{"id":"9fcc4e2f-19e3-5e79-897f-51cb207f99fe","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-mouse-nrk2-nr","predicate":"supports-production-of","statement":"Transient overexpression of active mouse NRK2 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"2bf7dc1f-a4a8-5f22-9c4c-14bada788e34","mechanism_event_label":"NR utilization depended on active riboside kinase in this cell model.","subject":{"id":"59f94a5e-64d2-5b46-9f3b-cb63fa7d577c","slug":"mouse-nmrk2","display_name":"Mouse nicotinamide riboside kinase 2 / Nmrk2","entity_type_key":"protein"},"object":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"2bf7dc1f-a4a8-5f22-9c4c-14bada788e34","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-mouse-nrk2-nr-event","event_type":"biochemical_relationship","label":"NR utilization depended on active riboside kinase in this cell model.","description":"Transient overexpression of active mouse NRK2 made NIH/3T3 fibroblasts responsive to nicotinamide riboside with increased cellular NAD+; the tested catalytically inactive kinase failed to support the response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"59f94a5e-64d2-5b46-9f3b-cb63fa7d577c","slug":"mouse-nmrk2","display_name":"Mouse nicotinamide riboside kinase 2 / Nmrk2","entity_type_key":"protein"},"role":"overexpressed enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f251e07c-2a21-57df-bd00-5cf2a08142d6","slug":"mouse-nmrk2-d35a","display_name":"Mouse NRK2 D35A mutant","entity_type_key":"protein_state"},"role":"inactive mutant comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7bb72d0e-e20d-51bc-b88b-7ff29dc2ad4a","slug":"nicotinamide-riboside","display_name":"Nicotinamide riboside","entity_type_key":"small_molecule"},"role":"precursor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d1c59139-db61-5fa0-a25d-40c3e625152e","slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"},"role":"pathway intermediate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"measured cellular pool","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 7–7 (0-based)\", \"start_char\": 5559, \"end_char\": 7104, \"file_sha256\": \"fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a\", \"text_sha256\": \"ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Forced expression in mouse fibroblasts; not a human supplementation study. 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Basal NAD was unchanged by active kinase overexpression without NR.\nexposure: Transient kinase overexpression with 4 micrograms plasmid; NR 0.5 mM for 6 h under the stated default protocol; mutant comparator NRK1-D36A or NRK2-D35A.\nevidence_span: {\"source_cache\": \"artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 7–7 (0-based)\", \"start_char\": 5559, \"end_char\": 7104, \"file_sha256\": \"fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a\", \"text_sha256\": \"ffb453285526cec1670cc565f0b57f3893b48aba7e5014f693f09ea75079348f\"}\nsupporting_evidence_spans: [{\"source_cache\": \"artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 30–30 (0-based)\", \"start_char\": 33613, \"end_char\": 35106, \"file_sha256\": \"fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a\", \"text_sha256\": \"e43865f05c251c7fbb357b31c7968056ae1b58fb1d0f4e61216e5013cb928a41\"}, {\"source_cache\": \"artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt\", \"locator\": \"Normalized full-text paragraphs 48–48 (0-based)\", \"start_char\": 46035, \"end_char\": 46419, \"file_sha256\": \"fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a\", \"text_sha256\": \"4261a1ca6a50f8b37fd569171c8a9111b9a5ee53b2504811a46cfb40badcb90c\"}]\n[b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. 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