{"gene":"TG_295850","gene_symbol":"AAP2","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2019,"finding":"AAP2 (along with AAP1, AAP3, AAP4, AAP5, Centrin2, and an apical annuli methyltransferase) was identified as a component of the apical annuli of Toxoplasma gondii, structures embedded within the inner membrane complex (IMC) sutures, validated by reciprocal proximity biotinylation (BioID).","method":"Reciprocal BioID proximity biotinylation proteomics; super-resolution microscopy","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal BioID with microscopy validation, single lab, two orthogonal methods","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"The apical annuli complex, which includes AAP2, is organized as a concentric structure comprising four rings with diameters ranging from 200 to 400 nm, located within IMC sutures connecting alveolar vesicles.","method":"Super-resolution microscopy","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct imaging with super-resolution microscopy, single lab","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"AAP2, as part of the apical annuli proteins, contains domain signatures shared with centrosomal proteins and is phylogenetically conserved narrowly in coccidian apicomplexan parasites that multiply by internal budding, suggesting a role tied to this replication mechanism.","method":"Phylogenetic analysis; domain signature analysis","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/phylogenetic analysis only, no direct functional experiment on AAP2 specifically","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AAP2 is a coiled-coil and signalling domain-containing protein localized to the apical annuli of Toxoplasma gondii, where it resides within the inner membrane complex sutures as part of a concentric pore-like structure (~200–400 nm rings) potentially involved in internal budding-based replication."},"narrative":{"mechanistic_narrative":"AAP2 is a component of the apical annuli of Toxoplasma gondii, ring-like structures embedded within the sutures of the inner membrane complex (IMC) [PMID:31470470]. It was identified alongside AAP1, AAP3, AAP4, AAP5, Centrin2, and an apical annuli methyltransferase by reciprocal proximity biotinylation and super-resolution microscopy, which localized these proteins to a concentric, pore-like assembly of four rings measuring 200–400 nm in diameter at the junctions connecting alveolar vesicles [PMID:31470470]. Beyond this localization within the apical annuli complex, no direct functional characterization of AAP2 has been established in the available corpus.","teleology":[{"year":2019,"claim":"Establishing AAP2 as a bona fide constituent of the apical annuli answered where this protein resides and which molecular neighborhood it belongs to within the parasite cortex.","evidence":"Reciprocal BioID proximity biotinylation proteomics with super-resolution microscopy validation in Toxoplasma gondii","pmids":["31470470"],"confidence":"Medium","gaps":["No functional assay (e.g. knockout/knockdown) defines what AAP2 contributes to the annuli","Direct binding partners of AAP2 versus mere proximity neighbors are not resolved","The molecular activity of AAP2 is undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Super-resolution imaging resolved the architecture of the annuli complex containing AAP2 as a concentric four-ring, pore-like structure within IMC sutures, giving a structural context for the assembly.","evidence":"Super-resolution microscopy of the apical annuli in Toxoplasma gondii","pmids":["31470470"],"confidence":"Medium","gaps":["The specific radial position of AAP2 within the four rings is not resolved","Whether the ring forms a functional pore is not tested","The stoichiometry and assembly order of AAP2 relative to other components are unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Domain and phylogenetic analysis linked AAP2-bearing annuli to centrosomal protein signatures and to coccidian parasites that replicate by internal budding, raising a candidate connection to the replication mechanism.","evidence":"Phylogenetic and domain-signature analysis (computational, no direct AAP2 functional experiment)","pmids":["31470470"],"confidence":"Low","gaps":["Computational inference only; no experimental test of an internal-budding role for AAP2","The functional significance of centrosomal domain signatures is not validated","No evidence connects AAP2 loss to a replication defect"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Apical annuli complex (AAP1, AAP2, AAP3, AAP4, AAP5, Centrin2, apical annuli methyltransferase)"],"partners":["AAP1","AAP3","AAP4","AAP5","CENTRIN2","APICAL ANNULI METHYLTRANSFERASE"],"other_free_text":["Annuli organized as four concentric rings, 200-400 nm diameter, within IMC sutures connecting alveolar vesicles","Contains domain signatures shared with centrosomal proteins; narrowly conserved in coccidian apicomplexans"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"31470470","id":"PMC_31470470","title":"The apical annuli of Toxoplasma gondii are composed of coiled-coil and signalling proteins embedded in the inner membrane complex sutures.","date":"2019","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31470470","citation_count":38,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2950,"output_tokens":829,"usd":0.010642,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5626,"output_tokens":1661,"usd":0.034827,"stage2_stop_reason":"end_turn"},"total_usd":0.094895,"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":"re-read with subject anchor"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"AAP2 (along with AAP1, AAP3, AAP4, AAP5, Centrin2, and an apical annuli methyltransferase) was identified as a component of the apical annuli of Toxoplasma gondii, structures embedded within the inner membrane complex (IMC) sutures, validated by reciprocal proximity biotinylation (BioID).\",\n      \"method\": \"Reciprocal BioID proximity biotinylation proteomics; super-resolution microscopy\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal BioID with microscopy validation, single lab, two orthogonal methods\",\n      \"pmids\": [\"31470470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The apical annuli complex, which includes AAP2, is organized as a concentric structure comprising four rings with diameters ranging from 200 to 400 nm, located within IMC sutures connecting alveolar vesicles.\",\n      \"method\": \"Super-resolution microscopy\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging with super-resolution microscopy, single lab\",\n      \"pmids\": [\"31470470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"AAP2, as part of the apical annuli proteins, contains domain signatures shared with centrosomal proteins and is phylogenetically conserved narrowly in coccidian apicomplexan parasites that multiply by internal budding, suggesting a role tied to this replication mechanism.\",\n      \"method\": \"Phylogenetic analysis; domain signature analysis\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/phylogenetic analysis only, no direct functional experiment on AAP2 specifically\",\n      \"pmids\": [\"31470470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"AAP2 is a coiled-coil and signalling domain-containing protein localized to the apical annuli of Toxoplasma gondii, where it resides within the inner membrane complex sutures as part of a concentric pore-like structure (~200–400 nm rings) potentially involved in internal budding-based replication.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AAP2 is a component of the apical annuli of Toxoplasma gondii, ring-like structures embedded within the sutures of the inner membrane complex (IMC) [#0]. It was identified alongside AAP1, AAP3, AAP4, AAP5, Centrin2, and an apical annuli methyltransferase by reciprocal proximity biotinylation and super-resolution microscopy, which localized these proteins to a concentric, pore-like assembly of four rings measuring 200–400 nm in diameter at the junctions connecting alveolar vesicles [#0, #1]. Beyond this localization within the apical annuli complex, no direct functional characterization of AAP2 has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing AAP2 as a bona fide constituent of the apical annuli answered where this protein resides and which molecular neighborhood it belongs to within the parasite cortex.\",\n      \"evidence\": \"Reciprocal BioID proximity biotinylation proteomics with super-resolution microscopy validation in Toxoplasma gondii\",\n      \"pmids\": [\n        \"31470470\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional assay (e.g. knockout/knockdown) defines what AAP2 contributes to the annuli\",\n        \"Direct binding partners of AAP2 versus mere proximity neighbors are not resolved\",\n        \"The molecular activity of AAP2 is undefined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Super-resolution imaging resolved the architecture of the annuli complex containing AAP2 as a concentric four-ring, pore-like structure within IMC sutures, giving a structural context for the assembly.\",\n      \"evidence\": \"Super-resolution microscopy of the apical annuli in Toxoplasma gondii\",\n      \"pmids\": [\n        \"31470470\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific radial position of AAP2 within the four rings is not resolved\",\n        \"Whether the ring forms a functional pore is not tested\",\n        \"The stoichiometry and assembly order of AAP2 relative to other components are unknown\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Domain and phylogenetic analysis linked AAP2-bearing annuli to centrosomal protein signatures and to coccidian parasites that replicate by internal budding, raising a candidate connection to the replication mechanism.\",\n      \"evidence\": \"Phylogenetic and domain-signature analysis (computational, no direct AAP2 functional experiment)\",\n      \"pmids\": [\n        \"31470470\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational inference only; no experimental test of an internal-budding role for AAP2\",\n        \"The functional significance of centrosomal domain signatures is not validated\",\n        \"No evidence connects AAP2 loss to a replication defect\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of AAP2, its direct interactions, and its causal role in apical annuli assembly or parasite replication remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype reported for AAP2\",\n        \"No biochemical activity assigned to its cyclic nucleotide-binding or signalling domains\",\n        \"No direct binary interaction partners confirmed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"apical annuli\",\n        \"supporting_discovery_ids\": [0, 1],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      },\n      {\n        \"term_id\": \"inner membrane complex sutures\",\n        \"supporting_discovery_ids\": [0, 1],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"internal budding replication (candidate)\",\n        \"supporting_discovery_ids\": [2],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Apical annuli complex (AAP1, AAP2, AAP3, AAP4, AAP5, Centrin2, apical annuli methyltransferase)\"\n    ],\n    \"partners\": [\n      \"AAP1\",\n      \"AAP3\",\n      \"AAP4\",\n      \"AAP5\",\n      \"Centrin2\",\n      \"apical annuli methyltransferase\"\n    ],\n    \"other_free_text\": [\n      \"Annuli organized as four concentric rings, 200-400 nm diameter, within IMC sutures connecting alveolar vesicles\",\n      \"Contains domain signatures shared with centrosomal proteins; narrowly conserved in coccidian apicomplexans\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_295850","name":"AAP2","product":"apical annuli protein AAP2","uniprot_acc":"A0A125YQM1","chromosome":"TGME49_chrIa","start_pos":1494198},{"strain":"GT1","gene_id":"TGGT1_295850","name":null,"product":"cyclic nucleotide-binding domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrIa","start_pos":1477996},{"strain":"RH88","gene_id":"TGRH88_020350","name":null,"product":"cyclic nucleotide-binding domain-containing protein","uniprot_acc":null,"chromosome":"CM023081","start_pos":1504158},{"strain":"VEG","gene_id":"TGVEG_295850","name":null,"product":"cyclic nucleotide-binding domain-containing protein","uniprot_acc":"A0A125YQM2","chromosome":"TGVEG_chrIa","start_pos":1509523}]}