{"id":"2ed7170f-9f3c-51db-9d20-824ff3c97e97","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-sod1-copper-loading","predicate":"promotes_copper_loading_of","statement":"Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"c1a594bc-d491-562b-a59e-329a23263939","mechanism_event_label":"The copper chaperone increased copper loading into zinc-containing SOD1.","subject":{"id":"51c0049d-9305-553a-ba5d-c1d3b1074801","slug":"ccs","display_name":"Human copper chaperone for SOD1 / CCS","entity_type_key":"protein"},"object":{"id":"19f2bdc0-4888-57d5-860f-119d5d478eb4","slug":"sod1","display_name":"Human copper-zinc superoxide dismutase / SOD1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c1a594bc-d491-562b-a59e-329a23263939","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-sod1-copper-loading-event","event_type":"biochemical_relationship","label":"The copper chaperone increased copper loading into zinc-containing SOD1.","description":"Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2a870bb5-05a0-5e51-a70c-a9a843a8b571","slug":"copper-ii","display_name":"Copper(II) ion","entity_type_key":"ion"},"role":"culture_exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"162020b5-1fa5-526e-8405-452891245722","slug":"copper-i","display_name":"Copper(I) ion","entity_type_key":"ion"},"role":"protein_bound_metal","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"existing_sod1_cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"51c0049d-9305-553a-ba5d-c1d3b1074801","slug":"ccs","display_name":"Human copper chaperone for SOD1 / CCS","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"19f2bdc0-4888-57d5-860f-119d5d478eb4","slug":"sod1","display_name":"Human copper-zinc superoxide dismutase / SOD1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The copper chaperone increased copper loading into zinc-containing SOD1.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human HEK293T cytoplasm","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6612ad45-b841-50c8-8149-c2ec70c539c2","evidence_kind":"source_excerpt","locator":"Lines 742-753","start_line":742,"end_line":753,"excerpt":"### zinc-enz-sod1-copper-loading\nCoexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The copper chaperone increased copper loading into zinc-containing SOD1.\norganism: Homo sapiens\ntissue_or_cell_type: Human HEK293T cytoplasm\nexperimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR\nlimitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.\nexposure: 10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h.\ncross_nutrient: true\n[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202","model_system":"Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}