UniProtKB - P0AEY8 (MDFA_ECOLI)
Protein
Multidrug transporter MdfA
Gene
mdfA
Organism
Escherichia coli (strain K12)
Status
Functioni
Efflux pump driven by the proton motive force. Confers resistance to a broad spectrum of chemically unrelated drugs. Confers resistance to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampicin, tetracycline, puromycin, and to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Overexpression results in isopropyl-beta-D-thiogalactopyranoside (IPTG) exclusion and spectinomycin sensitivity. Transport of neutral substrates is electrogenic, whereas transport of cationic substrates is electroneutral. In addition to its role in multidrug resistance, confers extreme alkaline pH resistance, allowing the growth under conditions that are close to those used normally by alkaliphiles. This activity requires Na+ or K+.5 Publications
Miscellaneous
A negative charge at position 26 is required for efficient transport of positively charged substrates, but not for neutral compounds. This negative charge does not play an essential role in the multidrug transport mechanism.
Has a sensitive conformational switch that can be triggered either by substrate binding or by attaching unrelated agents inside the pocket. Dissimilar substrates induce similar conformational changes.
Activity regulationi
Inhibited by CCCP.1 Publication
pH dependencei
Optimum pH is 6.5.1 Publication
GO - Molecular functioni
- potassium:proton antiporter activity Source: EcoCyc
- sodium:proton antiporter activity Source: EcoCyc
- xenobiotic transmembrane transporter activity Source: EcoCyc
GO - Biological processi
- drug transmembrane transport Source: EcoCyc
- regulation of cellular pH Source: EcoCyc
- response to antibiotic Source: EcoCyc
Keywordsi
Biological process | Antibiotic resistance, Transport |
Enzyme and pathway databases
BioCyci | EcoCyc:CMR-MONOMER ECOL316407:JW0826-MONOMER MetaCyc:CMR-MONOMER |
Protein family/group databases
TCDBi | 2.A.1.2.19 the major facilitator superfamily (mfs) |
Names & Taxonomyi
Protein namesi | Recommended name: Multidrug transporter MdfAAlternative name(s): Chloramphenicol resistance pump Cmr |
Gene namesi | Name:mdfA Synonyms:cmlA, cmr Ordered Locus Names:b0842, JW0826 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 14 | CytoplasmicCuratedAdd BLAST | 14 | |
Transmembranei | 15 – 32 | HelicalCuratedAdd BLAST | 18 | |
Topological domaini | 33 – 53 | PeriplasmicCuratedAdd BLAST | 21 | |
Transmembranei | 54 – 72 | HelicalCuratedAdd BLAST | 19 | |
Topological domaini | 73 – 82 | CytoplasmicCurated | 10 | |
Transmembranei | 83 – 103 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 104 – 109 | PeriplasmicCurated | 6 | |
Transmembranei | 110 – 130 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 131 – 144 | CytoplasmicCuratedAdd BLAST | 14 | |
Transmembranei | 145 – 165 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 166 | PeriplasmicCurated | 1 | |
Transmembranei | 167 – 187 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 188 – 226 | CytoplasmicCuratedAdd BLAST | 39 | |
Transmembranei | 227 – 247 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 248 – 255 | PeriplasmicCurated | 8 | |
Transmembranei | 256 – 276 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 277 – 287 | CytoplasmicCuratedAdd BLAST | 11 | |
Transmembranei | 288 – 308 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 309 – 314 | PeriplasmicCurated | 6 | |
Transmembranei | 315 – 335 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 336 – 346 | CytoplasmicCuratedAdd BLAST | 11 | |
Transmembranei | 347 – 367 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 368 – 378 | PeriplasmicCuratedAdd BLAST | 11 | |
Transmembranei | 379 – 399 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 400 – 410 | CytoplasmicCuratedAdd BLAST | 11 |
GO - Cellular componenti
- cell Source: GOC
- integral component of plasma membrane Source: EcoCyc
- plasma membrane Source: EcoCyc
Keywords - Cellular componenti
Cell inner membrane, Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 26 | E → A: Loss of ethidium bromide efflux activity. 1 Publication | 1 | |
Mutagenesisi | 26 | E → D: No change in ethidium bromide efflux activity. 1 Publication | 1 | |
Mutagenesisi | 26 | E → H: Almost no chloramphenicol efflux activity. Loss of ethidium bromide efflux activity. 1 Publication | 1 | |
Mutagenesisi | 26 | E → I or V: Slight decrease in chloramphenicol efflux activity. Exhibits low ethidium bromide efflux activity. 1 Publication | 1 | |
Mutagenesisi | 26 | E → K: Decrease in TPP efflux activity. Exhibits low ethidium bromide efflux activity. 1 Publication | 1 | |
Mutagenesisi | 26 | E → L or N: Strong decrease in chloramphenicol efflux activity. Loss of ethidium bromide and TPP efflux activities. 1 Publication | 1 | |
Mutagenesisi | 26 | E → Q: Slight decrease in chloramphenicol efflux activity. Loss of ethidium bromide efflux activity. 1 Publication | 1 | |
Mutagenesisi | 26 | E → T: Strong decrease in chloramphenicol efflux activity. Loss of ethidium bromide efflux activity. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL4785 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000173331 | 1 – 410 | Multidrug transporter MdfAAdd BLAST | 410 |
Proteomic databases
PaxDbi | P0AEY8 |
PRIDEi | P0AEY8 |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGridi | 4262828, 108 interactors |
DIPi | DIP-48116N |
IntActi | P0AEY8, 1 interactor |
STRINGi | 511145.b0842 |
Chemistry databases
BindingDBi | P0AEY8 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P0AEY8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG4107QF7 Bacteria ENOG410XT98 LUCA |
HOGENOMi | HOG000118215 |
InParanoidi | P0AEY8 |
KOi | K08160 |
PhylomeDBi | P0AEY8 |
Family and domain databases
InterProi | View protein in InterPro IPR011701 MFS IPR020846 MFS_dom IPR036259 MFS_trans_sf IPR005829 Sugar_transporter_CS |
Pfami | View protein in Pfam PF07690 MFS_1, 1 hit |
SUPFAMi | SSF103473 SSF103473, 1 hit |
PROSITEi | View protein in PROSITE PS50850 MFS, 1 hit |
i Sequence
Sequence statusi: Complete.
P0AEY8-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MQNKLASGAR LGRQALLFPL CLVLYEFSTY IGNDMIQPGM LAVVEQYQAG
60 70 80 90 100
IDWVPTSMTA YLAGGMFLQW LLGPLSDRIG RRPVMLAGVV WFIVTCLAIL
110 120 130 140 150
LAQNIEQFTL LRFLQGISLC FIGAVGYAAI QESFEEAVCI KITALMANVA
160 170 180 190 200
LIAPLLGPLV GAAWIHVLPW EGMFVLFAAL AAISFFGLQR AMPETATRIG
210 220 230 240 250
EKLSLKELGR DYKLVLKNGR FVAGALALGF VSLPLLAWIA QSPIIIITGE
260 270 280 290 300
QLSSYEYGLL QVPIFGALIA GNLLLARLTS RRTVRSLIIM GGWPIMIGLL
310 320 330 340 350
VAAAATVISS HAYLWMTAGL SIYAFGIGLA NAGLVRLTLF ASDMSKGTVS
360 370 380 390 400
AAMGMLQMLI FTVGIEISKH AWLNGGNGLF NLFNLVNGIL WLSLMVIFLK
410
DKQMGNSHEG
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 59 | T → N in CAA69997 (PubMed:9079913).Curated | 1 | |
Sequence conflicti | 225 – 240 | ALALG…LAWIA → GAGAADSLVCRCWRGSP in AAC44147 (PubMed:8655497).CuratedAdd BLAST | 16 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U44900 Genomic DNA Translation: AAC44147.1 Y08743 Genomic DNA Translation: CAA69997.1 U00096 Genomic DNA Translation: AAC73929.1 AP009048 Genomic DNA Translation: BAA35546.1 |
PIRi | B64822 |
RefSeqi | NP_415363.1, NC_000913.3 WP_001180089.1, NZ_SSZK01000002.1 |
Genome annotation databases
EnsemblBacteriai | AAC73929; AAC73929; b0842 BAA35546; BAA35546; BAA35546 |
GeneIDi | 945448 |
KEGGi | ag:CAA69997 ecj:JW0826 eco:b0842 |
PATRICi | fig|1411691.4.peg.1436 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U44900 Genomic DNA Translation: AAC44147.1 Y08743 Genomic DNA Translation: CAA69997.1 U00096 Genomic DNA Translation: AAC73929.1 AP009048 Genomic DNA Translation: BAA35546.1 |
PIRi | B64822 |
RefSeqi | NP_415363.1, NC_000913.3 WP_001180089.1, NZ_SSZK01000002.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4ZOW | X-ray | 2.45 | A | 10-400 | [»] | |
4ZP0 | X-ray | 2.00 | A | 9-400 | [»] | |
4ZP2 | X-ray | 2.20 | A | 9-400 | [»] | |
6EUQ | X-ray | 2.20 | A | 1-410 | [»] | |
6GV1 | X-ray | 3.40 | A | 1-410 | [»] | |
SMRi | P0AEY8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGridi | 4262828, 108 interactors |
DIPi | DIP-48116N |
IntActi | P0AEY8, 1 interactor |
STRINGi | 511145.b0842 |
Chemistry databases
BindingDBi | P0AEY8 |
ChEMBLi | CHEMBL4785 |
Protein family/group databases
TCDBi | 2.A.1.2.19 the major facilitator superfamily (mfs) |
Proteomic databases
PaxDbi | P0AEY8 |
PRIDEi | P0AEY8 |
Genome annotation databases
EnsemblBacteriai | AAC73929; AAC73929; b0842 BAA35546; BAA35546; BAA35546 |
GeneIDi | 945448 |
KEGGi | ag:CAA69997 ecj:JW0826 eco:b0842 |
PATRICi | fig|1411691.4.peg.1436 |
Organism-specific databases
EchoBASEi | EB3460 |
Phylogenomic databases
eggNOGi | ENOG4107QF7 Bacteria ENOG410XT98 LUCA |
HOGENOMi | HOG000118215 |
InParanoidi | P0AEY8 |
KOi | K08160 |
PhylomeDBi | P0AEY8 |
Enzyme and pathway databases
BioCyci | EcoCyc:CMR-MONOMER ECOL316407:JW0826-MONOMER MetaCyc:CMR-MONOMER |
Miscellaneous databases
PROi | PR:P0AEY8 |
Family and domain databases
InterProi | View protein in InterPro IPR011701 MFS IPR020846 MFS_dom IPR036259 MFS_trans_sf IPR005829 Sugar_transporter_CS |
Pfami | View protein in Pfam PF07690 MFS_1, 1 hit |
SUPFAMi | SSF103473 SSF103473, 1 hit |
PROSITEi | View protein in PROSITE PS50850 MFS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MDFA_ECOLI | |
Accessioni | P0AEY8Primary (citable) accession number: P0AEY8 Secondary accession number(s): P71226, P75807, Q46966 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | December 20, 2005 | |
Last modified: | November 13, 2019 | |
This is version 113 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Escherichia coli
Escherichia coli (strain K12): entries and cross-references to EcoGene - PDB cross-references
Index of Protein Data Bank (PDB) cross-references