UniProt functional annotation for P23895



	UniProt functional annotation for P23895

UniProt code: P23895.

Organism: Escherichia coli (strain K12).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.

Function: Multidrug efflux protein that confers resistance to a wide range of toxic compounds, including ethidium, methyl viologen, acriflavine, tetraphenylphosphonium (TPP(+)), benzalkonium, propidium, dequalinium and the aminoglycoside antibiotics streptomycin and tobramycin (PubMed:7896833, PubMed:9050242, PubMed:10681497, PubMed:11574548, PubMed:15371426, PubMed:18024586, PubMed:18295794, PubMed:23042996, PubMed:24448799). Can also transport the osmoprotectants betaine and choline (PubMed:22942246). The drug efflux is coupled to an influx of protons (PubMed:7896833, PubMed:15371426, PubMed:29114048). Can couple antiport of a drug to either one or two protons, performing both electrogenic and electroneutral transport of a single substrate (PubMed:29114048). Simultaneously binds and cotransports proton and drug (PubMed:29114048, PubMed:30287687). {ECO:0000269|PubMed:10681497, ECO:0000269|PubMed:11574548, ECO:0000269|PubMed:15371426, ECO:0000269|PubMed:18024586, ECO:0000269|PubMed:18295794, ECO:0000269|PubMed:22942246, ECO:0000269|PubMed:23042996, ECO:0000269|PubMed:24448799, ECO:0000269|PubMed:29114048, ECO:0000269|PubMed:30287687, ECO:0000269|PubMed:7896833, ECO:0000269|PubMed:9050242}.

Activity regulation: Substrate identity influences both the ground- state and transition-state energies for the conformational exchange process, emphasizing the coupling between substrate binding and transport. {ECO:0000269|PubMed:24448799}.

Biophysicochemical properties: Kinetic parameters: KM=247 uM for methyl viologen {ECO:0000269|PubMed:7896833}; Vmax=1572 nmol/min/mg enzyme with methyl viologen as substrate {ECO:0000269|PubMed:7896833}; pH dependence: Optimum pH is 8-8.5. Transport activity occurs from pH 7.5 to 9. {ECO:0000269|PubMed:10681497};

Subunit: Homodimer (PubMed:14633977, PubMed:15111102, PubMed:14755055, PubMed:15882076, PubMed:17003034, PubMed:18024586, PubMed:20551331, PubMed:22178925, PubMed:23920359). Forms an antiparallel dimeric structure (PubMed:17005200, PubMed:18024586, PubMed:20551331, PubMed:22178925, PubMed:23920359). Also forms dimers of homodimers (PubMed:14755055). {ECO:0000269|PubMed:14633977, ECO:0000269|PubMed:14755055, ECO:0000269|PubMed:15111102, ECO:0000269|PubMed:15882076, ECO:0000269|PubMed:17003034, ECO:0000269|PubMed:17005200, ECO:0000269|PubMed:18024586, ECO:0000269|PubMed:20551331, ECO:0000269|PubMed:22178925, ECO:0000269|PubMed:23920359}.

Subcellular location: Cell inner membrane {ECO:0000269|PubMed:15044024, ECO:0000269|PubMed:9688273}; Multi-pass membrane protein {ECO:0000269|PubMed:15044024, ECO:0000269|PubMed:17005200, ECO:0000269|PubMed:9688273}. Note=Forms antiparallel homodimers (PubMed:17005200, PubMed:18024586, PubMed:20508091, PubMed:20551331, PubMed:22178925, PubMed:23920359). The topology could be controlled by a single positively charged residue placed in different locations throughout the protein, including the very C terminus (PubMed:20508091). {ECO:0000269|PubMed:17005200, ECO:0000269|PubMed:18024586, ECO:0000269|PubMed:20508091, ECO:0000269|PubMed:20551331, ECO:0000269|PubMed:22178925, ECO:0000269|PubMed:23920359}.

Domain: Binds different substrates in the same active site (PubMed:18295794, PubMed:22178925). Binding of the substrate induces conformational changes of EmrE (PubMed:18295794, PubMed:20551331, PubMed:22178925). The asymmetric antiparallel homodimer exchanges between inward- and outward-facing states that are identical except that they have opposite orientation in the membrane (PubMed:22178925, PubMed:24448799). The conserved C-terminal tail is strongly coupled to EmrE's drug-binding domain and participates in secondary gating of EmrE-mediated proton/drug transport, occluding the binding pocket of fully protonated EmrE in the absence of drug to prevent dissipative proton transport (PubMed:30287687). {ECO:0000269|PubMed:18295794, ECO:0000269|PubMed:20551331, ECO:0000269|PubMed:22178925, ECO:0000269|PubMed:24448799, ECO:0000269|PubMed:30287687}.

Miscellaneous: Mutants designed to insert with biased topology are functional regardless of the topology. {ECO:0000269|PubMed:20308069}.

Miscellaneous: Encoded by the cryptic lambdoid prophage DLP12.

Similarity: Belongs to the drug/metabolite transporter (DMT) superfamily. Small multidrug resistance (SMR) (TC 2.A.7.1) family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Escherichia coli (strain K12).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.



Function:		Multidrug efflux protein that confers resistance to a wide range of toxic compounds, including ethidium, methyl viologen, acriflavine, tetraphenylphosphonium (TPP(+)), benzalkonium, propidium, dequalinium and the aminoglycoside antibiotics streptomycin and tobramycin (PubMed:7896833, PubMed:9050242, PubMed:10681497, PubMed:11574548, PubMed:15371426, PubMed:18024586, PubMed:18295794, PubMed:23042996, PubMed:24448799). Can also transport the osmoprotectants betaine and choline (PubMed:22942246). The drug efflux is coupled to an influx of protons (PubMed:7896833, PubMed:15371426, PubMed:29114048). Can couple antiport of a drug to either one or two protons, performing both electrogenic and electroneutral transport of a single substrate (PubMed:29114048). Simultaneously binds and cotransports proton and drug (PubMed:29114048, PubMed:30287687). {ECO:0000269\|PubMed:10681497, ECO:0000269\|PubMed:11574548, ECO:0000269\|PubMed:15371426, ECO:0000269\|PubMed:18024586, ECO:0000269\|PubMed:18295794, ECO:0000269\|PubMed:22942246, ECO:0000269\|PubMed:23042996, ECO:0000269\|PubMed:24448799, ECO:0000269\|PubMed:29114048, ECO:0000269\|PubMed:30287687, ECO:0000269\|PubMed:7896833, ECO:0000269\|PubMed:9050242}.


Activity regulation:		Substrate identity influences both the ground- state and transition-state energies for the conformational exchange process, emphasizing the coupling between substrate binding and transport. {ECO:0000269\|PubMed:24448799}.
Biophysicochemical properties:		Kinetic parameters: KM=247 uM for methyl viologen {ECO:0000269\|PubMed:7896833}; Vmax=1572 nmol/min/mg enzyme with methyl viologen as substrate {ECO:0000269\|PubMed:7896833}; pH dependence: Optimum pH is 8-8.5. Transport activity occurs from pH 7.5 to 9. {ECO:0000269\|PubMed:10681497};
Subunit:		Homodimer (PubMed:14633977, PubMed:15111102, PubMed:14755055, PubMed:15882076, PubMed:17003034, PubMed:18024586, PubMed:20551331, PubMed:22178925, PubMed:23920359). Forms an antiparallel dimeric structure (PubMed:17005200, PubMed:18024586, PubMed:20551331, PubMed:22178925, PubMed:23920359). Also forms dimers of homodimers (PubMed:14755055). {ECO:0000269\|PubMed:14633977, ECO:0000269\|PubMed:14755055, ECO:0000269\|PubMed:15111102, ECO:0000269\|PubMed:15882076, ECO:0000269\|PubMed:17003034, ECO:0000269\|PubMed:17005200, ECO:0000269\|PubMed:18024586, ECO:0000269\|PubMed:20551331, ECO:0000269\|PubMed:22178925, ECO:0000269\|PubMed:23920359}.
Subcellular location:		Cell inner membrane {ECO:0000269\|PubMed:15044024, ECO:0000269\|PubMed:9688273}; Multi-pass membrane protein {ECO:0000269\|PubMed:15044024, ECO:0000269\|PubMed:17005200, ECO:0000269\|PubMed:9688273}. Note=Forms antiparallel homodimers (PubMed:17005200, PubMed:18024586, PubMed:20508091, PubMed:20551331, PubMed:22178925, PubMed:23920359). The topology could be controlled by a single positively charged residue placed in different locations throughout the protein, including the very C terminus (PubMed:20508091). {ECO:0000269\|PubMed:17005200, ECO:0000269\|PubMed:18024586, ECO:0000269\|PubMed:20508091, ECO:0000269\|PubMed:20551331, ECO:0000269\|PubMed:22178925, ECO:0000269\|PubMed:23920359}.
Domain:		Binds different substrates in the same active site (PubMed:18295794, PubMed:22178925). Binding of the substrate induces conformational changes of EmrE (PubMed:18295794, PubMed:20551331, PubMed:22178925). The asymmetric antiparallel homodimer exchanges between inward- and outward-facing states that are identical except that they have opposite orientation in the membrane (PubMed:22178925, PubMed:24448799). The conserved C-terminal tail is strongly coupled to EmrE's drug-binding domain and participates in secondary gating of EmrE-mediated proton/drug transport, occluding the binding pocket of fully protonated EmrE in the absence of drug to prevent dissipative proton transport (PubMed:30287687). {ECO:0000269\|PubMed:18295794, ECO:0000269\|PubMed:20551331, ECO:0000269\|PubMed:22178925, ECO:0000269\|PubMed:24448799, ECO:0000269\|PubMed:30287687}.
Miscellaneous:		Mutants designed to insert with biased topology are functional regardless of the topology. {ECO:0000269\|PubMed:20308069}.
Miscellaneous:		Encoded by the cryptic lambdoid prophage DLP12.
Similarity:		Belongs to the drug/metabolite transporter (DMT) superfamily. Small multidrug resistance (SMR) (TC 2.A.7.1) family. {ECO:0000305}.