{"id":"f3677be8-e0c3-505e-a380-a2efb7dbf609","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-stim1-direct-orai1-gating","predicate":"activates","statement":"The cytosolic CRAC-activation domain of STIM1 binds ORAI1 directly and activates its calcium current.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"155db74e-b421-56b4-8503-7b49541cd9ee","mechanism_event_label":"STIM1 directly opens the ORAI1 calcium-entry pathway.","subject":{"id":"f143762c-e7f0-54de-8ae3-cb2dcda9040e","slug":"stim1","display_name":"STIM1","entity_type_key":"protein"},"object":{"id":"c214f817-afc5-567e-ae17-ab5558e88394","slug":"orai1","display_name":"ORAI1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"155db74e-b421-56b4-8503-7b49541cd9ee","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-stim1-direct-orai1-gating-event","event_type":"regulation","label":"STIM1 directly opens the ORAI1 calcium-entry pathway.","description":"The cytosolic CRAC-activation domain of STIM1 binds ORAI1 directly and activates its calcium current.","status":"provisional","compartment":{"slug":"er-membrane","display_name":"ER membrane"},"participants":[{"entity":{"id":"f143762c-e7f0-54de-8ae3-cb2dcda9040e","slug":"stim1","display_name":"STIM1","entity_type_key":"protein"},"role":"channel_activator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c214f817-afc5-567e-ae17-ab5558e88394","slug":"orai1","display_name":"ORAI1","entity_type_key":"protein"},"role":"regulated_channel","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7df03d06-a2b7-524a-aa99-c9cf6a3bf4c2","slug":"er-membrane","display_name":"ER membrane","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":3,"notes":"Study location; presence here is not a separate transport or causal claim."},{"entity":{"id":"f0b6bcb6-5d41-5d9d-af9f-6af1a94d5c5a","slug":"plasma-membrane","display_name":"Plasma membrane","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":4,"notes":"Study location; presence here is not a separate transport or causal claim."}]},"contexts":[{"dimension":"compartment_description","value_text":"ER-plasma-membrane junctions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HEK293/HEK293T expression, electrophysiology and purified protein-binding assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Domain-expression experiments isolate coupling; physiological amplitude depends on cellular context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"STIM1 directly opens the ORAI1 calcium-entry pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ca-park2009] STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1 (2009). https://pubmed.ncbi.nlm.nih.gov/19249086/ DOI: 10.1016/j.cell.2009.02.014","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"research_relationship_category","value_text":"regulation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293 expression system and purified proteins","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e4e4dc2c-ae08-5974-b36e-ddfe4e65dcc4","evidence_kind":"source_excerpt","locator":"Lines 531-542","start_line":531,"end_line":542,"excerpt":"### ca-stim1-direct-orai1-gating\nThe cytosolic CRAC-activation domain of STIM1 binds ORAI1 directly and activates its calcium current.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: STIM1 directly opens the ORAI1 calcium-entry pathway.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293 expression system and purified proteins\nexperimental_model: Human HEK293/HEK293T expression, electrophysiology and purified protein-binding assays\nlimitations: Domain-expression experiments isolate coupling; physiological amplitude depends on cellular context.\nresearch_relationship_category: regulation\ncompartment_description: ER-plasma-membrane junctions\n[ca-park2009] STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1 (2009). https://pubmed.ncbi.nlm.nih.gov/19249086/ DOI: 10.1016/j.cell.2009.02.014","model_system":"Human HEK293/HEK293T expression, electrophysiology and purified protein-binding assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ca-park2009] STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1 (2009). https://pubmed.ncbi.nlm.nih.gov/19249086/ DOI: 10.1016/j.cell.2009.02.014","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (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":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}