{"gene":"TG_242790","gene_symbol":"AAP1","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2019,"finding":"AAP1 (apical annuli protein 1) localizes to the apical annuli of Toxoplasma gondii, structures embedded within the inner membrane complex (IMC) sutures, as determined by reciprocal proximity biotinylation (BioID) and super-resolution microscopy.","method":"Reciprocal BioID proximity biotinylation; super-resolution microscopy; validation of localization","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal BioID with super-resolution microscopy validation, single lab, two orthogonal methods","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"The apical annuli, including AAP1-containing structures, are organized as four concentric rings with diameters ranging from 200 to 400 nm, positioned within IMC sutures connecting alveolar vesicles.","method":"Super-resolution microscopy; BioID proteome mapping","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — super-resolution imaging with BioID proteomics, single lab, two orthogonal methods","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"AAP1 shares domain signatures with centrosomal proteins and co-localizes with Centrin2 at the apical annuli, suggesting a structural and/or functional relationship between the annuli and centrosomes.","method":"BioID proteome mapping; phylogenetic and domain analysis; co-detection with Centrin2","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-detection by BioID and domain analysis, single lab, no direct functional validation of centrosomal relationship for AAP1 specifically","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"AAP1 is conserved narrowly among coccidian apicomplexans that multiply by internal budding, suggesting a role specific to this replication mechanism.","method":"Phylogenetic analysis","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/phylogenetic inference only, no direct functional experiment on AAP1 specifically","pmids":["31470470"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AAP1 is a coiled-coil/signalling domain-containing protein that localizes to the apical annuli of Toxoplasma gondii, structures embedded within the inner membrane complex sutures and organized as concentric rings (200–400 nm diameter), where it co-resides with Centrin2 and other annuli proteins; it is conserved only in coccidians that replicate by internal budding, suggesting a role in that process, but its precise molecular function remains uncharacterized."},"narrative":{"mechanistic_narrative":"AAP1 (apical annuli protein 1) is a component of the apical annuli of Toxoplasma gondii, structures embedded within the sutures of the inner membrane complex (IMC) where alveolar vesicles connect [PMID:31470470]. Reciprocal proximity biotinylation and super-resolution microscopy place AAP1 at these annuli, which are organized as concentric rings of 200–400 nm diameter [PMID:31470470]. Beyond this localization, the molecular function of AAP1 has not been characterized in the available corpus; its narrow conservation among coccidian apicomplexans that replicate by internal budding points to a role tied to that replication mode, and its co-detection with Centrin2 and shared domain signatures with centrosomal proteins hint at a structural link to the centrosome, but neither has been functionally tested [PMID:31470470].","teleology":[{"year":2019,"claim":"Establishing where AAP1 acts: it was unknown what protein composition defined the apical annuli, and localizing AAP1 to IMC sutures defined it as a bona fide annuli component.","evidence":"Reciprocal BioID proximity biotinylation and super-resolution microscopy in Toxoplasma gondii","pmids":["31470470"],"confidence":"Medium","gaps":["No functional perturbation (knockdown/knockout) of AAP1 to test its role at the annuli","Molecular activity of AAP1 not defined","Mechanism of recruitment to IMC sutures unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Resolving the architecture of the annuli: the physical organization was unknown, and imaging showed AAP1-containing annuli form concentric rings of defined dimensions within IMC sutures.","evidence":"Super-resolution microscopy with BioID proteome mapping in Toxoplasma gondii","pmids":["31470470"],"confidence":"Medium","gaps":["Does not establish AAP1's specific position or stoichiometry within the ring structure","No structural model of AAP1 itself"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Probing a possible centrosomal connection: it was unknown whether the annuli relate to the centrosome, and AAP1's co-localization with Centrin2 plus centrosomal domain signatures raised a candidate structural/functional link.","evidence":"BioID proteome mapping, domain analysis, and co-detection with Centrin2 in Toxoplasma gondii","pmids":["31470470"],"confidence":"Low","gaps":["Centrosomal relationship inferred from co-detection and domain analysis, not functionally validated for AAP1","No direct interaction assay between AAP1 and Centrin2 beyond proximity/co-detection"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Assessing conservation to infer function: it was unclear which parasites possess AAP1, and phylogenetic analysis showed restriction to coccidians that replicate by internal budding, suggesting a role in that process.","evidence":"Phylogenetic/comparative sequence analysis","pmids":["31470470"],"confidence":"Low","gaps":["Purely computational inference with no functional experiment linking AAP1 to internal budding","Role in replication not directly demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular function of AAP1 and its mechanistic role in internal budding or in any centrosome-annuli relationship remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function phenotype reported","No biochemical activity or defined interaction network beyond proximity data","No test of whether AAP1 is required for internal budding replication"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["CENTRIN2 (CO-LOCALIZATION/CO-DETECTION AT APICAL ANNULI)"],"other_free_text":["Annuli organized as four concentric rings, 200-400 nm diameter, within IMC sutures [#1]","Shares domain signatures with centrosomal proteins [#2]","Conserved narrowly among coccidian apicomplexans that replicate by internal budding [#3]"]},"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":958,"usd":0.01161,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5818,"output_tokens":1935,"usd":0.038733,"stage2_stop_reason":"end_turn"},"total_usd":0.050343,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"AAP1 (apical annuli protein 1) localizes to the apical annuli of Toxoplasma gondii, structures embedded within the inner membrane complex (IMC) sutures, as determined by reciprocal proximity biotinylation (BioID) and super-resolution microscopy.\",\n      \"method\": \"Reciprocal BioID proximity biotinylation; super-resolution microscopy; validation of localization\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal BioID with super-resolution 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, including AAP1-containing structures, are organized as four concentric rings with diameters ranging from 200 to 400 nm, positioned within IMC sutures connecting alveolar vesicles.\",\n      \"method\": \"Super-resolution microscopy; BioID proteome mapping\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — super-resolution imaging with BioID proteomics, 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\": \"AAP1 shares domain signatures with centrosomal proteins and co-localizes with Centrin2 at the apical annuli, suggesting a structural and/or functional relationship between the annuli and centrosomes.\",\n      \"method\": \"BioID proteome mapping; phylogenetic and domain analysis; co-detection with Centrin2\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-detection by BioID and domain analysis, single lab, no direct functional validation of centrosomal relationship for AAP1 specifically\",\n      \"pmids\": [\"31470470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"AAP1 is conserved narrowly among coccidian apicomplexans that multiply by internal budding, suggesting a role specific to this replication mechanism.\",\n      \"method\": \"Phylogenetic analysis\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/phylogenetic inference only, no direct functional experiment on AAP1 specifically\",\n      \"pmids\": [\"31470470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"AAP1 is a coiled-coil/signalling domain-containing protein that localizes to the apical annuli of Toxoplasma gondii, structures embedded within the inner membrane complex sutures and organized as concentric rings (200–400 nm diameter), where it co-resides with Centrin2 and other annuli proteins; it is conserved only in coccidians that replicate by internal budding, suggesting a role in that process, but its precise molecular function remains uncharacterized.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"AAP1 (apical annuli protein 1) is a component of the apical annuli of Toxoplasma gondii, structures embedded within the sutures of the inner membrane complex (IMC) where alveolar vesicles connect [#0]. Reciprocal proximity biotinylation and super-resolution microscopy place AAP1 at these annuli, which are organized as concentric rings of 200–400 nm diameter [#0, #1]. Beyond this localization, the molecular function of AAP1 has not been characterized in the available corpus; its narrow conservation among coccidian apicomplexans that replicate by internal budding points to a role tied to that replication mode, and its co-detection with Centrin2 and shared domain signatures with centrosomal proteins hint at a structural link to the centrosome, but neither has been functionally tested [#2, #3].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing where AAP1 acts: it was unknown what protein composition defined the apical annuli, and localizing AAP1 to IMC sutures defined it as a bona fide annuli component.\",\n      \"evidence\": \"Reciprocal BioID proximity biotinylation and super-resolution microscopy in Toxoplasma gondii\",\n      \"pmids\": [\"31470470\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional perturbation (knockdown/knockout) of AAP1 to test its role at the annuli\",\n        \"Molecular activity of AAP1 not defined\",\n        \"Mechanism of recruitment to IMC sutures unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resolving the architecture of the annuli: the physical organization was unknown, and imaging showed AAP1-containing annuli form concentric rings of defined dimensions within IMC sutures.\",\n      \"evidence\": \"Super-resolution microscopy with BioID proteome mapping in Toxoplasma gondii\",\n      \"pmids\": [\"31470470\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not establish AAP1's specific position or stoichiometry within the ring structure\",\n        \"No structural model of AAP1 itself\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Probing a possible centrosomal connection: it was unknown whether the annuli relate to the centrosome, and AAP1's co-localization with Centrin2 plus centrosomal domain signatures raised a candidate structural/functional link.\",\n      \"evidence\": \"BioID proteome mapping, domain analysis, and co-detection with Centrin2 in Toxoplasma gondii\",\n      \"pmids\": [\"31470470\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Centrosomal relationship inferred from co-detection and domain analysis, not functionally validated for AAP1\",\n        \"No direct interaction assay between AAP1 and Centrin2 beyond proximity/co-detection\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Assessing conservation to infer function: it was unclear which parasites possess AAP1, and phylogenetic analysis showed restriction to coccidians that replicate by internal budding, suggesting a role in that process.\",\n      \"evidence\": \"Phylogenetic/comparative sequence analysis\",\n      \"pmids\": [\"31470470\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational inference with no functional experiment linking AAP1 to internal budding\",\n        \"Role in replication not directly demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of AAP1 and its mechanistic role in internal budding or in any centrosome-annuli relationship remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype reported\",\n        \"No biochemical activity or defined interaction network beyond proximity data\",\n        \"No test of whether AAP1 is required for internal budding replication\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"apical annuli (inner membrane complex sutures)\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"internal budding replication (coccidian-specific, inferred)\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Centrin2 (co-localization/co-detection at apical annuli)\"],\n    \"other_free_text\": [\n      \"Annuli organized as four concentric rings, 200-400 nm diameter, within IMC sutures [#1]\",\n      \"Shares domain signatures with centrosomal proteins [#2]\",\n      \"Conserved narrowly among coccidian apicomplexans that replicate by internal budding [#3]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_242790","name":"AAP1","product":"apical annuli protein AAP1","uniprot_acc":"S8GPD1","chromosome":"TGME49_chrVI","start_pos":2287473},{"strain":"GT1","gene_id":"TGGT1_242790B","name":null,"product":"putative trichohyalin","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":2203879},{"strain":"RH88","gene_id":"TGRH88_029430","name":null,"product":"putative trichohyalin","uniprot_acc":null,"chromosome":"CM023087","start_pos":1418907},{"strain":"VEG","gene_id":"TGVEG_242790B","name":null,"product":"putative trichohyalin","uniprot_acc":"V4Z8F5","chromosome":"TGVEG_chrVI","start_pos":2296660}]}