{"id":"4538d27c-35d9-5bc1-8130-5cb08d0c324b","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-fbxl5-irp2","predicate":"targets_for_degradation","statement":"A SKP1-CUL1-FBXL5 ligase complex associated with IRP2 and promoted its iron-dependent ubiquitination and degradation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ae271b1b-4c84-5a35-b88d-b83495a73107","mechanism_event_label":"When iron is available, an enzyme complex can remove a regulator that otherwise favors iron acquisition.","subject":{"id":"42d152ce-1161-5c30-a6d7-ef02c2394575","slug":"scf-fbxl5","display_name":"Human SKP1-CUL1-FBXL5 ubiquitin ligase complex","entity_type_key":"protein_complex"},"object":{"id":"07c94c63-c207-5b14-912d-ab32f731d168","slug":"ireb2","display_name":"Human iron regulatory protein 2 / IREB2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ae271b1b-4c84-5a35-b88d-b83495a73107","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-fbxl5-irp2-event","event_type":"biochemical_relationship","label":"When iron is available, an enzyme complex can remove a regulator that otherwise favors iron acquisition.","description":"A SKP1-CUL1-FBXL5 ligase complex associated with IRP2 and promoted its iron-dependent ubiquitination and degradation.","status":"provisional","compartment":null,"participants":[{"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":"substrate_adaptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"42d152ce-1161-5c30-a6d7-ef02c2394575","slug":"scf-fbxl5","display_name":"Human SKP1-CUL1-FBXL5 ubiquitin ligase complex","entity_type_key":"protein_complex"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"07c94c63-c207-5b14-912d-ab32f731d168","slug":"ireb2","display_name":"Human iron regulatory protein 2 / IREB2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"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":"When iron is available, an enzyme complex can remove a regulator that otherwise favors iron acquisition.","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}],"evidence":[{"id":"7707c653-d9fc-5347-8f12-8eeab0d461da","evidence_kind":"source_excerpt","locator":"Lines 680-691","start_line":680,"end_line":691,"excerpt":"### iron-fbxl5-irp2\nA SKP1-CUL1-FBXL5 ligase complex associated with IRP2 and promoted its iron-dependent ubiquitination and degradation.\nCondition category: normal\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: When iron is available, an enzyme complex can remove a regulator that otherwise favors iron acquisition.\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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