{"id":"912673fa-f586-51d2-8b10-667f36fd473e","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-lmbd1-sorting-mutant","predicate":"mislocalizes-associated","statement":"In transfected HEK293 cells, LMBD1 carrying 233YERL-to-AAAA mislocalized partly to the cell surface; coexpressed ABCD4 followed its distribution instead of normal lysosomal targeting.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5c2197f4-00a6-55f0-8d17-13d8e2828bcf","mechanism_event_label":"Changing the escort’s sorting sequence sent the transporter to the wrong location.","subject":{"id":"60cd5b1a-5bfb-54af-b8ce-042b4474a611","slug":"lmbrd1-yerl233-aaaa","display_name":"Human LMBD1 233YERL-to-AAAA","entity_type_key":"protein_state"},"object":{"id":"831afa98-dacd-516d-ae1e-680432a78525","slug":"abcd4","display_name":"Human ABCD4 lysosomal cobalamin transporter","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"5c2197f4-00a6-55f0-8d17-13d8e2828bcf","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-lmbd1-sorting-mutant-event","event_type":"biochemical_relationship","label":"Changing the escort’s sorting sequence sent the transporter to the wrong location.","description":"In transfected HEK293 cells, LMBD1 carrying 233YERL-to-AAAA mislocalized partly to the cell surface; coexpressed ABCD4 followed its distribution instead of normal lysosomal targeting.","status":"provisional","compartment":{"slug":"lysosome","display_name":"Lysosome"},"participants":[{"entity":{"id":"3cf57c43-b33e-5c4e-a53d-dc80695775bb","slug":"lmbrd1","display_name":"Human LMBD1 lysosomal membrane protein","entity_type_key":"protein"},"role":"wild-type comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"related nutrient","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"60cd5b1a-5bfb-54af-b8ce-042b4474a611","slug":"lmbrd1-yerl233-aaaa","display_name":"Human LMBD1 233YERL-to-AAAA","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"831afa98-dacd-516d-ae1e-680432a78525","slug":"abcd4","display_name":"Human ABCD4 lysosomal cobalamin transporter","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Results: Figures 1, 6, 7; Methods: cell lines and CRISPR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HEK293 experimental sorting-motif mutagenesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Human LMBD1-GFP 233YERL/AAAA plus ABCD4-HA","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Experimental four-residue substitution; microscopy does not establish direct vitamin transport.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Changing the escort’s sorting sequence sent the transporter to the wrong location.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[kawaguchi-2016-lmbd1-escort] Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 (2016). https://pubmed.ncbi.nlm.nih.gov/27456980/ DOI: 10.1038/srep30183","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Embryonic kidney-derived cell line","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":"459149d6-3d5e-587c-a692-c1423db4d5cb","evidence_kind":"source_excerpt","locator":"Lines 599-611","start_line":599,"end_line":611,"excerpt":"### b12-lmbd1-sorting-mutant\nIn transfected HEK293 cells, LMBD1 carrying 233YERL-to-AAAA mislocalized partly to the cell surface; coexpressed ABCD4 followed its distribution instead of normal lysosomal targeting.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Changing the escort’s sorting sequence sent the transporter to the wrong location.\norganism: Homo sapiens\ntissue_or_cell_type: Embryonic kidney-derived cell line\nexperimental_model: HEK293 experimental sorting-motif mutagenesis\nlimitations: Experimental four-residue substitution; microscopy does not establish direct vitamin transport.\nexposure: Human LMBD1-GFP 233YERL/AAAA plus ABCD4-HA\ncross_nutrient: false\nevidence_location: Results: Figures 1, 6, 7; Methods: cell lines and CRISPR\n[kawaguchi-2016-lmbd1-escort] Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 (2016). https://pubmed.ncbi.nlm.nih.gov/27456980/ DOI: 10.1038/srep30183","model_system":"HEK293 experimental sorting-motif mutagenesis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [kawaguchi-2016-lmbd1-escort] Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 (2016). https://pubmed.ncbi.nlm.nih.gov/27456980/ DOI: 10.1038/srep30183","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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. Not publisher full text.","file_path":"","sha256":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}