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Protein

Multidrug resistance protein MexA

Gene

mexA

Organism
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The periplasmic linker component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Required for assembly of the MexA/MexB/OprM complex. Implicated in the secretion of the siderophore pyoverdine.
The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.

GO - Molecular functioni

  • drug transmembrane transporter activity Source: PseudoCAP

GO - Biological processi

  • drug transmembrane transport Source: GOC
  • response to antibiotic Source: PseudoCAP
Complete GO annotation...

Keywords - Biological processi

Antibiotic resistance, Transport

Protein family/group databases

TCDBi2.A.6.2.6. the resistance-nodulation-cell division (rnd) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Multidrug resistance protein MexA
Gene namesi
Name:mexA
Ordered Locus Names:PA0425
OrganismiPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Taxonomic identifieri208964 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPseudomonadalesPseudomonadaceaePseudomonas
Proteomesi
  • UP000002438 Componenti: Chromosome

Organism-specific databases

PseudoCAPiPA0425.

Subcellular locationi

  • Cell inner membrane 1 Publication; Lipid-anchor PROSITE-ProRule annotation1 Publication

  • Note: The membrane anchor is not necessary for antibiotic efflux as the protein is functional when targeted to the periplasm by a foreign signal peptide.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 241C → F or Y: No palmitoylation occurs. Some of the protein becomes soluble, some remains attached to the inner membrane. The protein functions normally in antibiotic efflux. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Add
BLAST
Chaini24 – 383360Multidrug resistance protein MexAPRO_0000018712Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi24 – 241N-palmitoyl cysteinePROSITE-ProRule annotation1 Publication
Lipidationi24 – 241S-diacylglycerol cysteine1 Publication

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

PaxDbiP52477.

Expressioni

Inductioni

By growth under severe iron limitation.

Interactioni

Subunit structurei

Component of the MexAB-OprM multidrug efflux complex composed of an unknown number of MexA subunits, MexB and an OprM homotrimer. The MexA subunits are thought to form a barrel between the MexB inner membrane transporter and the trimeric OprM outer membrane channel protein. The N-terminus of the MexA subunits are anchored to the inner membrane while the alpha-helices of each subunit are hypothesized to form the barrel which would allow substrates to pass directly from the cytoplasm/inner membrane to the external mileu. How the MexA subunits interact with OprM and MexB, and how the OprM channel is opened is unknown.

Protein-protein interaction databases

IntActiP52477. 1 interaction.
STRINGi208964.PA0425.

Structurei

Secondary structure

1
383
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi37 – 426Combined sources
Beta strandi51 – 577Combined sources
Beta strandi59 – 613Combined sources
Beta strandi63 – 664Combined sources
Beta strandi72 – 765Combined sources
Beta strandi81 – 855Combined sources
Beta strandi89 – 946Combined sources
Helixi97 – 12529Combined sources
Helixi131 – 15626Combined sources
Beta strandi159 – 1613Combined sources
Beta strandi163 – 1686Combined sources
Beta strandi187 – 1915Combined sources
Beta strandi194 – 1974Combined sources
Beta strandi200 – 2034Combined sources
Helixi204 – 21512Combined sources
Beta strandi217 – 2193Combined sources
Beta strandi221 – 2233Combined sources
Beta strandi226 – 2283Combined sources
Beta strandi229 – 2324Combined sources
Beta strandi238 – 2414Combined sources
Beta strandi244 – 2485Combined sources
Beta strandi254 – 2618Combined sources
Beta strandi263 – 2664Combined sources
Beta strandi268 – 2703Combined sources
Beta strandi277 – 2837Combined sources
Beta strandi286 – 2894Combined sources
Beta strandi292 – 2943Combined sources
Helixi295 – 2973Combined sources
Beta strandi299 – 3013Combined sources
Turni302 – 3043Combined sources
Beta strandi305 – 3117Combined sources
Beta strandi315 – 3228Combined sources
Beta strandi331 – 3377Combined sources
Beta strandi343 – 3475Combined sources
Turni348 – 3503Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1T5EX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L/M24-383[»]
1VF7X-ray2.40A/B/C/D/E/F/G/H/I/J/K/L/M25-383[»]
2V4DX-ray3.20A/B/C/D/E/F/G/H/I/J/K/L/M24-383[»]
4DK1X-ray3.50A/B/C/D95-158[»]
DisProtiDP00401.
ProteinModelPortaliP52477.
SMRiP52477. Positions 36-362.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52477.

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili97 – 15155Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiENOG4105C1P. Bacteria.
ENOG410XNVN. LUCA.
InParanoidiP52477.
KOiK03585.
OMAiINVRYTK.
OrthoDBiEOG6GJBSS.
PhylomeDBiP52477.

Family and domain databases

InterProiIPR032317. HlyD_D23.
IPR006143. RND_pump_MFP.
[Graphical view]
PfamiPF00529. HlyD. 1 hit.
PF16576. HlyD_D23. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01730. RND_mfp. 1 hit.
PROSITEiPS51257. PROKAR_LIPOPROTEIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P52477-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRTPAMRVL VPALLVAISA LSGCGKSEAP PPAQTPEVGI VTLEAQTVTL
60 70 80 90 100
NTELPGRTNA FRIAEVRPQV NGIILKRLFK EGSDVKAGQQ LYQIDPATYE
110 120 130 140 150
ADYQSAQANL ASTQEQAQRY KLLVADQAVS KQQYADANAA YLQSKAAVEQ
160 170 180 190 200
ARINLRYTKV LSPISGRIGR SAVTEGALVT NGQANAMATV QQLDPIYVDV
210 220 230 240 250
TQPSTALLRL RRELASGQLE RAGDNAAKVS LKLEDGSQYP LEGRLEFSEV
260 270 280 290 300
SVDEGTGSVT IRAVFPNPNN ELLPGMFVHA QLQEGVKQKA ILAPQQGVTR
310 320 330 340 350
DLKGQATALV VNAQNKVELR VIKADRVIGD KWLVTEGLNA GDKIITEGLQ
360 370 380
FVQPGVEVKT VPAKNVASAQ KADAAPAKTD SKG
Length:383
Mass (Da):40,970
Last modified:October 1, 1996 - v1
Checksum:i0D161F917B3529F2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti210 – 2101L → M in AAD45627 (PubMed:9989496).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11616 Genomic DNA. Translation: AAA74436.1.
AE004091 Genomic DNA. Translation: AAG03814.1.
AF092566 Genomic DNA. Translation: AAD45627.1.
PIRiS39629.
RefSeqiNP_249116.1. NC_002516.2.
WP_003118819.1. NZ_ASJY01000084.1.

Genome annotation databases

EnsemblBacteriaiAAG03814; AAG03814; PA0425.
GeneIDi877855.
KEGGipae:PA0425.
PATRICi19835092. VBIPseAer58763_0447.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11616 Genomic DNA. Translation: AAA74436.1.
AE004091 Genomic DNA. Translation: AAG03814.1.
AF092566 Genomic DNA. Translation: AAD45627.1.
PIRiS39629.
RefSeqiNP_249116.1. NC_002516.2.
WP_003118819.1. NZ_ASJY01000084.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1T5EX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L/M24-383[»]
1VF7X-ray2.40A/B/C/D/E/F/G/H/I/J/K/L/M25-383[»]
2V4DX-ray3.20A/B/C/D/E/F/G/H/I/J/K/L/M24-383[»]
4DK1X-ray3.50A/B/C/D95-158[»]
DisProtiDP00401.
ProteinModelPortaliP52477.
SMRiP52477. Positions 36-362.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP52477. 1 interaction.
STRINGi208964.PA0425.

Protein family/group databases

TCDBi2.A.6.2.6. the resistance-nodulation-cell division (rnd) superfamily.

Proteomic databases

PaxDbiP52477.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAG03814; AAG03814; PA0425.
GeneIDi877855.
KEGGipae:PA0425.
PATRICi19835092. VBIPseAer58763_0447.

Organism-specific databases

PseudoCAPiPA0425.

Phylogenomic databases

eggNOGiENOG4105C1P. Bacteria.
ENOG410XNVN. LUCA.
InParanoidiP52477.
KOiK03585.
OMAiINVRYTK.
OrthoDBiEOG6GJBSS.
PhylomeDBiP52477.

Miscellaneous databases

EvolutionaryTraceiP52477.

Family and domain databases

InterProiIPR032317. HlyD_D23.
IPR006143. RND_pump_MFP.
[Graphical view]
PfamiPF00529. HlyD. 1 hit.
PF16576. HlyD_D23. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01730. RND_mfp. 1 hit.
PROSITEiPS51257. PROKAR_LIPOPROTEIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequence analysis of an EnvCD homologue in Pseudomonas aeruginosa: regulation by iron and possible involvement in the secretion of the siderophore pyoverdine."
    Poole K., Heinrichs D.E., Neshat S.
    Mol. Microbiol. 10:529-544(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: PAO6609.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
  3. "Global analysis of the membrane subproteome of Pseudomonas aeruginosa using liquid chromatography-tandem mass spectrometry."
    Blonder J., Goshe M.B., Xiao W., Camp D.G. II, Wingerd M., Davis R.W., Smith R.D.
    J. Proteome Res. 3:434-444(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 63-76; 87-119; 263-287 AND 327-359, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
  4. "Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model."
    Mahajan-Miklos S., Tan M.-W., Rahme L.G., Ausubel F.M.
    Cell 96:47-56(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 182-383.
    Strain: PA14.
  5. "Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon."
    Poole K., Krebes K., McNally C., Neshat S.
    J. Bacteriol. 175:7363-7372(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ANTIBIOTIC EFFLUX PUMP.
    Strain: PAO6609.
  6. "Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa."
    Li X.-Z., Nikaido H., Poole K.
    Antimicrob. Agents Chemother. 39:1948-1953(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ANTIBIOTIC EFFLUX, ENERGETIC REQUIREMENTS.
    Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
  7. "Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance."
    Li X.-Z., Zhang L., Poole K.
    J. Bacteriol. 180:2987-2991(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN SOLVENT EFFLUX.
    Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
  8. "Function of the membrane fusion protein, MexA, of the MexA, B-OprM efflux pump in Pseudomonas aeruginosa without an anchoring membrane."
    Yoneyama H., Maseda H., Kamiguchi H., Nakae T.
    J. Biol. Chem. 275:4628-4634(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, DIACYLGLYCEROL AT CYS-24, PALMITOYLATION AT CYS-24, MUTAGENESIS OF CYS-24.
    Strain: PAO4290.
  9. "Role of the membrane fusion protein in the assembly of resistance-nodulation-cell division multidrug efflux pump in Pseudomonas aeruginosa."
    Mokhonov V.V., Mokhonova E.I., Akama H., Nakae T.
    Biochem. Biophys. Res. Commun. 322:483-489(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSEMBLY OF TRIPARTITE EFFLUX COMPLEX.
    Strain: PAO4290.
  10. "Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa."
    Akama H., Matsuura T., Kashiwagi S., Yoneyama H., Narita S., Tsukihara T., Nakagawa A., Nakae T.
    J. Biol. Chem. 279:25939-25942(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 25-383.
    Strain: PAO4290.
  11. "Structure of the periplasmic component of a bacterial drug efflux pump."
    Higgins M.K., Bokma E., Koronakis E., Hughes C., Koronakis V.
    Proc. Natl. Acad. Sci. U.S.A. 101:9994-9999(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 24-383.
    Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.

Entry informationi

Entry nameiMEXA_PSEAE
AccessioniPrimary (citable) accession number: P52477
Secondary accession number(s): Q9S506
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 11, 2015
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

In both X-ray crystal structures approximately the last 100 residues are not ordered.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.