{"id":"154d1a38-74ef-5538-b617-386f3d1ac7ce","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-lmbrd1-ko-localization","predicate":"deletion-reduces","statement":"CRISPR LMBRD1 knockout in HEK293 cells reduced the ABCD4 signal overlapping lysosomal fractions to about 40% of control, while total ABCD4 was similar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c9d4077a-f08a-5a79-a788-7ee4556e7098","mechanism_event_label":"Deleting the escort changed where the transporter was located.","subject":{"id":"16e73ac6-0b80-5df4-b477-a2215a39f675","slug":"lmbrd1-human-gene","display_name":"Human LMBRD1 gene","entity_type_key":"gene"},"object":{"id":"321f9fda-6723-5d46-88f1-cdb0459bc297","slug":"abcd4-lysosomal-localization","display_name":"ABCD4 localization to lysosomes","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c9d4077a-f08a-5a79-a788-7ee4556e7098","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-lmbrd1-ko-localization-event","event_type":"biochemical_relationship","label":"Deleting the escort changed where the transporter was located.","description":"CRISPR LMBRD1 knockout in HEK293 cells reduced the ABCD4 signal overlapping lysosomal fractions to about 40% of control, while total ABCD4 was similar.","status":"provisional","compartment":{"slug":"lysosome","display_name":"Lysosome"},"participants":[{"entity":{"id":"831afa98-dacd-516d-ae1e-680432a78525","slug":"abcd4","display_name":"Human ABCD4 lysosomal cobalamin transporter","entity_type_key":"protein"},"role":"measured protein","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":"16e73ac6-0b80-5df4-b477-a2215a39f675","slug":"lmbrd1-human-gene","display_name":"Human LMBRD1 gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"321f9fda-6723-5d46-88f1-cdb0459bc297","slug":"abcd4-lysosomal-localization","display_name":"ABCD4 localization to lysosomes","entity_type_key":"cellular_process"},"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 CRISPR knockout and density-gradient immunoblotting","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"LMBRD1 knockout versus wild type","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Fractionation-based localization; residual lysosomal signal remains and is not 40% residual transport activity.","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":"Deleting the escort changed where the transporter was located.","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":"Human 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":"b1168240-88bc-568f-a2a8-5b3cfdfab03b","evidence_kind":"source_excerpt","locator":"Lines 585-597","start_line":585,"end_line":597,"excerpt":"### b12-lmbrd1-ko-localization\nCRISPR LMBRD1 knockout in HEK293 cells reduced the ABCD4 signal overlapping lysosomal fractions to about 40% of control, while total ABCD4 was similar.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Deleting the escort changed where the transporter was located.\norganism: Homo sapiens\ntissue_or_cell_type: Human embryonic kidney-derived cell line\nexperimental_model: HEK293 CRISPR knockout and density-gradient immunoblotting\nlimitations: Fractionation-based localization; residual lysosomal signal remains and is not 40% residual transport activity.\nexposure: LMBRD1 knockout versus wild type\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 CRISPR knockout and density-gradient immunoblotting","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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