{"gene":"TG_210280","gene_symbol":"ARK1","run_date":"2026-09-08T11:06:21","timeline":{"discoveries":[{"year":2018,"finding":"TgArk1 (Aurora kinase 1) forms the Toxoplasma chromosomal passenger complex (CPC) together with TgINCENP1 and TgINCENP2, as demonstrated by interaction studies; TgArk1 interacts with both TgINCENPs.","method":"Co-immunoprecipitation / interaction assay identifying CPC subunit composition","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal interaction demonstrated in single study, single lab, with functional follow-up but no structural or in vitro reconstitution data reported in abstract","pmids":["30051161"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"TgINCENP2 is essential for the translocation of TgArk1 to the nucleus, establishing TgINCENP2 as the nuclear import adapter for TgArk1 within the CPC.","method":"Genetic perturbation (interference with TgINCENP2) combined with localization analysis showing failure of TgArk1 nuclear translocation","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization consequence of single-gene perturbation, single lab, single study","pmids":["30051161"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"TgArk1 exhibits dynamic, cell cycle-dependent subcellular localization consistent with its role in mitotic spindle organization during endodyogeny.","method":"Live/fixed imaging of tagged TgArk1 across cell cycle stages","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in single lab study, no independent replication reported","pmids":["30051161"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Interference with TgArk1 results in pronounced division and growth defects, establishing TgArk1 as essential for productive endodyogeny and functional mitotic spindle organization.","method":"Conditional knockdown / dominant-negative interference with defined cellular phenotype (division defects, growth deficiency)","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with defined cellular phenotype, single lab, single study","pmids":["30051161"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Treatment of Toxoplasma with low doses of hesperadin (a human Aurora kinase B inhibitor) phenocopies TgArk1 and TgINCENP2 mutant defects, indicating that the catalytic activity of TgArk1 is required for its function and that hesperadin inhibits TgArk1 at low concentrations.","method":"Pharmacological inhibition with hesperadin; phenotypic comparison to genetic mutants","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — pharmacological phenocopy of genetic mutant in single study, single lab; indirect evidence for kinase activity requirement","pmids":["30051161"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgArk1 (Aurora kinase 1) is a serine/threonine kinase that forms the Toxoplasma chromosomal passenger complex (CPC) with TgINCENP1 and TgINCENP2; TgINCENP2 is required for TgArk1 nuclear translocation, and the CPC exhibits cell cycle-dependent dynamic localization essential for organizing a functional mitotic spindle and ensuring faithful endodyogeny, with loss of TgArk1 or TgINCENP2 causing severe division and growth defects."},"narrative":{"mechanistic_narrative":"TgArk1 (Aurora kinase 1) is a serine/threonine kinase that organizes mitotic division in Toxoplasma gondii by serving as the enzymatic core of the chromosomal passenger complex (CPC), which it forms with TgINCENP1 and TgINCENP2 [PMID:30051161]. Within this complex, TgINCENP2 acts as the adapter required for TgArk1 nuclear translocation, so that CPC assembly and correct nuclear delivery are coupled [PMID:30051161]. TgArk1 displays dynamic, cell cycle-dependent subcellular localization consistent with a role in mitotic spindle organization during endodyogeny [PMID:30051161], and interference with the kinase produces pronounced division and growth defects, establishing it as essential for productive endodyogeny and functional spindle assembly [PMID:30051161]. Low-dose hesperadin, an inhibitor of human Aurora kinase B, phenocopies the TgArk1 and TgINCENP2 mutant defects, indicating that TgArk1 catalytic activity is required for its function [PMID:30051161]. Beyond CPC composition, nuclear import dependence, localization dynamics, and the loss-of-function phenotype, no direct substrates or structural detail have been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing the subunit composition of the Toxoplasma CPC answered which proteins partner with the Aurora kinase to drive division, defining TgArk1 as the kinase core of a TgINCENP1/TgINCENP2 complex.","evidence":"Co-immunoprecipitation / interaction assays showing TgArk1 binds both TgINCENPs","pmids":["30051161"],"confidence":"Medium","gaps":["No structural or in vitro reconstitution of the complex","Stoichiometry and direct vs bridged interactions among the three subunits not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Perturbing TgINCENP2 addressed how TgArk1 reaches its site of action, showing TgINCENP2 is the adapter required for TgArk1 nuclear translocation.","evidence":"Genetic interference with TgINCENP2 combined with TgArk1 localization analysis","pmids":["30051161"],"confidence":"Medium","gaps":["Molecular mechanism of the import (nuclear localization signal, transport machinery) not defined","Single-lab, single-study result"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Tracking TgArk1 through the cell cycle answered whether its localization is stage-restricted, revealing dynamic redistribution consistent with mitotic spindle organization during endodyogeny.","evidence":"Imaging of tagged TgArk1 across cell cycle stages","pmids":["30051161"],"confidence":"Medium","gaps":["Precise spindle/kinetochore structures engaged not molecularly defined","No independent replication reported"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Loss-of-function and pharmacological experiments together established that TgArk1 and its catalytic activity are essential for division, since knockdown caused division/growth defects and low-dose hesperadin phenocopied the mutants.","evidence":"Conditional knockdown/dominant-negative interference plus hesperadin inhibition with phenotypic comparison","pmids":["30051161"],"confidence":"Medium","gaps":["Kinase activity requirement inferred pharmacologically, not by kinase-dead allele or in vitro assay","Hesperadin specificity for TgArk1 over other targets not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct phosphorylation substrates of TgArk1 and the structural basis of CPC assembly and spindle regulation remain unidentified.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No TgArk1 substrates identified","No structural or biochemical reconstitution of the CPC","Mechanism linking CPC activity to spindle organization undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Chromosomal passenger complex (CPC): TgArk1 + TgINCENP1 + TgINCENP2"],"partners":["TGINCENP1","TGINCENP2"],"other_free_text":["TgINCENP2 is required for nuclear translocation of TgArk1.","Low-dose hesperadin (human Aurora kinase B inhibitor) phenocopies TgArk1/TgINCENP2 mutants, implicating TgArk1 catalytic activity.","Interference with TgArk1 causes division and growth defects during endodyogeny."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"26833682","id":"PMC_26833682","title":"The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/26833682","citation_count":37,"is_preprint":false},{"pmid":"30051161","id":"PMC_30051161","title":"Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny.","date":"2018","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/30051161","citation_count":22,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3696,"output_tokens":1236,"usd":0.014814,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6251,"output_tokens":2236,"usd":0.043577,"stage2_stop_reason":"end_turn"},"total_usd":0.058391,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"TgArk1 (Aurora kinase 1) forms the Toxoplasma chromosomal passenger complex (CPC) together with TgINCENP1 and TgINCENP2, as demonstrated by interaction studies; TgArk1 interacts with both TgINCENPs.\",\n      \"method\": \"Co-immunoprecipitation / interaction assay identifying CPC subunit composition\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal interaction demonstrated in single study, single lab, with functional follow-up but no structural or in vitro reconstitution data reported in abstract\",\n      \"pmids\": [\"30051161\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TgINCENP2 is essential for the translocation of TgArk1 to the nucleus, establishing TgINCENP2 as the nuclear import adapter for TgArk1 within the CPC.\",\n      \"method\": \"Genetic perturbation (interference with TgINCENP2) combined with localization analysis showing failure of TgArk1 nuclear translocation\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization consequence of single-gene perturbation, single lab, single study\",\n      \"pmids\": [\"30051161\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TgArk1 exhibits dynamic, cell cycle-dependent subcellular localization consistent with its role in mitotic spindle organization during endodyogeny.\",\n      \"method\": \"Live/fixed imaging of tagged TgArk1 across cell cycle stages\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in single lab study, no independent replication reported\",\n      \"pmids\": [\"30051161\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Interference with TgArk1 results in pronounced division and growth defects, establishing TgArk1 as essential for productive endodyogeny and functional mitotic spindle organization.\",\n      \"method\": \"Conditional knockdown / dominant-negative interference with defined cellular phenotype (division defects, growth deficiency)\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with defined cellular phenotype, single lab, single study\",\n      \"pmids\": [\"30051161\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Treatment of Toxoplasma with low doses of hesperadin (a human Aurora kinase B inhibitor) phenocopies TgArk1 and TgINCENP2 mutant defects, indicating that the catalytic activity of TgArk1 is required for its function and that hesperadin inhibits TgArk1 at low concentrations.\",\n      \"method\": \"Pharmacological inhibition with hesperadin; phenotypic comparison to genetic mutants\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — pharmacological phenocopy of genetic mutant in single study, single lab; indirect evidence for kinase activity requirement\",\n      \"pmids\": [\"30051161\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgArk1 (Aurora kinase 1) is a serine/threonine kinase that forms the Toxoplasma chromosomal passenger complex (CPC) with TgINCENP1 and TgINCENP2; TgINCENP2 is required for TgArk1 nuclear translocation, and the CPC exhibits cell cycle-dependent dynamic localization essential for organizing a functional mitotic spindle and ensuring faithful endodyogeny, with loss of TgArk1 or TgINCENP2 causing severe division and growth defects.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgArk1 (Aurora kinase 1) is a serine/threonine kinase that organizes mitotic division in Toxoplasma gondii by serving as the enzymatic core of the chromosomal passenger complex (CPC), which it forms with TgINCENP1 and TgINCENP2 [#0]. Within this complex, TgINCENP2 acts as the adapter required for TgArk1 nuclear translocation, so that CPC assembly and correct nuclear delivery are coupled [#1]. TgArk1 displays dynamic, cell cycle-dependent subcellular localization consistent with a role in mitotic spindle organization during endodyogeny [#2], and interference with the kinase produces pronounced division and growth defects, establishing it as essential for productive endodyogeny and functional spindle assembly [#3]. Low-dose hesperadin, an inhibitor of human Aurora kinase B, phenocopies the TgArk1 and TgINCENP2 mutant defects, indicating that TgArk1 catalytic activity is required for its function [#4]. Beyond CPC composition, nuclear import dependence, localization dynamics, and the loss-of-function phenotype, no direct substrates or structural detail have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing the subunit composition of the Toxoplasma CPC answered which proteins partner with the Aurora kinase to drive division, defining TgArk1 as the kinase core of a TgINCENP1/TgINCENP2 complex.\",\n      \"evidence\": \"Co-immunoprecipitation / interaction assays showing TgArk1 binds both TgINCENPs\",\n      \"pmids\": [\"30051161\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural or in vitro reconstitution of the complex\", \"Stoichiometry and direct vs bridged interactions among the three subunits not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Perturbing TgINCENP2 addressed how TgArk1 reaches its site of action, showing TgINCENP2 is the adapter required for TgArk1 nuclear translocation.\",\n      \"evidence\": \"Genetic interference with TgINCENP2 combined with TgArk1 localization analysis\",\n      \"pmids\": [\"30051161\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of the import (nuclear localization signal, transport machinery) not defined\", \"Single-lab, single-study result\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Tracking TgArk1 through the cell cycle answered whether its localization is stage-restricted, revealing dynamic redistribution consistent with mitotic spindle organization during endodyogeny.\",\n      \"evidence\": \"Imaging of tagged TgArk1 across cell cycle stages\",\n      \"pmids\": [\"30051161\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Precise spindle/kinetochore structures engaged not molecularly defined\", \"No independent replication reported\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Loss-of-function and pharmacological experiments together established that TgArk1 and its catalytic activity are essential for division, since knockdown caused division/growth defects and low-dose hesperadin phenocopied the mutants.\",\n      \"evidence\": \"Conditional knockdown/dominant-negative interference plus hesperadin inhibition with phenotypic comparison\",\n      \"pmids\": [\"30051161\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinase activity requirement inferred pharmacologically, not by kinase-dead allele or in vitro assay\", \"Hesperadin specificity for TgArk1 over other targets not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct phosphorylation substrates of TgArk1 and the structural basis of CPC assembly and spindle regulation remain unidentified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No TgArk1 substrates identified\", \"No structural or biochemical reconstitution of the CPC\", \"Mechanism linking CPC activity to spindle organization undefined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004674\", \"supporting_discovery_ids\": [0, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000278\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0007052\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Chromosomal passenger complex (CPC): TgArk1 + TgINCENP1 + TgINCENP2\"],\n    \"partners\": [\"TgINCENP1\", \"TgINCENP2\"],\n    \"other_free_text\": [\n      \"TgINCENP2 is required for nuclear translocation of TgArk1.\",\n      \"Low-dose hesperadin (human Aurora kinase B inhibitor) phenocopies TgArk1/TgINCENP2 mutants, implicating TgArk1 catalytic activity.\",\n      \"Interference with TgArk1 causes division and growth defects during endodyogeny.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_210280","name":"ARK1","product":"aurora-related kinase ARK1","uniprot_acc":"A0A125YY40","chromosome":"TGME49_chrIX","start_pos":4899522},{"strain":"GT1","gene_id":"TGGT1_210280","name":null,"product":"PEK kinase","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":4693013},{"strain":"RH88","gene_id":"TGRH88_016480","name":null,"product":"PEK kinase","uniprot_acc":null,"chromosome":"CM023090","start_pos":4969717},{"strain":"VEG","gene_id":"TGVEG_210280","name":null,"product":"PEK kinase","uniprot_acc":"A0A125YY41","chromosome":"TGVEG_chrIX","start_pos":4942937}]}