{"gene":"TG_218880","gene_symbol":"SFA3","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2012,"finding":"TgSFA3 is an essential component of the striated fiber assemblin (SFA) fiber that polymerizes from the centrosome immediately after its duplication; genetic deletion of TgSFA3 blocks cytokinesis at its earliest point—initiation of the daughter microtubule organizing center (MTOC)—while mitosis proceeds unimpeded, causing accumulation of multiple nuclei without daughter cell formation.","method":"Genetic knockout/conditional depletion in Toxoplasma gondii with phenotypic readout (cytokinesis block, nuclear accumulation assayed by microscopy); live-imaging of fiber dynamics from centrosome","journal":"PLoS Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic loss-of-function with specific cellular phenotype (cytokinesis block vs. intact mitosis), combined with direct localization of the fiber to centrosome, in a peer-reviewed study","pmids":["23239939"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"finding":"The SFA fiber, which includes TgSFA2 and TgSFA3, grows in a polarized fashion from the centrosome and physically tethers forming daughter cells at their apical end (conoid and polar ring), positioning the apical invasion complex during budding.","method":"Fluorescence microscopy of SFA fiber dynamics during parasite cell division; genetic epistasis with TgSFA2 and TgSFA3 knockouts","journal":"PLoS Biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization with functional consequence (tethering of daughter to centrosome) validated by two independent genetic knockouts in the same study","pmids":["23239939"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgSFA3 is an essential structural component of the polarized striated fiber assemblin (SFA) fiber that nucleates from the centrosome after its duplication, grows toward forming daughter cells, and physically tethers daughters at their apical end; loss of TgSFA3 abolishes the earliest step of daughter MTOC initiation and cytokinesis while leaving mitosis intact, establishing the SFA fiber as the primary spatial and temporal organizer of Toxoplasma gondii cell division."},"narrative":{"mechanistic_narrative":"TgSFA3 is an essential structural component of the striated fiber assemblin (SFA) fiber that organizes cell division in Toxoplasma gondii [PMID:23239939]. The SFA fiber, which incorporates TgSFA3 together with TgSFA2, polymerizes from the centrosome immediately after its duplication and grows in a polarized fashion toward the forming daughter cells, physically tethering the daughters at their apical end (conoid and polar ring) and positioning the apical invasion complex during budding [PMID:23239939]. Genetic deletion of TgSFA3 blocks cytokinesis at its earliest point—initiation of the daughter microtubule organizing center (MTOC)—while mitosis proceeds unimpeded, causing accumulation of multiple nuclei without daughter cell formation [PMID:23239939]. Beyond this role in SFA-fiber-mediated organization of budding, no further mechanistic detail about TgSFA3 has been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Establishing whether TgSFA3 is required for parasite cell division showed that it is an essential SFA fiber component acting at the earliest step of cytokinesis, defining the fiber as the temporal initiator of daughter formation.","evidence":"Genetic knockout/conditional depletion in Toxoplasma gondii with microscopy phenotyping (cytokinesis block, nuclear accumulation) and live-imaging of fiber dynamics from the centrosome","pmids":["23239939"],"confidence":"High","gaps":["The molecular composition and higher-order structure of the SFA fiber beyond TgSFA3 and TgSFA2 is not resolved","How TgSFA3 triggers daughter MTOC initiation mechanistically is not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"claim":"Determining how forming daughters remain spatially linked to the centrosome showed that the SFA fiber grows polarized from the centrosome and tethers daughters at their apical end, establishing the fiber as the spatial organizer positioning the apical invasion complex during budding.","evidence":"Fluorescence microscopy of SFA fiber dynamics during division and genetic epistasis with TgSFA2 and TgSFA3 knockouts in Toxoplasma gondii","pmids":["23239939"],"confidence":"High","gaps":["The mechanism of directional/polarized fiber growth is not defined","The interface by which the fiber engages the apical conoid/polar ring is uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Striated fiber assemblin (SFA) fiber"],"partners":["TGSFA2"],"other_free_text":["Essential for initiation of the daughter microtubule organizing center (MTOC); loss blocks cytokinesis while mitosis continues, yielding multinucleated parasites.","SFA fiber polymerizes from the centrosome after its duplication and grows polarized to tether daughter cells at their apical end (conoid and polar ring)."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"23239939","id":"PMC_23239939","title":"Cell division in Apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella.","date":"2012","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/23239939","citation_count":95,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3005,"output_tokens":823,"usd":0.01068,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5687,"output_tokens":1937,"usd":0.03843,"stage2_stop_reason":"end_turn"},"total_usd":0.093748,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","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\": 2012,\n      \"finding\": \"TgSFA3 is an essential component of the striated fiber assemblin (SFA) fiber that polymerizes from the centrosome immediately after its duplication; genetic deletion of TgSFA3 blocks cytokinesis at its earliest point—initiation of the daughter microtubule organizing center (MTOC)—while mitosis proceeds unimpeded, causing accumulation of multiple nuclei without daughter cell formation.\",\n      \"method\": \"Genetic knockout/conditional depletion in Toxoplasma gondii with phenotypic readout (cytokinesis block, nuclear accumulation assayed by microscopy); live-imaging of fiber dynamics from centrosome\",\n      \"journal\": \"PLoS Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic loss-of-function with specific cellular phenotype (cytokinesis block vs. intact mitosis), combined with direct localization of the fiber to centrosome, in a peer-reviewed study\",\n      \"pmids\": [\"23239939\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The SFA fiber, which includes TgSFA2 and TgSFA3, grows in a polarized fashion from the centrosome and physically tethers forming daughter cells at their apical end (conoid and polar ring), positioning the apical invasion complex during budding.\",\n      \"method\": \"Fluorescence microscopy of SFA fiber dynamics during parasite cell division; genetic epistasis with TgSFA2 and TgSFA3 knockouts\",\n      \"journal\": \"PLoS Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization with functional consequence (tethering of daughter to centrosome) validated by two independent genetic knockouts in the same study\",\n      \"pmids\": [\"23239939\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgSFA3 is an essential structural component of the polarized striated fiber assemblin (SFA) fiber that nucleates from the centrosome after its duplication, grows toward forming daughter cells, and physically tethers daughters at their apical end; loss of TgSFA3 abolishes the earliest step of daughter MTOC initiation and cytokinesis while leaving mitosis intact, establishing the SFA fiber as the primary spatial and temporal organizer of Toxoplasma gondii cell division.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgSFA3 is an essential structural component of the striated fiber assemblin (SFA) fiber that organizes cell division in Toxoplasma gondii [#0]. The SFA fiber, which incorporates TgSFA3 together with TgSFA2, polymerizes from the centrosome immediately after its duplication and grows in a polarized fashion toward the forming daughter cells, physically tethering the daughters at their apical end (conoid and polar ring) and positioning the apical invasion complex during budding [#1]. Genetic deletion of TgSFA3 blocks cytokinesis at its earliest point—initiation of the daughter microtubule organizing center (MTOC)—while mitosis proceeds unimpeded, causing accumulation of multiple nuclei without daughter cell formation [#0]. Beyond this role in SFA-fiber-mediated organization of budding, no further mechanistic detail about TgSFA3 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing whether TgSFA3 is required for parasite cell division showed that it is an essential SFA fiber component acting at the earliest step of cytokinesis, defining the fiber as the temporal initiator of daughter formation.\",\n      \"evidence\": \"Genetic knockout/conditional depletion in Toxoplasma gondii with microscopy phenotyping (cytokinesis block, nuclear accumulation) and live-imaging of fiber dynamics from the centrosome\",\n      \"pmids\": [\"23239939\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular composition and higher-order structure of the SFA fiber beyond TgSFA3 and TgSFA2 is not resolved\",\n        \"How TgSFA3 triggers daughter MTOC initiation mechanistically is not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Determining how forming daughters remain spatially linked to the centrosome showed that the SFA fiber grows polarized from the centrosome and tethers daughters at their apical end, establishing the fiber as the spatial organizer positioning the apical invasion complex during budding.\",\n      \"evidence\": \"Fluorescence microscopy of SFA fiber dynamics during division and genetic epistasis with TgSFA2 and TgSFA3 knockouts in Toxoplasma gondii\",\n      \"pmids\": [\"23239939\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The mechanism of directional/polarized fiber growth is not defined\",\n        \"The interface by which the fiber engages the apical conoid/polar ring is uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of TgSFA3 assembly into the fiber, its direct binding partners beyond co-membership with TgSFA2, and any regulation of fiber nucleation remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of TgSFA3 or the SFA fiber\",\n        \"Direct protein-protein contacts of TgSFA3 not mapped\",\n        \"Regulation of fiber timing relative to centrosome duplication not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000910\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Striated fiber assemblin (SFA) fiber\"],\n    \"partners\": [\"TgSFA2\"],\n    \"other_free_text\": [\n      \"Essential for initiation of the daughter microtubule organizing center (MTOC); loss blocks cytokinesis while mitosis continues, yielding multinucleated parasites.\",\n      \"SFA fiber polymerizes from the centrosome after its duplication and grows polarized to tether daughter cells at their apical end (conoid and polar ring).\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_218880","name":"SFA3","product":"striated fiber assemblin SFA3","uniprot_acc":"A0A125YP87","chromosome":"TGME49_chrXII","start_pos":1238250},{"strain":"GT1","gene_id":"TGGT1_218880","name":null,"product":"putative SF-assemblin","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":1177534},{"strain":"RH88","gene_id":"TGRH88_058620","name":null,"product":"putative SF-assemblin","uniprot_acc":null,"chromosome":"CM023093","start_pos":1250296},{"strain":"VEG","gene_id":"TGVEG_218880","name":null,"product":"putative SF-assemblin","uniprot_acc":"A0A125YP88","chromosome":"TGVEG_chrXII","start_pos":1212047}]}