{"id":"3ab9ccd1-f651-5efe-8dc0-a76cf0f558c4","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-tyr-variants","predicate":"when_variant_reduces","statement":"Human TYR R422Q and R422W variants had lower activity and temperature sensitivity compared with wild type.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4f288094-5765-5dc8-b12a-7ab301a7c1f5","mechanism_event_label":"Reduced pigment synthesis can reflect enzyme structure rather than low tyrosine.","subject":{"id":"d1ee71a8-af1f-5a6f-a879-e75134fa12af","slug":"tyr","display_name":"Human tyrosinase / TYR","entity_type_key":"protein"},"object":{"id":"0e67014d-2a4d-5093-908f-2b0c628637df","slug":"human-tyr-variant-pigment-enzyme-activity","display_name":"Human TYR R422Q/R422W pigment-enzyme activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4f288094-5765-5dc8-b12a-7ab301a7c1f5","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-tyr-variants-event","event_type":"observed_relationship","label":"Reduced pigment synthesis can reflect enzyme structure rather than low tyrosine.","description":"Human TYR R422Q and R422W variants had lower activity and temperature sensitivity compared with wild type.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d1ee71a8-af1f-5a6f-a879-e75134fa12af","slug":"tyr","display_name":"Human tyrosinase / TYR","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0e67014d-2a4d-5093-908f-2b0c628637df","slug":"human-tyr-variant-pigment-enzyme-activity","display_name":"Human TYR R422Q/R422W pigment-enzyme activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bcfef85f-831d-5439-ba51-1aef4b090441","slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d2e54a66-7f3c-5bcc-adbe-9f66ad4264f4","slug":"l-dopa","display_name":"L-3,4-Dihydroxyphenylalanine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b5e5b144-8a40-5163-959d-360f754e966a","slug":"dopaquinone","display_name":"Dopaquinone","entity_type_key":"small_molecule"},"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 abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human intramelanosomal domains expressed in insect cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"These variants retain activity; they should not be conflated with all albinism variants.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Reduced pigment synthesis can reflect enzyme structure rather than low tyrosine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494","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":"2abe5b8b-c2e0-5b26-bb14-39180415f113","evidence_kind":"source_excerpt","locator":"Lines 164-170","start_line":164,"end_line":170,"excerpt":"## l-tyrosine-tyr-variants\nReduced pigment synthesis can reflect enzyme structure rather than low tyrosine.\nHuman TYR R422Q and R422W variants had lower activity and temperature sensitivity compared with wild type.\nModel: Purified human intramelanosomal domains expressed in insect cells.\nLimitations: These variants retain activity; they should not be conflated with all albinism variants.\nEvidence access: Primary abstract\nAlbinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494","model_system":"Purified human intramelanosomal domains expressed in insect cells.","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":"12917df2-c6e0-5b61-850f-dbff6d4b4d30","stable_key":"import-63ce713e-6aea-59f6-9896-ca30e010b2ce","title":"L-Tyrosine: catecholamines, thyroid chemistry, pigment, 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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