{"id":"cc5a6f64-5ef3-5575-a777-df7f4121d52a","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-fbxl5-iron-sensing","predicate":"depletion_destabilizes","statement":"Iron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"fc4ede52-4a7a-517b-85b7-de46554fe188","mechanism_event_label":"The control system responds to both iron and oxygen availability.","subject":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"object":{"id":"128f2c8e-cfae-5c09-af83-3e9090ff6a6c","slug":"fbxl5","display_name":"Human F-box and leucine-rich repeat protein 5 / FBXL5","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"fc4ede52-4a7a-517b-85b7-de46554fe188","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-fbxl5-iron-sensing-event","event_type":"biochemical_relationship","label":"The control system responds to both iron and oxygen availability.","description":"Iron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"899c7ab0-6f81-5b38-a6bd-fbb33d66ac8d","slug":"oxygen","display_name":"Molecular oxygen","entity_type_key":"small_molecule"},"role":"separate_experimental_dependency","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"128f2c8e-cfae-5c09-af83-3e9090ff6a6c","slug":"fbxl5","display_name":"Human F-box and leucine-rich repeat protein 5 / FBXL5","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iron-research/19762596.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6\", \"start_char\": 0, \"end_char\": 824, \"text_sha256\": \"9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Protein association, ubiquitination and degradation experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Iron and oxygen availability; FBXL5 stability","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cellular sensing mechanism, not a serum-iron diagnostic rule.","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":"Mammalian cellular systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The control system responds to both iron and oxygen availability.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19762596/ DOI: 10.1126/science.1176333","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cytosolic iron regulation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"bcde4d19-fe96-53e7-b13c-909063fc3e44","evidence_kind":"source_excerpt","locator":"Lines 693-704","start_line":693,"end_line":704,"excerpt":"### iron-fbxl5-iron-sensing\nIron or oxygen depletion triggered FBXL5 degradation through a process requiring its N-terminal hemerythrin-like iron-binding domain.\nCondition category: nutrient_deficiency\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The control system responds to both iron and oxygen availability.\norganism: Mammalian cellular systems\ntissue_or_cell_type: Cytosolic iron regulation\nexperimental_model: Protein association, ubiquitination and degradation experiments\nlimitations: Cellular sensing mechanism, not a serum-iron diagnostic rule.\nexposure: Iron and oxygen availability; FBXL5 stability\nevidence_span: {\"source_cache\": \"artifacts/iron-research/19762596.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6\", \"start_char\": 0, \"end_char\": 824, \"text_sha256\": \"9308ac435b303ee150d6c92a21c3d68731fed61f0894312026a8a19e57d5aac6\"}\n[iron-p19762596] Control of iron homeostasis by an iron-regulated ubiquitin ligase. 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