{"id":"59c12e61-21fd-5710-b955-1b29290a3b70","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-hacl1-human-peroxisomal-targeting","predicate":"is-targeted-to","statement":"Human HACL1 expression increased lyase activity in mammalian cells, and GFP fusions showed that its C-terminal sequence could direct peroxisomal localization.","claim_class":"identity","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"cb946359-5a4e-541d-aea1-61a8ed5af2b2","mechanism_event_label":"The cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2.","subject":{"id":"e3c4136d-65a5-5331-b147-bf3f346d066f","slug":"hacl1","display_name":"Human 2-hydroxyacyl-CoA lyase 1 / HACL1","entity_type_key":"protein"},"object":{"id":"f9947344-ed9f-5e88-b03f-8727d07dcf56","slug":"peroxisome","display_name":"Peroxisome","entity_type_key":"organelle"},"evidence_count":1,"mechanism_event":{"id":"cb946359-5a4e-541d-aea1-61a8ed5af2b2","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-hacl1-human-peroxisomal-targeting-event","event_type":"biochemical_relationship","label":"The cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2.","description":"Human HACL1 expression increased lyase activity in mammalian cells, and GFP fusions showed that its C-terminal sequence could direct peroxisomal localization.","status":"provisional","compartment":{"slug":"peroxisome","display_name":"Peroxisome"},"participants":[{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"enzyme-family cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e3c4136d-65a5-5331-b147-bf3f346d066f","slug":"hacl1","display_name":"Human 2-hydroxyacyl-CoA lyase 1 / HACL1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f9947344-ed9f-5e88-b03f-8727d07dcf56","slug":"peroxisome","display_name":"Peroxisome","entity_type_key":"organelle"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence","value_text":"[{\"paper_key\": \"foulon-1999-hacl1\", \"source_bundle\": \"artifacts/thiamine_metabolism_sources.json\", \"passage_ids\": [\"abstract\", \"p-8\"], \"locator\": \"peroxisome targeting signal 1 variant\", \"preservation\": \"Exact text retained in the source bundle; full source document retained when openly retrievable.\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HACL1 expression and fluorescent localization constructs.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Localization and activity used expression constructs; metal-dependence measurements in this paper were on rat enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Thiamine (vitamin B1)","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Transfected mammalian cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8ecca7ab-a014-5943-ba4f-6202c7c4fb6f","evidence_kind":"source_excerpt","locator":"Lines 990-1001","start_line":990,"end_line":1001,"excerpt":"### b1-hacl1-human-peroxisomal-targeting\nHuman HACL1 expression increased lyase activity in mammalian cells, and GFP fusions showed that its C-terminal sequence could direct peroxisomal localization.\nCondition category: normal\nnutrient_topic: Thiamine research collection; 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Study references: [foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"158d2c03-ac8c-589f-8270-c468165ae346","stable_key":"import-46d15d9e-d3b5-544d-ba01-b785aa3e4f42","title":"Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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