{"id":"bc929f4e-c09f-5c53-9acc-66259a392865","stable_key":"488ea171-36b8-5ef6-b5d3-98563980fdbf:hbot-phd2-autoregulation","predicate":"increases","statement":"PHD2 is itself upregulated by hypoxia, providing a HIF-1-dependent auto-regulatory mechanism driven by oxygen tension.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ccd1979b-57b4-5eed-82ee-9a8400d942fc","mechanism_event_label":"The thermostat builds more of itself when oxygen is scarce, so the system resets when oxygen returns.","subject":{"id":"22b3e241-94b0-55fd-a233-c63af92520d8","slug":"hif1a","display_name":"HIF-1 alpha","entity_type_key":"protein"},"object":{"id":"8681acd7-4f56-59e0-a757-37b8376c8bde","slug":"egln1","display_name":"EGLN1 / PHD2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ccd1979b-57b4-5eed-82ee-9a8400d942fc","stable_key":"488ea171-36b8-5ef6-b5d3-98563980fdbf:hbot-phd2-autoregulation-event","event_type":"biochemical_relationship","label":"The thermostat builds more of itself when oxygen is scarce, so the system resets when oxygen returns.","description":"PHD2 is itself upregulated by hypoxia, providing a HIF-1-dependent auto-regulatory mechanism driven by oxygen tension.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"22b3e241-94b0-55fd-a233-c63af92520d8","slug":"hif1a","display_name":"HIF-1 alpha","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8681acd7-4f56-59e0-a757-37b8376c8bde","slug":"egln1","display_name":"EGLN1 / PHD2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/hbot-research/12912907.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e\", \"start_char\": 0, \"end_char\": 1190, \"text_sha256\": \"db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"PHD1, PHD2 and PHD3 silencing in normoxia and after brief hypoxia","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A silencing study assigning distinct roles. It establishes which isoform sets the resting level, not the oxygen concentration at which each acts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"hyperbaric-oxygen","display_name":"Hyperbaric oxygen therapy","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The thermostat builds more of itself when oxygen is scarce, so the system resets when oxygen returns.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[hbot-p12912907] HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. (2003). https://pubmed.ncbi.nlm.nih.gov/12912907/ DOI: 10.1093/emboj/cdg392","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cytosol","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f7d06bce-389f-5320-9312-fbfe01c58864","evidence_kind":"source_excerpt","locator":"Lines 946-957","start_line":946,"end_line":957,"excerpt":"### hbot-phd2-autoregulation\nPHD2 is itself upregulated by hypoxia, providing a HIF-1-dependent auto-regulatory mechanism driven by oxygen tension.\nCondition category: normal\nnutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.\nplain_language: The thermostat builds more of itself when oxygen is scarce, so the system resets when oxygen returns.\norganism: Human cells\ntissue_or_cell_type: Cytosol\nexperimental_model: Short interfering RNA silencing of each HIF prolyl-hydroxylase in human cells\nlimitations: A silencing study assigning distinct roles. It establishes which isoform sets the resting level, not the oxygen concentration at which each acts.\nexposure: PHD1, PHD2 and PHD3 silencing in normoxia and after brief hypoxia\nevidence_span: {\"source_cache\": \"artifacts/hbot-research/12912907.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e\", \"start_char\": 0, \"end_char\": 1190, \"text_sha256\": \"db0613321b1804356dbb60637bba0616eaaaeab041f63a095ecfcaeac3ec780e\"}\n[hbot-p12912907] HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. 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