{"id":"dda24d1c-b9af-5aae-bba6-206b2322dabd","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-trans-intestinal-zip14-absorptive","predicate":"increases","statement":"ZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"120d132e-1ef0-5899-be3e-ac44b71097b8","mechanism_event_label":"Without ZIP14, the cultured intestinal barrier passed more manganese toward the blood-facing side.","subject":{"id":"f2fad02e-7a5a-5387-8449-20b565db2784","slug":"caco2-slc39a14-knockout","display_name":"Caco-2 SLC39A14 knockout genotype","entity_type_key":"gene"},"object":{"id":"fcdb5768-cb42-5ca2-80a4-c231516355ff","slug":"intestinal-absorptive-manganese-flux","display_name":"Intestinal apical-to-basolateral manganese flux","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"120d132e-1ef0-5899-be3e-ac44b71097b8","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-trans-intestinal-zip14-absorptive-event","event_type":"biochemical_relationship","label":"Without ZIP14, the cultured intestinal barrier passed more manganese toward the blood-facing side.","description":"ZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d22c7213-0c72-51f5-bf27-f3635439c4e1","slug":"slc39a14","display_name":"Human ZIP14 (SLC39A14)","entity_type_key":"protein"},"role":"affected_transporter","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2fad02e-7a5a-5387-8449-20b565db2784","slug":"caco2-slc39a14-knockout","display_name":"Caco-2 SLC39A14 knockout genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"fcdb5768-cb42-5ca2-80a4-c231516355ff","slug":"intestinal-absorptive-manganese-flux","display_name":"Intestinal apical-to-basolateral manganese flux","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; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"ZIP14-deficient human Caco-2 Transwell monolayers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ZIP14-deficient versus control Caco-2 Transwell monolayers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Directional flux in a transformed cell-line model is not a human fractional-absorption estimate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Without ZIP14, the cultured intestinal barrier passed more manganese toward the blood-facing side.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Caco-2 intestinal epithelial model","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":"262c2e51-d326-5cb0-a41b-3fb12d5aca12","evidence_kind":"source_excerpt","locator":"Lines 201-212","start_line":201,"end_line":212,"excerpt":"### mn-trans-intestinal-zip14-absorptive\nZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport.\nCondition category: machinery_impairment\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Without ZIP14, the cultured intestinal barrier passed more manganese toward the blood-facing side.\norganism: Homo sapiens\ntissue_or_cell_type: Caco-2 intestinal epithelial model\nexperimental_model: ZIP14-deficient human Caco-2 Transwell monolayers\nlimitations: Directional flux in a transformed cell-line model is not a human fractional-absorption estimate.\nexposure: ZIP14-deficient versus control Caco-2 Transwell monolayers.\ncross_nutrient: false\n[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. 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