BMRA_BACSU
ID BMRA_BACSU Reviewed; 589 AA.
AC O06967; Q795F6;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Multidrug resistance ABC transporter ATP-binding/permease protein BmrA;
DE EC=7.6.2.-;
GN Name=bmrA; Synonyms=yvcC; OrderedLocusNames=BSU34820;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RA Denizot F.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [3]
RP BIOPHYSICOCHEMICAL PROPERTIES, HOECHST 33342 AS SUBSTRATE, AND INHIBITION
RP BY VANADATE.
RX PubMed=12225846; DOI=10.1016/s0005-2736(02)00515-1;
RA Steinfels E., Orelle C., Dalmas O., Penin F., Miroux B., Di Pietro A.,
RA Jault J.-M.;
RT "Highly efficient over-production in E. coli of YvcC, a multidrug-like ATP-
RT binding cassette transporter from Bacillus subtilis.";
RL Biochim. Biophys. Acta 1565:1-5(2002).
RN [4]
RP SUBUNIT, RING FORMATION, AND STRUCTURE BY ELECTRON MICROSCOPY.
RX PubMed=11827477; DOI=10.1006/jmbi.2001.5309;
RA Chami M., Steinfels E., Orelle C., Jault J.-M., Di Pietro A., Rigaud J.-L.,
RA Marco S.;
RT "Three-dimensional structure by cryo-electron microscopy of YvcC, an
RT homodimeric ATP-binding cassette transporter from Bacillus subtilis.";
RL J. Mol. Biol. 315:1075-1085(2002).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, PROBABLE CATALYTIC RESIDUE, AND MUTAGENESIS
RP OF GLU-504.
RX PubMed=12968023; DOI=10.1074/jbc.m308268200;
RA Orelle C., Dalmas O., Gros P., Di Pietro A., Jault J.-M.;
RT "The conserved glutamate residue adjacent to the Walker-B motif is the
RT catalytic base for ATP hydrolysis in the ATP-binding cassette transporter
RT BmrA.";
RL J. Biol. Chem. 278:47002-47008(2003).
RN [6]
RP SUBSTRATES, DISRUPTION PHENOTYPE, INHIBITION BY RESERPINE, AND MUTAGENESIS
RP OF LYS-380.
RX PubMed=15182191; DOI=10.1021/bi0362018;
RA Steinfels E., Orelle C., Fantino J.-R., Dalmas O., Rigaud J.-L.,
RA Denizot F., Di Pietro A., Jault J.-M.;
RT "Characterization of YvcC (BmrA), a multidrug ABC transporter
RT constitutively expressed in Bacillus subtilis.";
RL Biochemistry 43:7491-7502(2004).
RN [7]
RP SUBUNIT.
RX PubMed=15766260; DOI=10.1021/bi0482809;
RA Dalmas O., Do Cao M.-A., Lugo M.R., Sharom F.J., Di Pietro A., Jault J.-M.;
RT "Time-resolved fluorescence resonance energy transfer shows that the
RT bacterial multidrug ABC half-transporter BmrA functions as a homodimer.";
RL Biochemistry 44:4312-4321(2005).
RN [8]
RP CROSS-LINKING STUDIES, AND CATALYTIC MODEL.
RX PubMed=16107340; DOI=10.1074/jbc.m503266200;
RA Dalmas O., Orelle C., Foucher A.-E., Geourjon C., Crouzy S., Di Pietro A.,
RA Jault J.-M.;
RT "The Q-loop disengages from the first intracellular loop during the
RT catalytic cycle of the multidrug ABC transporter BmrA.";
RL J. Biol. Chem. 280:36857-36864(2005).
RN [9]
RP SUBUNIT, AND PH DEPENDENCE.
RX PubMed=16405427; DOI=10.1042/bj20051719;
RA Ravaud S., Do Cao M.-A., Jidenko M., Ebel C., Le Maire M., Jault J.-M.,
RA Di Pietro A., Haser R., Aghajari N.;
RT "The ABC transporter BmrA from Bacillus subtilis is a functional dimer when
RT in a detergent-solubilized state.";
RL Biochem. J. 395:345-353(2006).
RN [10]
RP ATP-BINDING OF MUTANTS, AND CATALYTIC MODEL.
RX PubMed=18215075; DOI=10.1021/bi702303s;
RA Orelle C., Gubellini F., Durand A., Marco S., Levy D., Gros P.,
RA Di Pietro A., Jault J.-M.;
RT "Conformational change induced by ATP binding in the multidrug ATP-binding
RT cassette transporter BmrA.";
RL Biochemistry 47:2404-2412(2008).
CC -!- FUNCTION: An efflux transporter able to transport Hoechst 33342,
CC ethidium bromide, doxorubicin and a number of other drugs in vitro into
CC inside out vesicles. The endogenous substrate is unknown. It has been
CC suggested that NBD dimerization induced by ATP-binding causes a large
CC conformational change responsible for substrate translocation
CC (PubMed:18215075). Transmembrane domains (TMD) form a pore in the inner
CC membrane and the ATP-binding domain (NBD) is responsible for energy
CC generation (Probable). {ECO:0000269|PubMed:18215075, ECO:0000305}.
CC -!- ACTIVITY REGULATION: 50% inhibited by vanadate; it has been suggested
CC that vanadate fully inhibits the dimer but not the monomer
CC (PubMed:15766260). Activated by 15 uM reserpine then inhibited by
CC higher concentrations. {ECO:0000269|PubMed:15766260}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=6.5 umol/min/mg enzyme for ATP {ECO:0000269|PubMed:12968023};
CC Note=Reconstituted in proteoliposomes (PubMed:12968023).;
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:12225846,
CC ECO:0000269|PubMed:12968023, ECO:0000269|PubMed:16405427};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11827477,
CC ECO:0000269|PubMed:15766260, ECO:0000269|PubMed:16405427}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- DOMAIN: In BmrA the ATP-binding domain (NBD) and the transmembrane
CC domain (TMD) are fused. This is considered to be a half-size
CC transporter that undergoes homodimerization to be functional.
CC -!- DISRUPTION PHENOTYPE: Not essential. {ECO:0000269|PubMed:15182191}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. {ECO:0000305}.
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DR EMBL; Z94043; CAB08051.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB15487.1; -; Genomic_DNA.
DR PIR; D70031; D70031.
DR RefSeq; NP_391362.1; NC_000964.3.
DR RefSeq; WP_003243345.1; NZ_JNCM01000033.1.
DR PDB; 6R72; X-ray; 3.95 A; A/B/C/D=1-589.
DR PDB; 6R81; EM; 3.90 A; A/B=1-589.
DR PDB; 7OW8; EM; 3.50 A; A/B=1-586.
DR PDBsum; 6R72; -.
DR PDBsum; 6R81; -.
DR PDBsum; 7OW8; -.
DR AlphaFoldDB; O06967; -.
DR SMR; O06967; -.
DR STRING; 224308.BSU34820; -.
DR TCDB; 3.A.1.117.3; the atp-binding cassette (abc) superfamily.
DR PaxDb; O06967; -.
DR PRIDE; O06967; -.
DR EnsemblBacteria; CAB15487; CAB15487; BSU_34820.
DR GeneID; 936559; -.
DR KEGG; bsu:BSU34820; -.
DR PATRIC; fig|224308.179.peg.3770; -.
DR eggNOG; COG1132; Bacteria.
DR InParanoid; O06967; -.
DR OMA; ERQRMTI; -.
DR PhylomeDB; O06967; -.
DR BioCyc; BSUB:BSU34820-MON; -.
DR SABIO-RK; O06967; -.
DR Proteomes; UP000001570; 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:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034040; F:ATPase-coupled lipid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; ATP-binding; Cell membrane; Membrane;
KW Nucleotide-binding; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..589
FT /note="Multidrug resistance ABC transporter ATP-
FT binding/permease protein BmrA"
FT /id="PRO_0000375872"
FT TRANSMEM 29..49
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 67..87
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 29..309
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 341..576
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT ACT_SITE 504
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 374..381
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MUTAGEN 380
FT /note="K->A: Complete loss of ATPase activity."
FT /evidence="ECO:0000269|PubMed:15182191"
FT MUTAGEN 380
FT /note="K->R: Retains 2% ATPase activity; unable to
FT transport Hoechst 33342. Traps ADP in a beryllium fluoride-
FT dependent manner, confirming ATPase activity. Probably
FT unable to undergo NBD dimerization."
FT /evidence="ECO:0000269|PubMed:15182191"
FT MUTAGEN 504
FT /note="E->A,C,D,Q,S: Complete loss of ATPase activity;
FT mutant proteins trap ATP in a vanadate-independent manner
FT whereas the wild-type protein traps ADP."
FT /evidence="ECO:0000269|PubMed:12968023"
FT HELIX 12..21
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 26..49
FT /evidence="ECO:0007829|PDB:7OW8"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 53..63
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 66..107
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 112..117
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 120..125
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 141..162
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 165..209
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 213..218
FT /evidence="ECO:0007829|PDB:7OW8"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 222..247
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 250..276
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 280..292
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 294..314
FT /evidence="ECO:0007829|PDB:7OW8"
FT TURN 315..319
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 381..386
FT /evidence="ECO:0007829|PDB:7OW8"
FT TURN 387..389
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 398..404
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 410..414
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 417..420
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 428..430
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 431..436
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 445..454
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 458..461
FT /evidence="ECO:0007829|PDB:7OW8"
FT TURN 462..468
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 474..476
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 483..494
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 498..504
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 507..509
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 511..524
FT /evidence="ECO:0007829|PDB:7OW8"
FT TURN 525..527
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 528..533
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 537..539
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 544..550
FT /evidence="ECO:0007829|PDB:7OW8"
FT STRAND 553..558
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 560..566
FT /evidence="ECO:0007829|PDB:7OW8"
FT HELIX 571..585
FT /evidence="ECO:0007829|PDB:7OW8"
SQ SEQUENCE 589 AA; 64519 MW; 8A15163B5698DA08 CRC64;
MPTKKQKSKS KLKPFFALVR RTNPSYGKLA FALALSVVTT LVSLLIPLLT KQLVDGFSMS
NLSGTQIGLI ALVFFVQAGL SAYATYALNY NGQKIISGLR ELLWKKLIKL PVSYFDTNAS
GETVSRVTND TMVVKELITT HISGFITGII SVIGSLTILF IMNWKLTLLV LVVVPLAALI
LVPIGRKMFS ISRETQDETA RFTGLLNQIL PEIRLVKASN AEDVEYGRGK MGISSLFKLG
VREAKVQSLV GPLISLVLMA ALVAVIGYGG MQVSSGELTA GALVAFILYL FQIIMPMGQI
TTFFTQLQKS IGATERMIEI LAEEEEDTVT GKQIENAHLP IQLDRVSFGY KPDQLILKEV
SAVIEAGKVT AIVGPSGGGK TTLFKLLERF YSPTAGTIRL GDEPVDTYSL ESWREHIGYV
SQESPLMSGT IRENICYGLE RDVTDAEIEK AAEMAYALNF IKELPNQFDT EVGERGIMLS
GGQRQRIAIA RALLRNPSIL MLDEATSSLD SQSEKSVQQA LEVLMEGRTT IVIAHRLSTV
VDADQLLFVE KGEITGRGTH HELMASHGLY RDFAEQQLKM NADLENKAG
