{"id":"aab004ae-df49-5e47-ba88-277294802925","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-hars2-charging","predicate":"forms","statement":"HARS2 provides histidyl-tRNA for mitochondrial translation; L200V and V368L variants reduced aminoacylation in the study assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"02dd5226-7665-55f8-8e14-b771ed70fc4b","mechanism_event_label":"Mitochondria have a separate histidine-charging requirement.","subject":{"id":"8f0018e1-087e-570e-ab8b-d1bc980d2a74","slug":"hars2","display_name":"Human mitochondrial histidyl-tRNA synthetase / HARS2","entity_type_key":"protein"},"object":{"id":"a8bfaa1d-d07c-5bbc-8e9f-6366a2297f5b","slug":"human-mitochondrial-histidyl-trna","display_name":"Human mitochondrial histidyl-tRNA","entity_type_key":"rna"},"evidence_count":1,"mechanism_event":{"id":"02dd5226-7665-55f8-8e14-b771ed70fc4b","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-hars2-charging-event","event_type":"observed_relationship","label":"Mitochondria have a separate histidine-charging requirement.","description":"HARS2 provides histidyl-tRNA for mitochondrial translation; L200V and V368L variants reduced aminoacylation in the study assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8f0018e1-087e-570e-ab8b-d1bc980d2a74","slug":"hars2","display_name":"Human mitochondrial histidyl-tRNA synthetase / HARS2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a8bfaa1d-d07c-5bbc-8e9f-6366a2297f5b","slug":"human-mitochondrial-histidyl-trna","display_name":"Human mitochondrial histidyl-tRNA","entity_type_key":"rna"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":"38870e9c-d956-51e4-8ce5-4609d071af95","evidence_kind":"source_excerpt","locator":"Lines 474-480","start_line":474,"end_line":480,"excerpt":"## histidine-hars2-charging\nMitochondria have a separate histidine-charging requirement.\nHARS2 provides histidyl-tRNA for mitochondrial translation; L200V and V368L variants reduced aminoacylation in the study assays.\nModel: Human family study with recombinant activity, transcript analysis and yeast/worm experiments.\nLimitations: Background role and measured variant impairment are distinguished; direct respiratory-chain failure in every affected tissue is not established here.\nEvidence access: Primary abstract\nMutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21464306/ · DOI 10.1073/pnas.1103471108","model_system":"Human family study with recombinant activity, transcript analysis and yeast/worm experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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