{"id":"a4d639b1-890f-5716-905a-353049108d70","stable_key":"stim1-activates-orai1","predicate":"activates","statement":"Oligomerized STIM1 activates ORAI1 and the CRAC channel state.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"supplied_source_only","direction":"positive","is_public":true,"mechanism_event_id":"3fe48d98-79ab-587e-8ceb-bda03cb9e7cc","mechanism_event_label":"Oligomerized STIM1 activates ORAI1","subject":{"id":"25d867e3-e95b-55be-b112-1b5e4d6d1d93","slug":"oligomerized-stim1","display_name":"Oligomerized STIM1","entity_type_key":"protein_state"},"object":{"id":"c214f817-afc5-567e-ae17-ab5558e88394","slug":"orai1","display_name":"ORAI1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"3fe48d98-79ab-587e-8ceb-bda03cb9e7cc","stable_key":"stim1-activates-orai1","event_type":"channel_activation","label":"Oligomerized STIM1 activates ORAI1","description":"Activated STIM1 engages ORAI1 to form the CRAC channel state.","status":"provisional","compartment":{"slug":"er-membrane","display_name":"ER membrane"},"participants":[{"entity":{"id":"25d867e3-e95b-55be-b112-1b5e4d6d1d93","slug":"oligomerized-stim1","display_name":"Oligomerized STIM1","entity_type_key":"protein_state"},"role":"activator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c214f817-afc5-567e-ae17-ab5558e88394","slug":"orai1","display_name":"ORAI1","entity_type_key":"protein"},"role":"channel_protein","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9abba65a-3548-5d24-96fe-238f951d853a","slug":"crac-channel","display_name":"CRAC channel","entity_type_key":"protein_complex"},"role":"active_complex","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":null,"comparator":null,"unit":null,"notes":"","entity":{"slug":"t-cell","display_name":"T cell","entity_type_key":"cell_type"}},{"dimension":"evidence_scope","value_text":"Source-derived draft; primary-source verification required","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":null,"comparator":null,"unit":null,"notes":"","entity":{"slug":"human","display_name":"Human","entity_type_key":"organism"}}],"evidence":[{"id":"682efd0c-f573-5577-8bfa-e1184c3cfbd4","evidence_kind":"source_passage","locator":"lines 30-38","start_line":30,"end_line":38,"excerpt":"5.  TCR → LCK → ZAP70 → LAT → PLCγ1 → PIP₂ → IP₃ + DAG\n\n6.  IP₃ → IP3R → ER Ca²⁺ release → store depletion\n\n7.  STIM1 oligomerizes → ORAI1 → CRAC channel → sustained Ca²⁺ entry\n\n8.  Ca²⁺/calmodulin → CALCINEURIN (PP2B) → dephosphorylates NFAT\n\n9.  NFAT → nucleus → partners with AP-1 → IL2, IFNG, CD25 transcription","model_system":"Source draft; model details require primary-source verification","directness":"reported_statement","verification_status":"source_derived_draft","notes":"TCR, IP3R, calcium, STIM1, ORAI1, calcineurin, NFAT, AP-1, and IL2 chain.","relationship":"supports","weight":1.0,"link_notes":"Passage support from supplied draft; not yet primary-source verified.","source":{"id":"221ea31f-3a75-5504-807d-e2ed46042b76","stable_key":"immune","title":"Selenium in immune cells","document_type":"user_supplied_markdown","citation_label":"Selenium immune-cell mechanism draft","file_path":"X:\\metabolic-ledger\\source_material\\selenium-immune-cells.md","sha256":"ad9305d9eea8566ba3197141c325d2d9a921fc4ee3d3466f211c792c16cded70","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","review_status":"unverified_draft","notes":"Retained as supplied source material. Primary literature verification is still required."}}],"relations":[],"conflicts":[],"corrections":[],"research":null}