{"id":"64606de9-c61a-5b9c-82f6-52f6050b8ec3","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ankh-atp-export","predicate":"mediates_export_of","statement":"ANKH expression drove ATP release from HEK293 cells even when ENPP1 was absent.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"5cacdde6-6c86-5c11-8178-f6800a0e9d55","mechanism_event_label":"ANKH can provide extracellular ATP for subsequent PPi production.","subject":{"id":"5c97d84f-c8a5-567f-8b4d-c18c9e045d2a","slug":"ankh","display_name":"Progressive ankylosis protein homolog ANKH","entity_type_key":"protein"},"object":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"5cacdde6-6c86-5c11-8178-f6800a0e9d55","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ankh-atp-export-event","event_type":"biochemical_relationship","label":"ANKH can provide extracellular ATP for subsequent PPi production.","description":"ANKH expression drove ATP release from HEK293 cells even when ENPP1 was absent.","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":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"exported_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3c0f7c97-f914-533c-a22c-39e48d23f743","slug":"enpp1","display_name":"Ectonucleotide pyrophosphatase/phosphodiesterase 1 ENPP1","entity_type_key":"protein"},"role":"downstream_enzyme_not_required_for_export","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f0b6bcb6-5d41-5d9d-af9f-6af1a94d5c5a","slug":"plasma-membrane","display_name":"Plasma membrane","entity_type_key":"organelle"},"role":"transport_boundary","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 medium","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"ANKH expression with ENPP1 deletion controls","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cellular export assay; it does not determine purified ANKH transport stoichiometry in every tissue.","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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"ANKH can provide extracellular ATP for subsequent PPi production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293 cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e527570f-ed35-5c38-87ca-f82bbb13491d","evidence_kind":"source_excerpt","locator":"Lines 1000-1010","start_line":1000,"end_line":1010,"excerpt":"### ankh-atp-export\nANKH expression drove ATP release from HEK293 cells even when ENPP1 was absent.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: ANKH can provide extracellular ATP for subsequent PPi production.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293 cells\nexperimental_model: ANKH expression with ENPP1 deletion controls\nlimitations: Cellular export assay; it does not determine purified ANKH transport stoichiometry in every tissue.\ncompartment_description: Cytosol to extracellular medium\n[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528","model_system":"ANKH expression with ENPP1 deletion controls","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (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":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"0f5b4b0b-8072-5411-9be9-cb622522547f","title":"ANKH-associated PPi: earlier transport interpretation versus extracellular ATP conversion","kind":"qualification","status":"open","why":"Early cellular PPi redistribution and oocyte PPi uptake supported direct-transport interpretations; later ENPP1 deletion separated ATP release from PPi appearance. Research comparison category: mechanism_and_model_difference.","resolution":"Curation interpretation: preserve the historical hypothesis and oocyte influx observation. Use ATP release followed by ENPP1 conversion for the tested HEK293 route; do not claim all PPi transport in every tissue has been excluded.","created_at":"2026-09-17 08:08:54","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/0f5b4b0b-8072-5411-9be9-cb622522547f","sides":[{"conflict_id":"0f5b4b0b-8072-5411-9be9-cb622522547f","ordinal":0,"label":"An older transport explanation was inferred from changes in PPi distribution.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":976,"end_line":986,"quote":"### ankh-historical-direct-ppi-export-hypothesis\nEarly ANK-dependent changes in cellular and extracellular PPi motivated a proposal that ANK directly exports PPi.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An older transport explanation was inferred from changes in PPi distribution.\norganism: Mus musculus protein; cultured mammalian cells\ntissue_or_cell_type: Joint-calcification context\nexperimental_model: Ank genetics and cell PPi measurements\nlimitations: Historical hypothesis, not a current unconditional transport assignment; later ATP/ENPP1 experiments require qualification.\ncompartment_description: Plasma membrane\n[ho2000] Role of the mouse ank gene in control of tissue calcification and arthritis (2000). https://pubmed.ncbi.nlm.nih.gov/10894769/ DOI: 10.1126/science.289.5477.265","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["9dc7f5ce-8e7a-55a8-b4d2-0076db7b7183"]},{"conflict_id":"0f5b4b0b-8072-5411-9be9-cb622522547f","ordinal":1,"label":"An earlier assay measured movement into an egg cell, not export from human bone cells.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":988,"end_line":998,"quote":"### ank-dependent-ppi-uptake-oocytes\nMouse ANK expression increased saturable radiolabeled PPi uptake into Xenopus oocytes.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An earlier assay measured movement into an egg cell, not export from human bone cells.\norganism: Mus musculus protein in Xenopus laevis oocytes\ntissue_or_cell_type: Oocyte plasma membrane\nexperimental_model: Heterologous expression and radiotracer uptake\nlimitations: Influx in this model does not establish physiological PPi efflux; retain alongside later ATP-release results.\ncompartment_description: Extracellular medium to oocyte\n[gurley2006] Biochemical and genetic analysis of ANK in arthritis and bone disease (2006). https://pubmed.ncbi.nlm.nih.gov/17186460/ DOI: 10.1086/509881","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["522b30b7-bc20-5e91-9c6a-4424110e7371"]},{"conflict_id":"0f5b4b0b-8072-5411-9be9-cb622522547f","ordinal":2,"label":"ANKH can provide extracellular ATP for subsequent PPi production.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":1000,"end_line":1010,"quote":"### ankh-atp-export\nANKH expression drove ATP release from HEK293 cells even when ENPP1 was absent.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: ANKH can provide extracellular ATP for subsequent PPi production.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293 cells\nexperimental_model: ANKH expression with ENPP1 deletion controls\nlimitations: Cellular export assay; it does not determine purified ANKH transport stoichiometry in every tissue.\ncompartment_description: Cytosol to extracellular medium\n[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["64606de9-c61a-5b9c-82f6-52f6050b8ec3"]},{"conflict_id":"0f5b4b0b-8072-5411-9be9-cb622522547f","ordinal":3,"label":"An extracellular enzyme converts exported ATP into a mineralization inhibitor.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":1012,"end_line":1022,"quote":"### enpp1-atp-to-pyrophosphate\nENPP1 converts extracellular ATP into AMP and PPi; ANKH-expressing cells lacking ENPP1 released ATP without the accompanying PPi accumulation.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An extracellular enzyme converts exported ATP into a mineralization inhibitor.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293 extracellular medium\nexperimental_model: ENPP1-proficient versus deficient cells\nlimitations: Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate.\ncompartment_description: Extracellular space\n[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["d58c332d-c2b0-5702-b062-452d2fdc6aae"]}]}],"corrections":[],"research":null}