MMPL4_MYCTU
ID MMPL4_MYCTU Reviewed; 967 AA.
AC P9WJV3; L0T3R9; O53735;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Siderophore exporter MmpL4 {ECO:0000305};
GN Name=mmpL4; OrderedLocusNames=Rv0450c; ORFNames=MTV037.14c;
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 VIRULENCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15908378; DOI=10.1128/iai.73.6.3492-3501.2005;
RA Domenech P., Reed M.B., Barry C.E. III;
RT "Contribution of the Mycobacterium tuberculosis MmpL protein family to
RT virulence and drug resistance.";
RL Infect. Immun. 73:3492-3501(2005).
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, AND INTERACTION WITH MMPS4.
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).
CC -!- FUNCTION: Part of an export system, which is required for biosynthesis
CC and secretion of siderophores (PubMed:23431276). Essential for normal
CC replication during the active-growth phase of the murine tuberculosis
CC model (PubMed:15908378). {ECO:0000269|PubMed:15908378,
CC ECO:0000269|PubMed:23431276}.
CC -!- SUBUNIT: Interacts with MmpS4. {ECO:0000269|PubMed:23431276}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:23431276}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Transcriptionally regulated by MmpR5 (PubMed:24737322).
CC Repressed by iron and IdeR (PubMed:12065475).
CC {ECO:0000269|PubMed:12065475, ECO:0000269|PubMed:24737322}.
CC -!- DISRUPTION PHENOTYPE: Inactivation increases mouse survival.
CC {ECO:0000269|PubMed:15908378}.
CC -!- SIMILARITY: Belongs to the resistance-nodulation-cell division (RND)
CC (TC 2.A.6) family. MmpL subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP43181.1; -; Genomic_DNA.
DR PIR; C70831; C70831.
DR RefSeq; NP_214964.1; NC_000962.3.
DR RefSeq; WP_003898458.1; NZ_NVQJ01000002.1.
DR AlphaFoldDB; P9WJV3; -.
DR STRING; 83332.Rv0450c; -.
DR PaxDb; P9WJV3; -.
DR DNASU; 886323; -.
DR GeneID; 886323; -.
DR KEGG; mtu:Rv0450c; -.
DR TubercuList; Rv0450c; -.
DR eggNOG; COG1033; Bacteria.
DR eggNOG; COG2409; Bacteria.
DR OMA; MIAMSED; -.
DR PhylomeDB; P9WJV3; -.
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:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR InterPro; IPR004869; MMPL_dom.
DR InterPro; IPR004707; MmpL_fam.
DR Pfam; PF03176; MMPL; 2.
DR TIGRFAMs; TIGR00833; actII; 1.
PE 1: Evidence at protein level;
KW Cell inner membrane; Cell membrane; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Virulence.
FT CHAIN 1..967
FT /note="Siderophore exporter MmpL4"
FT /id="PRO_0000103566"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 333..353
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 769..789
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 793..813
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 821..841
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 875..895
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 913..934
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 943..967
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 967 AA; 105234 MW; 6301014031480484 CRC64;
MSTKFANDSN TNARPEKPFI ARMIHAFAVP IILGWLAVCV VVTVFVPSLE AVGQERSVSL
SPKDAPSFEA MGRIGMVFKE GDSDSFAMVI IEGNQPLGDA AHKYYDGLVA QLRADKKHVQ
SVQDLWGDPL TAAGVQSNDG KAAYVQLSLA GNQGTPLANE SVEAVRSIVE STPAPPGIKA
YVTGPSALAA DMHHSGDRSM ARITMVTVAV IFIMLLLVYR SIITVVLLLI TVGVELTAAR
GVVAVLGHSG AIGLTTFAVS LLTSLAIAAG TDYGIFIIGR YQEARQAGED KEAAYYTMYR
GTAHVILGSG LTIAGATFCL SFARMPYFQT LGIPCAVGML VAVAVALTLG PAVLHVGSRF
GLFDPKRLLK VRGWRRVGTV VVRWPLPVLV ATCAIALVGL LALPGYKTSY NDRDYLPDFI
PANQGYAAAD RHFSQARMKP EILMIESDHD MRNPADFLVL DKLAKGIFRV PGISRVQAIT
RPEGTTMDHT SIPFQISMQN AGQLQTIKYQ RDRANDMLKQ ADEMATTIAV LTRMHSLMAE
MASTTHRMVG DTEEMKEITE ELRDHVADFD DFWRPIRSYF YWEKHCYGIP ICWSFRSIFD
ALDGIDKLSE QIGVLLGDLR EMDRLMPQMV AQIPPQIEAM ENMRTMILTM HSTMTGIFDQ
MLEMSDNATA MGKAFDAAKN DDSFYLPPEV FKNKDFQRAM KSFLSSDGHA ARFIILHRGD
PQSPEGIKSI DAIRTAAEES LKGTPLEDAK IYLAGTAAVF HDISEGAQWD LLIAAISSLC
LIFIIMLIIT RAFIAAAVIV GTVALSLGAS FGLSVLLWQH ILAIHLHWLV LAMSVIVLLA
VGSDYNLLLV SRFKQEIGAG LKTGIIRSMG GTGKVVTNAG LVFAVTMASM AVSDLRVIGQ
VGTTIGLGLL FDTLIVRSFM TPSIAALLGR WFWWPLRVRS RPARTPTVPS ETQPAGRPLA
MSSDRLG