The copA gene product, a putative copper-translocating P-type ATPase, has b
een shown to be involved in copper resistance in Escherichia coli. The copA
gene was disrupted by insertion of a kanamycin gene through homologous rec
ombination. The mutant strain was more sensitive to copper salts but not to
salts of other metals, suggesting a role in copper homeostasis. The copper
-sensitive phenotype could he rescued by complementation by a plasmid carry
ing copA from E. coli or copB from Enterococcus hirae. Expression of copA w
as induced by salts of copper or silver but not zinc or cobalt. Everted mem
brane vesicles from cells expressing copA exhibited ATP-coupled accumulatio
n of copper, presumably as Cu(I). The results indicate that CopA is a Cu(I)
-translocating efflux pump that is similar to the copper pumps related to M
enkes and Wilson diseases and provides a useful prokaryotic model for these
human diseases.