{"id":"192359c6-0bad-53ec-ab74-059153a1dd2e","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-steap-reduction","predicate":"supports","statement":"Steap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5c0a2bb7-0c42-568d-bf5d-59fac014cadb","mechanism_event_label":"Iron released from transferrin needs another chemical reduction step before it can leave the endosome.","subject":{"id":"cfa71918-1a1b-57ba-b28b-ce885f9919ee","slug":"mouse-steap3","display_name":"Mouse metalloreductase Steap3","entity_type_key":"protein"},"object":{"id":"d4d69860-dd2e-51af-8924-53fcb9c9977a","slug":"endosomal-iron-release","display_name":"Transferrin-dependent endosomal iron delivery to cytosol","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5c0a2bb7-0c42-568d-bf5d-59fac014cadb","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-steap-reduction-event","event_type":"biochemical_relationship","label":"Iron released from transferrin needs another chemical reduction step before it can leave the endosome.","description":"Steap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"964be7ac-43bd-5f3e-8326-94f0590de67a","slug":"iron-iii","display_name":"Ferric iron","entity_type_key":"ion"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"cfa71918-1a1b-57ba-b28b-ce885f9919ee","slug":"mouse-steap3","display_name":"Mouse metalloreductase Steap3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d4d69860-dd2e-51af-8924-53fcb9c9977a","slug":"endosomal-iron-release","display_name":"Transferrin-dependent endosomal iron delivery to cytosol","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iron-research/16227996.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b\", \"start_char\": 0, \"end_char\": 1006, \"text_sha256\": \"cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Positional cloning, overexpression and deficient-mouse experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Steap3 deficiency and overexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A dominant erythroid reduction pathway, not proof of equal dependence in every tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mice and mouse Steap3 expression systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Iron released from transferrin needs another chemical reduction step before it can leave the endosome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p16227996] Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. (2005). https://pubmed.ncbi.nlm.nih.gov/16227996/ DOI: 10.1038/ng1658","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Erythroid endosomes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1fb70ebf-d513-52ec-81a5-b37ff5e306de","evidence_kind":"source_excerpt","locator":"Lines 446-457","start_line":446,"end_line":457,"excerpt":"### iron-steap-reduction\nSteap3 colocalized with transferrin-cycle endosomes and promoted iron reduction and transferrin-dependent iron uptake.\nCondition category: normal\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Iron released from transferrin needs another chemical reduction step before it can leave the endosome.\norganism: Mice and mouse Steap3 expression systems\ntissue_or_cell_type: Erythroid endosomes\nexperimental_model: Positional cloning, overexpression and deficient-mouse experiments\nlimitations: A dominant erythroid reduction pathway, not proof of equal dependence in every tissue.\nexposure: Steap3 deficiency and overexpression\nevidence_span: {\"source_cache\": \"artifacts/iron-research/16227996.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b\", \"start_char\": 0, \"end_char\": 1006, \"text_sha256\": \"cd6e35b6ea534163d0db76cbdec2fa6c3c2dd998b0a1f66d9f16479bcb87711b\"}\n[iron-p16227996] Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. 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