{"id":"84ff291b-6a88-5d5b-89c4-d21f10f16fbd","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-cytosolic-keops","predicate":"acts_upstream_of","statement":"Cytosolic t6A formation uses sequential YRDC and OSGEP activities, with OSGEP operating within the KEOPS complex.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ca07874e-af8d-5c63-808b-0a2daa43daf4","mechanism_event_label":"The cytosol uses a different downstream machine from the mitochondrial pathway.","subject":{"id":"3114b5d2-04d2-59d6-88c3-c04eb28aeeff","slug":"yrdc","display_name":"Human threonylcarbamoyladenylate synthase / YRDC","entity_type_key":"protein"},"object":{"id":"df477465-d314-54c8-814e-88a3cc4db26d","slug":"osgep","display_name":"Human KEOPS catalytic subunit / OSGEP","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ca07874e-af8d-5c63-808b-0a2daa43daf4","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-cytosolic-keops-event","event_type":"observed_relationship","label":"The cytosol uses a different downstream machine from the mitochondrial pathway.","description":"Cytosolic t6A formation uses sequential YRDC and OSGEP activities, with OSGEP operating within the KEOPS complex.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3114b5d2-04d2-59d6-88c3-c04eb28aeeff","slug":"yrdc","display_name":"Human threonylcarbamoyladenylate synthase / YRDC","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"df477465-d314-54c8-814e-88a3cc4db26d","slug":"osgep","display_name":"Human KEOPS catalytic subunit / OSGEP","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8641c342-429b-55f7-a01d-5fe2b421031a","slug":"human-keops-complex","display_name":"Human KEOPS tRNA modification complex","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"cf664fc7-c0f3-589c-a191-27e1c2276175","slug":"threonylcarbamoyl-amp","display_name":"L-Threonylcarbamoyladenylate / TC-AMP","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"5c27b149-da7e-5a90-8bd3-d4b2a42bb2ef","slug":"trna-threonylcarbamoyladenosine","display_name":"tRNA-bound N6-threonylcarbamoyladenosine / t6A37","entity_type_key":"rna"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Primary human genetics and structural study of the t6A pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"OSGEP and mitochondrial OSGEPL1 are distinct proteins; threonyl-tRNA loading is a separate reaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The cytosol uses a different downstream machine from the mitochondrial pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fa4b4be2-b29a-5e7c-81ac-c74c487de493","evidence_kind":"source_excerpt","locator":"Lines 442-448","start_line":442,"end_line":448,"excerpt":"## l-threonine-cytosolic-keops\nThe cytosol uses a different downstream machine from the mitochondrial pathway.\nCytosolic t6A formation uses sequential YRDC and OSGEP activities, with OSGEP operating within the KEOPS complex.\nModel: Primary human genetics and structural study of the t6A pathway.\nLimitations: OSGEP and mitochondrial OSGEPL1 are distinct proteins; threonyl-tRNA loading is a separate reaction.\nEvidence access: Primary abstract\nDefects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x","model_system":"Primary human genetics and structural study of the t6A pathway.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"35396730-235a-537e-8a05-c6ef2960c509","stable_key":"import-97957230-601f-5dec-8524-0812be8fadbf","title":"L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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