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YebY negatively regulates activity of the copper importer YebZ (PubMed:40108346). At high copper concentrations, YebY may function as a safety valve, preventing toxic copper overload by inhibiting the import activity of YebZ and YobA (PubMed:40108346). The reduced form of YebY binds Cu(+) and Cu(2+) with low affinity (PubMed:34822841). It shows low specificity, and can also bind Co(2+), Ni(2+) and Ag(+) (PubMed:34822841). The low affinity of copper binding along with the stabilization imparted by the disulfide suggests that this metal binding is likely not physiologically relevant (PubMed:34822841). The AZY proteins link copper import to multiple antibiotic resistance (PubMed:40108346). They are necessary for the copper-dependent activation of the mar operon, thus leading to multidrug antibiotic resistance via the mar pathway (PubMed:40108346). The AZY proteins may also be involved in copper delivery to membrane proteins, but they are not involved in copper tolerance or antioxidant defense (PubMed:34822841). YebY is required for the activity of the copper-related NADH dehydrogenase II (NDH-2) (PubMed:34822841)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40108346"}],"value":"The AZY copper uptake system is composed of the copper transporter YebZ, the copper-binding protein YobA and YebY"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34822841"}],"value":"Periplasm","id":"SL-0200"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34822841"}],"value":"Part of the yobA-yebZ-yebY operon (AZY operon)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34822841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40108346"}],"value":"Deletion of the AZY operon does not affect copper tolerance or antioxidant defense (PubMed:34822841). The AZY deletion mutants have diminished copper import capacity, reduced activation of the mar operon and are significantly more susceptible to mar-related antibiotics than the wild-type cells (PubMed:40108346). Deletion of this gene affects NADH oxidation activity in membranes (PubMed:34822841)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the YebY family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":20,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":21,"modifier":"EXACT"},"end":{"value":113,"modifier":"EXACT"}},"description":"Protein YebY","featureId":"PRO_0000013861"},{"type":"Disulfide bond","location":{"start":{"value":48,"modifier":"EXACT"},"end":{"value":113,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34822841"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7N0J"}]},{"type":"Mutagenesis","location":{"start":{"value":48,"modifier":"EXACT"},"end":{"value":48,"modifier":"EXACT"}},"description":"Abrogates protein expression.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34822841"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["A","S"]}},{"type":"Mutagenesis","location":{"start":{"value":113,"modifier":"EXACT"},"end":{"value":113,"modifier":"EXACT"}},"description":"Abrogates protein expression.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34822841"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["A","S"]}},{"type":"Beta strand","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":28,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Helix","location":{"start":{"value":29,"modifier":"EXACT"},"end":{"value":32,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Turn","location":{"start":{"value":34,"modifier":"EXACT"},"end":{"value":36,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Beta strand","location":{"start":{"value":39,"modifier":"EXACT"},"end":{"value":49,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Turn","location":{"start":{"value":50,"modifier":"EXACT"},"end":{"value":52,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Beta strand","location":{"start":{"value":53,"modifier":"EXACT"},"end":{"value":57,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Turn","location":{"start":{"value":59,"modifier":"EXACT"},"end":{"value":61,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Beta strand","location":{"start":{"value":64,"modifier":"EXACT"},"end":{"value":66,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Helix","location":{"start":{"value":69,"modifier":"EXACT"},"end":{"value":76,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Helix","location":{"start":{"value":85,"modifier":"EXACT"},"end":{"value":87,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Helix","location":{"start":{"value":103,"modifier":"EXACT"},"end":{"value":109,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]},{"type":"Helix","location":{"start":{"value":110,"modifier":"EXACT"},"end":{"value":112,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"7N0J"}]}],"keywords":[{"id":"KW-0002","category":"Technical term","name":"3D-structure"},{"id":"KW-1015","category":"PTM","name":"Disulfide bond"},{"id":"KW-0574","category":"Cellular component","name":"Periplasm"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0732","category":"Domain","name":"Signal"}],"references":[{"referenceNumber":1,"citation":{"id":"9278503","citationType":"journal article","authors":["Blattner F.R.","Plunkett G. 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