{"id":"327873ce-3609-5828-b3fd-e769bf0e94ae","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ankh-citrate-export","predicate":"mediates_export_of","statement":"ANKH-expressing HEK293 cells released citrate; Ank-mutant mice also had depleted bone-matrix citrate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"2d303465-b9aa-5c2f-b744-c2dd4ed62e28","mechanism_event_label":"ANKH affects a mineral-associated organic component as well as PPi supply.","subject":{"id":"5c97d84f-c8a5-567f-8b4d-c18c9e045d2a","slug":"ankh","display_name":"Progressive ankylosis protein homolog ANKH","entity_type_key":"protein"},"object":{"id":"1c54abac-4dfd-5303-b0f4-37945245e18e","slug":"citrate","display_name":"Citrate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"2d303465-b9aa-5c2f-b744-c2dd4ed62e28","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ankh-citrate-export-event","event_type":"biochemical_relationship","label":"ANKH affects a mineral-associated organic component as well as PPi supply.","description":"ANKH-expressing HEK293 cells released citrate; Ank-mutant mice also had depleted bone-matrix citrate.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"5c97d84f-c8a5-567f-8b4d-c18c9e045d2a","slug":"ankh","display_name":"Progressive ankylosis protein homolog ANKH","entity_type_key":"protein"},"role":"export_mediator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1c54abac-4dfd-5303-b0f4-37945245e18e","slug":"citrate","display_name":"Citrate","entity_type_key":"small_molecule"},"role":"exported_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d515a301-29a6-5d2d-88db-44773711406a","slug":"hydroxyapatite","display_name":"Hydroxyapatite / biological substituted apatite","entity_type_key":"chemical_species"},"role":"associated_bone_mineral","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7dbb4c2f-3f94-5f0b-abfc-980d8a4105d5","slug":"bone-extracellular-matrix","display_name":"Bone extracellular matrix","entity_type_key":"tissue"},"role":"destination_context","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"bc9ed3a1-38d5-5bc3-b2a5-9f9f7633660b","slug":"cytosol","display_name":"Cytosol","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":4,"notes":"Study location; presence here is not a separate transport or causal claim."},{"entity":{"id":"3dcbbcaa-17df-54a0-a499-9b966a38631a","slug":"extracellular-space","display_name":"Extracellular space","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":5,"notes":"Study location; presence here is not a separate transport or causal claim."}]},"contexts":[{"dimension":"compartment_description","value_text":"Cytosol to extracellular space","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Metabolomics and Ank-mutant tissue measurements","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Citrate is a separate substrate; these findings do not prove that citrate alone explains altered bone strength.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens cells; Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"ANKH affects a mineral-associated organic component as well as PPi supply.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[szeri2020] The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP (2020). https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008884 DOI: 10.1371/journal.pgen.1008884","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell medium and bone matrix","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f094e117-b3f0-5074-929e-c7103020601c","evidence_kind":"source_excerpt","locator":"Lines 1024-1034","start_line":1024,"end_line":1034,"excerpt":"### ankh-citrate-export\nANKH-expressing HEK293 cells released citrate; Ank-mutant mice also had depleted bone-matrix citrate.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: ANKH affects a mineral-associated organic component as well as PPi supply.\norganism: Homo sapiens cells; Mus musculus\ntissue_or_cell_type: Cell medium and bone matrix\nexperimental_model: Metabolomics and Ank-mutant tissue measurements\nlimitations: Citrate is a separate substrate; these findings do not prove that citrate alone explains altered bone strength.\ncompartment_description: Cytosol to extracellular space\n[szeri2020] The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP (2020). https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008884 DOI: 10.1371/journal.pgen.1008884","model_system":"Metabolomics and Ank-mutant tissue measurements","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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