{"id":"a430dcab-e31e-5003-ae05-cdd3e42bb3b4","stable_key":"availability:selenok-insufficiency-ip3r:2","predicate":"can_impair_palmitoylation_of","statement":"The supplied draft reports failed IP3R palmitoylation when SELENOK is absent.","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":"0edb3dbf-2828-5693-a95c-f636a07e9e93","mechanism_event_label":"The supplied draft reports failed IP3R palmitoylation when SELENOK is absent.","subject":{"id":"83ea17c8-4611-596b-9be8-1a0df1c9b42e","slug":"selenok","display_name":"SELENOK","entity_type_key":"protein"},"object":{"id":"95e04a84-e498-5bb4-b7bc-480016de312d","slug":"ip3r","display_name":"IP3R","entity_type_key":"protein_family"},"evidence_count":2,"mechanism_event":{"id":"0edb3dbf-2828-5693-a95c-f636a07e9e93","stable_key":"availability:selenok-insufficiency-ip3r:2","event_type":"availability_dependent_change","label":"The supplied draft reports failed IP3R palmitoylation when SELENOK is absent.","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":"95e04a84-e498-5bb4-b7bc-480016de312d","slug":"ip3r","display_name":"IP3R","entity_type_key":"protein_family"},"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":"a1ce25c5-13e4-5162-bcc2-4edfe5fad42b","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":"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":"51f983aa-e9d6-5040-8b1a-c4a1f09aeb5b","evidence_kind":"source_passage","locator":"lines 139-139","start_line":139,"end_line":139,"excerpt":"**SELENOK** — not a peroxidase. It's the essential cofactor for **ZDHHC6**, the palmitoyl transferase. No SELENOK → failed palmitoylation of IP3R, calnexin, and others → broken Ca²⁺ flux in T cells. **Selenium regulating lipid post-translational modification.**","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":"07679ebe-47ad-573a-b248-73247acdac18","stable_key":"molecular","title":"Selenium: the molecular cascade","document_type":"user_supplied_markdown","citation_label":"Selenium molecular cascade draft","file_path":"X:\\metabolic-ledger\\source_material\\selenium-molecular-cascade.md","sha256":"3e60ca4f2c1f48c9604028d1ddd570dc4daa9d2004e9da010b9a295c5af16c47","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","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}