{"gene":"TG_316650","gene_symbol":"","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2023,"finding":"TGME49_316650 (TGGT1_316650) is a parasite-specific component of a partially conserved FHF (HOOK-FTS-FHIP) trafficking adaptor complex in T. gondii, consisting of HOOK, an FTS homolog, and two parasite-specific proteins including TGGT1_316650, which together support dynein-mediated apical trafficking of micronemes.","method":"Bio-orthogonal labeling of CDPK1 kinase substrates combined with sub-minute resolution phosphoproteomics; identification of the FHF complex composition by co-immunoprecipitation/complex characterization; loss-of-function analysis of HOOK and FTS showing impaired microneme protein secretion and host cell invasion block","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CDPK1 substrate phosphoproteomics plus complex membership assignment and functional readout (secretion, invasion), but TGGT1_316650 itself was not individually knocked out; functional phenotype attributed primarily to HOOK and FTS, single lab","pmids":["37933960"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TGME49_316650 is a parasite-specific subunit of the Toxoplasma FHF trafficking adaptor complex (comprising HOOK, FTS, and at least two apicomplexan-specific proteins) that is phosphorylated by CDPK1 and required for rapid apical trafficking of micronemes to support microneme exocytosis and host cell invasion."},"narrative":{"mechanistic_narrative":"TGME49_316650 is a parasite-specific subunit of a partially conserved FHF (HOOK-FTS-FHIP) trafficking adaptor complex in Toxoplasma gondii, where it associates with HOOK, an FTS homolog, and a second apicomplexan-specific protein to support dynein-mediated apical trafficking of micronemes [PMID:37933960]. The protein is a substrate of the calcium-dependent kinase CDPK1, linking its function to the signaling that drives microneme secretion and host cell invasion [PMID:37933960]. Loss of the complex's core HOOK and FTS components impairs microneme protein secretion and blocks invasion, but the individual functional contribution of TGME49_316650 has not been characterized in the available corpus.","teleology":[{"year":2023,"claim":"The composition of the Toxoplasma microneme-trafficking machinery was undefined; identifying TGME49_316650 as a parasite-specific member of an FHF adaptor complex established a molecular link between dynein-based transport and apical microneme delivery.","evidence":"CDPK1 substrate bio-orthogonal labeling with sub-minute phosphoproteomics, co-immunoprecipitation defining FHF complex membership, and loss-of-function of HOOK/FTS scoring microneme secretion and invasion in T. gondii","pmids":["37933960"],"confidence":"Medium","gaps":["TGME49_316650 was not individually knocked out, so its specific requirement for trafficking is unestablished","The invasion/secretion phenotype was attributed to HOOK and FTS, not to TGME49_316650 directly","The functional consequence of CDPK1 phosphorylation of TGME49_316650 is undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["FHF (HOOK-FTS-FHIP) trafficking adaptor complex"],"partners":["HOOK","FTS HOMOLOG","CDPK1 (KINASE)"],"other_free_text":["Parasite-specific subunit of the FHF adaptor complex supporting dynein-mediated apical trafficking of micronemes [#0].","CDPK1 phosphorylation substrate [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37933960","id":"PMC_37933960","title":"Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis in Toxoplasma.","date":"2023","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/37933960","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2972,"output_tokens":804,"usd":0.010488,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5625,"output_tokens":1842,"usd":0.037088,"stage2_stop_reason":"end_turn"},"total_usd":0.085007,"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\": 2023,\n      \"finding\": \"TGME49_316650 (TGGT1_316650) is a parasite-specific component of a partially conserved FHF (HOOK-FTS-FHIP) trafficking adaptor complex in T. gondii, consisting of HOOK, an FTS homolog, and two parasite-specific proteins including TGGT1_316650, which together support dynein-mediated apical trafficking of micronemes.\",\n      \"method\": \"Bio-orthogonal labeling of CDPK1 kinase substrates combined with sub-minute resolution phosphoproteomics; identification of the FHF complex composition by co-immunoprecipitation/complex characterization; loss-of-function analysis of HOOK and FTS showing impaired microneme protein secretion and host cell invasion block\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CDPK1 substrate phosphoproteomics plus complex membership assignment and functional readout (secretion, invasion), but TGGT1_316650 itself was not individually knocked out; functional phenotype attributed primarily to HOOK and FTS, single lab\",\n      \"pmids\": [\"37933960\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TGME49_316650 is a parasite-specific subunit of the Toxoplasma FHF trafficking adaptor complex (comprising HOOK, FTS, and at least two apicomplexan-specific proteins) that is phosphorylated by CDPK1 and required for rapid apical trafficking of micronemes to support microneme exocytosis and host cell invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TGME49_316650 is a parasite-specific subunit of a partially conserved FHF (HOOK-FTS-FHIP) trafficking adaptor complex in Toxoplasma gondii, where it associates with HOOK, an FTS homolog, and a second apicomplexan-specific protein to support dynein-mediated apical trafficking of micronemes [#0]. The protein is a substrate of the calcium-dependent kinase CDPK1, linking its function to the signaling that drives microneme secretion and host cell invasion [#0]. Loss of the complex's core HOOK and FTS components impairs microneme protein secretion and blocks invasion, but the individual functional contribution of TGME49_316650 has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"The composition of the Toxoplasma microneme-trafficking machinery was undefined; identifying TGME49_316650 as a parasite-specific member of an FHF adaptor complex established a molecular link between dynein-based transport and apical microneme delivery.\",\n      \"evidence\": \"CDPK1 substrate bio-orthogonal labeling with sub-minute phosphoproteomics, co-immunoprecipitation defining FHF complex membership, and loss-of-function of HOOK/FTS scoring microneme secretion and invasion in T. gondii\",\n      \"pmids\": [\"37933960\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"TGME49_316650 was not individually knocked out, so its specific requirement for trafficking is unestablished\",\n        \"The invasion/secretion phenotype was attributed to HOOK and FTS, not to TGME49_316650 directly\",\n        \"The functional consequence of CDPK1 phosphorylation of TGME49_316650 is undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TGME49_316650 is individually required for FHF complex assembly, microneme trafficking, or invasion, and the role of its CDPK1-dependent phosphorylation, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No dedicated knockout of TGME49_316650\",\n        \"No structural or biochemical mapping of its interactions within the FHF complex\",\n        \"No functional readout tied specifically to its phosphorylation sites\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0030705\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"FHF (HOOK-FTS-FHIP) trafficking adaptor complex\"],\n    \"partners\": [\"HOOK\", \"FTS homolog\", \"CDPK1 (kinase)\"],\n    \"other_free_text\": [\n      \"Parasite-specific subunit of the FHF adaptor complex supporting dynein-mediated apical trafficking of micronemes [#0].\",\n      \"CDPK1 phosphorylation substrate [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_316650","name":null,"product":"hypothetical protein","uniprot_acc":"A0A125YR17","chromosome":"TGME49_chrXI","start_pos":5456994},{"strain":"GT1","gene_id":"TGGT1_316650","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":5404029},{"strain":"RH88","gene_id":"TGRH88_055340","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023092","start_pos":5524563},{"strain":"VEG","gene_id":"TGVEG_316650","name":null,"product":"hypothetical protein","uniprot_acc":"B6K9V5","chromosome":"TGVEG_chrXI","start_pos":5480920}]}