{"id":"3b93db92-f9c5-5fad-b78e-e8b078c7c463","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-gly-serum-lot-context","predicate":"modified","statement":"Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"35e485ad-bfc2-5081-ad7d-abd31f023791","mechanism_event_label":"The same genetic defect behaved differently as the surrounding nutrient mixture changed.","subject":{"id":"b2aa56c5-3990-5ad2-88e8-e56b5c5bafdd","slug":"serum-lot-glycosylation-response","display_name":"Cell glycosylation response to serum-lot composition","entity_type_key":"cellular_process"},"object":{"id":"c918048d-68b3-5ec1-ba2c-aa71cb478b92","slug":"lamp2-n-glycosylation","display_name":"LAMP2 N-linked glycosylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"35e485ad-bfc2-5081-ad7d-abd31f023791","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-gly-serum-lot-context-event","event_type":"biochemical_relationship","label":"The same genetic defect behaved differently as the surrounding nutrient mixture changed.","description":"Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"567f9468-661b-59f8-a50d-408fe2133a87","slug":"tmem165","display_name":"TMEM165 Golgi cation-homeostasis protein","entity_type_key":"protein"},"role":"affected_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"medium_component","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b2aa56c5-3990-5ad2-88e8-e56b5c5bafdd","slug":"serum-lot-glycosylation-response","display_name":"Cell glycosylation response to serum-lot composition","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c918048d-68b3-5ec1-ba2c-aa71cb478b92","slug":"lamp2-n-glycosylation","display_name":"LAMP2 N-linked glycosylation","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":"TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (medium_component)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/manganese-glycosylation-sources/serum2020.txt\", \"locator\": \"Results; serum comparisons, ion measurements and manganese rescue\", \"file_sha256\": \"203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69\", \"start_char\": 6062, \"end_char\": 7726, \"text_sha256\": \"9456189117cfb9840785f8afffbb38c52f855aaccc9c03b6fc1d4719550600d4\", \"text_characters\": 1664}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"TMEM165-knockout HEK cell cultures with different fetal bovine serum lots","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Different serum lots; manganese, iron and galactose additions at the stated cellular concentrations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The same genetic defect behaved differently as the surrounding nutrient mixture changed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. 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These are medium concentrations, not blood thresholds or supplementation regimens.\nexposure: Different serum lots; manganese, iron and galactose additions at the stated cellular concentrations.\ncross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (medium_component)\nevidence_span: {\"source_cache\": \"artifacts/manganese-glycosylation-sources/serum2020.txt\", \"locator\": \"Results; serum comparisons, ion measurements and manganese rescue\", \"file_sha256\": \"203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69\", \"start_char\": 6062, \"end_char\": 7726, \"text_sha256\": \"9456189117cfb9840785f8afffbb38c52f855aaccc9c03b6fc1d4719550600d4\", \"text_characters\": 1664}\n[mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. 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