{"id":"c1f08adf-c388-54ed-98fb-9d06e3929fdf","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-extracellular-art2","predicate":"uses_extracellular_nad_to_activate","statement":"Extracellular NAD supported ART2.2-dependent ADP-ribosylation and activation of P2X7 in mouse regulatory T cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1a8295b6-c1b2-5208-be72-70f9a24e62f7","mechanism_event_label":"Outside the cell, NAD can act as a signaling substrate rather than an energy supplement.","subject":{"id":"b8cd8c8d-7836-5636-9b3b-35e4a59084a2","slug":"mouse-art2b","display_name":"Mouse ADP-ribosyltransferase ARTC2.2 / Art2b","entity_type_key":"protein"},"object":{"id":"5debceb9-d82b-5648-b271-807ad43ff66a","slug":"mouse-p2rx7","display_name":"Mouse purinergic receptor P2X7 / P2rx7","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1a8295b6-c1b2-5208-be72-70f9a24e62f7","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-extracellular-art2-event","event_type":"observed_relationship","label":"Outside the cell, NAD can act as a signaling substrate rather than an energy supplement.","description":"Extracellular NAD supported ART2.2-dependent ADP-ribosylation and activation of P2X7 in mouse regulatory T cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b8cd8c8d-7836-5636-9b3b-35e4a59084a2","slug":"mouse-art2b","display_name":"Mouse ADP-ribosyltransferase ARTC2.2 / Art2b","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5debceb9-d82b-5648-b271-807ad43ff66a","slug":"mouse-p2rx7","display_name":"Mouse purinergic receptor P2X7 / P2rx7","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse regulatory T-cell experiments with ART2.2 blockade.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mouse pathway; not a demonstrated human IV-NAD mechanism or toxicity threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Outside the cell, NAD can act as a signaling substrate rather than an energy supplement.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20975043/ · DOI 10.1084/jem.20091154","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e80e9d51-d6b6-51f1-b7b0-728c68ea2b50","evidence_kind":"source_excerpt","locator":"Lines 268-274","start_line":268,"end_line":274,"excerpt":"## nad-plus-extracellular-art2\nOutside the cell, NAD can act as a signaling substrate rather than an energy supplement.\nExtracellular NAD supported ART2.2-dependent ADP-ribosylation and activation of P2X7 in mouse regulatory T cells.\nModel: Mouse regulatory T-cell experiments with ART2.2 blockade.\nLimitations: Mouse pathway; not a demonstrated human IV-NAD mechanism or toxicity threshold.\nEvidence access: Primary full text\nExtracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20975043/ · DOI 10.1084/jem.20091154","model_system":"Mouse regulatory T-cell experiments with ART2.2 blockade.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f59aa302-d463-5462-876f-e21e64861eac","stable_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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