofazimine and
CC bedaquiline. {ECO:0000269|PubMed:18851927, ECO:0000269|PubMed:24590481,
CC ECO:0000269|PubMed:25010492}.
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DR EMBL; CP003248; AFN48550.1; -; Genomic_DNA.
DR EMBL; CP009480; AIR13406.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP43421.1; -; Genomic_DNA.
DR EMBL; JLDD01000006; KBJ39304.1; -; Genomic_DNA.
DR RefSeq; NP_215192.1; NC_000962.3.
DR RefSeq; WP_003403442.1; NZ_NVQJ01000007.1.
DR PDB; 4NB5; X-ray; 1.64 A; A/B/C/D=2-165.
DR PDBsum; 4NB5; -.
DR AlphaFoldDB; I6Y8F7; -.
DR SMR; I6Y8F7; -.
DR STRING; 83332.Rv0678; -.
DR PaxDb; I6Y8F7; -.
DR DNASU; 888235; -.
DR GeneID; 45424640; -.
DR GeneID; 888235; -.
DR KEGG; mtu:Rv0678; -.
DR KEGG; mtv:RVBD_0678; -.
DR PATRIC; fig|83332.111.peg.752; -.
DR TubercuList; Rv0678; -.
DR eggNOG; COG1510; Bacteria.
DR HOGENOM; CLU_120349_2_1_11; -.
DR OMA; TLAFFEF; -.
DR PhylomeDB; I6Y8F7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR SUPFAM; SSF46785; SSF46785; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..165
FT /note="HTH-type transcriptional regulator MmpR5"
FT /id="PRO_0000432768"
FT DOMAIN 1..151
FT /note="HTH marR-type"
FT /evidence="ECO:0000305"
FT DNA_BIND 53..76
FT /note="H-T-H motif"
FT /evidence="ECO:0000305"
FT VARIANT 63
FT /note="S -> R (in CFZ-R1; leads to increased expression of
FT mmpL5 and partial resistance to both clofazimine and
FT bedaquiline)"
FT /evidence="ECO:0000269|PubMed:24590481"
FT MUTAGEN 88
FT /note="D->A: Decreases DNA binding."
FT /evidence="ECO:0000269|PubMed:24737322"
FT MUTAGEN 90
FT /note="R->A: Decreases DNA binding."
FT /evidence="ECO:0000269|PubMed:24737322"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:4NB5"
FT HELIX 34..45
FT /evidence="ECO:0007829|PDB:4NB5"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:4NB5"
FT HELIX 53..60
FT /evidence="ECO:0007829|PDB:4NB5"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:4NB5"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4NB5"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:4NB5"
FT HELIX 99..124
FT /evidence="ECO:0007829|PDB:4NB5"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:4NB5"
FT HELIX 130..133
FT /evidence="ECO:0007829|PDB:4NB5"
FT HELIX 134..158
FT /evidence="ECO:0007829|PDB:4NB5"
SQ SEQUENCE 165 AA; 18379 MW; AD3C974B4DFCDF8A CRC64;
MSVNDGVDQM GAEPDIMEFV EQMGGYFESR SLTRLAGRLL GWLLVCDPER QSSEELATAL
AASSGGISTN ARMLIQFGFI ERLAVAGDRR TYFRLRPNAF AAGERERIRA MAELQDLADV
GLRALGDAPP QRSRRLREMR DLLAYMENVV SDALGRYSQR TGEDD
