{"gene":"TG_297245","gene_symbol":"AMT2","run_date":"2026-09-08T15:15:12","timeline":{"discoveries":[{"year":2024,"finding":"AMT2 (apicomplexan monocarboxylate transporter 2) was identified as an apicoplast transporter in Toxoplasma gondii using TurboID proximity labeling and genome engineering; protein depletion of AMT2 caused critical defects in parasite growth and virulence in mice.","method":"TurboID proximity labeling, genome engineering, conditional protein depletion, parasite growth assays, mouse virulence assays","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TurboID-based identification plus conditional knockdown with defined phenotypic readouts (growth, virulence), single lab, multiple orthogonal methods","pmids":["38502570"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"Metabolite analyses following AMT2 depletion support the role of AMT2 in facilitating flux of metabolites associated with isoprenoid and fatty acid biosynthesis within the apicoplast; stronger phenotypic defects were observed for AMT2 compared to AMT1.","method":"Conditional protein depletion, metabolite analysis","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional depletion coupled with metabolite profiling in a single lab, two orthogonal methods","pmids":["38502570"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"AMT1 and AMT2 are proposed to have evolved from a putative host cell that engulfed a red alga, placing them as evolutionarily distinct apicoplast transporters in apicomplexans.","method":"Phylogenetic/genome engineering analysis","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 4 / Weak — evolutionary inference from genome-level analysis, no direct biochemical validation of transport mechanism or evolutionary origin","pmids":["38502570"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AMT2 is an apicoplast-localized monocarboxylate transporter in Toxoplasma gondii that is essential for parasite growth and virulence, functioning to facilitate metabolite flux (particularly related to isoprenoid and fatty acid biosynthesis) across the apicoplast membranes, with stronger loss-of-function phenotypes than its paralog AMT1."},"narrative":{"mechanistic_narrative":"AMT2 (apicomplexan monocarboxylate transporter 2) is an apicoplast transporter in Toxoplasma gondii required for parasite growth and virulence [PMID:38502570]. Identified through TurboID proximity labeling and genome engineering, conditional depletion of AMT2 produces critical growth defects in culture and attenuates virulence in mice [PMID:38502570]. Metabolite profiling following depletion places AMT2 in the facilitation of metabolite flux linked to apicoplast isoprenoid and fatty acid biosynthesis, with loss of AMT2 causing stronger phenotypic defects than loss of its paralog AMT1 [PMID:38502570]. Beyond this proximity-labeling and depletion evidence, the specific transported substrates, transport directionality, and molecular mechanism of AMT2 have not been biochemically characterized in the available corpus.","teleology":[{"year":2024,"claim":"Establishing that AMT2 is an apicoplast-resident transporter whose loss cripples the parasite answered whether this protein is functionally important, defining it as essential for growth and virulence.","evidence":"TurboID proximity labeling, genome engineering, and conditional protein depletion with growth and mouse virulence assays in Toxoplasma gondii","pmids":["38502570"],"confidence":"Medium","gaps":["Direct transport activity and substrate specificity not demonstrated biochemically","Precise sub-membrane localization within the apicoplast not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Linking AMT2 depletion to altered metabolites of isoprenoid and fatty acid biosynthesis addressed which pathway it serves, and its stronger phenotype relative to AMT1 established functional non-redundancy between the paralogs.","evidence":"Conditional protein depletion coupled with metabolite analysis in Toxoplasma gondii","pmids":["38502570"],"confidence":"Medium","gaps":["Which specific monocarboxylate metabolites are transported remains undefined","Whether the metabolite changes are direct transport effects or downstream consequences is unresolved","Mechanistic basis for the AMT2 vs AMT1 phenotypic difference not determined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Phylogenetic placement addressed the evolutionary origin of AMT1/AMT2, proposing derivation from the red-algal secondary endosymbiont lineage.","evidence":"Phylogenetic and genome-level analysis in Toxoplasma gondii","pmids":["38502570"],"confidence":"Low","gaps":["Evolutionary inference from genome analysis with no biochemical validation of transport mechanism or origin"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct transported substrate(s), transport directionality, and structural basis of AMT2 selectivity remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted or heterologous transport assay establishing substrate identity","No structural model of the transporter","Mechanism coupling AMT2 activity to isoprenoid/fatty acid biosynthesis not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["AMT2 depletion causes critical defects in Toxoplasma gondii growth and attenuates virulence in mice [#0]","AMT2 shows stronger loss-of-function phenotypes than its paralog AMT1 [#1]","AMT1 and AMT2 proposed to derive from a red-algal secondary endosymbiont lineage (Low confidence) [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"38502570","id":"PMC_38502570","title":"The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/38502570","citation_count":12,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2846,"output_tokens":752,"usd":0.009909,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5545,"output_tokens":1809,"usd":0.036475,"stage2_stop_reason":"end_turn"},"total_usd":0.046384,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"AMT2 (apicomplexan monocarboxylate transporter 2) was identified as an apicoplast transporter in Toxoplasma gondii using TurboID proximity labeling and genome engineering; protein depletion of AMT2 caused critical defects in parasite growth and virulence in mice.\",\n      \"method\": \"TurboID proximity labeling, genome engineering, conditional protein depletion, parasite growth assays, mouse virulence assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TurboID-based identification plus conditional knockdown with defined phenotypic readouts (growth, virulence), single lab, multiple orthogonal methods\",\n      \"pmids\": [\"38502570\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Metabolite analyses following AMT2 depletion support the role of AMT2 in facilitating flux of metabolites associated with isoprenoid and fatty acid biosynthesis within the apicoplast; stronger phenotypic defects were observed for AMT2 compared to AMT1.\",\n      \"method\": \"Conditional protein depletion, metabolite analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional depletion coupled with metabolite profiling in a single lab, two orthogonal methods\",\n      \"pmids\": [\"38502570\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"AMT1 and AMT2 are proposed to have evolved from a putative host cell that engulfed a red alga, placing them as evolutionarily distinct apicoplast transporters in apicomplexans.\",\n      \"method\": \"Phylogenetic/genome engineering analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — evolutionary inference from genome-level analysis, no direct biochemical validation of transport mechanism or evolutionary origin\",\n      \"pmids\": [\"38502570\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"AMT2 is an apicoplast-localized monocarboxylate transporter in Toxoplasma gondii that is essential for parasite growth and virulence, functioning to facilitate metabolite flux (particularly related to isoprenoid and fatty acid biosynthesis) across the apicoplast membranes, with stronger loss-of-function phenotypes than its paralog AMT1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AMT2 (apicomplexan monocarboxylate transporter 2) is an apicoplast transporter in Toxoplasma gondii required for parasite growth and virulence [#0]. Identified through TurboID proximity labeling and genome engineering, conditional depletion of AMT2 produces critical growth defects in culture and attenuates virulence in mice [#0]. Metabolite profiling following depletion places AMT2 in the facilitation of metabolite flux linked to apicoplast isoprenoid and fatty acid biosynthesis, with loss of AMT2 causing stronger phenotypic defects than loss of its paralog AMT1 [#1]. Beyond this proximity-labeling and depletion evidence, the specific transported substrates, transport directionality, and molecular mechanism of AMT2 have not been biochemically characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Establishing that AMT2 is an apicoplast-resident transporter whose loss cripples the parasite answered whether this protein is functionally important, defining it as essential for growth and virulence.\",\n      \"evidence\": \"TurboID proximity labeling, genome engineering, and conditional protein depletion with growth and mouse virulence assays in Toxoplasma gondii\",\n      \"pmids\": [\"38502570\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct transport activity and substrate specificity not demonstrated biochemically\",\n        \"Precise sub-membrane localization within the apicoplast not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linking AMT2 depletion to altered metabolites of isoprenoid and fatty acid biosynthesis addressed which pathway it serves, and its stronger phenotype relative to AMT1 established functional non-redundancy between the paralogs.\",\n      \"evidence\": \"Conditional protein depletion coupled with metabolite analysis in Toxoplasma gondii\",\n      \"pmids\": [\"38502570\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Which specific monocarboxylate metabolites are transported remains undefined\",\n        \"Whether the metabolite changes are direct transport effects or downstream consequences is unresolved\",\n        \"Mechanistic basis for the AMT2 vs AMT1 phenotypic difference not determined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Phylogenetic placement addressed the evolutionary origin of AMT1/AMT2, proposing derivation from the red-algal secondary endosymbiont lineage.\",\n      \"evidence\": \"Phylogenetic and genome-level analysis in Toxoplasma gondii\",\n      \"pmids\": [\"38502570\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Evolutionary inference from genome analysis with no biochemical validation of transport mechanism or origin\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct transported substrate(s), transport directionality, and structural basis of AMT2 selectivity remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reconstituted or heterologous transport assay establishing substrate identity\",\n        \"No structural model of the transporter\",\n        \"Mechanism coupling AMT2 activity to isoprenoid/fatty acid biosynthesis not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008028\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009507\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0008299\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006633\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"AMT2 depletion causes critical defects in Toxoplasma gondii growth and attenuates virulence in mice [#0]\",\n      \"AMT2 shows stronger loss-of-function phenotypes than its paralog AMT1 [#1]\",\n      \"AMT1 and AMT2 proposed to derive from a red-algal secondary endosymbiont lineage (Low confidence) [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_297245","name":"AMT2","product":"apicoplast monocarboxylate transporter AMT2","uniprot_acc":"S8FEC1","chromosome":"TGME49_chrII","start_pos":1636541},{"strain":"GT1","gene_id":"TGGT1_297245","name":null,"product":"transporter, major facilitator family protein","uniprot_acc":null,"chromosome":"TGGT1_chrII","start_pos":1613632},{"strain":"RH88","gene_id":"TGRH88_002090","name":null,"product":"transporter, major facilitator family protein","uniprot_acc":null,"chromosome":"CM023083","start_pos":1812764},{"strain":"VEG","gene_id":"TGVEG_297245","name":null,"product":"transporter, major facilitator family protein","uniprot_acc":"V4ZC10","chromosome":"TGVEG_chrII","start_pos":1647518}]}