{"id":"cd1fca55-d262-506f-815f-918647759225","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-amn-endocytic-signal-loss","predicate":"impairs","statement":"Disruption of both human AMN FXNPXF motifs impaired IF-B12 internalization and degradation in CHO-K1 cells despite preserved cubam surface expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c03c1c0a-a829-5347-8077-3aedfe53793a","mechanism_event_label":"A receptor can reach the surface yet fail to internalize its cargo.","subject":{"id":"d4999ada-7554-5890-827d-8e37b122f71c","slug":"amn-double-endocytic-signal-mutant","display_name":"Human AMN double FXNPXF-signal mutant","entity_type_key":"protein_state"},"object":{"id":"ffacb0b0-ba03-59b7-aa3a-b2839cfb7d5b","slug":"cubam-if-cobalamin-endocytosis","display_name":"Cubam-mediated IF-cobalamin endocytosis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c03c1c0a-a829-5347-8077-3aedfe53793a","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-amn-endocytic-signal-loss-event","event_type":"biochemical_relationship","label":"A receptor can reach the surface yet fail to internalize its cargo.","description":"Disruption of both human AMN FXNPXF motifs impaired IF-B12 internalization and degradation in CHO-K1 cells despite preserved cubam surface expression.","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":"bbd594ac-365b-507f-954d-20a0df38312d","slug":"amn","display_name":"Human amnionless / AMN","entity_type_key":"protein"},"role":"wild-type-comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b6fc3dff-b990-5b47-be50-a469eee88d9e","slug":"rat-mini-cubilin-cub1-8","display_name":"Rat cubilin 1-1389 minireceptor","entity_type_key":"protein_state"},"role":"binding-subunit","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d4999ada-7554-5890-827d-8e37b122f71c","slug":"amn-double-endocytic-signal-mutant","display_name":"Human AMN double FXNPXF-signal mutant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ffacb0b0-ba03-59b7-aa3a-b2839cfb7d5b","slug":"cubam-if-cobalamin-endocytosis","display_name":"Cubam-mediated IF-cobalamin endocytosis","entity_type_key":"cellular_process"},"role":"target","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":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human AMN double-signal mutant plus rat cubilin 1-1389 in CHO-K1 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Both cytoplasmic motifs disrupted; wild-type and single-motif mutants as comparators","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered trafficking defect, not a patient genotype. Surface binding and intracellular entry are separate readouts.","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":"Human AMN; rat cubilin; Chinese hamster host cells; human/porcine IF reagents","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A receptor can reach the surface yet fail to internalize its cargo.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Engineered receptor internalization 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":"a98bc8a6-076b-508c-8530-2956aeebda26","evidence_kind":"source_excerpt","locator":"Lines 491-502","start_line":491,"end_line":502,"excerpt":"### b12-abs-amn-endocytic-signal-loss\nDisruption of both human AMN FXNPXF motifs impaired IF-B12 internalization and degradation in CHO-K1 cells despite preserved cubam surface expression.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A receptor can reach the surface yet fail to internalize its cargo.\norganism: Human AMN; rat cubilin; Chinese hamster host cells; human/porcine IF reagents\ntissue_or_cell_type: Engineered receptor internalization model\nexperimental_model: Human AMN double-signal mutant plus rat cubilin 1-1389 in CHO-K1 cells\nlimitations: Engineered trafficking defect, not a patient genotype. Surface binding and intracellular entry are separate readouts.\nexposure: Both cytoplasmic motifs disrupted; wild-type and single-motif mutants as comparators\ncross_nutrient: false\n[pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x","model_system":"Human AMN double-signal mutant plus rat cubilin 1-1389 in CHO-K1 cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x","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}