{"id":"8d2695c2-4ef6-54c3-af40-52c7cc1c1ee5","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-hartnup-partners","predicate":"depends_on_context","statement":"Human B0AT1 D173N and P265L variants retained activation by coexpressed mouse ACE2 but not human collectrin; A69T and R240Q were not activated by either partner.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1afdb498-93e9-54ad-b890-b64da1b6f4fc","mechanism_event_label":"The same transporter mutation can behave differently with different helper proteins.","subject":{"id":"10307ad9-80a3-56be-a7f5-740c9362297f","slug":"slc6a19","display_name":"Human neutral amino acid transporter B0AT1 / SLC6A19","entity_type_key":"protein"},"object":{"id":"2b390ede-04b6-52e7-a560-ff32c23799f7","slug":"human-b0at1-accessory-response","display_name":"Accessory-protein response of human B0AT1 variants","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1afdb498-93e9-54ad-b890-b64da1b6f4fc","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-hartnup-partners-event","event_type":"observed_relationship","label":"The same transporter mutation can behave differently with different helper proteins.","description":"Human B0AT1 D173N and P265L variants retained activation by coexpressed mouse ACE2 but not human collectrin; A69T and R240Q were not activated by either partner.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"10307ad9-80a3-56be-a7f5-740c9362297f","slug":"slc6a19","display_name":"Human neutral amino acid transporter B0AT1 / SLC6A19","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2b390ede-04b6-52e7-a560-ff32c23799f7","slug":"human-b0at1-accessory-response","display_name":"Accessory-protein response of human B0AT1 variants","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c85b327e-f132-5d9a-8e4b-c2976fcc0373","slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"64525e58-23a1-591e-b5f6-4548607600d2","slug":"collectrin","display_name":"Human collectrin / TMEM27","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"51b5a82d-32e8-5223-b384-026dd7cead16","slug":"mouse-ace2","display_name":"Mouse angiotensin-converting enzyme 2 / Ace2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human transporter variants in Xenopus oocytes with mouse ACE2 or human collectrin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mixed-species expression system; not a direct measurement of each patient intestine or kidney.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The same transporter mutation can behave differently with different helper proteins.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19185582/ · DOI 10.1053/j.gastro.2008.10.055","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":"7281e30d-7021-5b9d-ba2c-8f421cb583c3","evidence_kind":"source_excerpt","locator":"Lines 34-40","start_line":34,"end_line":40,"excerpt":"## isoleucine-hartnup-partners\nThe same transporter mutation can behave differently with different helper proteins.\nHuman B0AT1 D173N and P265L variants retained activation by coexpressed mouse ACE2 but not human collectrin; A69T and R240Q were not activated by either partner.\nModel: Human transporter variants in Xenopus oocytes with mouse ACE2 or human collectrin.\nLimitations: Mixed-species expression system; not a direct measurement of each patient intestine or kidney.\nEvidence access: Primary full text\nTissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19185582/ · DOI 10.1053/j.gastro.2008.10.055","model_system":"Human transporter variants in Xenopus oocytes with mouse ACE2 or human collectrin.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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