{"id":"6365ffc5-9f16-5225-85ec-31b1eb64c32f","stable_key":"palmitoylated-ip3r-is-functional","predicate":"supports_state_of","statement":"Palmitoylated IP3R is described as stable, correctly localized, and functional.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"supplied_source_only","direction":"positive","is_public":true,"mechanism_event_id":"4126a151-6a78-5692-953b-197a15d19ac2","mechanism_event_label":"Palmitoylation supports stable functional IP3R","subject":{"id":"74a40a11-3b82-5343-ad34-7757a3ae349a","slug":"palmitoylated-ip3r","display_name":"Palmitoylated IP3R","entity_type_key":"protein_state"},"object":{"id":"70bb8e6d-23ec-5c55-893d-b14ecf799963","slug":"functional-ip3r","display_name":"Stable functional IP3R","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"4126a151-6a78-5692-953b-197a15d19ac2","stable_key":"palmitoylation-stabilizes-ip3r","event_type":"protein_state_transition","label":"Palmitoylation supports stable functional IP3R","description":"The palmitoylated receptor is represented as stable, localized, and functional.","status":"provisional","compartment":{"slug":"er-membrane","display_name":"ER membrane"},"participants":[{"entity":{"id":"74a40a11-3b82-5343-ad34-7757a3ae349a","slug":"palmitoylated-ip3r","display_name":"Palmitoylated IP3R","entity_type_key":"protein_state"},"role":"input_state","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70bb8e6d-23ec-5c55-893d-b14ecf799963","slug":"functional-ip3r","display_name":"Stable functional IP3R","entity_type_key":"protein_state"},"role":"output_state","stoichiometry":null,"state_label":"stable and functional","sequence_order":2,"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":"05c79de7-a4ed-5e45-b68d-985dafd03905","evidence_kind":"source_passage","locator":"lines 22-28","start_line":22,"end_line":28,"excerpt":"3.  ZDHHC6 palmitoylates:\n        • IP3R  (all three isoforms)\n        • calnexin\n        • itself (autopalmitoylation)\n\n4.  Palmitoylated IP3R = stable, correctly localized, functional channel\n    Non-palmitoylated IP3R = degraded / non-functional","model_system":"Source draft; model details require primary-source verification","directness":"reported_statement","verification_status":"source_derived_draft","notes":"ZDHHC6 substrates and palmitoylated-IP3R state statement.","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":[{"id":"e12f1876-6ef0-5e4f-9719-91888d9cbe65","title":"Catalytic and regulatory ZDHHC6 acylation are distinct","kind":"qualification","status":"qualified","why":"Transient catalytic self-acylation is not ZDHHC16/APT2-controlled regulatory S-palmitoylation.","resolution":"Retain SELENOK catalytic support and model regulatory sites/cycle independently in the additions catalog.","created_at":"2026-09-17 07:19:34","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/e12f1876-6ef0-5e4f-9719-91888d9cbe65","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1606,"end_line":1612,"papers":[{"paper_key":"fredericks-2018","title":"Selenoprotein K Increases Efficiency of DHHC6 Catalyzed Protein Palmitoylation by Stabilizing the Acyl-DHHC6 Intermediate","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5789314/","doi":"10.3390/antiox7010004","year":2018,"model":"Recombinant proteins/peptides and mouse splenocyte microsomes","summary":"Supports SELENOK stabilization of catalytic acyl intermediate, distinct from regulatory palmitoylation."},{"paper_key":"abrami-2017-zdhhc-cascade","title":"Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade","url":"https://elifesciences.org/articles/27826","doi":"10.7554/eLife.27826","year":2017,"model":"Human HeLa/HAP1 perturbations, cysteine mutants and kinetic modeling","summary":"Separates ZDHHC16-mediated regulatory palmitoylation from APT2-dependent removal and measures consequences for ZDHHC6 activity."}]},"sides":[{"conflict_id":"e12f1876-6ef0-5e4f-9719-91888d9cbe65","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":18,"end_line":25,"quote":"2.  SELENOK binds ZDHHC6 (ER palmitoyl-S-acyltransferase, DHHC motif)\n    → SELENOK is required as a COFACTOR to stabilize the\n      palmitoyl-ZDHHC6 acyl-enzyme intermediate\n\n3.  ZDHHC6 palmitoylates:\n        • IP3R  (all three isoforms)\n        • calnexin\n        • itself (autopalmitoylation)","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"e12f1876-6ef0-5e4f-9719-91888d9cbe65","ordinal":1,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1606,"end_line":1612,"quote":"## Catalytic and regulatory ZDHHC6 acylation are distinct\n\nTransient catalytic self-acylation is not ZDHHC16/APT2-controlled regulatory S-palmitoylation.\n\nRetain SELENOK catalytic support and model regulatory sites/cycle independently in the additions catalog.\nPrimary reference: [Selenoprotein K Increases Efficiency of DHHC6 Catalyzed Protein Palmitoylation by Stabilizing the Acyl-DHHC6 Intermediate](https://pmc.ncbi.nlm.nih.gov/articles/PMC5789314/)\nPrimary reference: [Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade](https://elifesciences.org/articles/27826)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":null}