ACRA_ECOLI
ID ACRA_ECOLI Reviewed; 397 AA.
AC P0AE06; P31223; Q2MBW4;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Multidrug efflux pump subunit AcrA;
DE AltName: Full=AcrAB-TolC multidrug efflux pump subunit AcrA;
DE AltName: Full=Acridine resistance protein A;
DE Flags: Precursor;
GN Name=acrA; Synonyms=lir, mtcA; OrderedLocusNames=b0463, JW0452;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W4573;
RX PubMed=8407802; DOI=10.1128/jb.175.19.6299-6313.1993;
RA Ma D., Cook D.N., Alberti M., Pon N.G., Nikaido H., Hearst J.E.;
RT "Molecular cloning and characterization of acrA and acrE genes of
RT Escherichia coli.";
RL J. Bacteriol. 175:6299-6313(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Xu J., Bertrand K.P.;
RT "Nucleotide sequence of the acrAB operon from Escherichia coli.";
RL Submitted (MAY-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP CHARACTERIZATION.
RX PubMed=7651136; DOI=10.1111/j.1365-2958.1995.tb02390.x;
RA Ma D., Cook D.N., Alberti M., Pon N.G., Nikaido H., Hearst J.E.;
RT "Genes acrA and acrB encode a stress-induced efflux system of Escherichia
RT coli.";
RL Mol. Microbiol. 16:45-55(1995).
RN [7]
RP FUNCTION IN EFFLUX, SUBUNIT, PALMITOYLATION AT CYS-25, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=9878415; DOI=10.1006/jmbi.1998.2313;
RA Zgurskaya H.I., Nikaido H.;
RT "AcrA is a highly asymmetric protein capable of spanning the periplasm.";
RL J. Mol. Biol. 285:409-420(1999).
RN [8]
RP PROTEOLYTIC PROCESSING, AND INTERACTION WITH ACRB.
RX PubMed=10920254; DOI=10.1093/oxfordjournals.jbchem.a022741;
RA Kawabe T., Fujihira E., Yamaguchi A.;
RT "Molecular construction of a multidrug exporter system, AcrAB: molecular
RT interaction between AcrA and AcrB, and cleavage of the N-terminal signal
RT sequence of AcrA.";
RL J. Biochem. 128:195-200(2000).
RN [9]
RP INTERACTION WITH ACRB AND TOLC, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=K12 / MC1061 / ATCC 53338 / DSM 7140;
RX PubMed=15228545; DOI=10.1111/j.1365-2958.2004.04158.x;
RA Touze T., Eswaran J., Bokma E., Koronakis E., Hughes C., Koronakis V.;
RT "Interactions underlying assembly of the Escherichia coli AcrAB-TolC
RT multidrug efflux system.";
RL Mol. Microbiol. 53:697-706(2004).
RN [10]
RP HOMOTRIMERIZATION, AND SUBCELLULAR LOCATION.
RC STRAIN=BL21-DE3;
RX PubMed=16079137; DOI=10.1074/jbc.m506479200;
RA Stenberg F., Chovanec P., Maslen S.L., Robinson C.V., Ilag L.,
RA von Heijne G., Daley D.O.;
RT "Protein complexes of the Escherichia coli cell envelope.";
RL J. Biol. Chem. 280:34409-34419(2005).
RN [11]
RP SUBUNIT.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=23010927; DOI=10.1073/pnas.1210093109;
RA Hobbs E.C., Yin X., Paul B.J., Astarita J.L., Storz G.;
RT "Conserved small protein associates with the multidrug efflux pump AcrB and
RT differentially affects antibiotic resistance.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:16696-16701(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 45-312, AND MUTAGENESIS OF
RP 223-MET-MET-224 AND 287-LEU-LEU-288.
RC STRAIN=K12 / JM101 / ATCC 33876 / DSM 3948 / NCIMB 11926;
RX PubMed=16531241; DOI=10.1016/j.str.2005.11.015;
RA Mikolosko J., Bobyk K., Zgurskaya H.I., Ghosh P.;
RT "Conformational flexibility in the multidrug efflux system protein AcrA.";
RL Structure 14:577-587(2006).
CC -!- FUNCTION: AcrA-AcrB-AcrZ-TolC is a drug efflux protein complex with
CC broad substrate specificity that uses the proton motive force to export
CC substrates. This subunit may act as an adapter protein that links AcrB
CC and TolC stably together. It is elongated in shape, being long enough
CC to span the periplasm. {ECO:0000269|PubMed:9878415}.
CC -!- SUBUNIT: Monomeric in solution. Homotrimeric; interacts independently
CC with AcrB and TolC as well as AcrZ. Part of the AcrA-AcrB-TolC efflux
CC pump. Complex assembly is independent of an efflux substrate and
CC appears to be constitutive. {ECO:0000269|PubMed:10920254,
CC ECO:0000269|PubMed:15228545, ECO:0000269|PubMed:23010927,
CC ECO:0000269|PubMed:9878415}.
CC -!- INTERACTION:
CC P0AE06; P0AE06: acrA; NbExp=6; IntAct=EBI-875601, EBI-875601;
CC P0AE06; P02930: tolC; NbExp=2; IntAct=EBI-875601, EBI-875614;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:15228545,
CC ECO:0000269|PubMed:16079137}; Lipid-anchor {ECO:0000255|PROSITE-
CC ProRule:PRU00303, ECO:0000269|PubMed:15228545,
CC ECO:0000269|PubMed:16079137}. Note=An unlipidated version of this
CC protein (directed to the periplasm by the OmpA signal sequence)
CC functions normally.
CC -!- DISRUPTION PHENOTYPE: Cannot grow on efflux substrates novobiocin or
CC fusidic acid. {ECO:0000269|PubMed:9878415}.
CC -!- SIMILARITY: Belongs to the membrane fusion protein (MFP) (TC 8.A.1)
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U00734; AAA67134.1; -; Genomic_DNA.
DR EMBL; M94248; AAA23410.1; -; Genomic_DNA.
DR EMBL; U82664; AAB40217.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73565.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76242.1; -; Genomic_DNA.
DR PIR; A36938; A36938.
DR RefSeq; NP_414996.1; NC_000913.3.
DR RefSeq; WP_001295324.1; NZ_STEB01000007.1.
DR PDB; 2F1M; X-ray; 2.71 A; A/B/C/D=45-312.
DR PDB; 5NG5; EM; 6.50 A; A/B/D/E/G/H=25-397.
DR PDB; 5O66; EM; 5.90 A; D/E/F/G/H/I=25-397.
DR PDB; 5V5S; EM; 6.50 A; D/E/F/G/H/I=1-397.
DR PDBsum; 2F1M; -.
DR PDBsum; 5NG5; -.
DR PDBsum; 5O66; -.
DR PDBsum; 5V5S; -.
DR AlphaFoldDB; P0AE06; -.
DR SMR; P0AE06; -.
DR BioGRID; 4259860; 404.
DR BioGRID; 849501; 3.
DR ComplexPortal; CPX-4263; AcrAB-TolC multidrug efflux transport complex.
DR ComplexPortal; CPX-4264; AcrAD-TolC multidrug efflux transport complex.
DR DIP; DIP-29039N; -.
DR IntAct; P0AE06; 5.
DR STRING; 511145.b0463; -.
DR TCDB; 8.A.1.6.1; the membrane fusion protein (mfp) family.
DR jPOST; P0AE06; -.
DR PaxDb; P0AE06; -.
DR PRIDE; P0AE06; -.
DR EnsemblBacteria; AAC73565; AAC73565; b0463.
DR EnsemblBacteria; BAE76242; BAE76242; BAE76242.
DR GeneID; 66671235; -.
DR GeneID; 945112; -.
DR KEGG; ecj:JW0452; -.
DR KEGG; eco:b0463; -.
DR PATRIC; fig|1411691.4.peg.1813; -.
DR EchoBASE; EB1654; -.
DR eggNOG; COG0845; Bacteria.
DR HOGENOM; CLU_018816_2_1_6; -.
DR InParanoid; P0AE06; -.
DR OMA; INVRYTK; -.
DR PhylomeDB; P0AE06; -.
DR BioCyc; EcoCyc:EG11703-MON; -.
DR BioCyc; MetaCyc:EG11703-MON; -.
DR EvolutionaryTrace; P0AE06; -.
DR PRO; PR:P0AE06; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:1990281; C:efflux pump complex; IPI:ComplexPortal.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IBA:GO_Central.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IDA:EcoCyc.
DR GO; GO:0098567; C:periplasmic side of plasma membrane; IC:ComplexPortal.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0015721; P:bile acid and bile salt transport; IMP:EcoCyc.
DR GO; GO:0046677; P:response to antibiotic; IMP:EcoCyc.
DR GO; GO:0140330; P:xenobiotic detoxification by transmembrane export across the cell outer membrane; IDA:ComplexPortal.
DR GO; GO:0042908; P:xenobiotic transport; IMP:EcoCyc.
DR InterPro; IPR043602; CusB_dom_1.
DR InterPro; IPR032317; HlyD_D23.
DR InterPro; IPR006143; RND_pump_MFP.
DR Pfam; PF00529; CusB_dom_1; 1.
DR Pfam; PF16576; HlyD_D23; 1.
DR TIGRFAMs; TIGR01730; RND_mfp; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Cell inner membrane; Cell membrane;
KW Coiled coil; Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW Transport.
FT SIGNAL 1..24
FT CHAIN 25..397
FT /note="Multidrug efflux pump subunit AcrA"
FT /id="PRO_0000018687"
FT REGION 172..397
FT /note="Interaction with AcrB"
FT REGION 313..397
FT /note="Required for growth on efflux drugs"
FT REGION 377..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 98..172
FT LIPID 25
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:9878415"
FT LIPID 25
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000305"
FT MUTAGEN 1..25
FT /note="MNKNRGFTPLAVVLMLSGSLALTGC->MKKTAIAIAVALAGFATVAQA:
FT Fully functional (replaces endogenous signal and lipid
FT anchor with periplasmic signal for OmpA)."
FT MUTAGEN 223..224
FT /note="FL->MM: Wild-type resistance to efflux substrates.
FT Protein unstable; when associated with 287-M-M-288."
FT /evidence="ECO:0000269|PubMed:16531241"
FT MUTAGEN 287..288
FT /note="LL->MM: Wild-type resistance to efflux substrates.
FT Protein unstable; when associated with 223-M-M-224."
FT /evidence="ECO:0000269|PubMed:16531241"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:2F1M"
FT HELIX 99..130
FT /evidence="ECO:0007829|PDB:2F1M"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:2F1M"
FT HELIX 140..172
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 210..219
FT /evidence="ECO:0007829|PDB:2F1M"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:2F1M"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:2F1M"
FT STRAND 292..297
FT /evidence="ECO:0007829|PDB:2F1M"
SQ SEQUENCE 397 AA; 42197 MW; 5B81DD5BC2B0A077 CRC64;
MNKNRGFTPL AVVLMLSGSL ALTGCDDKQA QQGGQQMPAV GVVTVKTEPL QITTELPGRT
SAYRIAEVRP QVSGIILKRN FKEGSDIEAG VSLYQIDPAT YQATYDSAKG DLAKAQAAAN
IAQLTVNRYQ KLLGTQYISK QEYDQALADA QQANAAVTAA KAAVETARIN LAYTKVTSPI
SGRIGKSNVT EGALVQNGQA TALATVQQLD PIYVDVTQSS NDFLRLKQEL ANGTLKQENG
KAKVSLITSD GIKFPQDGTL EFSDVTVDQT TGSITLRAIF PNPDHTLLPG MFVRARLEEG
LNPNAILVPQ QGVTRTPRGD ATVLVVGADD KVETRPIVAS QAIGDKWLVT EGLKAGDRVV
ISGLQKVRPG VQVKAQEVTA DNNQQAASGA QPEQSKS
