{"gene":"TG_249480","gene_symbol":"UNC","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2017,"finding":"TgUNC acts as a chaperone dedicated to the folding, assembly, and function of all Toxoplasma myosins; conditional ablation of TgUNC recapitulates the phenotypes of all known myosins, including defects in motility, invasion, egress, organelle positioning, basal complex constriction, and synchronized division within the parasitophorous vacuole.","method":"Conditional knockdown/ablation with phenotypic readouts (motility, invasion, egress, constriction, division synchrony assays)","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional ablation with multiple orthogonal phenotypic readouts recapitulating the full myosin phenome, single lab but comprehensive coverage","pmids":["28593938"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"finding":"TgUNC (a UCS family myosin co-chaperone) is required for solubility and functionality of TgMyoA (class XIVa myosin) when expressed in Sf9 insect cells; the tetratricopeptide repeat (TPR) domain of TgUNC was not essential for obtaining functional myosin, implying other mechanisms recruit Hsp90.","method":"Baculovirus/Sf9 heterologous expression system with co-expression of TgUNC; in vitro actin gliding motility assay; domain deletion mutagenesis of TPR domain","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with functional motility assay and domain mutagenesis, single lab","pmids":["25231988"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgUNC is a UCS-family myosin co-chaperone in Toxoplasma gondii that is required for the folding, assembly, and function of all parasite myosins (demonstrated both in heterologous Sf9 expression with in vitro motility assays and by conditional ablation in the parasite), with its TPR domain being dispensable for this chaperone activity; loss of TgUNC recapitulates the combined phenotypes of all known myosins, including defects in motility, invasion, egress, apicoplast inheritance, basal complex constriction, and intravacuolar synchronized division."},"narrative":{"mechanistic_narrative":"TgUNC is a UCS-family myosin co-chaperone in Toxoplasma gondii that is dedicated to the folding, assembly, and function of the parasite's myosins [PMID:28593938, PMID:25231988]. In a heterologous Sf9 expression system, co-expression of TgUNC is required to produce soluble, functional TgMyoA (class XIVa myosin), and the resulting myosin is competent for actin-based gliding motility in vitro; the tetratricopeptide repeat (TPR) domain of TgUNC is dispensable for generating functional myosin, indicating that Hsp90 recruitment occurs through other means [PMID:25231988]. Conditional ablation of TgUNC in the parasite recapitulates the combined phenotypes of all known myosins, producing defects in motility, invasion, egress, organelle positioning, basal complex constriction, and synchronized intravacuolar division, establishing TgUNC as a shared chaperone upon which the entire myosin repertoire depends [PMID:28593938].","teleology":[{"year":2014,"claim":"Establishing whether Toxoplasma myosins require a dedicated co-chaperone to fold correctly, this work showed that TgUNC is needed to produce soluble, motility-competent TgMyoA and that its TPR domain is not required for that activity.","evidence":"Baculovirus/Sf9 heterologous co-expression with in vitro actin gliding motility assay and TPR-domain deletion mutagenesis","pmids":["25231988"],"confidence":"High","gaps":["How Hsp90 is recruited if not via the TPR domain was not resolved","Tested on TgMyoA in a heterologous system; whether other parasite myosins depend on TgUNC was not addressed here","No in vivo requirement demonstrated in the parasite"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"Extending the co-chaperone role from a single myosin in vitro to the whole parasite, conditional ablation showed TgUNC is required for the function of all Toxoplasma myosins, recapitulating the entire myosin phenome.","evidence":"Conditional knockdown/ablation in the parasite with motility, invasion, egress, basal complex constriction, and division-synchrony readouts","pmids":["28593938"],"confidence":"High","gaps":["Direct biochemical demonstration that each individual myosin physically depends on TgUNC was not shown for every myosin","Molecular mechanism of the folding/assembly cycle (client engagement, ATP dependence) not resolved","Single lab; comprehensive but not independently replicated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TgUNC engages Hsp90 in the absence of a required TPR domain, and the structural basis of client myosin folding, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["Mechanism of Hsp90 recruitment independent of the TPR domain is unknown","No structural model of the TgUNC-myosin chaperone complex","Client-specificity determinants across the myosin repertoire not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGMYOA (CLASS XIVA MYOSIN)","HSP90"],"other_free_text":["UCS-family myosin co-chaperone; TPR domain dispensable for producing functional myosin","Loss of function recapitulates the combined phenotypes of all known Toxoplasma myosins: motility, invasion, egress, organelle/apicoplast positioning, basal complex constriction, and synchronized intravacuolar division"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"28593938","id":"PMC_28593938","title":"Myosin-dependent cell-cell communication controls synchronicity of division in acute and chronic stages of Toxoplasma gondii.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28593938","citation_count":90,"is_preprint":false},{"pmid":"25231988","id":"PMC_25231988","title":"A Toxoplasma gondii class XIV myosin, expressed in Sf9 cells with a parasite co-chaperone, requires two light chains for fast motility.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25231988","citation_count":36,"is_preprint":false},{"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},{"pmid":"37815466","id":"PMC_37815466","title":"The SUN-like protein TgSLP1 is essential for nuclear division in the apicomplexan parasite Toxoplasma gondii.","date":"2023","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/37815466","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4188,"output_tokens":701,"usd":0.011539,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5420,"output_tokens":1694,"usd":0.034725,"stage2_stop_reason":"end_turn"},"total_usd":0.046264,"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\": 2017,\n      \"finding\": \"TgUNC acts as a chaperone dedicated to the folding, assembly, and function of all Toxoplasma myosins; conditional ablation of TgUNC recapitulates the phenotypes of all known myosins, including defects in motility, invasion, egress, organelle positioning, basal complex constriction, and synchronized division within the parasitophorous vacuole.\",\n      \"method\": \"Conditional knockdown/ablation with phenotypic readouts (motility, invasion, egress, constriction, division synchrony assays)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional ablation with multiple orthogonal phenotypic readouts recapitulating the full myosin phenome, single lab but comprehensive coverage\",\n      \"pmids\": [\"28593938\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"TgUNC (a UCS family myosin co-chaperone) is required for solubility and functionality of TgMyoA (class XIVa myosin) when expressed in Sf9 insect cells; the tetratricopeptide repeat (TPR) domain of TgUNC was not essential for obtaining functional myosin, implying other mechanisms recruit Hsp90.\",\n      \"method\": \"Baculovirus/Sf9 heterologous expression system with co-expression of TgUNC; in vitro actin gliding motility assay; domain deletion mutagenesis of TPR domain\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with functional motility assay and domain mutagenesis, single lab\",\n      \"pmids\": [\"25231988\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgUNC is a UCS-family myosin co-chaperone in Toxoplasma gondii that is required for the folding, assembly, and function of all parasite myosins (demonstrated both in heterologous Sf9 expression with in vitro motility assays and by conditional ablation in the parasite), with its TPR domain being dispensable for this chaperone activity; loss of TgUNC recapitulates the combined phenotypes of all known myosins, including defects in motility, invasion, egress, apicoplast inheritance, basal complex constriction, and intravacuolar synchronized division.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgUNC is a UCS-family myosin co-chaperone in Toxoplasma gondii that is dedicated to the folding, assembly, and function of the parasite's myosins [#0, #1]. In a heterologous Sf9 expression system, co-expression of TgUNC is required to produce soluble, functional TgMyoA (class XIVa myosin), and the resulting myosin is competent for actin-based gliding motility in vitro; the tetratricopeptide repeat (TPR) domain of TgUNC is dispensable for generating functional myosin, indicating that Hsp90 recruitment occurs through other means [#1]. Conditional ablation of TgUNC in the parasite recapitulates the combined phenotypes of all known myosins, producing defects in motility, invasion, egress, organelle positioning, basal complex constriction, and synchronized intravacuolar division, establishing TgUNC as a shared chaperone upon which the entire myosin repertoire depends [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing whether Toxoplasma myosins require a dedicated co-chaperone to fold correctly, this work showed that TgUNC is needed to produce soluble, motility-competent TgMyoA and that its TPR domain is not required for that activity.\",\n      \"evidence\": \"Baculovirus/Sf9 heterologous co-expression with in vitro actin gliding motility assay and TPR-domain deletion mutagenesis\",\n      \"pmids\": [\n        \"25231988\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How Hsp90 is recruited if not via the TPR domain was not resolved\",\n        \"Tested on TgMyoA in a heterologous system; whether other parasite myosins depend on TgUNC was not addressed here\",\n        \"No in vivo requirement demonstrated in the parasite\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extending the co-chaperone role from a single myosin in vitro to the whole parasite, conditional ablation showed TgUNC is required for the function of all Toxoplasma myosins, recapitulating the entire myosin phenome.\",\n      \"evidence\": \"Conditional knockdown/ablation in the parasite with motility, invasion, egress, basal complex constriction, and division-synchrony readouts\",\n      \"pmids\": [\n        \"28593938\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct biochemical demonstration that each individual myosin physically depends on TgUNC was not shown for every myosin\",\n        \"Molecular mechanism of the folding/assembly cycle (client engagement, ATP dependence) not resolved\",\n        \"Single lab; comprehensive but not independently replicated\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgUNC engages Hsp90 in the absence of a required TPR domain, and the structural basis of client myosin folding, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism of Hsp90 recruitment independent of the TPR domain is unknown\",\n        \"No structural model of the TgUNC-myosin chaperone complex\",\n        \"Client-specificity determinants across the myosin repertoire not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0051087\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0031034\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"TgMyoA (class XIVa myosin)\",\n      \"Hsp90\"\n    ],\n    \"other_free_text\": [\n      \"UCS-family myosin co-chaperone; TPR domain dispensable for producing functional myosin\",\n      \"Loss of function recapitulates the combined phenotypes of all known Toxoplasma myosins: motility, invasion, egress, organelle/apicoplast positioning, basal complex constriction, and synchronized intravacuolar division\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_249480","name":"UNC","product":"co-chaperone UNC","uniprot_acc":"A0A125YTB0","chromosome":"TGME49_chrXII","start_pos":4567963},{"strain":"GT1","gene_id":"TGGT1_249480","name":null,"product":"tetratricopeptide repeat-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":4502413},{"strain":"RH88","gene_id":"TGRH88_063230","name":null,"product":"tetratricopeptide repeat-containing protein","uniprot_acc":null,"chromosome":"CM023093","start_pos":4624117},{"strain":"VEG","gene_id":"TGVEG_249480","name":null,"product":"tetratricopeptide repeat-containing protein","uniprot_acc":"B6KHF9","chromosome":"TGVEG_chrXII","start_pos":4542963}]}