{"id":"6bcd28e7-79b1-5d40-a8a8-d1b067575ccc","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-mouse-nrk1-nr","predicate":"supports-production-of","statement":"Transient overexpression of active mouse NRK1 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":"2b1acd96-baf6-5a30-9be6-74efbe4ba0c7","mechanism_event_label":"NR utilization depended on active riboside kinase in this cell model.","subject":{"id":"4f53cbd9-c87e-5132-99e5-62ae8a85b62b","slug":"mouse-nmrk1","display_name":"Mouse nicotinamide riboside kinase 1 / Nmrk1","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":"2b1acd96-baf6-5a30-9be6-74efbe4ba0c7","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-pre-mouse-nrk1-nr-event","event_type":"biochemical_relationship","label":"NR utilization depended on active riboside kinase in this cell model.","description":"Transient overexpression of active mouse NRK1 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":"4f53cbd9-c87e-5132-99e5-62ae8a85b62b","slug":"mouse-nmrk1","display_name":"Mouse nicotinamide riboside kinase 1 / Nmrk1","entity_type_key":"protein"},"role":"overexpressed enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"72ed864c-2855-53e0-a201-71df35512ef7","slug":"mouse-nmrk1-d36a","display_name":"Mouse NRK1 D36A 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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