Multicopper oxidase involved in copper homeostasis and copper tolerance under aerobic conditions (PubMed:11222619, PubMed:11399769, PubMed:11527384, PubMed:15516598). Is responsible for the oxidation of Cu(+) to the less harmful Cu(2+) in the periplasm, thereby preventing Cu(+) from entering the cytoplasm (PubMed:15516598, PubMed:20088522, PubMed:25679350). Probably primarily functions as a cuprous oxidase in vivo (PubMed:20088522). In vitro, in the presence of excess copper ions, exhibits ferroxidase and phenoloxidase activities (PubMed:11466290, PubMed:11527384, PubMed:11867755, PubMed:15317788, PubMed:15516598, PubMed:17804014, PubMed:25679350). Fe(2+) is an excellent substrate in the presence of excess Cu(2+), but is inactive in the absence of Cu(2+) (PubMed:15516598, PubMed:17804014). Oxidizes the phenolate iron siderophores enterobactin, 2,3-dihydroxybenzoate (2,3-DHB) and 3-hydroxyanthranilate (3-HAA) (PubMed:11466290, PubMed:15317788). Oxidation and thus inactivation of enterobactin could protect cells from the interaction of enterobactin with copper and play a central role as an interface between copper detoxification and iron homeostasis (PubMed:11466290, PubMed:15317788). Also oxidizes a variety of phenolic model substrates, including 2,2'-azinobis(3-ethylbenzthiazolinesulfonic acid) (ABTS), p-phenylenediamine (pPD), 2,6-dimethoxyphenol (2,6-DMP) and 3,4-dihydroxybenzoic acid (3,4-DHB) (PubMed:11466290, PubMed:11527384, PubMed:17804014, PubMed:25679350). 4 Cu(+) + 4 H(+) + O2 = 4 Cu(2+) + 2 H2O Binds 4 Cu cations per monomer (PubMed:11527384, PubMed:11867755, PubMed:12794077, PubMed:17217912, PubMed:17804014, PubMed:21903583, PubMed:24598746, PubMed:27380373, PubMed:30250139). Contains a mononuclear type 1 (T1) or 'blue' copper site, and a trinuclear copper center consisting of one type 2 (T2) or 'normal' copper site, and two type 3 (T3) or 'binuclear' copper sites (PubMed:11867755). Ferroxidase and phenoloxidase activities are enhanced considerably in the presence of excess copper ions (PubMed:11466290, PubMed:11527384, PubMed:11867755, PubMed:15516598, PubMed:17804014). A labile regulatory copper ion near the T1 copper site is important for the copper associated activation of enzyme activity (PubMed:12794077). Ag(+) acts as a potent inhibitor of oxidase activity by binding at Cu(+) binding sites, blocking Cu(+) substrate binding and oxidation (PubMed:21903583). pPD oxidase activity is strongly inhibited by sodium azide, an inhibitor of the electron transfer (PubMed:11527384). kcat is 914 min(-1) with Cu(+) as substrate (at pH 5.0, in the absence of added Cu(2+)) (PubMed:15516598). kcat is 651 min(-1) with Cu(+) as substrate (at pH 5.0, in the presence of 1 mM Cu(2+)) (PubMed:15516598). kcat is 57 min(-1) with Cu(+) as substrate (at pH 7.0, in the presence of 1 mM Cu(2+)) (PubMed:15516598). kcat is 215 min(-1) with Fe(2+) as substrate (at pH 5.0, in the presence of 1 mM Cu(2+)) (PubMed:15516598). kcat is 120 sec(-1) with 2,6-DMP as substrate (PubMed:11867755). Optimum pH is 6.5 with 2,6-DMP as substrate (PubMed:11867755). The pH dependence of the reaction as monitored by oxygen consumption shows a broad activity peak between pH 5 and 6 and a second activity peak at pH 8 (PubMed:12794077). Optimum temperature is 55 degrees Celsius with 2,6-DMP as substrate. Monomer. Exported via the Tat pathway (PubMed:10766774, PubMed:17218314, PubMed:27129241). Cytoplasmic CueO does not contain copper, even under copper stress conditions, and is transported as an apo-protein to the periplasm. Periplasmic CueO is readily activated by the addition of copper ions in vitro or under copper stress conditions in vivo (PubMed:27129241). Can also be exported by the Sec system (PubMed:17218314). By CueR, in response to increasing copper concentrations. Contains a methionine-rich region, which includes a helix that covers the entrance to the type 1 (T1) copper site and blocks access to the T1 site in the absence of excess copper (PubMed:11867755, PubMed:21903583). This methionine-rich insert is involved in the binding and oxidation of Cu(+) (PubMed:21903583). It also binds additional copper ions, which are important for the copper-associated regulation of activity (PubMed:11867755, PubMed:12794077, PubMed:21903583). The methionine-rich region provides at least three additional Cu(+) binding sites: Cu5 (sCu), Cu6 and Cu7, which play related but distinct roles in CueO oxidase activities (PubMed:25679350). The internal Cu5 site functions as an electron-transfer mediator connecting surface-exposed sites Cu6 and Cu7 to site T1. Both Cu6 and Cu7 are probable substrate oxidation sites on the protein surface (PubMed:25679350). Exported by the Tat system (PubMed:10766774, PubMed:17218314, PubMed:27129241). The position of the signal peptide cleavage has been experimentally proven (PubMed:9298646). Disruption mutant is slightly more copper sensitive on complex medium than wild-type strain under aerobic conditions (PubMed:11222619, PubMed:11399769). Deletion of the gene does not affect copper sensitivity under anaerobic growth conditions (PubMed:11399769). Deletion of the gene leads to elevated biosynthesis of enterobactin under conditions of iron scarcity when copper is present (PubMed:15317788). Triggering CueO activity at need by the addition of copper salts with minor toxic effects on E.coli cells could be used as a simple tool for biosynthetic purposes (PubMed:33332702). The protein was also identified as robust host protein for use in biosensing and drug-screening applications (PubMed:30770473). Belongs to the multicopper oxidase family.