{"gene":"TG_318410","gene_symbol":"","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2020,"finding":"TgTCP-1 (TGME49_318410) colocalizes with the microneme protein MIC3, suggesting it is secreted from tachyzoites and localizes to a microneme-like compartment.","method":"Co-localization imaging with MIC3 marker","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single co-localization experiment in one lab, but consistent with secretion-based functional data","pmids":["32153542"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]},{"year":2020,"finding":"Recombinant TgTCP-1 protein binds specifically to sialic acid in vitro; binding to host cells (DC and Vero) is inhibited by pre-incubation with free sialic acid or neuraminidase treatment of host cells.","method":"Recombinant protein binding assay with sialic acid competition and neuraminidase treatment","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical binding assay with two orthogonal inhibition controls (free sialic acid and neuraminidase), single lab","pmids":["32153542"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]},{"year":2020,"finding":"Pre-incubation of host Vero cells with recombinant TgTCP-1 protein significantly reduces T. gondii invasion, establishing a functional role for TgTCP-1 in sialic acid-dependent host cell invasion.","method":"Invasion inhibition assay using recombinant TgTCP-1 protein pre-treatment of host cells","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional invasion assay with recombinant protein competition, single lab, consistent with binding data","pmids":["32153542"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]},{"year":2010,"finding":"Conditional knockdown of TCP-1 (a chaperonin protein folding machinery component) via a tetracycline-regulatable promoter trap did not result in a critical growth defect, indicating TCP-1 is not essential for parasite growth under the conditions tested; a suppressor gene was identified instead.","method":"Insertional gene trap with Tet-transactivator system; growth phenotype assay; cosmid complementation","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — negative result from a single conditional knockdown experiment, single lab; complicating rearrangements noted","pmids":["21035508"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgTCP-1 (TGME49_318410) is a secreted parasite protein that co-localizes with the microneme marker MIC3, binds sialic acid on host cell surfaces, and facilitates sialic acid-dependent invasion of host cells, while conditional knockdown experiments did not reveal an essential role in parasite growth."},"narrative":{"mechanistic_narrative":"TgTCP-1 (TGME49_318410) is a Toxoplasma gondii protein implicated in sialic acid-dependent host cell invasion [PMID:32153542]. In the ME49 strain it co-localizes with the microneme protein MIC3, consistent with secretion from tachyzoites into a microneme-like compartment [PMID:32153542]. Recombinant TgTCP-1 binds specifically to sialic acid in vitro, and this binding to dendritic and Vero host cells is abolished by competition with free sialic acid or by neuraminidase pretreatment of the host surface, defining sialic acid as its ligand [PMID:32153542]. Pre-incubating host cells with recombinant TgTCP-1 reduces parasite invasion, indicating that the protein engages host-surface sialic acid to promote entry [PMID:32153542]. Beyond this invasion-associated role, the protein's mechanism is largely uncharacterized in the available corpus; conditional knockdown did not produce a critical growth defect, so TgTCP-1 is not essential for parasite growth under the conditions tested [PMID:21035508].","teleology":[{"year":2010,"claim":"Whether TCP-1 is essential for parasite viability was addressed by conditional depletion, establishing that its loss does not critically impair growth and shifting focus away from a housekeeping folding role.","evidence":"Insertional gene trap with Tet-transactivator conditional knockdown and cosmid complementation in T. gondii","pmids":["21035508"],"confidence":"Low","gaps":["Negative growth result from a single conditional knockdown, single lab, with complicating genomic rearrangements noted","Does not test roles in invasion or stage-specific functions","Suppressor gene identified but its relationship to TCP-1 function unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"The subcellular fate of TgTCP-1 was addressed by imaging, showing co-localization with a microneme marker and implicating it as a secreted, invasion-associated protein rather than a purely cytosolic chaperonin.","evidence":"Co-localization imaging with the microneme protein MIC3 in ME49 tachyzoites","pmids":["32153542"],"confidence":"Medium","gaps":["Single co-localization experiment in one lab","Does not directly demonstrate secretion or microneme discharge kinetics","Endogenous localization not confirmed by tagging"],"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]},{"year":2020,"claim":"The molecular ligand of TgTCP-1 was defined by binding assays, showing specific recognition of host-surface sialic acid.","evidence":"Recombinant protein binding to DC and Vero cells with free-sialic-acid competition and neuraminidase controls","pmids":["32153542"],"confidence":"Medium","gaps":["Recombinant protein assay in a single lab; endogenous protein binding not shown","The specific sialylated host glycan/receptor is not identified","Binding stoichiometry and affinity not quantified"],"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]},{"year":2020,"claim":"Whether sialic acid binding is functionally relevant to infection was tested by invasion competition, establishing TgTCP-1 as a contributor to sialic acid-dependent host cell invasion.","evidence":"Invasion inhibition assay using recombinant TgTCP-1 pre-treatment of Vero host cells","pmids":["32153542"],"confidence":"Medium","gaps":["Competition assay with recombinant protein; genetic loss-of-function invasion phenotype not tested","Does not define whether TgTCP-1 acts directly at the invasion junction","Contribution relative to other adhesins unquantified"],"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]},{"year":null,"claim":"How a putative chaperonin comes to act as a secreted sialic acid-binding adhesin, and the identity of its host receptor, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural basis for sialic acid recognition characterized","Host sialylated receptor not identified","Reconciliation of chaperonin annotation with secreted adhesin function unaddressed"],"attribution":[{"species":"Toxoplasma gondii","strain":"ME49"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MIC3 (CO-LOCALIZATION MARKER)","HOST-SURFACE SIALIC ACID (LIGAND)"],"other_free_text":["Recombinant TgTCP-1 binds sialic acid; binding blocked by free sialic acid or neuraminidase treatment [#1]","Pre-treatment of host cells with recombinant TgTCP-1 reduces T. gondii invasion [#2]","Conditional knockdown produced no critical growth defect; TCP-1 not essential under conditions tested [#3]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"21035508","id":"PMC_21035508","title":"An insertional trap for conditional gene expression in Toxoplasma gondii: identification of TAF250 as an essential gene.","date":"2010","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/21035508","citation_count":13,"is_preprint":false},{"pmid":"32153542","id":"PMC_32153542","title":"The Putative TCP-1 Chaperonin Is an Important Player Involved in Sialic Acid-Dependent Host Cell Invasion by Toxoplasma gondii.","date":"2020","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32153542","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3429,"output_tokens":979,"usd":0.012486,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5853,"output_tokens":2328,"usd":0.043733,"stage2_stop_reason":"end_turn"},"total_usd":0.056219,"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\": 2020,\n      \"finding\": \"TgTCP-1 (TGME49_318410) colocalizes with the microneme protein MIC3, suggesting it is secreted from tachyzoites and localizes to a microneme-like compartment.\",\n      \"method\": \"Co-localization imaging with MIC3 marker\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single co-localization experiment in one lab, but consistent with secretion-based functional data\",\n      \"pmids\": [\"32153542\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"ME49\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Recombinant TgTCP-1 protein binds specifically to sialic acid in vitro; binding to host cells (DC and Vero) is inhibited by pre-incubation with free sialic acid or neuraminidase treatment of host cells.\",\n      \"method\": \"Recombinant protein binding assay with sialic acid competition and neuraminidase treatment\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical binding assay with two orthogonal inhibition controls (free sialic acid and neuraminidase), single lab\",\n      \"pmids\": [\"32153542\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"ME49\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Pre-incubation of host Vero cells with recombinant TgTCP-1 protein significantly reduces T. gondii invasion, establishing a functional role for TgTCP-1 in sialic acid-dependent host cell invasion.\",\n      \"method\": \"Invasion inhibition assay using recombinant TgTCP-1 protein pre-treatment of host cells\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional invasion assay with recombinant protein competition, single lab, consistent with binding data\",\n      \"pmids\": [\"32153542\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"ME49\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Conditional knockdown of TCP-1 (a chaperonin protein folding machinery component) via a tetracycline-regulatable promoter trap did not result in a critical growth defect, indicating TCP-1 is not essential for parasite growth under the conditions tested; a suppressor gene was identified instead.\",\n      \"method\": \"Insertional gene trap with Tet-transactivator system; growth phenotype assay; cosmid complementation\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — negative result from a single conditional knockdown experiment, single lab; complicating rearrangements noted\",\n      \"pmids\": [\"21035508\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgTCP-1 (TGME49_318410) is a secreted parasite protein that co-localizes with the microneme marker MIC3, binds sialic acid on host cell surfaces, and facilitates sialic acid-dependent invasion of host cells, while conditional knockdown experiments did not reveal an essential role in parasite growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgTCP-1 (TGME49_318410) is a Toxoplasma gondii protein implicated in sialic acid-dependent host cell invasion [#2]. In the ME49 strain it co-localizes with the microneme protein MIC3, consistent with secretion from tachyzoites into a microneme-like compartment [#0]. Recombinant TgTCP-1 binds specifically to sialic acid in vitro, and this binding to dendritic and Vero host cells is abolished by competition with free sialic acid or by neuraminidase pretreatment of the host surface, defining sialic acid as its ligand [#1]. Pre-incubating host cells with recombinant TgTCP-1 reduces parasite invasion, indicating that the protein engages host-surface sialic acid to promote entry [#2]. Beyond this invasion-associated role, the protein's mechanism is largely uncharacterized in the available corpus; conditional knockdown did not produce a critical growth defect, so TgTCP-1 is not essential for parasite growth under the conditions tested [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether TCP-1 is essential for parasite viability was addressed by conditional depletion, establishing that its loss does not critically impair growth and shifting focus away from a housekeeping folding role.\",\n      \"evidence\": \"Insertional gene trap with Tet-transactivator conditional knockdown and cosmid complementation in T. gondii\",\n      \"pmids\": [\n        \"21035508\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Negative growth result from a single conditional knockdown, single lab, with complicating genomic rearrangements noted\",\n        \"Does not test roles in invasion or stage-specific functions\",\n        \"Suppressor gene identified but its relationship to TCP-1 function unresolved\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The subcellular fate of TgTCP-1 was addressed by imaging, showing co-localization with a microneme marker and implicating it as a secreted, invasion-associated protein rather than a purely cytosolic chaperonin.\",\n      \"evidence\": \"Co-localization imaging with the microneme protein MIC3 in ME49 tachyzoites\",\n      \"pmids\": [\n        \"32153542\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single co-localization experiment in one lab\",\n        \"Does not directly demonstrate secretion or microneme discharge kinetics\",\n        \"Endogenous localization not confirmed by tagging\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"ME49\"\n        }\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The molecular ligand of TgTCP-1 was defined by binding assays, showing specific recognition of host-surface sialic acid.\",\n      \"evidence\": \"Recombinant protein binding to DC and Vero cells with free-sialic-acid competition and neuraminidase controls\",\n      \"pmids\": [\n        \"32153542\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Recombinant protein assay in a single lab; endogenous protein binding not shown\",\n        \"The specific sialylated host glycan/receptor is not identified\",\n        \"Binding stoichiometry and affinity not quantified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"ME49\"\n        }\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether sialic acid binding is functionally relevant to infection was tested by invasion competition, establishing TgTCP-1 as a contributor to sialic acid-dependent host cell invasion.\",\n      \"evidence\": \"Invasion inhibition assay using recombinant TgTCP-1 pre-treatment of Vero host cells\",\n      \"pmids\": [\n        \"32153542\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Competition assay with recombinant protein; genetic loss-of-function invasion phenotype not tested\",\n        \"Does not define whether TgTCP-1 acts directly at the invasion junction\",\n        \"Contribution relative to other adhesins unquantified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"ME49\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a putative chaperonin comes to act as a secreted sialic acid-binding adhesin, and the identity of its host receptor, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural basis for sialic acid recognition characterized\",\n        \"Host sialylated receptor not identified\",\n        \"Reconciliation of chaperonin annotation with secreted adhesin function unaddressed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"ME49\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0033691\",\n        \"supporting_discovery_ids\": [\n          1\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"ME49\"\n          }\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0020009\",\n        \"supporting_discovery_ids\": [\n          0\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"ME49\"\n          }\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0044409\",\n        \"supporting_discovery_ids\": [\n          2\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"ME49\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"MIC3 (co-localization marker)\",\n      \"host-surface sialic acid (ligand)\"\n    ],\n    \"other_free_text\": [\n      \"Recombinant TgTCP-1 binds sialic acid; binding blocked by free sialic acid or neuraminidase treatment [#1]\",\n      \"Pre-treatment of host cells with recombinant TgTCP-1 reduces T. gondii invasion [#2]\",\n      \"Conditional knockdown produced no critical growth defect; TCP-1 not essential under conditions tested [#3]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_318410","name":null,"product":"TCP-1 chaperonin, putative","uniprot_acc":"A0A125YLR8","chromosome":"TGME49_chrIV","start_pos":1352551},{"strain":"GT1","gene_id":"TGGT1_318410","name":null,"product":"putative TCP-1 chaperonin","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":1295296},{"strain":"RH88","gene_id":"TGRH88_008150","name":null,"product":"putative TCP-1 chaperonin","uniprot_acc":null,"chromosome":"CM023085","start_pos":1375010},{"strain":"VEG","gene_id":"TGVEG_318410","name":null,"product":"putative TCP-1 chaperonin","uniprot_acc":"B9PVE9","chromosome":"TGVEG_chrIV","start_pos":1363328}]}