{"id":"9e97604d-07bc-5cf8-ab13-55ffffa27aca","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:shmt1-transgene-nuclear-mislocalization","predicate":"reduces","statement":"Shmt1-transgenic mouse liver had lower nuclear SHMT1/TYMS and lower nuclear de novo dTMP synthesis despite higher total enzyme abundance.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3d3e0bb9-f468-5256-8519-e8b67bcc7d52","mechanism_event_label":"More enzyme in the whole cell did not mean more at DNA-replication sites.","subject":{"id":"2f89e068-401a-576a-8721-7ce8e50eae34","slug":"mouse-shmt1-gene","display_name":"Mouse Shmt1 gene","entity_type_key":"gene"},"object":{"id":"62cc6e56-d93e-54f5-9883-bd8ec32a9174","slug":"nuclear-dtmp-synthesis","display_name":"Nuclear de novo thymidylate synthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3d3e0bb9-f468-5256-8519-e8b67bcc7d52","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:shmt1-transgene-nuclear-mislocalization-event","event_type":"biochemical_relationship","label":"More enzyme in the whole cell did not mean more at DNA-replication sites.","description":"Shmt1-transgenic mouse liver had lower nuclear SHMT1/TYMS and lower nuclear de novo dTMP synthesis despite higher total enzyme abundance.","status":"provisional","compartment":{"slug":"nucleus","display_name":"Nucleus"},"participants":[{"entity":{"id":"2cda8fe4-b431-5b37-8fba-621816a93481","slug":"mouse-shmt1","display_name":"Mouse Shmt1 protein","entity_type_key":"protein"},"role":"mislocalized enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"69e1aaba-5f73-5800-9466-ccb62b87ae6a","slug":"mouse-tyms","display_name":"Mouse Tyms protein","entity_type_key":"protein"},"role":"mislocalized enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2f89e068-401a-576a-8721-7ce8e50eae34","slug":"mouse-shmt1-gene","display_name":"Mouse Shmt1 gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"62cc6e56-d93e-54f5-9883-bd8ec32a9174","slug":"nuclear-dtmp-synthesis","display_name":"Nuclear de novo thymidylate synthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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Study references: [macfarlane-2011] Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA (2011). https://pubmed.ncbi.nlm.nih.gov/22057276/ DOI: 10.1074/jbc.m111.307629","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}