{"gene":"PF3D7_1014600","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2004,"finding":"ADA2 (PfADA2, PF3D7_1014600) physically interacts with PfGCN5 as demonstrated by yeast two-hybrid and in vitro binding assays, and this interaction was confirmed in vivo by co-immunoprecipitation showing that anti-PfADA2 antibodies precipitate GCN5-like HAT activity from parasite lysate.","method":"Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation with HAT activity readout","journal":"Eukaryotic cell / Gene","confidence":"High","confidence_rationale":"Tier 2 / Strong — interaction confirmed by three orthogonal methods (yeast two-hybrid, in vitro pulldown, co-IP with functional readout) across two papers from the same lab","pmids":["15075257","15246536"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"ADA2 (PfADA2, PF3D7_1014600) encodes a 2578-amino-acid protein with an ADA2-like domain near the C-terminus; Northern analysis detected a major ~8.5 kb transcript in erythrocytic stage parasites, and antiserum against the ADA2-like domain detected multiple proteins from mixed blood stages, suggesting the protein may be proteolytically processed.","method":"Northern blot, antiserum immunodetection (Western blot)","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — two orthogonal detection methods (Northern and Western) in one study; proteolytic processing is inferred from band pattern, not directly demonstrated","pmids":["15246536"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"The ADA2-like domain of ADA2 (PfADA2, PF3D7_1014600) failed to rescue a yeast ada2 deletion mutant, indicating significant functional divergence from yeast ADA2 despite conserved domain architecture.","method":"Yeast complementation assay","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — negative complementation result is clean and directly experimentally tested; single lab, single method","pmids":["15246536"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Quantitative interaction proteomics identified two distinct GCN5/ADA2 complexes in P. falciparum, placing ADA2 (PF3D7_1014600) as a component of at least one of these epigenetic complexes and revealing a remarkable degree of interaction between these complexes and other epigenetic subcomplexes.","method":"Tagging and quantitative interaction proteomics (mass spectrometry)","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — quantitative proteomics is a rigorous method but the abstract does not specify which proteins were tagged or whether ADA2 itself was tagged; single study","pmids":["31728527"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"ADA2 (PF3D7_1014600) is a conserved transcriptional coactivator in P. falciparum that physically associates with the histone acetyltransferase PfGCN5 both in vitro and in vivo, forming at least one (and possibly two) GCN5/ADA2-containing HAT complexes implicated in chromatin remodeling and gene regulation during the erythrocytic stages; its ADA2-like domain is located near the C-terminus and, unlike yeast ADA2, cannot rescue a yeast ada2 deletion, indicating functional divergence."},"narrative":{"mechanistic_narrative":"ADA2 (PF3D7_1014600) is a transcriptional coactivator in Plasmodium falciparum that functions as a partner of the histone acetyltransferase PfGCN5 within GCN5/ADA2-containing complexes implicated in chromatin regulation during the erythrocytic stages [PMID:15075257, PMID:15246536, PMID:31728527]. Physical association with PfGCN5 was established through yeast two-hybrid and in vitro binding assays and confirmed in vivo, where anti-ADA2 antibodies co-precipitate GCN5-like HAT activity from parasite lysate [PMID:15075257, PMID:15246536]. Quantitative interaction proteomics places ADA2 as a component of at least one of two distinct GCN5/ADA2 complexes that show extensive interconnection with other epigenetic subcomplexes [PMID:31728527]. ADA2 carries an ADA2-like domain near the C-terminus, but this domain fails to rescue a yeast ada2 deletion, indicating functional divergence from its yeast counterpart despite conserved domain architecture [PMID:15246536]. The protein is expressed in erythrocytic-stage parasites and its immunodetection pattern is consistent with proteolytic processing [PMID:15246536]. Beyond its role as a PfGCN5-associated coactivator, no direct catalytic or gene-target-level function for ADA2 has been characterized in the available corpus.","teleology":[{"year":2004,"claim":"Establishing that ADA2 physically partners the PfGCN5 acetyltransferase answered whether P. falciparum builds a GCN5/ADA2-type coactivator module, anchoring ADA2 in chromatin-modifying machinery.","evidence":"Yeast two-hybrid and in vitro binding assays plus co-immunoprecipitation reading out associated GCN5-like HAT activity from parasite lysate","pmids":["15075257","15246536"],"confidence":"High","gaps":["Does not identify the histone residues acetylated by the ADA2-associated activity","Does not define which genes the ADA2/PfGCN5 module regulates","Does not resolve stoichiometry or full subunit composition of the in vivo complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Characterizing the ADA2 transcript and protein defined its erythrocytic-stage expression and domain layout, and raised the possibility that the protein is proteolytically processed.","evidence":"Northern blot detecting a ~8.5 kb transcript and antiserum Western detection of multiple protein species in mixed blood stages","pmids":["15246536"],"confidence":"Medium","gaps":["Proteolytic processing is inferred from band pattern, not directly demonstrated","Processing sites and functional consequence of any cleavage are unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Testing cross-species function showed that the ADA2-like domain cannot substitute for yeast ADA2, establishing that the Plasmodium protein has functionally diverged despite conserved architecture.","evidence":"Yeast ada2-deletion complementation assay with the ADA2-like domain","pmids":["15246536"],"confidence":"Medium","gaps":["Single lab, single negative complementation assay","Does not determine which residues or interactions underlie the functional divergence"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Quantitative interaction proteomics refined the picture by revealing two distinct GCN5/ADA2 complexes and placing ADA2 within this interconnected epigenetic network.","evidence":"Tagging and quantitative interaction proteomics by mass spectrometry in P. falciparum","pmids":["31728527"],"confidence":"Medium","gaps":["Abstract does not specify whether ADA2 itself was the tagged bait","Does not assign ADA2 to a specific one of the two complexes with certainty","Functional distinction between the two complexes is not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct molecular contribution of ADA2 to complex assembly, acetyltransferase targeting, and specific gene regulation during the parasite life cycle remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout or knockdown phenotype for ADA2 in the corpus","No identified target genes or chromatin loci","No structural model of the ADA2/PfGCN5 interface"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GCN5/ADA2 histone acetyltransferase complex (P. falciparum)"],"partners":["PFGCN5 (HISTONE ACETYLTRANSFERASE)"],"other_free_text":["ADA2-like domain located near the C-terminus of a 2578-amino-acid protein [#1]","ADA2-like domain does not rescue a yeast ada2 deletion, indicating functional divergence from yeast ADA2 [#2]","Expressed as a ~8.5 kb transcript in erythrocytic-stage parasites; immunodetection pattern consistent with possible proteolytic processing [#1]","Quantitative proteomics indicates existence of two distinct GCN5/ADA2 complexes interconnected with other epigenetic subcomplexes [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15075257","id":"PMC_15075257","title":"Plasmodium falciparum histone acetyltransferase, a yeast GCN5 homologue involved in chromatin remodeling.","date":"2004","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/15075257","citation_count":92,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADA2","PfADA2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31728527","id":"PMC_31728527","title":"Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31728527","citation_count":48,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADA2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15246536","id":"PMC_15246536","title":"PfADA2, a Plasmodium falciparum homologue of the transcriptional coactivator ADA2 and its in vivo association with the histone acetyltransferase PfGCN5.","date":"2004","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/15246536","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ADA2","PfADA2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4619,"output_tokens":1145,"usd":0.015516,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5960,"output_tokens":2241,"usd":0.042912,"stage2_stop_reason":"end_turn"},"total_usd":0.058428,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"ADA2 (PfADA2, PF3D7_1014600) physically interacts with PfGCN5 as demonstrated by yeast two-hybrid and in vitro binding assays, and this interaction was confirmed in vivo by co-immunoprecipitation showing that anti-PfADA2 antibodies precipitate GCN5-like HAT activity from parasite lysate.\",\n      \"method\": \"Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation with HAT activity readout\",\n      \"journal\": \"Eukaryotic cell / Gene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — interaction confirmed by three orthogonal methods (yeast two-hybrid, in vitro pulldown, co-IP with functional readout) across two papers from the same lab\",\n      \"pmids\": [\"15075257\", \"15246536\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"ADA2 (PfADA2, PF3D7_1014600) encodes a 2578-amino-acid protein with an ADA2-like domain near the C-terminus; Northern analysis detected a major ~8.5 kb transcript in erythrocytic stage parasites, and antiserum against the ADA2-like domain detected multiple proteins from mixed blood stages, suggesting the protein may be proteolytically processed.\",\n      \"method\": \"Northern blot, antiserum immunodetection (Western blot)\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — two orthogonal detection methods (Northern and Western) in one study; proteolytic processing is inferred from band pattern, not directly demonstrated\",\n      \"pmids\": [\"15246536\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The ADA2-like domain of ADA2 (PfADA2, PF3D7_1014600) failed to rescue a yeast ada2 deletion mutant, indicating significant functional divergence from yeast ADA2 despite conserved domain architecture.\",\n      \"method\": \"Yeast complementation assay\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — negative complementation result is clean and directly experimentally tested; single lab, single method\",\n      \"pmids\": [\"15246536\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Quantitative interaction proteomics identified two distinct GCN5/ADA2 complexes in P. falciparum, placing ADA2 (PF3D7_1014600) as a component of at least one of these epigenetic complexes and revealing a remarkable degree of interaction between these complexes and other epigenetic subcomplexes.\",\n      \"method\": \"Tagging and quantitative interaction proteomics (mass spectrometry)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — quantitative proteomics is a rigorous method but the abstract does not specify which proteins were tagged or whether ADA2 itself was tagged; single study\",\n      \"pmids\": [\"31728527\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ADA2 (PF3D7_1014600) is a conserved transcriptional coactivator in P. falciparum that physically associates with the histone acetyltransferase PfGCN5 both in vitro and in vivo, forming at least one (and possibly two) GCN5/ADA2-containing HAT complexes implicated in chromatin remodeling and gene regulation during the erythrocytic stages; its ADA2-like domain is located near the C-terminus and, unlike yeast ADA2, cannot rescue a yeast ada2 deletion, indicating functional divergence.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ADA2 (PF3D7_1014600) is a transcriptional coactivator in Plasmodium falciparum that functions as a partner of the histone acetyltransferase PfGCN5 within GCN5/ADA2-containing complexes implicated in chromatin regulation during the erythrocytic stages [#0, #3]. Physical association with PfGCN5 was established through yeast two-hybrid and in vitro binding assays and confirmed in vivo, where anti-ADA2 antibodies co-precipitate GCN5-like HAT activity from parasite lysate [#0]. Quantitative interaction proteomics places ADA2 as a component of at least one of two distinct GCN5/ADA2 complexes that show extensive interconnection with other epigenetic subcomplexes [#3]. ADA2 carries an ADA2-like domain near the C-terminus, but this domain fails to rescue a yeast ada2 deletion, indicating functional divergence from its yeast counterpart despite conserved domain architecture [#1, #2]. The protein is expressed in erythrocytic-stage parasites and its immunodetection pattern is consistent with proteolytic processing [#1]. Beyond its role as a PfGCN5-associated coactivator, no direct catalytic or gene-target-level function for ADA2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing that ADA2 physically partners the PfGCN5 acetyltransferase answered whether P. falciparum builds a GCN5/ADA2-type coactivator module, anchoring ADA2 in chromatin-modifying machinery.\",\n      \"evidence\": \"Yeast two-hybrid and in vitro binding assays plus co-immunoprecipitation reading out associated GCN5-like HAT activity from parasite lysate\",\n      \"pmids\": [\"15075257\", \"15246536\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not identify the histone residues acetylated by the ADA2-associated activity\",\n        \"Does not define which genes the ADA2/PfGCN5 module regulates\",\n        \"Does not resolve stoichiometry or full subunit composition of the in vivo complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Characterizing the ADA2 transcript and protein defined its erythrocytic-stage expression and domain layout, and raised the possibility that the protein is proteolytically processed.\",\n      \"evidence\": \"Northern blot detecting a ~8.5 kb transcript and antiserum Western detection of multiple protein species in mixed blood stages\",\n      \"pmids\": [\"15246536\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Proteolytic processing is inferred from band pattern, not directly demonstrated\",\n        \"Processing sites and functional consequence of any cleavage are unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Testing cross-species function showed that the ADA2-like domain cannot substitute for yeast ADA2, establishing that the Plasmodium protein has functionally diverged despite conserved architecture.\",\n      \"evidence\": \"Yeast ada2-deletion complementation assay with the ADA2-like domain\",\n      \"pmids\": [\"15246536\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single negative complementation assay\",\n        \"Does not determine which residues or interactions underlie the functional divergence\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Quantitative interaction proteomics refined the picture by revealing two distinct GCN5/ADA2 complexes and placing ADA2 within this interconnected epigenetic network.\",\n      \"evidence\": \"Tagging and quantitative interaction proteomics by mass spectrometry in P. falciparum\",\n      \"pmids\": [\"31728527\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Abstract does not specify whether ADA2 itself was the tagged bait\",\n        \"Does not assign ADA2 to a specific one of the two complexes with certainty\",\n        \"Functional distinction between the two complexes is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular contribution of ADA2 to complex assembly, acetyltransferase targeting, and specific gene regulation during the parasite life cycle remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout or knockdown phenotype for ADA2 in the corpus\",\n        \"No identified target genes or chromatin loci\",\n        \"No structural model of the ADA2/PfGCN5 interface\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003713\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0006338\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\n      \"GCN5/ADA2 histone acetyltransferase complex (P. falciparum)\"\n    ],\n    \"partners\": [\n      \"PfGCN5 (histone acetyltransferase)\"\n    ],\n    \"other_free_text\": [\n      \"ADA2-like domain located near the C-terminus of a 2578-amino-acid protein [#1]\",\n      \"ADA2-like domain does not rescue a yeast ada2 deletion, indicating functional divergence from yeast ADA2 [#2]\",\n      \"Expressed as a ~8.5 kb transcript in erythrocytic-stage parasites; immunodetection pattern consistent with possible proteolytic processing [#1]\",\n      \"Quantitative proteomics indicates existence of two distinct GCN5/ADA2 complexes interconnected with other epigenetic subcomplexes [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1014600","name":null,"product":"transcriptional coactivator ADA2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1213000","name":null,"product":"transcriptional coactivator ADA2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0814700","name":null,"product":"transcriptional coactivator ADA2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ADA2","evaluation":null}