{"id":"412cba32-831e-5208-b5c3-d85bd5d268f5","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-itpr3-calcium-coactivation","predicate":"regulates","statement":"Calcium binding participates in ITPR3 gating after IP3/ATP priming, with both active and inactive calcium-bound conformations resolved.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"44726d06-082f-5483-8e43-7f3506685a3e","mechanism_event_label":"Calcium helps control ITPR3 opening; binding does not guarantee that the channel stays open.","subject":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"object":{"id":"a9ba94eb-da8a-5bdb-b087-36571977c52b","slug":"itpr3","display_name":"Inositol 1,4,5-trisphosphate receptor type 3 / ITPR3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"44726d06-082f-5483-8e43-7f3506685a3e","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-itpr3-calcium-coactivation-event","event_type":"regulation","label":"Calcium helps control ITPR3 opening; binding does not guarantee that the channel stays open.","description":"Calcium binding participates in ITPR3 gating after IP3/ATP priming, with both active and inactive calcium-bound conformations resolved.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"regulatory_ligand","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a9ba94eb-da8a-5bdb-b087-36571977c52b","slug":"itpr3","display_name":"Inositol 1,4,5-trisphosphate receptor type 3 / ITPR3","entity_type_key":"protein"},"role":"regulated_channel","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7005bbc2-d4b5-5903-b776-94dd2288d35f","slug":"ip3","display_name":"IP3","entity_type_key":"small_molecule"},"role":"coactivator","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"allosteric_modulator","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"bc9ed3a1-38d5-5bc3-b2a5-9f9f7633660b","slug":"cytosol","display_name":"Cytosol","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."},{"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":5,"notes":"Study location; presence here is not a separate transport or causal claim."}]},"contexts":[{"dimension":"compartment_description","value_text":"Cytosolic regulatory regions of ER channel","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human ITPR3; cryo-EM in ligand-bound gating states","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structural populations do not define a universal calcium threshold or prove all calcium-bound channels are active.","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":"Calcium helps control ITPR3 opening; binding does not guarantee that the channel stays open.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2","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":"Recombinant ITPR3","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"528e9026-1e7a-5096-bcfc-6b0ec45cb71f","evidence_kind":"source_excerpt","locator":"Lines 492-503","start_line":492,"end_line":503,"excerpt":"### ca-itpr3-calcium-coactivation\nCalcium binding participates in ITPR3 gating after IP3/ATP priming, with both active and inactive calcium-bound conformations resolved.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Calcium helps control ITPR3 opening; binding does not guarantee that the channel stays open.\norganism: Homo sapiens\ntissue_or_cell_type: Recombinant ITPR3\nexperimental_model: Recombinant human ITPR3; cryo-EM in ligand-bound gating states\nlimitations: Structural populations do not define a universal calcium threshold or prove all calcium-bound channels are active.\nresearch_relationship_category: regulation\ncompartment_description: Cytosolic regulatory regions of ER channel\n[ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2","model_system":"Recombinant human ITPR3; cryo-EM in ligand-bound gating states","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2","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}