{"id":"acfaf59e-210b-5227-90d1-9dd66122bffc","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-cubn-p1297l-affinity","predicate":"reduces-affinity-for","statement":"The human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"8cb8c8e1-5367-5380-98f7-ed689c6beee3","mechanism_event_label":"This cubilin variant binds its B12 carrier less efficiently.","subject":{"id":"3fd81875-3727-5c1f-a129-de4eaaf8c10e","slug":"cubn-p1297l","display_name":"Human cubilin P1297L variant","entity_type_key":"protein_state"},"object":{"id":"1e7fbe30-20c5-5229-97de-84ad5c3dde84","slug":"human-if-cobalamin","display_name":"Human intrinsic factor-cobalamin complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"8cb8c8e1-5367-5380-98f7-ed689c6beee3","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-cubn-p1297l-affinity-event","event_type":"biochemical_relationship","label":"This cubilin variant binds its B12 carrier less efficiently.","description":"The human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7a3dab53-fbcd-58da-9942-21f1a3ed088d","slug":"cubn","display_name":"Human cubilin / CUBN","entity_type_key":"protein"},"role":"wild-type-comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3fd81875-3727-5c1f-a129-de4eaaf8c10e","slug":"cubn-p1297l","display_name":"Human cubilin P1297L variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1e7fbe30-20c5-5229-97de-84ad5c3dde84","slug":"human-if-cobalamin","display_name":"Human intrinsic factor-cobalamin complex","entity_type_key":"protein_complex"},"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":"experimental_model","value_text":"Human wild-type/P1297L fragments expressed in CHO cells; SPR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Site-directed P1297L substitution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Fragment binding assay; not every CUBN variant shares this mechanism.","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":"This cubilin variant binds its B12 carrier less efficiently.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Ileal receptor ligand-binding model","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":"83daba50-e503-5019-b812-2bc6f18618ca","evidence_kind":"source_excerpt","locator":"Lines 270-281","start_line":270,"end_line":281,"excerpt":"### b12-abs-cubn-p1297l-affinity\nThe human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This cubilin variant binds its B12 carrier less efficiently.\norganism: Homo sapiens\ntissue_or_cell_type: Ileal receptor ligand-binding model\nexperimental_model: Human wild-type/P1297L fragments expressed in CHO cells; SPR\nlimitations: Fragment binding assay; not every CUBN variant shares this mechanism.\nexposure: Site-directed P1297L substitution\ncross_nutrient: false\n[kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405","model_system":"Human wild-type/P1297L fragments expressed in CHO cells; SPR","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405","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. 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