{"gene":"TG_227020","gene_symbol":"SIR2","run_date":"2026-09-08T11:06:46","timeline":{"discoveries":[{"year":2021,"finding":"Recombinant TgSIR2 (rTgSIR2) promoted proliferation, apoptosis, and phagocytosis of murine Ana-1 macrophages, and modulated secretion of nitric oxide (NO), pro-inflammatory cytokines, and anti-inflammatory cytokines in vitro, demonstrating a functional role in modulating host macrophage responses.","method":"In vitro treatment of murine Ana-1 macrophages with recombinant TgSIR2 protein, with assessment of proliferation, apoptosis, phagocytosis, and cytokine/NO secretion","journal":"Microbial pathogenesis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single set of in vitro assays with recombinant protein, no mechanistic pathway placement or mutagenesis","pmids":["33731306"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"current_model":"TgSIR2 is a histone deacetylase (HDAC/sirtuin-family) protein in Toxoplasma gondii that, when supplied as a recombinant protein exogenously, can modulate murine macrophage functions including proliferation, apoptosis, phagocytosis, and cytokine/NO secretion in vitro, but its intrinsic enzymatic mechanism and in-parasite substrates remain uncharacterized."},"narrative":{"mechanistic_narrative":"TgSIR2 is annotated as a sirtuin-family (HDAC-type) protein in Toxoplasma gondii whose only characterized activity in the available corpus is an immunomodulatory effect on host macrophages. When supplied exogenously as recombinant protein (rTgSIR2), it altered proliferation, apoptosis, and phagocytosis of murine Ana-1 macrophages and modulated secretion of nitric oxide and pro- and anti-inflammatory cytokines in vitro, in the RH strain context [PMID:33731306]. Beyond this single in vitro observation, the protein's intrinsic deacetylase mechanism, in-parasite substrates, and pathway placement have not been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Whether TgSIR2 has any role beyond a presumed intracellular deacetylase was unknown; treating host macrophages with the recombinant protein established that it can modulate host immune-cell behavior.","evidence":"In vitro treatment of murine Ana-1 macrophages with recombinant TgSIR2 protein, assessing proliferation, apoptosis, phagocytosis, and cytokine/NO secretion","pmids":["33731306"],"confidence":"Low","gaps":["Single lab, single set of in vitro assays with recombinant protein; not independently confirmed","No enzymatic (deacetylase) activity demonstrated and no substrate identified","No in-parasite loss-of-function or mutagenesis to establish endogenous function or pathway placement"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":null,"claim":"The intrinsic enzymatic mechanism of TgSIR2 and its authentic in-parasite substrates and localization remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstration of NAD-dependent deacetylase activity","No identified histone or non-histone substrates within the parasite","No genetic requirement or subcellular localization established"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Recombinant TgSIR2 modulates murine macrophage proliferation, apoptosis, phagocytosis, and cytokine/NO secretion in vitro [#0]","Annotated as a sirtuin-family (HDAC-type) protein, but intrinsic deacetylase activity and in-parasite substrates are uncharacterized in the corpus"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"34683874","id":"PMC_34683874","title":"Nano DNA Vaccine Encoding Toxoplasma gondii Histone Deacetylase SIR2 Enhanced Protective Immunity in Mice.","date":"2021","source":"Pharmaceutics","url":"https://pubmed.ncbi.nlm.nih.gov/34683874","citation_count":8,"is_preprint":false},{"pmid":"33731306","id":"PMC_33731306","title":"Histone deacetylase SIR2 in Toxoplasma gondii modulates functions of murine macrophages in vitro and protects mice against acute toxoplasmosis in vivo.","date":"2021","source":"Microbial pathogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/33731306","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3631,"output_tokens":425,"usd":0.008634,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5023,"output_tokens":1035,"usd":0.025495,"stage2_stop_reason":"end_turn"},"total_usd":0.034129,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"Recombinant TgSIR2 (rTgSIR2) promoted proliferation, apoptosis, and phagocytosis of murine Ana-1 macrophages, and modulated secretion of nitric oxide (NO), pro-inflammatory cytokines, and anti-inflammatory cytokines in vitro, demonstrating a functional role in modulating host macrophage responses.\",\n      \"method\": \"In vitro treatment of murine Ana-1 macrophages with recombinant TgSIR2 protein, with assessment of proliferation, apoptosis, phagocytosis, and cytokine/NO secretion\",\n      \"journal\": \"Microbial pathogenesis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single set of in vitro assays with recombinant protein, no mechanistic pathway placement or mutagenesis\",\n      \"pmids\": [\"33731306\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgSIR2 is a histone deacetylase (HDAC/sirtuin-family) protein in Toxoplasma gondii that, when supplied as a recombinant protein exogenously, can modulate murine macrophage functions including proliferation, apoptosis, phagocytosis, and cytokine/NO secretion in vitro, but its intrinsic enzymatic mechanism and in-parasite substrates remain uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgSIR2 is annotated as a sirtuin-family (HDAC-type) protein in Toxoplasma gondii whose only characterized activity in the available corpus is an immunomodulatory effect on host macrophages. When supplied exogenously as recombinant protein (rTgSIR2), it altered proliferation, apoptosis, and phagocytosis of murine Ana-1 macrophages and modulated secretion of nitric oxide and pro- and anti-inflammatory cytokines in vitro, in the RH strain context [#0]. Beyond this single in vitro observation, the protein's intrinsic deacetylase mechanism, in-parasite substrates, and pathway placement have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether TgSIR2 has any role beyond a presumed intracellular deacetylase was unknown; treating host macrophages with the recombinant protein established that it can modulate host immune-cell behavior.\",\n      \"evidence\": \"In vitro treatment of murine Ana-1 macrophages with recombinant TgSIR2 protein, assessing proliferation, apoptosis, phagocytosis, and cytokine/NO secretion\",\n      \"pmids\": [\"33731306\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, single set of in vitro assays with recombinant protein; not independently confirmed\",\n        \"No enzymatic (deacetylase) activity demonstrated and no substrate identified\",\n        \"No in-parasite loss-of-function or mutagenesis to establish endogenous function or pathway placement\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic enzymatic mechanism of TgSIR2 and its authentic in-parasite substrates and localization remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstration of NAD-dependent deacetylase activity\",\n        \"No identified histone or non-histone substrates within the parasite\",\n        \"No genetic requirement or subcellular localization established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Recombinant TgSIR2 modulates murine macrophage proliferation, apoptosis, phagocytosis, and cytokine/NO secretion in vitro [#0]\",\n      \"Annotated as a sirtuin-family (HDAC-type) protein, but intrinsic deacetylase activity and in-parasite substrates are uncharacterized in the corpus\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_227020","name":"SIR2","product":"histone deacetylase SIR2","uniprot_acc":"S8EUT2","chromosome":"TGME49_chrX","start_pos":1131266},{"strain":"GT1","gene_id":"TGGT1_227020","name":null,"product":"histone deacetylase SIR2","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":1038642},{"strain":"RH88","gene_id":"TGRH88_046640","name":null,"product":"histone deacetylase SIR2","uniprot_acc":null,"chromosome":"CM023091","start_pos":6437768},{"strain":"VEG","gene_id":"TGVEG_227020","name":null,"product":"histone deacetylase SIR2","uniprot_acc":"B9PMV3","chromosome":"TGVEG_chrX","start_pos":1022810}]}