{"gene":"TG_306430","gene_symbol":"SAS6","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2015,"finding":"TgSas-6 (the cartwheel protein) localizes to the outer core of the bipartite Toxoplasma centrosome, which is distal from the nucleus and contains TgCentrin1/TgSfi1 and a novel Aurora-related kinase; this outer core functions primarily in cytokinesis (budding), as demonstrated by a temperature-sensitive mutant of TgSfi1 that caused loss of outer cores and a severe block to daughter parasite budding.","method":"Fluorescence localization, genetic analysis with temperature-sensitive mutant (ts-TgSfi1), live imaging of centrosome core duplication order","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct genetic epistasis via temperature-sensitive mutant with defined cytokinesis phenotype, combined with spatial localization and cell-cycle staging in Toxoplasma gondii","pmids":["25734885"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"finding":"The outer centrosome core (containing TgSas-6) duplicates before the inner core during S phase, ensuring sequential core duplication; the outer core duplicate first and inner core second, so each daughter parasite inherits one copy of each centrosome core type.","method":"Cell-cycle staging combined with fluorescence microscopy of centrosome core markers","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment tracking duplication order, single lab, multiple markers","pmids":["25734885"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"TgSas-6 localizes to the centriole in Toxoplasma gondii, consistent with its role in centriole biogenesis; by contrast, the related SAS6L protein localizes above the conoid (not the centriole), establishing distinct subcellular localizations for these two family members.","method":"Fluorescence localization (immunofluorescence/live imaging) in Toxoplasma tachyzoites","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment distinguishing SAS-6 vs SAS6L compartments, single lab","pmids":["23687115"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"finding":"Apicomplexan genomes encode UNIMOD components including SAS6, SAS4/CPAP, and BLD10/CEP135, suggesting conserved use of these factors in basal body/centriole assembly; however, many widely conserved basal body and flagellar biogenesis elements are absent from apicomplexan genomes, indicating variations in the biogenesis pathway.","method":"Comparative genomics / genome analysis","journal":"Cilia","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/genomic survey with no direct functional experiment on TgSAS6","pmids":["26855772"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"In Toxoplasma gondii, TgSas-6 is a cartwheel protein that localizes to the centriole and to the outer core of the bipartite centrosome (together with TgCentrin1/TgSfi1 and a novel Aurora-related kinase); this outer core duplicates first during S phase and is functionally dedicated to cytokinesis (daughter budding), while a distinct SAS6-like paralog (SAS6L) localizes above the conoid and is functionally unrelated to centriole biogenesis."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, TgSas-6 is a cartwheel component of the centriole that participates in the parasite's centriole/basal body assembly machinery [PMID:23687115, PMID:26855772]. It localizes both to the centriole and to the outer core of the bipartite Toxoplasma centrosome, a compartment positioned distal from the nucleus that also contains TgCentrin1/TgSfi1 and a novel Aurora-related kinase and is functionally dedicated to cytokinesis; a temperature-sensitive TgSfi1 mutant that eliminates outer cores blocks daughter parasite budding, establishing the outer core as the driver of budding [PMID:25734885]. During S phase the TgSas-6-containing outer core duplicates before the inner core, ensuring each daughter inherits one copy of each core type [PMID:25734885]. The distinct SAS6-like paralog SAS6L localizes above the conoid rather than to the centriole, marking it as functionally separate from centriole biogenesis [PMID:23687115]. Beyond these localization and cell-cycle findings, direct biochemical characterization of TgSas-6 (its cartwheel assembly partners, structural organization, and molecular activity) has not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing where TgSas-6 acts required distinguishing it from its paralog; showing TgSas-6 at the centriole while SAS6L sits above the conoid defined two spatially and functionally separate family members.","evidence":"Fluorescence localization of SAS-6 versus SAS6L in Toxoplasma tachyzoites","pmids":["23687115"],"confidence":"Medium","gaps":["No functional perturbation of TgSas-6 itself","Cartwheel assembly role inferred from localization, not tested biochemically"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"claim":"It was unclear how the bipartite Toxoplasma centrosome partitions its functions; placing TgSas-6 in the distal outer core and linking outer-core loss to a budding block showed this compartment drives cytokinesis.","evidence":"Fluorescence localization plus genetic epistasis via a temperature-sensitive TgSfi1 mutant with a defined budding phenotype","pmids":["25734885"],"confidence":"High","gaps":["Cytokinesis phenotype was demonstrated through TgSfi1, not by direct TgSas-6 depletion","Molecular mechanism linking outer core to budding not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"claim":"How the two centrosome cores are faithfully inherited was unknown; tracking duplication order showed the TgSas-6 outer core duplicates before the inner core, ensuring sequential inheritance of one of each core per daughter.","evidence":"Cell-cycle staging with fluorescence microscopy of centrosome core markers","pmids":["25734885"],"confidence":"Medium","gaps":["Mechanism enforcing sequential duplication order unknown","Role of TgSas-6 in setting duplication timing not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"claim":"Whether apicomplexans use canonical centriole factors was open; genomic survey showed SAS6, SAS4/CPAP, and BLD10/CEP135 are conserved while many other basal body/flagellar components are absent, framing a divergent biogenesis pathway.","evidence":"Comparative genomics of apicomplexan genomes","pmids":["26855772"],"confidence":"Low","gaps":["Computational inference only, no functional test of TgSAS6","Does not establish which conserved factors interact with TgSas-6"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical basis of TgSas-6 cartwheel assembly, its direct partners within the outer core, and its structural contribution to centriole/budding remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct TgSas-6 loss-of-function phenotype reported","No structural or interaction data for the cartwheel"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGCENTRIN1","TGSFI1","NOVEL AURORA-RELATED KINASE (CO-LOCALIZED IN THE OUTER CENTROSOME CORE)"],"other_free_text":["TgSas-6 is a cartwheel protein of the centriole [#2].","TgSas-6 marks the distal outer core of the bipartite Toxoplasma centrosome, which is dedicated to cytokinesis/daughter budding [#0].","The TgSas-6 outer core duplicates before the inner core during S phase, ensuring sequential core inheritance [#1].","The paralog SAS6L localizes above the conoid and is distinct from TgSas-6/centriole biogenesis [#2].","SAS6 is among conserved UNIMOD centriole factors retained in apicomplexan genomes [#3]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25734885","id":"PMC_25734885","title":"A novel bipartite centrosome coordinates the apicomplexan cell cycle.","date":"2015","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/25734885","citation_count":112,"is_preprint":false},{"pmid":"23687115","id":"PMC_23687115","title":"A SAS-6-like protein suggests that the Toxoplasma conoid complex evolved from flagellar components.","date":"2013","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/23687115","citation_count":58,"is_preprint":false},{"pmid":"26855772","id":"PMC_26855772","title":"Basal body structure and composition in the apicomplexans Toxoplasma and Plasmodium.","date":"2016","source":"Cilia","url":"https://pubmed.ncbi.nlm.nih.gov/26855772","citation_count":51,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4096,"output_tokens":1101,"usd":0.014401,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6034,"output_tokens":2252,"usd":0.043235,"stage2_stop_reason":"end_turn"},"total_usd":0.057636,"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\": 2015,\n      \"finding\": \"TgSas-6 (the cartwheel protein) localizes to the outer core of the bipartite Toxoplasma centrosome, which is distal from the nucleus and contains TgCentrin1/TgSfi1 and a novel Aurora-related kinase; this outer core functions primarily in cytokinesis (budding), as demonstrated by a temperature-sensitive mutant of TgSfi1 that caused loss of outer cores and a severe block to daughter parasite budding.\",\n      \"method\": \"Fluorescence localization, genetic analysis with temperature-sensitive mutant (ts-TgSfi1), live imaging of centrosome core duplication order\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct genetic epistasis via temperature-sensitive mutant with defined cytokinesis phenotype, combined with spatial localization and cell-cycle staging in Toxoplasma gondii\",\n      \"pmids\": [\"25734885\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The outer centrosome core (containing TgSas-6) duplicates before the inner core during S phase, ensuring sequential core duplication; the outer core duplicate first and inner core second, so each daughter parasite inherits one copy of each centrosome core type.\",\n      \"method\": \"Cell-cycle staging combined with fluorescence microscopy of centrosome core markers\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment tracking duplication order, single lab, multiple markers\",\n      \"pmids\": [\"25734885\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TgSas-6 localizes to the centriole in Toxoplasma gondii, consistent with its role in centriole biogenesis; by contrast, the related SAS6L protein localizes above the conoid (not the centriole), establishing distinct subcellular localizations for these two family members.\",\n      \"method\": \"Fluorescence localization (immunofluorescence/live imaging) in Toxoplasma tachyzoites\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment distinguishing SAS-6 vs SAS6L compartments, single lab\",\n      \"pmids\": [\"23687115\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Apicomplexan genomes encode UNIMOD components including SAS6, SAS4/CPAP, and BLD10/CEP135, suggesting conserved use of these factors in basal body/centriole assembly; however, many widely conserved basal body and flagellar biogenesis elements are absent from apicomplexan genomes, indicating variations in the biogenesis pathway.\",\n      \"method\": \"Comparative genomics / genome analysis\",\n      \"journal\": \"Cilia\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/genomic survey with no direct functional experiment on TgSAS6\",\n      \"pmids\": [\"26855772\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In Toxoplasma gondii, TgSas-6 is a cartwheel protein that localizes to the centriole and to the outer core of the bipartite centrosome (together with TgCentrin1/TgSfi1 and a novel Aurora-related kinase); this outer core duplicates first during S phase and is functionally dedicated to cytokinesis (daughter budding), while a distinct SAS6-like paralog (SAS6L) localizes above the conoid and is functionally unrelated to centriole biogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, TgSas-6 is a cartwheel component of the centriole that participates in the parasite's centriole/basal body assembly machinery [#2, #3]. It localizes both to the centriole and to the outer core of the bipartite Toxoplasma centrosome, a compartment positioned distal from the nucleus that also contains TgCentrin1/TgSfi1 and a novel Aurora-related kinase and is functionally dedicated to cytokinesis; a temperature-sensitive TgSfi1 mutant that eliminates outer cores blocks daughter parasite budding, establishing the outer core as the driver of budding [#0]. During S phase the TgSas-6-containing outer core duplicates before the inner core, ensuring each daughter inherits one copy of each core type [#1]. The distinct SAS6-like paralog SAS6L localizes above the conoid rather than to the centriole, marking it as functionally separate from centriole biogenesis [#2]. Beyond these localization and cell-cycle findings, direct biochemical characterization of TgSas-6 (its cartwheel assembly partners, structural organization, and molecular activity) has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing where TgSas-6 acts required distinguishing it from its paralog; showing TgSas-6 at the centriole while SAS6L sits above the conoid defined two spatially and functionally separate family members.\",\n      \"evidence\": \"Fluorescence localization of SAS-6 versus SAS6L in Toxoplasma tachyzoites\",\n      \"pmids\": [\"23687115\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional perturbation of TgSas-6 itself\", \"Cartwheel assembly role inferred from localization, not tested biochemically\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unclear how the bipartite Toxoplasma centrosome partitions its functions; placing TgSas-6 in the distal outer core and linking outer-core loss to a budding block showed this compartment drives cytokinesis.\",\n      \"evidence\": \"Fluorescence localization plus genetic epistasis via a temperature-sensitive TgSfi1 mutant with a defined budding phenotype\",\n      \"pmids\": [\"25734885\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Cytokinesis phenotype was demonstrated through TgSfi1, not by direct TgSas-6 depletion\", \"Molecular mechanism linking outer core to budding not defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"How the two centrosome cores are faithfully inherited was unknown; tracking duplication order showed the TgSas-6 outer core duplicates before the inner core, ensuring sequential inheritance of one of each core per daughter.\",\n      \"evidence\": \"Cell-cycle staging with fluorescence microscopy of centrosome core markers\",\n      \"pmids\": [\"25734885\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism enforcing sequential duplication order unknown\", \"Role of TgSas-6 in setting duplication timing not tested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether apicomplexans use canonical centriole factors was open; genomic survey showed SAS6, SAS4/CPAP, and BLD10/CEP135 are conserved while many other basal body/flagellar components are absent, framing a divergent biogenesis pathway.\",\n      \"evidence\": \"Comparative genomics of apicomplexan genomes\",\n      \"pmids\": [\"26855772\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational inference only, no functional test of TgSAS6\", \"Does not establish which conserved factors interact with TgSas-6\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical basis of TgSas-6 cartwheel assembly, its direct partners within the outer core, and its structural contribution to centriole/budding remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct TgSas-6 loss-of-function phenotype reported\", \"No structural or interaction data for the cartwheel\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005814\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0098534\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000910\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgCentrin1\", \"TgSfi1\", \"novel Aurora-related kinase (co-localized in the outer centrosome core)\"],\n    \"other_free_text\": [\n      \"TgSas-6 is a cartwheel protein of the centriole [#2].\",\n      \"TgSas-6 marks the distal outer core of the bipartite Toxoplasma centrosome, which is dedicated to cytokinesis/daughter budding [#0].\",\n      \"The TgSas-6 outer core duplicates before the inner core during S phase, ensuring sequential core inheritance [#1].\",\n      \"The paralog SAS6L localizes above the conoid and is distinct from TgSas-6/centriole biogenesis [#2].\",\n      \"SAS6 is among conserved UNIMOD centriole factors retained in apicomplexan genomes [#3].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_306430","name":"SAS6","product":"spindle assembly abnormal protein 6","uniprot_acc":"S8F1W0","chromosome":"TGME49_chrIX","start_pos":6069280},{"strain":"GT1","gene_id":"TGGT1_306430","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":5848968},{"strain":"RH88","gene_id":"TGRH88_017880","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023090","start_pos":6192497},{"strain":"VEG","gene_id":"TGVEG_306430","name":null,"product":"hypothetical protein","uniprot_acc":"A0A0F7V199","chromosome":"TGVEG_chrIX","start_pos":6108420}]}