MEXA_PSEAE
ID MEXA_PSEAE Reviewed; 383 AA.
AC P52477; Q9S506;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Multidrug resistance protein MexA;
DE Flags: Precursor;
GN Name=mexA; OrderedLocusNames=PA0425;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=PAO6609;
RX PubMed=7968531; DOI=10.1111/j.1365-2958.1993.tb00925.x;
RA Poole K., Heinrichs D.E., Neshat S.;
RT "Cloning and sequence analysis of an EnvCD homologue in Pseudomonas
RT aeruginosa: regulation by iron and possible involvement in the secretion of
RT the siderophore pyoverdine.";
RL Mol. Microbiol. 10:529-544(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [3]
RP PROTEIN SEQUENCE OF 63-76; 87-119; 263-287 AND 327-359, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=15253424; DOI=10.1021/pr034074w;
RA Blonder J., Goshe M.B., Xiao W., Camp D.G. II, Wingerd M., Davis R.W.,
RA Smith R.D.;
RT "Global analysis of the membrane subproteome of Pseudomonas aeruginosa
RT using liquid chromatography-tandem mass spectrometry.";
RL J. Proteome Res. 3:434-444(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 182-383.
RC STRAIN=PA14;
RX PubMed=9989496; DOI=10.1016/s0092-8674(00)80958-7;
RA Mahajan-Miklos S., Tan M.-W., Rahme L.G., Ausubel F.M.;
RT "Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas
RT aeruginosa-Caenorhabditis elegans pathogenesis model.";
RL Cell 96:47-56(1999).
RN [5]
RP FUNCTION AS AN ANTIBIOTIC EFFLUX PUMP.
RC STRAIN=PAO6609;
RX PubMed=8226684; DOI=10.1128/jb.175.22.7363-7372.1993;
RA Poole K., Krebes K., McNally C., Neshat S.;
RT "Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for
RT involvement of an efflux operon.";
RL J. Bacteriol. 175:7363-7372(1993).
RN [6]
RP FUNCTION IN ANTIBIOTIC EFFLUX, AND ENERGETIC REQUIREMENTS.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=8540696; DOI=10.1128/aac.39.9.1948;
RA Li X.-Z., Nikaido H., Poole K.;
RT "Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa.";
RL Antimicrob. Agents Chemother. 39:1948-1953(1995).
RN [7]
RP FUNCTION IN SOLVENT EFFLUX.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=9603892; DOI=10.1128/jb.180.11.2987-2991.1998;
RA Li X.-Z., Zhang L., Poole K.;
RT "Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic
RT solvent tolerance.";
RL J. Bacteriol. 180:2987-2991(1998).
RN [8]
RP SUBCELLULAR LOCATION, DIACYLGLYCEROL AT CYS-24, PALMITOYLATION AT CYS-24,
RP AND MUTAGENESIS OF CYS-24.
RC STRAIN=PAO4290;
RX PubMed=10671490; DOI=10.1074/jbc.275.7.4628;
RA Yoneyama H., Maseda H., Kamiguchi H., Nakae T.;
RT "Function of the membrane fusion protein, MexA, of the MexA, B-OprM efflux
RT pump in Pseudomonas aeruginosa without an anchoring membrane.";
RL J. Biol. Chem. 275:4628-4634(2000).
RN [9]
RP ASSEMBLY OF TRIPARTITE EFFLUX COMPLEX.
RC STRAIN=PAO4290;
RX PubMed=15325256; DOI=10.1016/j.bbrc.2004.07.140;
RA Mokhonov V.V., Mokhonova E.I., Akama H., Nakae T.;
RT "Role of the membrane fusion protein in the assembly of resistance-
RT nodulation-cell division multidrug efflux pump in Pseudomonas aeruginosa.";
RL Biochem. Biophys. Res. Commun. 322:483-489(2004).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 25-383.
RC STRAIN=PAO4290;
RX PubMed=15117957; DOI=10.1074/jbc.c400164200;
RA Akama H., Matsuura T., Kashiwagi S., Yoneyama H., Narita S., Tsukihara T.,
RA Nakagawa A., Nakae T.;
RT "Crystal structure of the membrane fusion protein, MexA, of the multidrug
RT transporter in Pseudomonas aeruginosa.";
RL J. Biol. Chem. 279:25939-25942(2004).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 24-383.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=15226509; DOI=10.1073/pnas.0400375101;
RA Higgins M.K., Bokma E., Koronakis E., Hughes C., Koronakis V.;
RT "Structure of the periplasmic component of a bacterial drug efflux pump.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:9994-9999(2004).
CC -!- FUNCTION: The periplasmic linker component of the MexAB-OprM efflux
CC system that confers multidrug resistance. Also functions as the major
CC efflux pump for n-hexane and p-xylene efflux. Over-expression of the
CC pump increases antibiotic and solvent efflux capacities. Required for
CC assembly of the MexA/MexB/OprM complex. Implicated in the secretion of
CC the siderophore pyoverdine.
CC -!- FUNCTION: The ability to export antibiotics and solvents is
CC dramatically decreased in the presence of the proton conductor carbonyl
CC cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner
CC membrane is required for efflux. It is thought that the MexB subunit is
CC a proton antiporter.
CC -!- SUBUNIT: Component of the MexAB-OprM multidrug efflux complex composed
CC of an unknown number of MexA subunits, MexB and an OprM homotrimer. The
CC MexA subunits are thought to form a barrel between the MexB inner
CC membrane transporter and the trimeric OprM outer membrane channel
CC protein. The N-terminus of the MexA subunits are anchored to the inner
CC membrane while the alpha-helices of each subunit are hypothesized to
CC form the barrel which would allow substrates to pass directly from the
CC cytoplasm/inner membrane to the external mileu. How the MexA subunits
CC interact with OprM and MexB, and how the OprM channel is opened is
CC unknown.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:10671490}; Lipid-anchor {ECO:0000255|PROSITE-
CC ProRule:PRU00303, ECO:0000269|PubMed:10671490}. Note=The membrane
CC anchor is not necessary for antibiotic efflux as the protein is
CC functional when targeted to the periplasm by a foreign signal peptide.
CC -!- INDUCTION: By growth under severe iron limitation.
CC -!- MISCELLANEOUS: In both X-ray crystal structures approximately the last
CC 100 residues are not ordered.
CC -!- SIMILARITY: Belongs to the membrane fusion protein (MFP) (TC 8.A.1)
CC family. {ECO:0000305}.
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DR EMBL; L11616; AAA74436.1; -; Genomic_DNA.
DR EMBL; AE004091; AAG03814.1; -; Genomic_DNA.
DR EMBL; AF092566; AAD45627.1; -; Genomic_DNA.
DR PIR; S39629; S39629.
DR RefSeq; NP_249116.1; NC_002516.2.
DR RefSeq; WP_003118819.1; NZ_QZGE01000016.1.
DR PDB; 1T5E; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M=24-383.
DR PDB; 1VF7; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L/M=25-383.
DR PDB; 2V4D; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M=24-383.
DR PDB; 4DK1; X-ray; 3.50 A; A/B/C/D=95-158.
DR PDB; 6IOK; EM; 3.64 A; I/J/K/L/M/N=25-383.
DR PDB; 6IOL; EM; 3.76 A; I/J/K/L/M/N=25-383.
DR PDB; 6TA5; EM; 3.20 A; D/E/F/G/H/I=24-383.
DR PDB; 6TA6; EM; 3.20 A; D/E/F/G/H/I=24-383.
DR PDBsum; 1T5E; -.
DR PDBsum; 1VF7; -.
DR PDBsum; 2V4D; -.
DR PDBsum; 4DK1; -.
DR PDBsum; 6IOK; -.
DR PDBsum; 6IOL; -.
DR PDBsum; 6TA5; -.
DR PDBsum; 6TA6; -.
DR AlphaFoldDB; P52477; -.
DR SMR; P52477; -.
DR IntAct; P52477; 1.
DR STRING; 287.DR97_3393; -.
DR ChEMBL; CHEMBL4523990; -.
DR DrugBank; DB14879; Cefiderocol.
DR TCDB; 2.A.6.2.6; the resistance-nodulation-cell division (rnd) superfamily.
DR PaxDb; P52477; -.
DR PRIDE; P52477; -.
DR EnsemblBacteria; AAG03814; AAG03814; PA0425.
DR GeneID; 877855; -.
DR KEGG; pae:PA0425; -.
DR PATRIC; fig|208964.12.peg.447; -.
DR PseudoCAP; PA0425; -.
DR HOGENOM; CLU_018816_2_1_6; -.
DR InParanoid; P52477; -.
DR OMA; INVRYTK; -.
DR PhylomeDB; P52477; -.
DR BioCyc; PAER208964:G1FZ6-429-MON; -.
DR EvolutionaryTrace; P52477; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IMP:CAFA.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0051260; P:protein homooligomerization; IMP:CAFA.
DR GO; GO:0046677; P:response to antibiotic; IDA:PseudoCAP.
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; Direct protein sequencing; Lipoprotein; Membrane; Palmitate;
KW Reference proteome; Signal; Transport.
FT SIGNAL 1..23
FT CHAIN 24..383
FT /note="Multidrug resistance protein MexA"
FT /id="PRO_0000018712"
FT COILED 97..151
FT LIPID 24
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303,
FT ECO:0000269|PubMed:10671490"
FT LIPID 24
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000305|PubMed:10671490"
FT MUTAGEN 24
FT /note="C->F,Y: No palmitoylation occurs. Some of the
FT protein becomes soluble, some remains attached to the inner
FT membrane. The protein functions normally in antibiotic
FT efflux."
FT /evidence="ECO:0000269|PubMed:10671490"
FT CONFLICT 210
FT /note="L -> M (in Ref. 4; AAD45627)"
FT /evidence="ECO:0000305"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:1VF7"
FT HELIX 97..125
FT /evidence="ECO:0007829|PDB:1VF7"
FT HELIX 131..156
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 200..203
FT /evidence="ECO:0007829|PDB:1VF7"
FT HELIX 204..215
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:1T5E"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 244..248
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 277..283
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:1VF7"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:2V4D"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:2V4D"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 305..311
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 315..322
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:6TA6"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 343..347
FT /evidence="ECO:0007829|PDB:2V4D"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:2V4D"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:6TA5"
SQ SEQUENCE 383 AA; 40970 MW; 0D161F917B3529F2 CRC64;
MQRTPAMRVL VPALLVAISA LSGCGKSEAP PPAQTPEVGI VTLEAQTVTL NTELPGRTNA
FRIAEVRPQV NGIILKRLFK EGSDVKAGQQ LYQIDPATYE ADYQSAQANL ASTQEQAQRY
KLLVADQAVS KQQYADANAA YLQSKAAVEQ ARINLRYTKV LSPISGRIGR SAVTEGALVT
NGQANAMATV QQLDPIYVDV TQPSTALLRL RRELASGQLE RAGDNAAKVS LKLEDGSQYP
LEGRLEFSEV SVDEGTGSVT IRAVFPNPNN ELLPGMFVHA QLQEGVKQKA ILAPQQGVTR
DLKGQATALV VNAQNKVELR VIKADRVIGD KWLVTEGLNA GDKIITEGLQ FVQPGVEVKT
VPAKNVASAQ KADAAPAKTD SKG
