{"gene":"TG_309190","gene_symbol":"AIP","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2016,"finding":"AIP (ARO-interacting protein) localizes to a rhoptry subcompartment in Toxoplasma gondii, and in the absence of AIP, adenylate cyclase β (ACβ) disappears from the rhoptries, indicating AIP is required for ACβ retention at rhoptries.","method":"Fluorescence localization imaging and conditional depletion/knockout of AIP with assessment of ACβ localization by immunofluorescence","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence (loss-of-function showing ACβ displacement), single lab, two orthogonal readouts (localization + partner loss)","pmids":["26769898"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"finding":"AIP is a binding partner of ARO (armadillo repeats only protein); ARO interacts with AIP and adenylate cyclase β (ACβ) at the rhoptry subcompartment, placing AIP within the ARO-dependent rhoptry positioning and biogenesis pathway.","method":"Co-immunoprecipitation / pulldown and localization studies identifying ARO partners","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, interaction inferred from co-localization and partner-dependency experiments described in abstract without explicit reciprocal Co-IP detail","pmids":["26769898"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"AIP (ARO-interacting protein) localizes to a rhoptry subcompartment in Toxoplasma gondii where it functions downstream of ARO to retain adenylate cyclase β (ACβ) at rhoptries, placing it within the ARO-dependent pathway of rhoptry biogenesis and organization."},"narrative":{"mechanistic_narrative":"AIP (ARO-interacting protein) is a component of the ARO-dependent rhoptry biogenesis and positioning pathway in Toxoplasma gondii [PMID:26769898]. It localizes to a rhoptry subcompartment, where it binds the armadillo repeats only protein ARO and, together with ARO, associates with adenylate cyclase β (ACβ) [PMID:26769898]. Functionally, AIP is required to retain ACβ at the rhoptries: conditional depletion or knockout of AIP causes ACβ to disappear from this compartment [PMID:26769898]. Beyond this ACβ-retention role within the ARO pathway, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Whether an ARO-associated factor organizes specific rhoptry cargo was unknown; identifying AIP as an ARO binding partner localized to a rhoptry subcompartment placed a new protein within the ARO-dependent rhoptry positioning and biogenesis pathway.","evidence":"Co-immunoprecipitation/pulldown and localization studies identifying ARO partners in T. gondii","pmids":["26769898"],"confidence":"Medium","gaps":["Reciprocal Co-IP and direct binding interface between AIP and ARO not explicitly demonstrated","Whether AIP binds ACβ directly or only via ARO is unresolved","The identity of the rhoptry subcompartment and how AIP is targeted there is undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"claim":"The functional consequence of AIP was unknown; loss-of-function showed AIP is required to retain adenylate cyclase β at the rhoptries, establishing a specific cargo-retention role downstream of ARO.","evidence":"Conditional depletion/knockout of AIP with assessment of ACβ localization by immunofluorescence in T. gondii","pmids":["26769898"],"confidence":"Medium","gaps":["Mechanism by which AIP retains ACβ (anchoring vs. stabilization vs. trafficking) is not defined","Downstream signaling or invasion consequences of ACβ loss were not established","Whether AIP affects other rhoptry cargo beyond ACβ is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular basis of AIP function — how it is recruited to the rhoptry subcompartment, whether its ACβ interaction is direct, and its role in signaling or invasion — remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or domain-level characterization of AIP","No demonstration of direct AIP–ACβ binding","No phenotypic link to invasion or cAMP signaling"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["ARO–AIP–ACβ rhoptry subcompartment assembly"],"partners":["ARO (ARMADILLO REPEATS ONLY PROTEIN)","ADENYLATE CYCLASE Β (ACΒ)"],"other_free_text":["AIP is required to retain adenylate cyclase β (ACβ) at the rhoptries; its loss causes ACβ to disappear from the rhoptry compartment [#0].","AIP functions within the ARO-dependent rhoptry positioning and biogenesis pathway [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"26769898","id":"PMC_26769898","title":"Structural and functional dissection of Toxoplasma gondii armadillo repeats only protein.","date":"2016","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26769898","citation_count":26,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2888,"output_tokens":579,"usd":0.008674,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5319,"output_tokens":1615,"usd":0.033485,"stage2_stop_reason":"end_turn"},"total_usd":0.042159,"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\": 2016,\n      \"finding\": \"AIP (ARO-interacting protein) localizes to a rhoptry subcompartment in Toxoplasma gondii, and in the absence of AIP, adenylate cyclase β (ACβ) disappears from the rhoptries, indicating AIP is required for ACβ retention at rhoptries.\",\n      \"method\": \"Fluorescence localization imaging and conditional depletion/knockout of AIP with assessment of ACβ localization by immunofluorescence\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence (loss-of-function showing ACβ displacement), single lab, two orthogonal readouts (localization + partner loss)\",\n      \"pmids\": [\"26769898\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"AIP is a binding partner of ARO (armadillo repeats only protein); ARO interacts with AIP and adenylate cyclase β (ACβ) at the rhoptry subcompartment, placing AIP within the ARO-dependent rhoptry positioning and biogenesis pathway.\",\n      \"method\": \"Co-immunoprecipitation / pulldown and localization studies identifying ARO partners\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, interaction inferred from co-localization and partner-dependency experiments described in abstract without explicit reciprocal Co-IP detail\",\n      \"pmids\": [\"26769898\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"AIP (ARO-interacting protein) localizes to a rhoptry subcompartment in Toxoplasma gondii where it functions downstream of ARO to retain adenylate cyclase β (ACβ) at rhoptries, placing it within the ARO-dependent pathway of rhoptry biogenesis and organization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AIP (ARO-interacting protein) is a component of the ARO-dependent rhoptry biogenesis and positioning pathway in Toxoplasma gondii [#1]. It localizes to a rhoptry subcompartment, where it binds the armadillo repeats only protein ARO and, together with ARO, associates with adenylate cyclase \\u03b2 (AC\\u03b2) [#1]. Functionally, AIP is required to retain AC\\u03b2 at the rhoptries: conditional depletion or knockout of AIP causes AC\\u03b2 to disappear from this compartment [#0]. Beyond this AC\\u03b2-retention role within the ARO pathway, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether an ARO-associated factor organizes specific rhoptry cargo was unknown; identifying AIP as an ARO binding partner localized to a rhoptry subcompartment placed a new protein within the ARO-dependent rhoptry positioning and biogenesis pathway.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown and localization studies identifying ARO partners in T. gondii\",\n      \"pmids\": [\"26769898\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Reciprocal Co-IP and direct binding interface between AIP and ARO not explicitly demonstrated\",\n        \"Whether AIP binds AC\\u03b2 directly or only via ARO is unresolved\",\n        \"The identity of the rhoptry subcompartment and how AIP is targeted there is undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The functional consequence of AIP was unknown; loss-of-function showed AIP is required to retain adenylate cyclase \\u03b2 at the rhoptries, establishing a specific cargo-retention role downstream of ARO.\",\n      \"evidence\": \"Conditional depletion/knockout of AIP with assessment of AC\\u03b2 localization by immunofluorescence in T. gondii\",\n      \"pmids\": [\"26769898\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which AIP retains AC\\u03b2 (anchoring vs. stabilization vs. trafficking) is not defined\",\n        \"Downstream signaling or invasion consequences of AC\\u03b2 loss were not established\",\n        \"Whether AIP affects other rhoptry cargo beyond AC\\u03b2 is unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular basis of AIP function \\u2014 how it is recruited to the rhoptry subcompartment, whether its AC\\u03b2 interaction is direct, and its role in signaling or invasion \\u2014 remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or domain-level characterization of AIP\",\n        \"No demonstration of direct AIP\\u2013AC\\u03b2 binding\",\n        \"No phenotypic link to invasion or cAMP signaling\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0043159\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"ARO\\u2013AIP\\u2013AC\\u03b2 rhoptry subcompartment assembly\"],\n    \"partners\": [\"ARO (armadillo repeats only protein)\", \"adenylate cyclase \\u03b2 (AC\\u03b2)\"],\n    \"other_free_text\": [\n      \"AIP is required to retain adenylate cyclase \\u03b2 (AC\\u03b2) at the rhoptries; its loss causes AC\\u03b2 to disappear from the rhoptry compartment [#0].\",\n      \"AIP functions within the ARO-dependent rhoptry positioning and biogenesis pathway [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_309190","name":"AIP","product":"ARO-interacting protein AIP","uniprot_acc":"S8G3Y3","chromosome":"TGME49_chrXI","start_pos":542856},{"strain":"GT1","gene_id":"TGGT1_309190","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":506755},{"strain":"RH88","gene_id":"TGRH88_048890","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023092","start_pos":582864},{"strain":"VEG","gene_id":"TGVEG_309190","name":null,"product":"hypothetical protein","uniprot_acc":"V4ZHW7","chromosome":"TGVEG_chrXI","start_pos":552785}]}