{"id":"d22246e6-4d8f-54dc-861f-a9d10746b7d8","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-ubiad1-knockdown","predicate":"loss_reduces","statement":"UBIAD1-targeted siRNA inhibited labeled MK-4 formation in human cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3a381a05-a538-56b7-a5b7-d6fb689d5ce5","mechanism_event_label":"A synthesis defect is different from simply eating little K2.","subject":{"id":"190c8a9f-60f4-5341-898e-187a0c697624","slug":"ubiad1","display_name":"Human UBIAD1 prenyltransferase","entity_type_key":"protein"},"object":{"id":"c06c54bb-69ce-58a3-a904-0647dbaf3577","slug":"mk4-biosynthesis","display_name":"Menaquinone-4 biosynthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3a381a05-a538-56b7-a5b7-d6fb689d5ce5","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-ubiad1-knockdown-event","event_type":"biochemical_relationship","label":"A synthesis defect is different from simply eating little K2.","description":"UBIAD1-targeted siRNA inhibited labeled MK-4 formation in human cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"190c8a9f-60f4-5341-898e-187a0c697624","slug":"ubiad1","display_name":"Human UBIAD1 prenyltransferase","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c06c54bb-69ce-58a3-a904-0647dbaf3577","slug":"mk4-biosynthesis","display_name":"Menaquinone-4 biosynthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/k2-research/20953171.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3\", \"start_char\": 0, \"end_char\": 2006, \"text_sha256\": \"b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Gene knockdown, heterologous expression, isotope conversion and NMR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Labeled vitamin K precursors, UBIAD1 knockdown and expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. 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(2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"MK-4 synthesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"91d95646-87d3-58f6-b7f4-126f66b4dff9","evidence_kind":"source_excerpt","locator":"Lines 149-160","start_line":149,"end_line":160,"excerpt":"### k2-ubiad1-knockdown\nUBIAD1-targeted siRNA inhibited labeled MK-4 formation in human cells.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A synthesis defect is different from simply eating little K2.\norganism: Human UBIAD1 in human and insect-cell systems; mouse localization\ntissue_or_cell_type: MK-4 synthesis\nexperimental_model: Gene knockdown, heterologous expression, isotope conversion and NMR\nlimitations: Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors.\nexposure: Labeled vitamin K precursors, UBIAD1 knockdown and expression\nevidence_span: {\"source_cache\": \"artifacts/k2-research/20953171.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3\", \"start_char\": 0, \"end_char\": 2006, \"text_sha256\": \"b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3\"}\n[k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464","model_system":"Gene knockdown, heterologous expression, isotope conversion and NMR","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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