{"id":"cb690e05-c049-5431-9a67-1261dc2b6f5f","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-sit1-variant","predicate":"loses_capacity_with","statement":"SIT1 T199M reduced maximal proline-induced transport current about threefold, supporting a defect in gate dynamics implicated in iminoglycinuria.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cd44a6dc-a116-5066-a243-d4ce32f45405","mechanism_event_label":"A transporter can reach the assay system yet move substrate less efficiently.","subject":{"id":"01b4d4c1-f1a8-59e3-84e3-fb851d5ddf46","slug":"slc6a20","display_name":"Human imino-acid transporter / SLC6A20","entity_type_key":"protein"},"object":{"id":"c374abb1-815e-57e5-9756-836f399798af","slug":"human-sit1-t199m-transport","display_name":"Human SIT1 T199M proline transport capacity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cd44a6dc-a116-5066-a243-d4ce32f45405","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-sit1-variant-event","event_type":"observed_relationship","label":"A transporter can reach the assay system yet move substrate less efficiently.","description":"SIT1 T199M reduced maximal proline-induced transport current about threefold, supporting a defect in gate dynamics implicated in iminoglycinuria.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"01b4d4c1-f1a8-59e3-84e3-fb851d5ddf46","slug":"slc6a20","display_name":"Human imino-acid transporter / SLC6A20","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c374abb1-815e-57e5-9756-836f399798af","slug":"human-sit1-t199m-transport","display_name":"Human SIT1 T199M proline transport capacity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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unverified.","entity":null}],"evidence":[{"id":"e09160c3-0070-592d-b85d-de6ab6edfe72","evidence_kind":"source_excerpt","locator":"Lines 198-204","start_line":198,"end_line":204,"excerpt":"## l-proline-sit1-variant\nA transporter can reach the assay system yet move substrate less efficiently.\nSIT1 T199M reduced maximal proline-induced transport current about threefold, supporting a defect in gate dynamics implicated in iminoglycinuria.\nModel: Human SIT1 variant expressed in Xenopus oocytes with structural interpretation.\nLimitations: The proposed packing mechanism is an interpretation informed by structure, while reduced current was measured.\nEvidence access: Primary full text\nStructure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38951531/ · DOI 10.1038/s41467-024-48921-x","model_system":"Human SIT1 variant expressed in Xenopus oocytes with structural interpretation.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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