ID   MMPS5_MYCTU             Reviewed;         142 AA.
AC   P9WJS7; L0T4E2; O53785; P65380;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 31.
DE   RecName: Full=Siderophore export accessory protein MmpS5 {ECO:0000305};
GN   Name=mmpS5; OrderedLocusNames=Rv0677c; ORFNames=MTV040.05c;
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   INDUCTION.
RC   STRAIN=H37Rv;
RX   PubMed=12065475; DOI=10.1128/iai.70.7.3371-3381.2002;
RA   Rodriguez G.M., Voskuil M.I., Gold B., Schoolnik G.K., Smith I.;
RT   "IdeR, an essential gene in Mycobacterium tuberculosis: role of IdeR in
RT   iron-dependent gene expression, iron metabolism, and oxidative stress
RT   response.";
RL   Infect. Immun. 70:3371-3381(2002).
RN   [3]
RP   FUNCTION IN AZOLE RESISTANCE.
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   [4]
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   [5]
RP   FUNCTION, INTERACTION WITH MMPL5, SUBCELLULAR LOCATION, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=H37Rv;
RX   PubMed=23431276; DOI=10.1371/journal.ppat.1003120;
RA   Wells R.M., Jones C.M., Xi Z., Speer A., Danilchanka O., Doornbos K.S.,
RA   Sun P., Wu F., Tian C., Niederweis M.;
RT   "Discovery of a siderophore export system essential for virulence of
RT   Mycobacterium tuberculosis.";
RL   PLoS Pathog. 9:E1003120-E1003120(2013).
RN   [6]
RP   INDUCTION.
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).
RN   [7]
RP   FUNCTION IN ANTIBIOTIC RESISTANCE.
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).
CC   -!- FUNCTION: Part of an export system, which is required for biosynthesis
CC       and secretion of siderophores. Essential for virulence.
CC       {ECO:0000269|PubMed:23431276}.
CC   -!- FUNCTION: Overexpression of the system confers non-target based
CC       resistance to azoles, clofazimine and bedaquiline, via an efflux
CC       mechanism. {ECO:0000269|PubMed:18851927, ECO:0000269|PubMed:25010492}.
CC   -!- SUBUNIT: Interacts with MmpL5. {ECO:0000269|PubMed:23431276}.
CC   -!- SUBCELLULAR LOCATION: Cell inner membrane
CC       {ECO:0000269|PubMed:23431276}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- INDUCTION: Repressed by MmpR5 (PubMed:24737322). Repressed by iron
CC       (PubMed:12065475). Regulation is IdeR-independent (PubMed:12065475).
CC       {ECO:0000269|PubMed:12065475, ECO:0000269|PubMed:24737322}.
CC   -!- DISRUPTION PHENOTYPE: Deletion mutant does not exhibit a low iron
CC       growth phenotype, but has attenuated virulence compared to the wild-
CC       type strain. Deletion of both mmpS4 and mmpS5 drastically decreases
CC       synthesis and secretion of siderophores, and greatly reduces virulence
CC       in mice. {ECO:0000269|PubMed:23431276}.
CC   -!- SIMILARITY: Belongs to the MmpS family. {ECO:0000305}.
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DR   EMBL; AL123456; CCP43420.1; -; Genomic_DNA.
DR   PIR; F70826; F70826.
DR   RefSeq; NP_215191.1; NC_000962.3.
DR   RefSeq; WP_003403439.1; NZ_NVQJ01000007.1.
DR   AlphaFoldDB; P9WJS7; -.
DR   SMR; P9WJS7; -.
DR   STRING; 83332.Rv0677c; -.
DR   PaxDb; P9WJS7; -.
DR   DNASU; 888233; -.
DR   GeneID; 45424639; -.
DR   GeneID; 888233; -.
DR   KEGG; mtu:Rv0677c; -.
DR   TubercuList; Rv0677c; -.
DR   eggNOG; ENOG50329W4; Bacteria.
DR   OMA; VHALTFC; -.
DR   PhylomeDB; P9WJS7; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   Gene3D; 2.60.40.2880; -; 1.
DR   InterPro; IPR008693; MmpS.
DR   InterPro; IPR038468; MmpS_C.
DR   Pfam; PF05423; Mycobact_memb; 1.
PE   1: Evidence at protein level;
KW   Cell inner membrane; Cell membrane; Membrane; Reference proteome;
KW   Transmembrane; Transmembrane helix; Virulence.
FT   CHAIN           1..142
FT                   /note="Siderophore export accessory protein MmpS5"
FT                   /id="PRO_0000216160"
FT   TRANSMEM        7..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   142 AA;  15249 MW;  055BD99A3F46E8F5 CRC64;
     MIGTLKRAWI PLLILVVVAI AGFTVQRIRT FFGSEGILVT PKVFADDPEP FDPKVVEYEV
     SGSGSYVNIN YLDLDAKPQR IDGAALPWSL TLKTTAPSAA PNILAQGDGT SITCRITVDG
     EVKDERTATG VDALTYCFVK SA