{"id":"7e7b5136-2081-54ea-94cb-f99bc05f233d","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:kdm4a-h3k9-demethylation","predicate":"demethylates","statement":"KDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d9331d4c-41a6-58e1-ab90-ffa37c0e8bd4","mechanism_event_label":"An iron-dependent enzyme erases a different class of methyl mark.","subject":{"id":"dc7a3481-f615-5b9f-9b71-25f0b5d1c63b","slug":"kdm4a","display_name":"KDM4A","entity_type_key":"protein"},"object":{"id":"bccfc0ea-bf38-599d-bfef-8f5c225e4dae","slug":"h3k9me3","display_name":"Histone H3 trimethylated at K9","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"d9331d4c-41a6-58e1-ab90-ffa37c0e8bd4","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:kdm4a-h3k9-demethylation-event","event_type":"biochemical_relationship","label":"An iron-dependent enzyme erases a different class of methyl mark.","description":"KDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate.","status":"provisional","compartment":{"slug":"nucleus","display_name":"Nucleus"},"participants":[{"entity":{"id":"dc7a3481-f615-5b9f-9b71-25f0b5d1c63b","slug":"kdm4a","display_name":"KDM4A","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bccfc0ea-bf38-599d-bfef-8f5c225e4dae","slug":"h3k9me3","display_name":"Histone H3 trimethylated at K9","entity_type_key":"protein_state"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"481d42aa-76f5-5f0a-b85b-8ffd85e4e41a","slug":"h3k9me2","display_name":"Histone H3 dimethylated at K9","entity_type_key":"protein_state"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"cofactor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"899c7ab0-6f81-5b38-a6bd-fbb33d66ac8d","slug":"oxygen","display_name":"Molecular oxygen","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"628ddc2d-e4d9-59c7-ae76-0c0cab80a6b1","slug":"2-oxoglutarate","display_name":"2-Oxoglutarate","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"528300c2-5f81-5188-b14c-eafc747cd15b","slug":"formaldehyde","display_name":"Formaldehyde","entity_type_key":"small_molecule"},"role":"coproduct","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"462f63ce-a2c1-5312-9c14-70b8b12e1d6e","slug":"succinate","display_name":"Succinate","entity_type_key":"small_molecule"},"role":"coproduct","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""},{"entity":{"id":"966f14e5-c82f-5535-ad89-bfcc0adb2232","slug":"carbon-dioxide","display_name":"Carbon dioxide","entity_type_key":"small_molecule"},"role":"coproduct","stoichiometry":null,"state_label":"","sequence_order":8,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Human JMJD2A catalytic-domain structures and methylated peptide assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An iron-dependent enzyme erases a different class of methyl mark.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024\n[kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Not specified as a whole tissue; see experimental model.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"43e3ade7-cb87-538e-971b-be704b8d0be8","evidence_kind":"source_excerpt","locator":"Lines 567-576","start_line":567,"end_line":576,"excerpt":"### kdm4a-h3k9-demethylation\nKDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate.\nPlain language: An iron-dependent enzyme erases a different class of methyl mark.\nCondition category: normal\norganism: Human\ntissue_or_cell_type: Not specified as a whole tissue; see experimental model.\nexperimental_model: Human JMJD2A catalytic-domain structures and methylated peptide assays.\nlimitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.\n[kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024\n[kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273","model_system":"Human JMJD2A catalytic-domain structures and methylated peptide assays.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact quote from the accompanying curation document, not from publisher text. Original study references: [kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024; [kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"7633bde7-dcc9-5086-91c6-a45eb96857f3","stable_key":"import-c3df3634-4c3a-5099-a5d9-e4f6344c1084","title":"L-Lysine: 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. 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