{"id":"2c54914d-a06f-5664-8d64-ca202a64c057","stable_key":"availability:selenok-insufficiency-ip3r:3","predicate":"can_blunt","statement":"SELENOK-null mice show blunted immune-cell calcium flux in the source-described IP3R-dependent ER calcium-release pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Animal knockout and cell/biochemical mechanism reported by an unverified supplied draft.","direction":"negative","is_public":true,"mechanism_event_id":"133dc641-5c7a-5494-8d4f-e3c5152ef6f9","mechanism_event_label":"SELENOK-null mice show blunted immune-cell calcium flux in the source-described IP3R-dependent ER calcium-release pathway.","subject":{"id":"83ea17c8-4611-596b-9be8-1a0df1c9b42e","slug":"selenok","display_name":"SELENOK","entity_type_key":"protein"},"object":{"id":"092bae47-1801-5c38-aca4-9da2e7125458","slug":"er-calcium-release","display_name":"ER calcium release","entity_type_key":"cellular_process"},"evidence_count":2,"mechanism_event":{"id":"133dc641-5c7a-5494-8d4f-e3c5152ef6f9","stable_key":"availability:selenok-insufficiency-ip3r:3","event_type":"availability_dependent_change","label":"SELENOK-null mice show blunted immune-cell calcium flux in the source-described IP3R-dependent ER calcium-release pathway.","description":"Insufficient or absent SELENOK function; the reported phenotype comes from SELENOK-null mice. SELENOK loss-of-function animal model and supplied biochemical mechanism, including T-cell context.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"83ea17c8-4611-596b-9be8-1a0df1c9b42e","slug":"selenok","display_name":"SELENOK","entity_type_key":"protein"},"role":"condition_input","stoichiometry":null,"state_label":"Insufficient or absent SELENOK function; the reported phenotype comes from SELENOK-null mice.","sequence_order":0,"notes":""},{"entity":{"id":"092bae47-1801-5c38-aca4-9da2e7125458","slug":"er-calcium-release","display_name":"ER calcium release","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Insufficient or absent SELENOK function; the reported phenotype comes from SELENOK-null mice.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Insufficient or absent SELENOK function; the reported phenotype comes from SELENOK-null mice.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"SELENOK loss-of-function animal model and supplied biochemical mechanism, including T-cell context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Dietary selenium restriction is not proven equivalent to SELENOK knockout. No selenium concentration is mapped to this phenotype, and this scenario does not invert every downstream normal-path arrow.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"03215cd8-913c-51d5-a5ea-630c8f7f6797","evidence_kind":"source_passage","locator":"lines 27-32","start_line":27,"end_line":32,"excerpt":"4.  Palmitoylated IP3R = stable, correctly localized, functional channel\n    Non-palmitoylated IP3R = degraded / non-functional\n\n5.  TCR → LCK → ZAP70 → LAT → PLCγ1 → PIP₂ → IP₃ + DAG\n\n6.  IP₃ → IP3R → ER Ca²⁺ release → store depletion","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","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."}},{"id":"5856514b-ab23-5661-bdad-f7452e8741b4","evidence_kind":"source_passage","locator":"lines 42-42","start_line":42,"end_line":42,"excerpt":"**Kill SELENOK and you lose step 4.** The phenotype in SELENOK⁻/⁻ mice is exactly what the chain predicts: blunted Ca²⁺ flux in **T cells, B cells, neutrophils, and macrophages**; reduced TCR-driven proliferation; impaired chemotaxis; reduced IL-2.","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","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}