{"gene":"TG_204280","gene_symbol":"DYRK1","run_date":"2026-09-11T11:01:00","timeline":{"discoveries":[{"year":2023,"finding":"DYRK1 was identified as a potential functional partner of the plant-like protein phosphatase PPKL via Co-Immunoprecipitation and proximity labeling, and complete knockout of DYRK1 phenocopies the loss of PPKL (uncoupling of division with normal DNA duplication but severe defects in forming daughter parasites), strongly suggesting a functional relationship between these two signaling proteins in daughter parasite development.","method":"Co-Immunoprecipitation, proximity labeling, and complete gene knockout with phenotypic readout (daughter parasite formation defects)","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP/proximity labeling plus genetic epistasis (knockout phenocopy), but single lab, preprint, and the functional relationship is inferred from phenocopy rather than direct biochemical reconstitution","pmids":["37398039"],"is_preprint":true,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"DYRK1 is a kinase that functions as a putative partner of the plant-like phosphatase PPKL in Toxoplasma gondii; its complete knockout phenocopies PPKL depletion, causing severe defects in daughter parasite formation while leaving DNA duplication intact, placing DYRK1 in a signaling pathway that controls cortical cytoskeleton organization and daughter cell assembly during parasite division."},"narrative":{"mechanistic_narrative":"DYRK1 is a kinase implicated in the control of daughter parasite assembly during Toxoplasma gondii division, where it functions as a putative partner of the plant-like protein phosphatase PPKL [PMID:37398039]. It was identified as a functional partner of PPKL by reciprocal Co-immunoprecipitation and proximity labeling, and complete knockout of DYRK1 phenocopies loss of PPKL, uncoupling division from DNA duplication: DNA replication proceeds normally while daughter parasite formation is severely defective [PMID:37398039]. This genetic epistasis places DYRK1 in a PPKL-associated signaling pathway for daughter cell assembly. Beyond this single-study association [PMID:37398039], no direct substrates, catalytic characterization, or biochemical reconstitution of the DYRK1–PPKL relationship have been characterized in the available corpus.","teleology":[{"year":2023,"claim":"It was unknown which factors cooperate with the phosphatase PPKL to drive daughter parasite formation; identifying DYRK1 as a PPKL partner whose loss phenocopies PPKL depletion established a candidate kinase-phosphatase signaling module controlling division.","evidence":"Co-immunoprecipitation, proximity labeling, and complete gene knockout with phenotypic readout of daughter parasite formation in Toxoplasma gondii (preprint)","pmids":["37398039"],"confidence":"Medium","gaps":["Functional relationship inferred from phenocopy rather than direct biochemical reconstitution of a DYRK1-PPKL interaction","No DYRK1 substrates or phosphorylation targets identified","Single lab, preprint status, and no confirmation of catalytic activity or the molecular basis of cortical cytoskeleton/daughter cell defects"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct substrates of DYRK1, the biochemical nature of its coupling to PPKL, and the mechanism by which it controls cortical cytoskeleton organization during daughter cell assembly remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No identified phosphorylation substrates","No structural or reconstituted evidence for a DYRK1-PPKL complex","Mechanism linking DYRK1 activity to daughter parasite formation uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PPKL (PLANT-LIKE PROTEIN PHOSPHATASE) [#0]"],"other_free_text":["Complete knockout phenocopies PPKL loss: normal DNA duplication but severe defects in daughter parasite formation [#0]","Implicated in cortical cytoskeleton organization and daughter cell assembly during Toxoplasma division [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37398039","id":"PMC_37398039","title":"The protein phosphatase PPKL is a key regulator of daughter parasite development in Toxoplasma gondii.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37398039","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3017,"output_tokens":417,"usd":0.007653,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5050,"output_tokens":1357,"usd":0.029587,"stage2_stop_reason":"end_turn"},"total_usd":0.03724,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard","hand_review_patch":"2026-09-11 AK hand-review verdicts (handoff/tools_2026-09-11/patch)","hand_review_verdict":"edit"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"DYRK1 was identified as a potential functional partner of the plant-like protein phosphatase PPKL via Co-Immunoprecipitation and proximity labeling, and complete knockout of DYRK1 phenocopies the loss of PPKL (uncoupling of division with normal DNA duplication but severe defects in forming daughter parasites), strongly suggesting a functional relationship between these two signaling proteins in daughter parasite development.\",\n      \"method\": \"Co-Immunoprecipitation, proximity labeling, and complete gene knockout with phenotypic readout (daughter parasite formation defects)\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP/proximity labeling plus genetic epistasis (knockout phenocopy), but single lab, preprint, and the functional relationship is inferred from phenocopy rather than direct biochemical reconstitution\",\n      \"pmids\": [\"37398039\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"DYRK1 is a kinase that functions as a putative partner of the plant-like phosphatase PPKL in Toxoplasma gondii; its complete knockout phenocopies PPKL depletion, causing severe defects in daughter parasite formation while leaving DNA duplication intact, placing DYRK1 in a signaling pathway that controls cortical cytoskeleton organization and daughter cell assembly during parasite division.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DYRK1 is a kinase implicated in the control of daughter parasite assembly during Toxoplasma gondii division, where it functions as a putative partner of the plant-like protein phosphatase PPKL [#0]. It was identified as a functional partner of PPKL by reciprocal Co-immunoprecipitation and proximity labeling, and complete knockout of DYRK1 phenocopies loss of PPKL, uncoupling division from DNA duplication: DNA replication proceeds normally while daughter parasite formation is severely defective [#0]. This genetic epistasis places DYRK1 in a PPKL-associated signaling pathway governing cortical cytoskeleton organization and daughter cell assembly. Beyond this single-study association [#0], no direct substrates, catalytic characterization, or biochemical reconstitution of the DYRK1–PPKL relationship have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown which factors cooperate with the phosphatase PPKL to drive daughter parasite formation; identifying DYRK1 as a PPKL partner whose loss phenocopies PPKL depletion established a candidate kinase-phosphatase signaling module controlling division.\",\n      \"evidence\": \"Co-immunoprecipitation, proximity labeling, and complete gene knockout with phenotypic readout of daughter parasite formation in Toxoplasma gondii (preprint)\",\n      \"pmids\": [\n        \"37398039\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional relationship inferred from phenocopy rather than direct biochemical reconstitution of a DYRK1-PPKL interaction\",\n        \"No DYRK1 substrates or phosphorylation targets identified\",\n        \"Single lab, preprint status, and no confirmation of catalytic activity or the molecular basis of cortical cytoskeleton/daughter cell defects\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct substrates of DYRK1, the biochemical nature of its coupling to PPKL, and the mechanism by which it controls cortical cytoskeleton organization during daughter cell assembly remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No identified phosphorylation substrates\",\n        \"No structural or reconstituted evidence for a DYRK1-PPKL complex\",\n        \"Mechanism linking DYRK1 activity to daughter parasite formation uncharacterized\"\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:0004672\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0051301\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PPKL (plant-like protein phosphatase) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Complete knockout phenocopies PPKL loss: normal DNA duplication but severe defects in daughter parasite formation [#0]\",\n      \"Implicated in cortical cytoskeleton organization and daughter cell assembly during Toxoplasma division [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":{"gene":"TG_204280","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"uncited_synthesis","uniprot_band":"empty","rules_fired":"R8","issue":"R8: 1/3 claims uncited (33%)"},"strains":[{"strain":"ME49","gene_id":"TGME49_204280","name":"DYRK1","product":"cell-cycle-associated protein kinase DYRK1","uniprot_acc":"S8F8Y6","chromosome":"TGME49_chrVIIa","start_pos":1922292},{"strain":"GT1","gene_id":"TGGT1_204280","name":null,"product":"putative cell-cycle-associated protein kinase DYRK","uniprot_acc":null,"chromosome":"TGGT1_chrVIIa","start_pos":1825877},{"strain":"RH88","gene_id":"TGRH88_034860","name":null,"product":"putative cell-cycle-associated protein kinase DYRK","uniprot_acc":null,"chromosome":"CM023088","start_pos":2015491},{"strain":"VEG","gene_id":"TGVEG_204280","name":null,"product":"putative cell-cycle-associated protein kinase DYRK","uniprot_acc":"B9QFF6","chromosome":"TGVEG_chrVIIa","start_pos":2007461}]}