{"gene":"TG_318330","gene_symbol":"MYSTA","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2005,"finding":"Recombinant TgMYST-A exhibits histone acetyltransferase activity in vitro, with a predilection to acetylate histone H4 at lysines 5, 8, 12, and 16.","method":"In vitro histone acetyltransferase assay with recombinant protein","journal":"Eukaryotic cell","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro enzymatic assay with recombinant protein and site-specific substrate identification in a single focused study","pmids":["16339723"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2005,"finding":"TgMYST-A protein (both long and short isoforms) localizes to both the nucleus and cytoplasm, as determined by antibody staining.","method":"Immunofluorescence/immunolocalization with TgMYST-A-specific antibody","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct antibody-based localization showing dual nuclear and cytoplasmic distribution, single lab, no functional consequence linked","pmids":["16339723"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2005,"finding":"The TgMYST-A genomic locus generates a ~3.5-kb transcript encoding two isoforms (411 or 471 amino acids), both of which contain a MYST HAT catalytic domain, an atypical C2HC zinc finger, and a chromodomain.","method":"Genomic/transcriptomic analysis and bioinformatics domain identification","journal":"Eukaryotic cell","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — domain architecture established by bioinformatics and transcript analysis without functional mutagenesis of domains","pmids":["16339723"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2005,"finding":"TgMYST-A protein is far more abundant in tachyzoites than in bradyzoites, suggesting stage-regulated expression linked to replication status.","method":"Immunoblot/antibody-based detection comparing tachyzoite and bradyzoite stages","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct protein-level comparison between life stages using antibody, single lab","pmids":["16339723"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgMYST-A (MYSTA) is a MYST-family lysine acetyltransferase in Toxoplasma gondii that acetylates histone H4 at lysines 5, 8, 12, and 16 in vitro; it localizes to both the nucleus and cytoplasm and is expressed predominantly in the rapidly replicating tachyzoite stage, with its catalytic domain, C2HC zinc finger, and chromodomain defining its conserved domain architecture."},"narrative":{"mechanistic_narrative":"TgMYST-A (MYSTA) is a MYST-family lysine acetyltransferase of Toxoplasma gondii that acetylates histone H4 at lysines 5, 8, 12, and 16 in vitro, implicating it in chromatin-associated regulation [PMID:16339723]. The protein localizes to both the nucleus and cytoplasm and is far more abundant in the rapidly replicating tachyzoite stage than in bradyzoites, linking its expression to replicative status [PMID:16339723]. Beyond its in vitro acetyltransferase activity, dual localization, and stage-regulated abundance, no in vivo substrate, protein partner, or genetic loss-of-function phenotype has been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Establishing whether TgMYST-A is a functional acetyltransferase and what it targets was needed to place it in Toxoplasma chromatin biology; the recombinant enzyme was shown to acetylate histone H4 at specific lysines, defining it as a bona fide MYST HAT.","evidence":"In vitro histone acetyltransferase assay with recombinant protein and site-specific substrate mapping","pmids":["16339723"],"confidence":"High","gaps":["No in vivo substrate confirmed","Non-histone substrates not tested","Catalytic residues not mutated to confirm activity"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2005,"claim":"To connect enzymatic activity to a cellular compartment, antibody staining showed both isoforms distribute to nucleus and cytoplasm, indicating potential roles beyond chromatin.","evidence":"Immunofluorescence/immunolocalization with TgMYST-A-specific antibody","pmids":["16339723"],"confidence":"Medium","gaps":["Cytoplasmic function unknown","No functional consequence linked to localization","Single lab, one antibody"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2005,"claim":"Whether TgMYST-A expression tracks the parasite life cycle was addressed by comparing stages, revealing predominant tachyzoite abundance and a link to replication status.","evidence":"Immunoblot/antibody-based detection comparing tachyzoite and bradyzoite stages","pmids":["16339723"],"confidence":"Medium","gaps":["Mechanism of stage regulation unknown","No causal role in stage conversion tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2005,"claim":"Domain architecture was defined to predict regulatory features, identifying a MYST catalytic domain, an atypical C2HC zinc finger, and a chromodomain across two isoforms.","evidence":"Genomic/transcriptomic analysis and bioinformatics domain identification","pmids":["16339723"],"confidence":"Low","gaps":["Domains established by bioinformatics without functional mutagenesis","Chromodomain binding target untested","Functional distinction between isoforms unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether TgMYST-A is essential and what genes or non-histone substrates it regulates in vivo remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout or conditional depletion","No in vivo substrate or genomic target identified","No interacting protein complex defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Two isoforms of 411 and 471 amino acids arise from a ~3.5-kb transcript [#2]","Conserved domain architecture comprises a MYST HAT catalytic domain, an atypical C2HC zinc finger, and a chromodomain [#2]","Expression predominates in the replicating tachyzoite stage over bradyzoites [#3]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"16339723","id":"PMC_16339723","title":"MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii.","date":"2005","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/16339723","citation_count":36,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3514,"output_tokens":957,"usd":0.012448,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5796,"output_tokens":1935,"usd":0.038677,"stage2_stop_reason":"end_turn"},"total_usd":0.051125,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"Recombinant TgMYST-A exhibits histone acetyltransferase activity in vitro, with a predilection to acetylate histone H4 at lysines 5, 8, 12, and 16.\",\n      \"method\": \"In vitro histone acetyltransferase assay with recombinant protein\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro enzymatic assay with recombinant protein and site-specific substrate identification in a single focused study\",\n      \"pmids\": [\"16339723\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"TgMYST-A protein (both long and short isoforms) localizes to both the nucleus and cytoplasm, as determined by antibody staining.\",\n      \"method\": \"Immunofluorescence/immunolocalization with TgMYST-A-specific antibody\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct antibody-based localization showing dual nuclear and cytoplasmic distribution, single lab, no functional consequence linked\",\n      \"pmids\": [\"16339723\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The TgMYST-A genomic locus generates a ~3.5-kb transcript encoding two isoforms (411 or 471 amino acids), both of which contain a MYST HAT catalytic domain, an atypical C2HC zinc finger, and a chromodomain.\",\n      \"method\": \"Genomic/transcriptomic analysis and bioinformatics domain identification\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — domain architecture established by bioinformatics and transcript analysis without functional mutagenesis of domains\",\n      \"pmids\": [\"16339723\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"TgMYST-A protein is far more abundant in tachyzoites than in bradyzoites, suggesting stage-regulated expression linked to replication status.\",\n      \"method\": \"Immunoblot/antibody-based detection comparing tachyzoite and bradyzoite stages\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct protein-level comparison between life stages using antibody, single lab\",\n      \"pmids\": [\"16339723\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgMYST-A (MYSTA) is a MYST-family lysine acetyltransferase in Toxoplasma gondii that acetylates histone H4 at lysines 5, 8, 12, and 16 in vitro; it localizes to both the nucleus and cytoplasm and is expressed predominantly in the rapidly replicating tachyzoite stage, with its catalytic domain, C2HC zinc finger, and chromodomain defining its conserved domain architecture.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgMYST-A (MYSTA) is a MYST-family lysine acetyltransferase of Toxoplasma gondii that acetylates histone H4 at lysines 5, 8, 12, and 16 in vitro, implicating it in chromatin-associated regulation [#0]. The protein localizes to both the nucleus and cytoplasm and is far more abundant in the rapidly replicating tachyzoite stage than in bradyzoites, linking its expression to replicative status [#1, #3]. Beyond its in vitro acetyltransferase activity, dual localization, and stage-regulated abundance, no in vivo substrate, protein partner, or genetic loss-of-function phenotype has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing whether TgMYST-A is a functional acetyltransferase and what it targets was needed to place it in Toxoplasma chromatin biology; the recombinant enzyme was shown to acetylate histone H4 at specific lysines, defining it as a bona fide MYST HAT.\",\n      \"evidence\": \"In vitro histone acetyltransferase assay with recombinant protein and site-specific substrate mapping\",\n      \"pmids\": [\"16339723\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No in vivo substrate confirmed\", \"Non-histone substrates not tested\", \"Catalytic residues not mutated to confirm activity\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"To connect enzymatic activity to a cellular compartment, antibody staining showed both isoforms distribute to nucleus and cytoplasm, indicating potential roles beyond chromatin.\",\n      \"evidence\": \"Immunofluorescence/immunolocalization with TgMYST-A-specific antibody\",\n      \"pmids\": [\"16339723\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cytoplasmic function unknown\", \"No functional consequence linked to localization\", \"Single lab, one antibody\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Whether TgMYST-A expression tracks the parasite life cycle was addressed by comparing stages, revealing predominant tachyzoite abundance and a link to replication status.\",\n      \"evidence\": \"Immunoblot/antibody-based detection comparing tachyzoite and bradyzoite stages\",\n      \"pmids\": [\"16339723\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of stage regulation unknown\", \"No causal role in stage conversion tested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Domain architecture was defined to predict regulatory features, identifying a MYST catalytic domain, an atypical C2HC zinc finger, and a chromodomain across two isoforms.\",\n      \"evidence\": \"Genomic/transcriptomic analysis and bioinformatics domain identification\",\n      \"pmids\": [\"16339723\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Domains established by bioinformatics without functional mutagenesis\", \"Chromodomain binding target untested\", \"Functional distinction between isoforms unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TgMYST-A is essential and what genes or non-histone substrates it regulates in vivo remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No genetic knockout or conditional depletion\", \"No in vivo substrate or genomic target identified\", \"No interacting protein complex defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004402\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0043982\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016573\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Two isoforms of 411 and 471 amino acids arise from a ~3.5-kb transcript [#2]\",\n      \"Conserved domain architecture comprises a MYST HAT catalytic domain, an atypical C2HC zinc finger, and a chromodomain [#2]\",\n      \"Expression predominates in the replicating tachyzoite stage over bradyzoites [#3]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_318330","name":"MYSTA","product":"histone lysine acetyltransferase MYST-A","uniprot_acc":"S8GS75","chromosome":"TGME49_chrIV","start_pos":1409895},{"strain":"GT1","gene_id":"TGGT1_318330","name":null,"product":"histone lysine acetyltransferase MYST-A","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":1351264},{"strain":"RH88","gene_id":"TGRH88_008220","name":null,"product":"histone lysine acetyltransferase MYST-A","uniprot_acc":null,"chromosome":"CM023085","start_pos":1431704},{"strain":"VEG","gene_id":"TGVEG_318330","name":null,"product":"histone lysine acetyltransferase MYST-A","uniprot_acc":"V4Z703","chromosome":"TGVEG_chrIV","start_pos":1419286}]}