{"gene":"TG_211220","gene_symbol":"ORC4","run_date":"2026-09-08T11:06:23","timeline":{"discoveries":[{"year":2024,"finding":"TgORC4 was identified as a phosphorylation substrate of the TgCrk4-TgCyc4 complex by global phosphoproteome analysis, placing TgORC4 downstream of TgCrk4 kinase activity during cell cycle regulation.","method":"Global phosphoproteome analysis (mass spectrometry-based substrate identification)","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — phosphoproteomic substrate identification in a single study, no direct mutagenesis or in vitro kinase assay confirming TgCrk4 directly phosphorylates TgORC4","pmids":["38600241"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgORC4 is a putative phosphorylation substrate of the TgCrk4-TgCyc4 CDK complex in Toxoplasma gondii, placing it downstream of this G2/M regulatory kinase, though the functional consequence of this phosphorylation has not yet been experimentally defined."},"narrative":{"mechanistic_narrative":"TgORC4 has been identified in Toxoplasma gondii as a phosphorylation substrate of the TgCrk4-TgCyc4 CDK complex, placing it downstream of this kinase during cell cycle regulation [PMID:38600241]. Beyond this single phosphoproteomic assignment, no further mechanistic detail—including the functional consequence of this phosphorylation, its substrates, or its molecular role—has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Whether TgORC4 lies downstream of the TgCrk4-TgCyc4 G2/M kinase was unknown; global phosphoproteomics placed TgORC4 among the substrates modulated by TgCrk4 activity, linking it to cell cycle regulation.","evidence":"Global phosphoproteome analysis (mass spectrometry-based substrate identification) in Toxoplasma gondii","pmids":["38600241"],"confidence":"Medium","gaps":["No direct in vitro kinase assay or mutagenesis confirming TgCrk4 directly phosphorylates TgORC4","Functional consequence of the phosphorylation event is undefined","The phosphorylation site(s) and their role in TgORC4 activity are not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular function of TgORC4, its localization, and the biological outcome of its phosphorylation by the TgCrk4-TgCyc4 complex remain to be established.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No characterization of TgORC4's intrinsic function in the available corpus","No structural or localization data","No demonstrated phenotype tied to loss or altered phosphorylation of TgORC4"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGCRK4-TGCYC4 CDK COMPLEX (KINASE ACTING ON TGORC4)"],"other_free_text":["TgORC4 is a putative phosphorylation substrate of the TgCrk4-TgCyc4 complex, identified by phosphoproteomics without direct kinase-assay confirmation [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"38600241","id":"PMC_38600241","title":"The Crk4-Cyc4 complex regulates G2/M transition in Toxoplasma gondii.","date":"2024","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/38600241","citation_count":16,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2925,"output_tokens":342,"usd":0.006953,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4914,"output_tokens":1000,"usd":0.024785,"stage2_stop_reason":"end_turn"},"total_usd":0.031738,"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\": 2024,\n      \"finding\": \"TgORC4 was identified as a phosphorylation substrate of the TgCrk4-TgCyc4 complex by global phosphoproteome analysis, placing TgORC4 downstream of TgCrk4 kinase activity during cell cycle regulation.\",\n      \"method\": \"Global phosphoproteome analysis (mass spectrometry-based substrate identification)\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — phosphoproteomic substrate identification in a single study, no direct mutagenesis or in vitro kinase assay confirming TgCrk4 directly phosphorylates TgORC4\",\n      \"pmids\": [\"38600241\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgORC4 is a putative phosphorylation substrate of the TgCrk4-TgCyc4 CDK complex in Toxoplasma gondii, placing it downstream of this G2/M regulatory kinase, though the functional consequence of this phosphorylation has not yet been experimentally defined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgORC4 has been identified in Toxoplasma gondii as a phosphorylation substrate of the TgCrk4-TgCyc4 CDK complex, placing it downstream of this kinase during cell cycle regulation [#0]. Beyond this single phosphoproteomic assignment, no further mechanistic detail—including the functional consequence of this phosphorylation, its substrates, or its molecular role—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether TgORC4 lies downstream of the TgCrk4-TgCyc4 G2/M kinase was unknown; global phosphoproteomics placed TgORC4 among the substrates modulated by TgCrk4 activity, linking it to cell cycle regulation.\",\n      \"evidence\": \"Global phosphoproteome analysis (mass spectrometry-based substrate identification) in Toxoplasma gondii\",\n      \"pmids\": [\"38600241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct in vitro kinase assay or mutagenesis confirming TgCrk4 directly phosphorylates TgORC4\",\n        \"Functional consequence of the phosphorylation event is undefined\",\n        \"The phosphorylation site(s) and their role in TgORC4 activity are not mapped\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of TgORC4, its localization, and the biological outcome of its phosphorylation by the TgCrk4-TgCyc4 complex remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No characterization of TgORC4's intrinsic function in the available corpus\",\n        \"No structural or localization data\",\n        \"No demonstrated phenotype tied to loss or altered phosphorylation of TgORC4\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0051726\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgCrk4-TgCyc4 CDK complex (kinase acting on TgORC4)\"],\n    \"other_free_text\": [\n      \"TgORC4 is a putative phosphorylation substrate of the TgCrk4-TgCyc4 complex, identified by phosphoproteomics without direct kinase-assay confirmation [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_211220","name":"ORC4","product":"origin recognition complex subunit 4, putative","uniprot_acc":"A0A125YUR8","chromosome":"TGME49_chrIV","start_pos":1910319},{"strain":"GT1","gene_id":"TGGT1_211220","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":1841664},{"strain":"RH88","gene_id":"TGRH88_008840","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023085","start_pos":1933738},{"strain":"VEG","gene_id":"TGVEG_211220","name":null,"product":"putative origin recognition complex subunit","uniprot_acc":"V4YMZ6","chromosome":"TGVEG_chrIV","start_pos":1936325}]}