{"gene":"KAT2A","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":2025,"finding":"SAGA CORE module subunits TADA1, TAF5L, and TAF6L are required for KAT2A protein stability; loss of these subunits releases KAT2A from chromatin and leads to its proteasomal degradation, resulting in reduced H3K9 acetylation. The E3 ligase UBR5 and deubiquitinase OTUD5 were identified as regulators of KAT2A degradation when the SAGA CORE is disrupted.","method":"Fluorescence-based KAT2A stability reporter, systematic genetic perturbation of SAGA subunits, proteomic profiling, focused CRISPR screen of ubiquitin-proteasome system genes","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (stability reporter, proteomics, CRISPR screen) in single lab; preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.07.24.666361"],"is_preprint":true},{"year":2025,"finding":"The cancer-specific protein MAGE-A10 stabilizes KAT2A by antagonizing binding of KAT2A to the E3 ubiquitin ligase complex CUL4A-DDB1, thereby reducing K63-linked ubiquitination of KAT2A and preventing its p62-mediated autophagic degradation, leading to increased histone acetylation.","method":"Co-immunoprecipitation, ubiquitination assays, autophagy pathway analysis, overexpression/knockdown experiments","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic dissection with Co-IP and ubiquitination assays in single lab; preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.03.05.641767"],"is_preprint":true},{"year":2025,"finding":"KAT2A functions as a lactyl-transferase mediating histone lactylation in the context of HIV-1 latency reversal under hypoxic/hyperglycemic conditions; this activity promotes chromatin accessibility at the HIV promoter.","method":"Pharmacological inhibition, metabolomic profiling, chromatin accessibility assays, identification of KAT2A as lactyl-transferase via functional experiments","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method implied in abstract, preprint with limited mechanistic detail on direct enzymatic characterization","pmids":["bio_10.1101_2025.09.14.676169"],"is_preprint":true},{"year":2025,"finding":"Upon DNA damage, Chk1 remodels Sp1-associated chromatin complexes to a transcriptionally active state that includes recruitment of the histone acetyltransferase KAT2A to the CD59 promoter, thereby enhancing CD59 transcription.","method":"Co-immunoprecipitation mass spectrometry, kinase inhibitor screen, transcriptional assays","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP/MS from single lab, single study, preprint; KAT2A recruitment inferred from complex membership without direct enzymatic validation","pmids":["bio_10.1101_2025.02.17.638751"],"is_preprint":true}],"current_model":"KAT2A is the catalytic histone acetyltransferase subunit of the SAGA co-activator complex, where its stability depends on intact SAGA CORE subunits (TADA1, TAF5L, TAF6L); when unassembled, KAT2A is targeted for proteasomal degradation via UBR5 or autophagic degradation via CUL4A-DDB1-mediated K63-ubiquitination, and beyond canonical H3K9 acetylation, KAT2A can also act as a lactyl-transferase and is recruited to specific gene promoters (e.g., CD59) as part of transcriptionally active complexes."},"narrative":{"mechanistic_narrative":"KAT2A is a histone acetyltransferase whose activity is governed by its assembly into the SAGA co-activator complex: its protein stability depends on the integrity of the SAGA CORE module subunits TADA1, TAF5L, and TAF6L, and loss of these subunits releases KAT2A from chromatin and triggers its proteasomal degradation with consequent loss of H3K9 acetylation, a process regulated by the E3 ligase UBR5 and the deubiquitinase OTUD5 [PMID:bio_10.1101_2025.07.24.666361]. An independent degradation route operates through the CUL4A-DDB1 ligase, which directs K63-linked ubiquitination and p62-mediated autophagic turnover of KAT2A; the cancer-specific protein MAGE-A10 stabilizes KAT2A by antagonizing this interaction and thereby raising histone acetylation [PMID:bio_10.1101_2025.03.05.641767]. Beyond canonical H3K9 acetylation, KAT2A acts as a histone lactyl-transferase that promotes chromatin accessibility at the HIV-1 promoter under hypoxic/hyperglycemic conditions [PMID:bio_10.1101_2025.09.14.676169], and it is recruited to specific gene promoters such as CD59 within transcriptionally active, Chk1-remodeled Sp1 complexes following DNA damage [PMID:bio_10.1101_2025.02.17.638751].","teleology":[{"year":2025,"claim":"Established that KAT2A's stability and chromatin association are coupled to SAGA CORE assembly, explaining how the cell links co-activator integrity to histone acetylation output.","evidence":"Fluorescence-based stability reporter, genetic perturbation of SAGA subunits, proteomics, and a focused CRISPR screen of ubiquitin-proteasome genes","pmids":["bio_10.1101_2025.07.24.666361"],"confidence":"Medium","gaps":["Direct substrate engagement by UBR5 and reversal by OTUD5 not reconstituted in vitro","Preprint not yet peer-reviewed","Whether SAGA-independent KAT2A pools exist is not resolved"]},{"year":2025,"claim":"Defined a second, autophagy-linked degradation axis for KAT2A and its antagonism by MAGE-A10, showing how cancer-specific factors can elevate histone acetylation by blocking turnover.","evidence":"Co-immunoprecipitation, ubiquitination assays, autophagy pathway analysis, and overexpression/knockdown in a single lab","pmids":["bio_10.1101_2025.03.05.641767"],"confidence":"Medium","gaps":["Direct CUL4A-DDB1 ubiquitination site on KAT2A not mapped","Relationship between the UBR5/proteasomal and CUL4A/autophagic routes not integrated","Preprint not yet peer-reviewed"]},{"year":2025,"claim":"Extended KAT2A's catalytic repertoire beyond acetylation to histone lactylation, linking it to metabolic state and chromatin accessibility at the HIV-1 promoter.","evidence":"Pharmacological inhibition, metabolomic profiling, and chromatin accessibility assays in a latency-reversal model","pmids":["bio_10.1101_2025.09.14.676169"],"confidence":"Low","gaps":["Direct enzymatic characterization of KAT2A lactyl-transferase activity not demonstrated in a reconstituted system","Single lab, single study, preprint","Substrate residues for lactylation not defined"]},{"year":2025,"claim":"Placed KAT2A in a DNA-damage-responsive promoter-recruitment circuit, showing it is brought to the CD59 promoter within a Chk1-remodeled Sp1 complex to enhance transcription.","evidence":"Co-immunoprecipitation mass spectrometry, kinase inhibitor screen, and transcriptional assays","pmids":["bio_10.1101_2025.02.17.638751"],"confidence":"Low","gaps":["KAT2A recruitment inferred from complex membership without direct enzymatic validation at CD59","Mechanism of Chk1-dependent recruitment not defined","Single lab, preprint"]},{"year":null,"claim":"How the distinct KAT2A degradation routes, its acetyl- versus lactyl-transferase activities, and its promoter-specific recruitment are integrated into a unified regulatory logic remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model linking SAGA assembly state to degron exposure","Relative contributions of proteasomal versus autophagic turnover in physiological contexts unknown","Genome-wide map of KAT2A-dependent acetylation versus lactylation targets not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,2]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,3]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,2,3]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[3]}],"complexes":["SAGA"],"partners":["TADA1","TAF5L","TAF6L","UBR5","OTUD5","CUL4A","DDB1","MAGEA10"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q92830","full_name":"Histone acetyltransferase KAT2A","aliases":["General control of amino acid synthesis protein 5-like 2","Histone acetyltransferase GCN5","hGCN5","Histone glutaryltransferase KAT2A","Histone succinyltransferase KAT2A","Lysine acetyltransferase 2A","STAF97"],"length_aa":837,"mass_kda":93.9,"function":"Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context (PubMed:29211711, PubMed:35995428). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755, PubMed:21131905). Has a a strong preference for acetylation of H3 at 'Lys-9' (H3K9ac) (PubMed:21131905). Also catalyzes acetylation of histone H1.4 (H1-4) at 'Lys-34' (H1.4K34ac), a modification enriched at promoters of active genes (PubMed:22465951). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (PubMed:29973595, PubMed:31527837). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (By similarity). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC) pluripotency and differentiation (By similarity). Also acetylates non-histone proteins, such as CEBPB, MRE11, PPARGC1A, PLK4 and TBX5 (PubMed:16753578, PubMed:17301242, PubMed:27796307, PubMed:29174768, PubMed:38128537). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A (PubMed:16753578, PubMed:23142079). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (PubMed:31542297) (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes","subcellular_location":"Nucleus; Chromosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q92830/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KAT2A","classification":"Not Classified","n_dependent_lines":161,"n_total_lines":1208,"dependency_fraction":0.13327814569536423},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TAF12","stoichiometry":10.0},{"gene":"TRRAP","stoichiometry":10.0},{"gene":"ENY2","stoichiometry":0.2},{"gene":"SF3B3","stoichiometry":0.2},{"gene":"SF3B5","stoichiometry":0.2},{"gene":"USP22","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KAT2A","total_profiled":1310},"omim":[{"mim_id":"617989","title":"N-ALPHA-ACETYLTRANSFERASE 30, NatC CATALYTIC SUBUNIT; NAA30","url":"https://www.omim.org/entry/617989"},{"mim_id":"617501","title":"LYSINE ACETYLTRANSFERASE 14; KAT14","url":"https://www.omim.org/entry/617501"},{"mim_id":"616510","title":"GLUCOSAMINE-PHOSPHATE N-ACETYLTRANSFERASE 1; GNPNAT1","url":"https://www.omim.org/entry/616510"},{"mim_id":"615556","title":"ALPHA-TUBULIN ACETYLTRANSFERASE 1; ATAT1","url":"https://www.omim.org/entry/615556"},{"mim_id":"613374","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 101; CCDC101","url":"https://www.omim.org/entry/613374"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/KAT2A"},"hgnc":{"alias_symbol":["GCN5","PCAF-b"],"prev_symbol":["GCN5L2"]},"alphafold":{"accession":"Q92830","domains":[{"cath_id":"-","chopping":"98-127_142-212","consensus_level":"medium","plddt":92.6009,"start":98,"end":212},{"cath_id":"-","chopping":"232-369","consensus_level":"medium","plddt":91.1923,"start":232,"end":369},{"cath_id":"3.40.630.30","chopping":"487-667","consensus_level":"high","plddt":91.3093,"start":487,"end":667},{"cath_id":"1.20.920.10","chopping":"731-833","consensus_level":"high","plddt":92.6239,"start":731,"end":833}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92830","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92830-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92830-F1-predicted_aligned_error_v6.png","plddt_mean":77.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KAT2A","jax_strain_url":"https://www.jax.org/strain/search?query=KAT2A"},"sequence":{"accession":"Q92830","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92830.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92830/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92830"}},"corpus_meta":[{"pmid":null,"id":"bio_10.1101_2025.07.24.666361","title":"Disruption of the SAGA CORE triggers collateral degradation of KAT2A","date":"2025-07-25","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.24.666361","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.04.686676","title":"RainBar: Optical Barcoding for Pooled Live-Cell Imaging with Single-Cell Resolution","date":"2025-11-05","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.04.686676","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.05.641767","title":"A Cancer-Specific Antigen Drives Histone Acetylation by Stabilizing the Acetyltransferases","date":"2025-03-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.05.641767","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.14.676169","title":"Glucose-Fueled Histone Modifications Drive HIV-1 Latency Reversal at Hypoxia","date":"2025-09-16","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.14.676169","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.02.17.638751","title":"Genotoxic chemotherapy impedes complement dependent cytotoxicity via Chk1-mediated CD59 regulation","date":"2025-02-22","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.17.638751","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4840,"output_tokens":1156,"usd":0.01593,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7690,"output_tokens":2133,"usd":0.045887,"stage2_stop_reason":"end_turn"},"total_usd":0.061817,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"SAGA CORE module subunits TADA1, TAF5L, and TAF6L are required for KAT2A protein stability; loss of these subunits releases KAT2A from chromatin and leads to its proteasomal degradation, resulting in reduced H3K9 acetylation. The E3 ligase UBR5 and deubiquitinase OTUD5 were identified as regulators of KAT2A degradation when the SAGA CORE is disrupted.\",\n      \"method\": \"Fluorescence-based KAT2A stability reporter, systematic genetic perturbation of SAGA subunits, proteomic profiling, focused CRISPR screen of ubiquitin-proteasome system genes\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (stability reporter, proteomics, CRISPR screen) in single lab; preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.07.24.666361\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The cancer-specific protein MAGE-A10 stabilizes KAT2A by antagonizing binding of KAT2A to the E3 ubiquitin ligase complex CUL4A-DDB1, thereby reducing K63-linked ubiquitination of KAT2A and preventing its p62-mediated autophagic degradation, leading to increased histone acetylation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, autophagy pathway analysis, overexpression/knockdown experiments\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic dissection with Co-IP and ubiquitination assays in single lab; preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.03.05.641767\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"KAT2A functions as a lactyl-transferase mediating histone lactylation in the context of HIV-1 latency reversal under hypoxic/hyperglycemic conditions; this activity promotes chromatin accessibility at the HIV promoter.\",\n      \"method\": \"Pharmacological inhibition, metabolomic profiling, chromatin accessibility assays, identification of KAT2A as lactyl-transferase via functional experiments\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method implied in abstract, preprint with limited mechanistic detail on direct enzymatic characterization\",\n      \"pmids\": [\"bio_10.1101_2025.09.14.676169\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Upon DNA damage, Chk1 remodels Sp1-associated chromatin complexes to a transcriptionally active state that includes recruitment of the histone acetyltransferase KAT2A to the CD59 promoter, thereby enhancing CD59 transcription.\",\n      \"method\": \"Co-immunoprecipitation mass spectrometry, kinase inhibitor screen, transcriptional assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP/MS from single lab, single study, preprint; KAT2A recruitment inferred from complex membership without direct enzymatic validation\",\n      \"pmids\": [\"bio_10.1101_2025.02.17.638751\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"KAT2A is the catalytic histone acetyltransferase subunit of the SAGA co-activator complex, where its stability depends on intact SAGA CORE subunits (TADA1, TAF5L, TAF6L); when unassembled, KAT2A is targeted for proteasomal degradation via UBR5 or autophagic degradation via CUL4A-DDB1-mediated K63-ubiquitination, and beyond canonical H3K9 acetylation, KAT2A can also act as a lactyl-transferase and is recruited to specific gene promoters (e.g., CD59) as part of transcriptionally active complexes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KAT2A is a histone acetyltransferase whose activity is governed by its assembly into the SAGA co-activator complex: its protein stability depends on the integrity of the SAGA CORE module subunits TADA1, TAF5L, and TAF6L, and loss of these subunits releases KAT2A from chromatin and triggers its proteasomal degradation with consequent loss of H3K9 acetylation, a process regulated by the E3 ligase UBR5 and the deubiquitinase OTUD5 [#0]. An independent degradation route operates through the CUL4A-DDB1 ligase, which directs K63-linked ubiquitination and p62-mediated autophagic turnover of KAT2A; the cancer-specific protein MAGE-A10 stabilizes KAT2A by antagonizing this interaction and thereby raising histone acetylation [#1]. Beyond canonical H3K9 acetylation, KAT2A acts as a histone lactyl-transferase that promotes chromatin accessibility at the HIV-1 promoter under hypoxic/hyperglycemic conditions [#2], and it is recruited to specific gene promoters such as CD59 within transcriptionally active, Chk1-remodeled Sp1 complexes following DNA damage [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Established that KAT2A's stability and chromatin association are coupled to SAGA CORE assembly, explaining how the cell links co-activator integrity to histone acetylation output.\",\n      \"evidence\": \"Fluorescence-based stability reporter, genetic perturbation of SAGA subunits, proteomics, and a focused CRISPR screen of ubiquitin-proteasome genes\",\n      \"pmids\": [\"bio_10.1101_2025.07.24.666361\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct substrate engagement by UBR5 and reversal by OTUD5 not reconstituted in vitro\",\n        \"Preprint not yet peer-reviewed\",\n        \"Whether SAGA-independent KAT2A pools exist is not resolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a second, autophagy-linked degradation axis for KAT2A and its antagonism by MAGE-A10, showing how cancer-specific factors can elevate histone acetylation by blocking turnover.\",\n      \"evidence\": \"Co-immunoprecipitation, ubiquitination assays, autophagy pathway analysis, and overexpression/knockdown in a single lab\",\n      \"pmids\": [\"bio_10.1101_2025.03.05.641767\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct CUL4A-DDB1 ubiquitination site on KAT2A not mapped\",\n        \"Relationship between the UBR5/proteasomal and CUL4A/autophagic routes not integrated\",\n        \"Preprint not yet peer-reviewed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended KAT2A's catalytic repertoire beyond acetylation to histone lactylation, linking it to metabolic state and chromatin accessibility at the HIV-1 promoter.\",\n      \"evidence\": \"Pharmacological inhibition, metabolomic profiling, and chromatin accessibility assays in a latency-reversal model\",\n      \"pmids\": [\"bio_10.1101_2025.09.14.676169\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Direct enzymatic characterization of KAT2A lactyl-transferase activity not demonstrated in a reconstituted system\",\n        \"Single lab, single study, preprint\",\n        \"Substrate residues for lactylation not defined\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed KAT2A in a DNA-damage-responsive promoter-recruitment circuit, showing it is brought to the CD59 promoter within a Chk1-remodeled Sp1 complex to enhance transcription.\",\n      \"evidence\": \"Co-immunoprecipitation mass spectrometry, kinase inhibitor screen, and transcriptional assays\",\n      \"pmids\": [\"bio_10.1101_2025.02.17.638751\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"KAT2A recruitment inferred from complex membership without direct enzymatic validation at CD59\",\n        \"Mechanism of Chk1-dependent recruitment not defined\",\n        \"Single lab, preprint\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the distinct KAT2A degradation routes, its acetyl- versus lactyl-transferase activities, and its promoter-specific recruitment are integrated into a unified regulatory logic remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model linking SAGA assembly state to degron exposure\",\n        \"Relative contributions of proteasomal versus autophagic turnover in physiological contexts unknown\",\n        \"Genome-wide map of KAT2A-dependent acetylation versus lactylation targets not established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"SAGA\"],\n    \"partners\": [\"TADA1\", \"TAF5L\", \"TAF6L\", \"UBR5\", \"OTUD5\", \"CUL4A\", \"DDB1\", \"MAGEA10\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win"}}