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2.A.1.2.19
The multidrug (chloramphenicol, tetracycline, norfloxacin, doxorubicin, trimethoprim, acriflavin, ethidium bromide, tetraphenylphosphonium, TPP, benzalkonium, ciprofloxacin, thiamphenicol, IPTG) resistance exporter, MdfA (catalyzes both electrogenic and electroneutral transport) (Adler and Bibi, 2004). Can function as a Na+ (K+)/H+ antiporter (Lewinson and Bibi 2001; Higgins, 2007). Is known to provide resistance to a wide variety of dissimilar toxic compounds, including neutral, cationic and zwitterionic substances.  Crystals that diffracted to 3.4 Å resolution and belonged to the hexagonal space group P6122 have been obtained (Nagarathinam et al. 2017). For review of MdfA see Lewinson et al., 2006. The conformational switch accompanying transport is induced by promiscuous binding of substrates and/or inhibitors to the binding pocket (Fluman et al., 2009). Normally extrudes monovalent cationic drugs in exchange for a single proton, but it transports divalent cationic drugs poorly. It can be mutated to antiport a divalent cationic drug for 2 protons (Tirosh et al., 2012).

Accession Number:P0AEY8
Protein Name:Multidrug translocase MdfA aka CMR aka B0842
Length:410
Molecular Weight:44321.00
Species:Escherichia coli [83333]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell inner membrane1 / Multi-pass membrane protein2
Substrate Chloramphenicol, tetracycline, norfloxacin, doxorubicin, Trimethoprim, acriflavin, ethidium bromide, tetraphenylphosphonium, Benzalkonium, Ciprofloxacin, Thiamphenicol, IPTG

Cross database links:

Genevestigator: P0AEY8
EchoBASE: EB3460
EcoGene: EG13696
eggNOG: COG0477
HEGENOM: HBG289858
DIP: DIP-48116N
RefSeq: AP_001473.1    NP_415363.1   
Entrez Gene ID: 945448   
Pfam: PF07690   
BioCyc: EcoCyc:CMR-MONOMER    ECOL168927:B0842-MONOMER   
KEGG: ecj:JW0826    eco:b0842   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0005215 F:transporter activity
GO:0055085 P:transmembrane transport

References (7)

[1] “Isolation of cmr, a novel Escherichia coli chloramphenicol resistance gene encoding a putative efflux pump.”  Nilsen I.W.et.al.   8655497
[2] “MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition.”  Edgar R.et.al.   9079913
[3] “A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map.”  Oshima T.et.al.   8905232
[4] “The complete genome sequence of Escherichia coli K-12.”  Blattner F.R.et.al.   9278503
[5] “Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110.”  Hayashi K.et.al.   16738553
[6] “A single membrane-embedded negative charge is critical for recognizing positively charged drugs by the Escherichia coli multidrug resistance protein MdfA.”  Edgar R.et.al.   10022825
[7] “Global topology analysis of the Escherichia coli inner membrane proteome.”  Daley D.O.et.al.   15919996
Structure:
4ZOW   4ZP0   4ZP2     

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MQNKLASGAR LGRQALLFPL CLVLYEFSTY IGNDMIQPGM LAVVEQYQAG IDWVPTSMTA 
61:	YLAGGMFLQW LLGPLSDRIG RRPVMLAGVV WFIVTCLAIL LAQNIEQFTL LRFLQGISLC 
121:	FIGAVGYAAI QESFEEAVCI KITALMANVA LIAPLLGPLV GAAWIHVLPW EGMFVLFAAL 
181:	AAISFFGLQR AMPETATRIG EKLSLKELGR DYKLVLKNGR FVAGALALGF VSLPLLAWIA 
241:	QSPIIIITGE QLSSYEYGLL QVPIFGALIA GNLLLARLTS RRTVRSLIIM GGWPIMIGLL 
301:	VAAAATVISS HAYLWMTAGL SIYAFGIGLA NAGLVRLTLF ASDMSKGTVS AAMGMLQMLI 
361:	FTVGIEISKH AWLNGGNGLF NLFNLVNGIL WLSLMVIFLK DKQMGNSHEG