VMLR_BACSU
ID VMLR_BACSU Reviewed; 547 AA.
AC P39115;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Ribosome protection protein VmlR {ECO:0000255|HAMAP-Rule:MF_00846, ECO:0000303|PubMed:30126986};
DE AltName: Full=Multidrug resistance system ATP-binding protein VmlR {ECO:0000303|PubMed:16109936};
GN Name=vmlR {ECO:0000255|HAMAP-Rule:MF_00846, ECO:0000303|PubMed:16109936};
GN Synonyms=expZ {ECO:0000303|Ref.3}; OrderedLocusNames=BSU05610;
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 Kasahara Y., Nakai S., Lee S., Sadaie Y., Ogasawara N.;
RT "A 148 kbp sequence of the region between 35 and 47 degree of the Bacillus
RT subtilis genome.";
RL Submitted (MAR-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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 123-547.
RC STRAIN=168 / GM122;
RA Deutscher J., Bergstedt U., Bourson C., Panayotova-Heiermann M.;
RL Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, INDUCTION BY ANTIBIOTICS VIRGINIAMYCIN M AND LINCOMYCIN, OPERON,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=16109936; DOI=10.1128/jb.187.17.5946-5954.2005;
RA Ohki R., Tateno K., Takizawa T., Aiso T., Murata M.;
RT "Transcriptional termination control of a novel ABC transporter gene
RT involved in antibiotic resistance in Bacillus subtilis.";
RL J. Bacteriol. 187:5946-5954(2005).
RN [5]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, FAMILY, AND MUTAGENESIS OF
RP GLU-129 AND GLU-432.
RC STRAIN=168;
RX PubMed=30597160; DOI=10.1016/j.jmb.2018.12.013;
RA Murina V., Kasari M., Takada H., Hinnu M., Saha C.K., Grimshaw J.W.,
RA Seki T., Reith M., Putrins M., Tenson T., Strahl H., Hauryliuk V.,
RA Atkinson G.C.;
RT "ABCF ATPases involved in protein synthesis, ribosome assembly and
RT antibiotic resistance: structural and functional diversification across the
RT tree of life.";
RL J. Mol. Biol. 431:3568-3590(2019).
RN [6] {ECO:0007744|PDB:6HA8}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 2-485 WITH
RP VIRGINIAMYCIN M IN COMPLEX WITH 70S RIBOSOMES, FUNCTION, REACTION
RP MECHANISM, INTERACTION WITH RIBOSOMAL PROTEINS L1; L5; L33-1; S7 AND S11,
RP SUBUNIT, DOMAIN, DISRUPTION PHENOTYPE, MUTAGENESIS OF GLU-129; PHE-237;
RP GLU-432 AND 492-ARG--ASP-547, ATP-BINDING, RRNA-BINDING, AND TRNA-BINDING.
RC STRAIN=168;
RX PubMed=30126986; DOI=10.1073/pnas.1808535115;
RA Crowe-McAuliffe C., Graf M., Huter P., Takada H., Abdelshahid M.,
RA Novacek J., Murina V., Atkinson G.C., Hauryliuk V., Wilson D.N.;
RT "Structural basis for antibiotic resistance mediated by the Bacillus
RT subtilis ABCF ATPase VmlR.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:8978-8983(2018).
CC -!- FUNCTION: Recognizes and binds in the vacant E-site of ribosomes
CC stalled by some peptidyltransferase center (PTC)-targeting antibiotics.
CC Makes contact with the PTC and both ribosomal subunits. Induces
CC conformational changes in the P-site, which allows it to dislodge the
CC antibiotic from its PTC binding site. Binds to ribosomes either
CC directly following translation initation or subsequent to E tRNA
CC release during elongation (PubMed:30126986). Involved in resistance to
CC a narrow spectrum of antibiotics (the streptogramin A antibiotic
CC virginiamycin M, the lincosamide antibiotic lincomycin and the
CC pleuromutilin antibiotic tiamulin) (PubMed:16109936, PubMed:30126986).
CC {ECO:0000269|PubMed:16109936, ECO:0000269|PubMed:30126986}.
CC -!- SUBUNIT: Binds within the E-site of the 70S ribosome, where it contacts
CC ribosomal proteins L1, L5, L33-1, S7, S11, the 16 and 23S rRNAs and the
CC acceptor arm of the P-site tRNA. {ECO:0000269|PubMed:30126986}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00846,
CC ECO:0000269|PubMed:30597160}. Note=Does not stably associate with
CC ribosomes. {ECO:0000255|HAMAP-Rule:MF_00846,
CC ECO:0000269|PubMed:30597160}.
CC -!- INDUCTION: Expressed during all growth phases; expression is higher
CC during early log phase and decreases as growth continues. Expression is
CC dramatically increased in the presence of antibiotics virginiamycin M
CC and lincomycin. A monocistronic operon. {ECO:0000269|PubMed:16109936}.
CC -!- DOMAIN: The antibiotic resistance domain (ARD) is packed between the
CC 23S rRNA and the acceptor arm of the P-site tRNA and inserts into the
CC peptidyltransferase center (PTC). The C-terminal extension (CTE)
CC contacts the small ribosomal subunit, positioned in the Shine-Dalgarno-
CC anti-Shine-Dalgarno cavity. {ECO:0000255|HAMAP-Rule:MF_00846,
CC ECO:0000269|PubMed:30126986}.
CC -!- DISRUPTION PHENOTYPE: Hypersensitivity toward the antibiotics
CC virginiamycin M and lincomycin, mildly increased sensitivity to
CC erythromycin, clindamycin and oleandomycin (PubMed:16109936).
CC Hypersensitivity toward the antibiotics virginiamycin M, lincomycin and
CC tiamulin, in this study has no effect on sensitivity to erythromycin,
CC chloramphenicol or linezolid (PubMed:30126986).
CC {ECO:0000269|PubMed:16109936, ECO:0000269|PubMed:30126986}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCF family.
CC ARE2 subfamily. {ECO:0000255|HAMAP-Rule:MF_00846,
CC ECO:0000303|PubMed:30126986, ECO:0000303|PubMed:30597160}.
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DR EMBL; AB001488; BAA19394.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB12368.1; -; Genomic_DNA.
DR EMBL; X79387; CAA55930.1; -; Genomic_DNA.
DR PIR; G69620; G69620.
DR RefSeq; NP_388442.1; NC_000964.3.
DR RefSeq; WP_003234144.1; NZ_JNCM01000031.1.
DR PDB; 6HA8; EM; 3.50 A; V=2-485.
DR PDBsum; 6HA8; -.
DR AlphaFoldDB; P39115; -.
DR SMR; P39115; -.
DR STRING; 224308.BSU05610; -.
DR TCDB; 3.A.1.121.3; the atp-binding cassette (abc) superfamily.
DR PaxDb; P39115; -.
DR PRIDE; P39115; -.
DR EnsemblBacteria; CAB12368; CAB12368; BSU_05610.
DR GeneID; 938053; -.
DR KEGG; bsu:BSU05610; -.
DR PATRIC; fig|224308.179.peg.603; -.
DR eggNOG; COG0488; Bacteria.
DR InParanoid; P39115; -.
DR OMA; FKEYHRV; -.
DR PhylomeDB; P39115; -.
DR BioCyc; BSUB:BSU05610-MON; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0019843; F:rRNA binding; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 3.
DR HAMAP; MF_00846; VmlR; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR032781; ABC_tran_Xtn.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR043684; VmlR.
DR Pfam; PF00005; ABC_tran; 3.
DR Pfam; PF12848; ABC_tran_Xtn; 1.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; ATP-binding; Coiled coil; Cytoplasm;
KW Nucleotide-binding; Reference proteome; Repeat; RNA-binding; rRNA-binding;
KW tRNA-binding.
FT CHAIN 1..547
FT /note="Ribosome protection protein VmlR"
FT /id="PRO_0000092323"
FT DOMAIN 5..200
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT DOMAIN 292..504
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT REGION 183..289
FT /note="Antibiotic resistance domain (ARD)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846,
FT ECO:0000269|PubMed:30126986"
FT REGION 483..547
FT /note="C-terminal extension (CTE)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846,
FT ECO:0000269|PubMed:30126986"
FT COILED 193..222
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT COILED 245..269
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT COILED 488..543
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT BINDING 37..44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT BINDING 324..331
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00846"
FT MUTAGEN 129
FT /note="E->Q: Probably has no ATPase activity, does not
FT confer lincomycin resistance, cells enter stationary phase
FT at lower cell density, almost all protein is bound to
FT ribosomes; when associated with Q-432 (called EQ2). Used
FT for electron microscopy."
FT /evidence="ECO:0000269|PubMed:30126986,
FT ECO:0000269|PubMed:30597160"
FT MUTAGEN 237
FT /note="F->A: No longer confers resistance to virginiamycin
FT M, still confers resistance to lincomycin and tiamycin."
FT /evidence="ECO:0000269|PubMed:30126986"
FT MUTAGEN 237
FT /note="F->V: Still confers resistance to virginiamycin M,
FT lincomycin and tiamycin."
FT /evidence="ECO:0000269|PubMed:30126986"
FT MUTAGEN 432
FT /note="E->Q: Probably has no ATPase activity, does not
FT confer lincomycin resistance, cells enter stationary phase
FT at lower cell density, almost all protein is bound to
FT ribosomes; when associated with Q-129 (called EQ2). Used
FT for electron microscopy."
FT /evidence="ECO:0000269|PubMed:30126986,
FT ECO:0000269|PubMed:30597160"
FT MUTAGEN 492..547
FT /note="Missing: No longer confers resistance to
FT virginiamycin M."
FT /evidence="ECO:0000269|PubMed:30126986"
SQ SEQUENCE 547 AA; 62738 MW; 34B5E29E0A0760D6 CRC64;
MKEIVTLTNV SYEVKDQTVF KHVNASVQQG DIIGIIGKNG AGKSTLLHLI HNDLAPAQGQ
ILRKDIKLAL VEQETAAYSF ADQTPAEKKL LEKWHVPLRD FHQLSGGEKL KARLAKGLSE
DADLLLLDEP TNHLDEKSLQ FLIQQLKHYN GTVILVSHDR YFLDEAATKI WSLEDQTLIE
FKGNYSGYMK FREKKRLTQQ REYEKQQKMV ERIEAQMNGL ASWSEKAHAQ STKKEGFKEY
HRVKAKRTDA QIKSKQKRLE KELEKAKAEP VTPEYTVRFS IDTTHKTGKR FLEVQNVTKA
FGERTLFKNA NFTIQHGEKV AIIGPNGSGK TTLLNIILGQ ETAEGSVWVS PSANIGYLTQ
EVFDLPLEQT PEELFENETF KARGHVQNLM RHLGFTAAQW TEPIKHMSMG ERVKIKLMAY
ILEEKDVLIL DEPTNHLDLP SREQLEETLS QYSGTLLAVS HDRYFLEKTT NSKLVISNNG
IEKQLNDVPS ERNEREELRL KLETERQEVL GKLSFMTPND KGYKELDQAF NELTKRIKEL
DHQDKKD
