{"gene":"TG_232660","gene_symbol":"HIP","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2023,"finding":"TgHIP (HOOK Interacting Partner) is a coccidian-specific protein that forms a trimeric complex with TgHOOK and TgFTS (Fused Toes). All three proteins co-localize at the parasite apical tip, with TgHOOK displaying an apically enriched vesicular pattern that concentrates at the apical tip where it colocalizes with TgFTS and TgHIP.","method":"Co-immunoprecipitation, fluorescence microscopy/co-localization, proximity ligation assays","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification by Co-IP combined with direct localization by fluorescence microscopy in multiple orthogonal experiments in a single focused study","pmids":["37093045"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"Conditional depletion of TgHIP impairs microneme apical positioning and secretion (exocytosis), and leads to severe defects in parasite egress, motility, host cell attachment, and invasion — phenotypes more severe than those caused by depletion of TgHOOK alone but similar in nature to TgFTS depletion.","method":"Conditional knockdown (auxin-inducible degron or similar inducible system), invasion assays, egress assays, motility assays, secretion assays","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional loss-of-function with multiple defined cellular phenotypic readouts (egress, motility, invasion, secretion) in a single rigorous study with orthogonal assays","pmids":["37093045"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"The TgHOOK-TgFTS-TgHIP complex functions as an endosomal trafficking regulator involved in the apical exocytosis of micronemes and, as a consequence or directly, the discharge of rhoptries, placing TgHIP in the endosomal trafficking pathway for secretory organelle discharge.","method":"Genetic epistasis via conditional depletion combined with secretion assays and organelle positioning analysis by electron microscopy/fluorescence","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — pathway placement by conditional KD with multiple orthogonal functional readouts (organelle positioning, secretion, invasion) in one focused mechanistic study","pmids":["37093045"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgHIP is a coccidian-specific endosomal trafficking regulator that forms a trimeric complex with TgHOOK and TgFTS at the parasite apical tip, where it is required for apical positioning and exocytosis of micronemes (and consequent rhoptry discharge), thereby contributing critically to parasite motility, host cell invasion, and egress."},"narrative":{"mechanistic_narrative":"TgHIP (HOOK Interacting Partner) is a coccidian-specific endosomal trafficking regulator that governs apical secretory organelle positioning and discharge in Toxoplasma gondii [PMID:37093045]. It forms a trimeric complex with TgHOOK and TgFTS (Fused Toes), and all three proteins co-localize at the parasite apical tip, where TgHOOK displays an apically enriched vesicular pattern concentrating at the tip [PMID:37093045]. Through this complex, TgHIP acts in the endosomal trafficking pathway required for apical positioning and exocytosis of micronemes and, as a consequence, rhoptry discharge [PMID:37093045]. Conditional depletion of TgHIP impairs microneme apical positioning and secretion and produces severe defects in parasite egress, motility, host cell attachment, and invasion — phenotypes more severe than TgHOOK depletion but comparable to TgFTS depletion [PMID:37093045]. Beyond these findings from a single focused study, no further mechanistic detail on TgHIP has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"It was unknown how the HOOK adaptor operates in apicomplexans; identifying TgHIP as a partner in a defined trimeric complex established the molecular architecture at the parasite apical tip.","evidence":"Co-immunoprecipitation, fluorescence co-localization, and proximity ligation assays in Toxoplasma gondii","pmids":["37093045"],"confidence":"High","gaps":["Stoichiometry and direct binding interfaces among TgHIP, TgHOOK, and TgFTS not resolved","No structural model of the complex","Whether TgHIP has activity independent of the complex is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Whether TgHIP was functionally required was untested; conditional depletion demonstrated it is essential for microneme positioning and secretion and for the downstream lytic cycle steps of egress, motility, attachment, and invasion.","evidence":"Conditional knockdown with invasion, egress, motility, and secretion assays in Toxoplasma gondii","pmids":["37093045"],"confidence":"High","gaps":["Molecular basis of why TgHIP loss is more severe than TgHOOK loss not defined","Direct trafficking cargo or vesicle intermediates not identified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"The pathway placement of the complex was open; epistasis and organelle-positioning analysis placed TgHIP in the endosomal trafficking pathway controlling apical microneme exocytosis and, consequently, rhoptry discharge.","evidence":"Genetic epistasis via conditional depletion combined with secretion assays and organelle positioning analysis (EM/fluorescence) in Toxoplasma gondii","pmids":["37093045"],"confidence":"High","gaps":["Whether rhoptry discharge defect is direct or a secondary consequence of microneme dysfunction not resolved","Molecular link between endosomal trafficking and apical exocytic machinery undefined","Role in other coccidian species not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How the TgHIP-TgHOOK-TgFTS complex mechanistically couples endosomal trafficking to apical positioning and exocytosis of secretory organelles remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No identified motor or cytoskeletal linkage mediating apical transport","No direct cargo defined","No structural characterization of TgHIP or the complex"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TgHOOK-TgFTS-TgHIP trimeric complex"],"partners":["TGHOOK","TGFTS (FUSED TOES)"],"other_free_text":["Coccidian-specific protein required for microneme apical positioning and exocytosis, with downstream effects on rhoptry discharge, parasite motility, host cell attachment, invasion, and egress in Toxoplasma gondii [#1, #2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37093045","id":"PMC_37093045","title":"Toxoplasma gondii HOOK-FTS-HIP Complex is Critical for Secretory Organelle Discharge during Motility, Invasion, and Egress.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37093045","citation_count":6,"is_preprint":false},{"pmid":"38726453","id":"PMC_38726453","title":"Anti-Toxoplasma gondii activity of rose hip oil-solid lipid nanoparticles.","date":"2024","source":"Food science & nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/38726453","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16291,"output_tokens":1008,"usd":0.031996,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5710,"output_tokens":1930,"usd":0.0384,"stage2_stop_reason":"end_turn"},"total_usd":0.070396,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"Looking at the corpus, I need to identify which papers are about the gene \"HIP\" in Toxoplasma gondii. Based on the paper titles and abstracts, paper [12] (PMID:37093045) is clearly about TgHIP (HOOK Interacting Partner) — a coccidian-specific protein that forms a complex with TgHOOK and TgFTS. The other papers are primarily about TgHSP70, which is a different gene. Let me extract mechanistic discoveries accordingly.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"TgHIP (HOOK Interacting Partner) is a coccidian-specific protein that forms a trimeric complex with TgHOOK and TgFTS (Fused Toes). All three proteins co-localize at the parasite apical tip, with TgHOOK displaying an apically enriched vesicular pattern that concentrates at the apical tip where it colocalizes with TgFTS and TgHIP.\",\n      \"method\": \"Co-immunoprecipitation, fluorescence microscopy/co-localization, proximity ligation assays\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification by Co-IP combined with direct localization by fluorescence microscopy in multiple orthogonal experiments in a single focused study\",\n      \"pmids\": [\"37093045\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Conditional depletion of TgHIP impairs microneme apical positioning and secretion (exocytosis), and leads to severe defects in parasite egress, motility, host cell attachment, and invasion — phenotypes more severe than those caused by depletion of TgHOOK alone but similar in nature to TgFTS depletion.\",\n      \"method\": \"Conditional knockdown (auxin-inducible degron or similar inducible system), invasion assays, egress assays, motility assays, secretion assays\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional loss-of-function with multiple defined cellular phenotypic readouts (egress, motility, invasion, secretion) in a single rigorous study with orthogonal assays\",\n      \"pmids\": [\"37093045\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The TgHOOK-TgFTS-TgHIP complex functions as an endosomal trafficking regulator involved in the apical exocytosis of micronemes and, as a consequence or directly, the discharge of rhoptries, placing TgHIP in the endosomal trafficking pathway for secretory organelle discharge.\",\n      \"method\": \"Genetic epistasis via conditional depletion combined with secretion assays and organelle positioning analysis by electron microscopy/fluorescence\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — pathway placement by conditional KD with multiple orthogonal functional readouts (organelle positioning, secretion, invasion) in one focused mechanistic study\",\n      \"pmids\": [\"37093045\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgHIP is a coccidian-specific endosomal trafficking regulator that forms a trimeric complex with TgHOOK and TgFTS at the parasite apical tip, where it is required for apical positioning and exocytosis of micronemes (and consequent rhoptry discharge), thereby contributing critically to parasite motility, host cell invasion, and egress.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgHIP (HOOK Interacting Partner) is a coccidian-specific endosomal trafficking regulator that governs apical secretory organelle positioning and discharge in Toxoplasma gondii [#0, #2]. It forms a trimeric complex with TgHOOK and TgFTS (Fused Toes), and all three proteins co-localize at the parasite apical tip, where TgHOOK displays an apically enriched vesicular pattern concentrating at the tip [#0]. Through this complex, TgHIP acts in the endosomal trafficking pathway required for apical positioning and exocytosis of micronemes and, as a consequence, rhoptry discharge [#2]. Conditional depletion of TgHIP impairs microneme apical positioning and secretion and produces severe defects in parasite egress, motility, host cell attachment, and invasion — phenotypes more severe than TgHOOK depletion but comparable to TgFTS depletion [#1]. Beyond these findings from a single focused study, no further mechanistic detail on TgHIP has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown how the HOOK adaptor operates in apicomplexans; identifying TgHIP as a partner in a defined trimeric complex established the molecular architecture at the parasite apical tip.\",\n      \"evidence\": \"Co-immunoprecipitation, fluorescence co-localization, and proximity ligation assays in Toxoplasma gondii\",\n      \"pmids\": [\"37093045\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and direct binding interfaces among TgHIP, TgHOOK, and TgFTS not resolved\", \"No structural model of the complex\", \"Whether TgHIP has activity independent of the complex is unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether TgHIP was functionally required was untested; conditional depletion demonstrated it is essential for microneme positioning and secretion and for the downstream lytic cycle steps of egress, motility, attachment, and invasion.\",\n      \"evidence\": \"Conditional knockdown with invasion, egress, motility, and secretion assays in Toxoplasma gondii\",\n      \"pmids\": [\"37093045\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of why TgHIP loss is more severe than TgHOOK loss not defined\", \"Direct trafficking cargo or vesicle intermediates not identified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The pathway placement of the complex was open; epistasis and organelle-positioning analysis placed TgHIP in the endosomal trafficking pathway controlling apical microneme exocytosis and, consequently, rhoptry discharge.\",\n      \"evidence\": \"Genetic epistasis via conditional depletion combined with secretion assays and organelle positioning analysis (EM/fluorescence) in Toxoplasma gondii\",\n      \"pmids\": [\"37093045\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether rhoptry discharge defect is direct or a secondary consequence of microneme dysfunction not resolved\", \"Molecular link between endosomal trafficking and apical exocytic machinery undefined\", \"Role in other coccidian species not tested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the TgHIP-TgHOOK-TgFTS complex mechanistically couples endosomal trafficking to apical positioning and exocytosis of secretory organelles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No identified motor or cytoskeletal linkage mediating apical transport\", \"No direct cargo defined\", \"No structural characterization of TgHIP or the complex\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0017112\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006887\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"TgHOOK-TgFTS-TgHIP trimeric complex\"],\n    \"partners\": [\"TgHOOK\", \"TgFTS (Fused Toes)\"],\n    \"other_free_text\": [\n      \"Coccidian-specific protein required for microneme apical positioning and exocytosis, with downstream effects on rhoptry discharge, parasite motility, host cell attachment, invasion, and egress in Toxoplasma gondii [#1, #2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_232660","name":"HIP","product":"Hsp70 interacting protein HIP","uniprot_acc":"S8GK24","chromosome":"TGME49_chrVIII","start_pos":2210021},{"strain":"GT1","gene_id":"TGGT1_232660","name":null,"product":"Hsp70 interacting protein HIP","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":2206171},{"strain":"RH88","gene_id":"TGRH88_076740","name":null,"product":"Hsp70 interacting protein HIP","uniprot_acc":null,"chromosome":"CM023089","start_pos":7316452},{"strain":"VEG","gene_id":"TGVEG_232660","name":null,"product":"Hsp70 interacting protein HIP","uniprot_acc":"B9Q4N1","chromosome":"TGVEG_chrVIII","start_pos":2219078}]}