{"id":"763d1662-a441-515d-9c9f-74855c7dd990","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-rfc-methylfolate-binding","predicate":"binds","statement":"Cryo-EM resolved 5-methyltetrahydrofolate in the central substrate pocket of human SLC19A1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"20637be9-10bb-5893-825d-26fe570b5a13","mechanism_event_label":"RFC directly recognizes methylfolate.","subject":{"id":"61cc45e4-4f8d-5e18-8473-7aab0dde6d22","slug":"slc19a1","display_name":"Human reduced folate carrier / SLC19A1","entity_type_key":"protein"},"object":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"20637be9-10bb-5893-825d-26fe570b5a13","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-rfc-methylfolate-binding-event","event_type":"biochemical_relationship","label":"RFC directly recognizes methylfolate.","description":"Cryo-EM resolved 5-methyltetrahydrofolate in the central substrate pocket of human SLC19A1.","status":"provisional","compartment":{"slug":"plasma-membrane","display_name":"Plasma membrane"},"participants":[{"entity":{"id":"61cc45e4-4f8d-5e18-8473-7aab0dde6d22","slug":"slc19a1","display_name":"Human reduced folate carrier / SLC19A1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Human SLC19A1 structures and HEK293F uptake assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"5-MTHF-bound cryo-EM complex","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Static inward-facing structure does not itself measure a complete transport cycle.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"RFC directly recognizes methylfolate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified transporter and HEK293F cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"14e816e4-94b6-5439-92c4-a40ee6dd111e","evidence_kind":"source_excerpt","locator":"Lines 155-165","start_line":155,"end_line":165,"excerpt":"### folate-rfc-methylfolate-binding\nCryo-EM resolved 5-methyltetrahydrofolate in the central substrate pocket of human SLC19A1.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: RFC directly recognizes methylfolate.\norganism: Homo sapiens\ntissue_or_cell_type: Purified transporter and HEK293F cells\nexperimental_model: Human SLC19A1 structures and HEK293F uptake assays\nlimitations: Static inward-facing structure does not itself measure a complete transport cycle.\nexposure: 5-MTHF-bound cryo-EM complex\n[dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w","model_system":"Human SLC19A1 structures and HEK293F uptake assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w","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}