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). Substrate identity influences both the ground-state and transition-state energies for the conformational exchange process, emphasizing the coupling between substrate binding and transport. Optimum pH is 8-8.5. Transport activity occurs from pH 7.5 to 9. 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). 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). 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). Mutants designed to insert with biased topology are functional regardless of the topology. Encoded by the cryptic lambdoid prophage DLP12. Belongs to the drug/metabolite transporter (DMT) superfamily. Small multidrug resistance (SMR) (TC 2.A.7.1) family. The membrane insertion topology of the two monomers was controversial and some studies originally suggested a parallel arrangement of the two monomers in the EmrE dimer. The antiparallel dimeric structure is now the generally accepted functional topology.