Glutathione-regulated potassium-efflux system protein KefB <p>The CPA2 family is a moderately large family (over 100 sequenced members) from bacteria, archaea and eukaryotes. Among the functionally well-characterised members of the family are (1) the KefB/KefC K+ efflux proteins of <taxon tax_id="562">Escherichia coli</taxon> which may be capable of catalysing both K+/H+ antiport and K+ uniport, depending on conditions [<cite idref="PUB00053152"/>, <cite idref="PUB00003817"/>], (2) the Na+/H+ antiporter of <taxon tax_id="1354">Enterococcus hirae</taxon> [<cite idref="PUB00053153"/>] and (3) the K+/H+ antiporter of <taxon tax_id="4932">Saccharomyces cerevisiae</taxon>. It has been proposed that under normal physiological conditions, these proteins may function by essentially the same mechanism [<cite idref="PUB00053154"/>].</p><p>KefC and KefB of E. coli are responsible for glutathione-gated K+ efflux [<cite idref="PUB00053155"/>, <cite idref="PUB00053156"/>]. Each of these proteins consists of a transmembrane hydrophobic N-terminal domain, and a less well-conserved C-terminal hydrophilic domain. Each protein interacts with a second protein encoded by genes that overlap the gene encoding the primary transporter. The KefB ancillary protein is YheR. The ancillary proteins stimulate transport activity about 10-fold [<cite idref="PUB00053157"/>]. They are important for cell survival during exposure to toxic metabolites, possibly because they can release K+, allowing H+ uptake. Activation of the KefB or KefC K+ efflux system only occurs in the presence of glutathione and a reactive electrophile such as methylglyoxal or N-ethylmaleimide. Formation of the methylglyoxal-glutathione conjugate, S-lactoylglutathione, is catalysed by glyoxalase I, and S-lactoylglutathione activates KefB and KefC [<cite idref="PUB00053158"/>]. H+ uptake (acidification of the cytoplasm) accompanying or following K+ efflux may serve as a further protective mechanism against electrophile toxicity [<cite idref="PUB00053155"/>, <cite idref="PUB00053156"/>]. Inhibition of transport by glutathione is enhanced by NADH [<cite idref="PUB00044836"/>]. </p><p>This entry represents the Glutathione-regulated potassium-efflux system protein KefB.</p>