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Protein

Multidrug resistance ABC transporter ATP-binding/permease protein BmrA

Gene

bmrA

Organism
Bacillus subtilis (strain 168)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

An efflux transporter able to transport Hoechst 33342, ethidium bromide, doxorubicin and a number of other drugs in vitro into inside out vesicles. The endogenous substrate is unknown. It has been suggested that NBD dimerization induced by ATP-binding causes a large conformational change responsible for substrate translocation (PubMed:18215075). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (Probable).Curated1 Publication

Enzyme regulationi

50% inhibited by vanadate; it has been suggested that vanadate fully inhibits the dimer but not the monomer (PubMed:15766260). Activated by 15 µM reserpine then inhibited by higher concentrations.1 Publication

Kineticsi

Reconstituted in proteoliposomes, PubMed:12968023.

    1. Vmax=6.5 µmol/min/mg enzyme for ATP2 Publications

    pH dependencei

    Optimum pH is 8.0.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei504 – 5041Proton acceptorCurated

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi374 – 3818ATPCurated

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Antibiotic resistance, Transport

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciBSUB:BSU34820-MONOMER.
    SABIO-RKO06967.

    Protein family/group databases

    TCDBi3.A.1.117.3. the atp-binding cassette (abc) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Multidrug resistance ABC transporter ATP-binding/permease protein BmrA (EC:3.6.3.-)
    Gene namesi
    Name:bmrA
    Synonyms:yvcC
    Ordered Locus Names:BSU34820
    OrganismiBacillus subtilis (strain 168)
    Taxonomic identifieri224308 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesBacillaceaeBacillus
    Proteomesi
    • UP000001570 Componenti: Chromosome

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei29 – 4921HelicalPROSITE-ProRule annotationAdd
    BLAST
    Transmembranei67 – 8721HelicalPROSITE-ProRule annotationAdd
    BLAST
    Transmembranei142 – 16221HelicalPROSITE-ProRule annotationAdd
    BLAST
    Transmembranei164 – 18421HelicalPROSITE-ProRule annotationAdd
    BLAST
    Transmembranei249 – 26921HelicalPROSITE-ProRule annotationAdd
    BLAST
    Transmembranei278 – 29821HelicalPROSITE-ProRule annotationAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Not essential.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi380 – 3801K → A: Complete loss of ATPase activity. 1 Publication
    Mutagenesisi380 – 3801K → R: Retains 2% ATPase activity; unable to transport Hoechst 33342. Traps ADP in a beryllium fluoride-dependent manner, confirming ATPase activity. Probably unable to undergo NBD dimerization. 1 Publication
    Mutagenesisi504 – 5041E → A, C, D, Q or S: Complete loss of ATPase activity; mutant proteins trap ATP in a vanadate-independent manner whereas the wild-type protein traps ADP. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 589589Multidrug resistance ABC transporter ATP-binding/permease protein BmrAPRO_0000375872Add
    BLAST

    Proteomic databases

    PaxDbiO06967.

    Interactioni

    Subunit structurei

    Homodimer.3 Publications

    Protein-protein interaction databases

    STRINGi224308.Bsubs1_010100018856.

    Structurei

    3D structure databases

    ProteinModelPortaliO06967.
    SMRiO06967. Positions 15-580.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini29 – 309281ABC transmembrane type-1PROSITE-ProRule annotationAdd
    BLAST
    Domaini341 – 576236ABC transporterPROSITE-ProRule annotationAdd
    BLAST

    Domaini

    In BmrA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. This is considered to be a half-size transporter that undergoes homodimerization to be functional.

    Sequence similaritiesi

    Belongs to the ABC transporter superfamily.Curated
    Contains 1 ABC transmembrane type-1 domain.PROSITE-ProRule annotation
    Contains 1 ABC transporter domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiENOG4105BZ1. Bacteria.
    COG1132. LUCA.
    InParanoidiO06967.
    KOiK18104.
    OMAiSSINWGM.
    OrthoDBiEOG6T7N3V.
    PhylomeDBiO06967.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR003593. AAA+_ATPase.
    IPR011527. ABC1_TM_dom.
    IPR003439. ABC_transporter-like.
    IPR017871. ABC_transporter_CS.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF00664. ABC_membrane. 1 hit.
    PF00005. ABC_tran. 1 hit.
    [Graphical view]
    SMARTiSM00382. AAA. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    SSF90123. SSF90123. 1 hit.
    PROSITEiPS50929. ABC_TM1F. 1 hit.
    PS00211. ABC_TRANSPORTER_1. 1 hit.
    PS50893. ABC_TRANSPORTER_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O06967-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPTKKQKSKS KLKPFFALVR RTNPSYGKLA FALALSVVTT LVSLLIPLLT
    60 70 80 90 100
    KQLVDGFSMS NLSGTQIGLI ALVFFVQAGL SAYATYALNY NGQKIISGLR
    110 120 130 140 150
    ELLWKKLIKL PVSYFDTNAS GETVSRVTND TMVVKELITT HISGFITGII
    160 170 180 190 200
    SVIGSLTILF IMNWKLTLLV LVVVPLAALI LVPIGRKMFS ISRETQDETA
    210 220 230 240 250
    RFTGLLNQIL PEIRLVKASN AEDVEYGRGK MGISSLFKLG VREAKVQSLV
    260 270 280 290 300
    GPLISLVLMA ALVAVIGYGG MQVSSGELTA GALVAFILYL FQIIMPMGQI
    310 320 330 340 350
    TTFFTQLQKS IGATERMIEI LAEEEEDTVT GKQIENAHLP IQLDRVSFGY
    360 370 380 390 400
    KPDQLILKEV SAVIEAGKVT AIVGPSGGGK TTLFKLLERF YSPTAGTIRL
    410 420 430 440 450
    GDEPVDTYSL ESWREHIGYV SQESPLMSGT IRENICYGLE RDVTDAEIEK
    460 470 480 490 500
    AAEMAYALNF IKELPNQFDT EVGERGIMLS GGQRQRIAIA RALLRNPSIL
    510 520 530 540 550
    MLDEATSSLD SQSEKSVQQA LEVLMEGRTT IVIAHRLSTV VDADQLLFVE
    560 570 580
    KGEITGRGTH HELMASHGLY RDFAEQQLKM NADLENKAG
    Length:589
    Mass (Da):64,519
    Last modified:July 1, 1997 - v1
    Checksum:i8A15163B5698DA08
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z94043 Genomic DNA. Translation: CAB08051.1.
    AL009126 Genomic DNA. Translation: CAB15487.1.
    PIRiD70031.
    RefSeqiNP_391362.1. NC_000964.3.
    WP_003243345.1. NZ_JNCM01000033.1.

    Genome annotation databases

    EnsemblBacteriaiCAB15487; CAB15487; BSU34820.
    GeneIDi936559.
    KEGGibsu:BSU34820.
    PATRICi18978970. VBIBacSub10457_3647.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z94043 Genomic DNA. Translation: CAB08051.1.
    AL009126 Genomic DNA. Translation: CAB15487.1.
    PIRiD70031.
    RefSeqiNP_391362.1. NC_000964.3.
    WP_003243345.1. NZ_JNCM01000033.1.

    3D structure databases

    ProteinModelPortaliO06967.
    SMRiO06967. Positions 15-580.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi224308.Bsubs1_010100018856.

    Protein family/group databases

    TCDBi3.A.1.117.3. the atp-binding cassette (abc) superfamily.

    Proteomic databases

    PaxDbiO06967.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCAB15487; CAB15487; BSU34820.
    GeneIDi936559.
    KEGGibsu:BSU34820.
    PATRICi18978970. VBIBacSub10457_3647.

    Phylogenomic databases

    eggNOGiENOG4105BZ1. Bacteria.
    COG1132. LUCA.
    InParanoidiO06967.
    KOiK18104.
    OMAiSSINWGM.
    OrthoDBiEOG6T7N3V.
    PhylomeDBiO06967.

    Enzyme and pathway databases

    BioCyciBSUB:BSU34820-MONOMER.
    SABIO-RKO06967.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR003593. AAA+_ATPase.
    IPR011527. ABC1_TM_dom.
    IPR003439. ABC_transporter-like.
    IPR017871. ABC_transporter_CS.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF00664. ABC_membrane. 1 hit.
    PF00005. ABC_tran. 1 hit.
    [Graphical view]
    SMARTiSM00382. AAA. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    SSF90123. SSF90123. 1 hit.
    PROSITEiPS50929. ABC_TM1F. 1 hit.
    PS00211. ABC_TRANSPORTER_1. 1 hit.
    PS50893. ABC_TRANSPORTER_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Denizot F.
      Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 168.
    2. "The complete genome sequence of the Gram-positive bacterium Bacillus subtilis."
      Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V., Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R., Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S., Bruschi C.V.
      , Caldwell B., Capuano V., Carter N.M., Choi S.-K., Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F., Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D., Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M., Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P., Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K., Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S., Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y., Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G., Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J., Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C., Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S., Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B., Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S., Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M., Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y., Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J., Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A., Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M., Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S., Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E., Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K., Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E., Yoshikawa H., Danchin A.
      Nature 390:249-256(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: 168.
    3. "Highly efficient over-production in E. coli of YvcC, a multidrug-like ATP-binding cassette transporter from Bacillus subtilis."
      Steinfels E., Orelle C., Dalmas O., Penin F., Miroux B., Di Pietro A., Jault J.-M.
      Biochim. Biophys. Acta 1565:1-5(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, HOECHST 33342 AS SUBSTRATE, INHIBITION BY VANADATE.
    4. "Three-dimensional structure by cryo-electron microscopy of YvcC, an homodimeric ATP-binding cassette transporter from Bacillus subtilis."
      Chami M., Steinfels E., Orelle C., Jault J.-M., Di Pietro A., Rigaud J.-L., Marco S.
      J. Mol. Biol. 315:1075-1085(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, RING FORMATION, CRYO-ELECTRON MICROSCOPY.
    5. "The conserved glutamate residue adjacent to the Walker-B motif is the catalytic base for ATP hydrolysis in the ATP-binding cassette transporter BmrA."
      Orelle C., Dalmas O., Gros P., Di Pietro A., Jault J.-M.
      J. Biol. Chem. 278:47002-47008(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, PROBABLE CATALYTIC RESIDUE, MUTAGENESIS OF GLU-504.
    6. "Characterization of YvcC (BmrA), a multidrug ABC transporter constitutively expressed in Bacillus subtilis."
      Steinfels E., Orelle C., Fantino J.-R., Dalmas O., Rigaud J.-L., Denizot F., Di Pietro A., Jault J.-M.
      Biochemistry 43:7491-7502(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBSTRATES, DISRUPTION PHENOTYPE, INHIBITION BY RESERPINE, MUTAGENESIS OF LYS-380.
    7. "Time-resolved fluorescence resonance energy transfer shows that the bacterial multidrug ABC half-transporter BmrA functions as a homodimer."
      Dalmas O., Do Cao M.-A., Lugo M.R., Sharom F.J., Di Pietro A., Jault J.-M.
      Biochemistry 44:4312-4321(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    8. "The Q-loop disengages from the first intracellular loop during the catalytic cycle of the multidrug ABC transporter BmrA."
      Dalmas O., Orelle C., Foucher A.-E., Geourjon C., Crouzy S., Di Pietro A., Jault J.-M.
      J. Biol. Chem. 280:36857-36864(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: CROSS-LINKING STUDIES, CATALYTIC MODEL.
    9. "The ABC transporter BmrA from Bacillus subtilis is a functional dimer when in a detergent-solubilized state."
      Ravaud S., Do Cao M.-A., Jidenko M., Ebel C., Le Maire M., Jault J.-M., Di Pietro A., Haser R., Aghajari N.
      Biochem. J. 395:345-353(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, PH DEPENDENCE.
    10. "Conformational change induced by ATP binding in the multidrug ATP-binding cassette transporter BmrA."
      Orelle C., Gubellini F., Durand A., Marco S., Levy D., Gros P., Di Pietro A., Jault J.-M.
      Biochemistry 47:2404-2412(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: ATP-BINDING OF MUTANTS, CATALYTIC MODEL.

    Entry informationi

    Entry nameiBMRA_BACSU
    AccessioniPrimary (citable) accession number: O06967
    Secondary accession number(s): Q795F6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 26, 2009
    Last sequence update: July 1, 1997
    Last modified: February 17, 2016
    This is version 123 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Bacillus subtilis
      Bacillus subtilis (strain 168): entries, gene names and cross-references to SubtiList
    2. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.