{"gene":"TG_229200","gene_symbol":"CYC1","run_date":"2026-09-08T11:06:48","timeline":{"discoveries":[{"year":2002,"finding":"TgCYC1 (a cyclin H class protein) specifically interacts with the T. gondii cdc2-related kinase TgCRK2, identified by a GAL4-based yeast two-hybrid screen of 3.2 million transformants.","method":"Yeast two-hybrid interactive screen","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single yeast two-hybrid interaction assay, single lab, no reciprocal validation reported in abstract","pmids":["11897124"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2002,"finding":"TgCYC1 mRNA levels are unchanged across synchronous tachyzoite populations, indicating TgCYC1 is not cell-cycle regulated at the mRNA level.","method":"mRNA quantification in synchronized tachyzoite populations","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct experimental measurement in synchronized parasites, single lab, single method","pmids":["11897124"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2002,"finding":"TgCYC1 functionally rescues the G1/S cyclin cell cycle defect in S. cerevisiae strain DL1, demonstrating it can substitute for a canonical G1/S cyclin function in a heterologous system.","method":"Heterologous complementation in S. cerevisiae cyclin-deficient strain DL1","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — functional complementation assay in an established heterologous model, single lab, single method","pmids":["11897124"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2022,"finding":"TgCyc1 forms a complex with the atypical Cdk-related kinase TgCrk6; loss of either TgCrk6 or TgCyc1 causes identical mitotic defects, indicating cooperative action of both complex components during endodyogeny.","method":"Protein complex identification (proteomics/co-immunoprecipitation), conditional expression knockdown models, quantitative fluorescence microscopy","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal genetic and proteomic evidence, conditional knockdowns of both components yielding identical phenotypes, quantitative microscopy, single lab but multiple orthogonal methods","pmids":["35130726"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"The TgCrk6/TgCyc1 complex regulates metaphase and controls the spindle assembly checkpoint (SAC) in T. gondii, specifically governing the centromere-associated network during mitosis coupled to cytokinesis (endodyogeny).","method":"Conditional expression knockdown, quantitative fluorescence microscopy of mitotic structures, global proteomics and phosphoproteomics","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional knockdowns with defined mitotic phenotype, phosphoproteomics revealing pathway-level regulation, single lab but multiple orthogonal methods","pmids":["35130726"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgCyc1 is a parasite-specific cyclin H-class protein that forms a functional complex with the atypical Cdk-related kinase TgCrk6 (and was originally identified as an interactor of TgCRK2), is not regulated at the mRNA level through the cell cycle, and cooperatively with TgCrk6 controls metaphase and the spindle assembly checkpoint—specifically the centromere-associated network—during Toxoplasma gondii endodyogeny."},"narrative":{"mechanistic_narrative":"TgCyc1 is a parasite cyclin H-class protein that functions as the activating partner of a Cdk-related kinase to control mitotic progression during Toxoplasma gondii endodyogeny [PMID:35130726]. It was first identified as an interactor of the cdc2-related kinase TgCRK2 and can functionally substitute for a canonical G1/S cyclin, rescuing a cyclin-deficient S. cerevisiae strain [PMID:11897124]. Its expression is constitutive rather than periodic, as TgCYC1 mRNA levels do not vary across the tachyzoite cell cycle [PMID:11897124]. In its characterized cellular role, TgCyc1 forms a complex with the atypical kinase TgCrk6, and loss of either component produces identical mitotic defects, establishing that the two act cooperatively [PMID:35130726]. The TgCrk6/TgCyc1 complex regulates metaphase and the spindle assembly checkpoint, specifically governing the centromere-associated network during mitosis coupled to cytokinesis [PMID:35130726].","teleology":[{"year":2002,"claim":"Establishing which kinase TgCyc1 partners with was the first step in assigning it a cell-cycle role; a yeast two-hybrid screen identified TgCRK2 as its interactor, placing TgCyc1 within the parasite Cdk-cyclin machinery.","evidence":"GAL4-based yeast two-hybrid screen of 3.2 million transformants","pmids":["11897124"],"confidence":"Medium","gaps":["Single Y2H interaction without reciprocal validation","Functional consequence of the TgCRK2 interaction not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2002,"claim":"To ask whether TgCyc1 acts as a periodic cell-cycle timer, its transcript was measured across synchronized parasites; mRNA levels were invariant, indicating regulation is not achieved at the transcript level.","evidence":"mRNA quantification in synchronized tachyzoite populations","pmids":["11897124"],"confidence":"Medium","gaps":["Does not address protein-level or activity-level cell-cycle regulation","Single method, single lab"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2002,"claim":"To test whether TgCyc1 retains genuine cyclin function, it was expressed in a cyclin-deficient yeast; it rescued the G1/S defect, demonstrating conserved cyclin activity in a heterologous system.","evidence":"Heterologous complementation in S. cerevisiae cyclin-deficient strain DL1","pmids":["11897124"],"confidence":"Medium","gaps":["Heterologous rescue does not establish the native G1/S role in Toxoplasma","Does not identify the native cognate kinase"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2022,"claim":"Defining TgCyc1's native functional partner and phenotype resolved its endogenous role: it forms a complex with TgCrk6, and knockdown of either produces identical mitotic defects, establishing cooperative kinase-cyclin action in endodyogeny.","evidence":"Co-immunoprecipitation/proteomics with conditional knockdowns of both components and quantitative fluorescence microscopy","pmids":["35130726"],"confidence":"High","gaps":["Direct kinase-activation mechanism by TgCyc1 not biochemically dissected","Relationship to the earlier TgCRK2 interaction unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Placing the complex in a pathway showed that TgCrk6/TgCyc1 governs metaphase and the spindle assembly checkpoint, specifically the centromere-associated network during mitosis coupled to cytokinesis.","evidence":"Conditional knockdown, quantitative microscopy of mitotic structures, global proteomics and phosphoproteomics","pmids":["35130726"],"confidence":"High","gaps":["Direct substrates phosphorylated by the complex not individually validated","How the complex is activated at metaphase onset is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TgCyc1's two reported kinase associations (TgCRK2 and TgCrk6) are reconciled, and the mechanism by which the cyclin activates its kinase to enforce the spindle checkpoint, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the cyclin-kinase complex","Direct catalytic substrates unmapped","Relationship between TgCRK2 and TgCrk6 associations unexplained"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TgCrk6/TgCyc1 Cdk-cyclin complex"],"partners":["TGCRK6 (ATYPICAL CDK-RELATED KINASE)","TGCRK2 (CDC2-RELATED KINASE)"],"other_free_text":["Cyclin H-class protein that functionally complements a G1/S cyclin defect in S. cerevisiae strain DL1 [#2].","TgCYC1 mRNA is not cell-cycle regulated across synchronized tachyzoites [#1].","The TgCrk6/TgCyc1 complex governs the centromere-associated network during endodyogeny (mitosis coupled to cytokinesis) [#4]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"11897124","id":"PMC_11897124","title":"Isolation of a Toxoplasma gondii cyclin by yeast two-hybrid interactive screen.","date":"2002","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11897124","citation_count":17,"is_preprint":false},{"pmid":"35130726","id":"PMC_35130726","title":"Novel CRK-Cyclin Complex Controls Spindle Assembly Checkpoint in Toxoplasma Endodyogeny.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35130726","citation_count":17,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3659,"output_tokens":1216,"usd":0.014608,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6228,"output_tokens":2398,"usd":0.045545,"stage2_stop_reason":"end_turn"},"total_usd":0.060153,"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\": 2002,\n      \"finding\": \"TgCYC1 (a cyclin H class protein) specifically interacts with the T. gondii cdc2-related kinase TgCRK2, identified by a GAL4-based yeast two-hybrid screen of 3.2 million transformants.\",\n      \"method\": \"Yeast two-hybrid interactive screen\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single yeast two-hybrid interaction assay, single lab, no reciprocal validation reported in abstract\",\n      \"pmids\": [\"11897124\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"TgCYC1 mRNA levels are unchanged across synchronous tachyzoite populations, indicating TgCYC1 is not cell-cycle regulated at the mRNA level.\",\n      \"method\": \"mRNA quantification in synchronized tachyzoite populations\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct experimental measurement in synchronized parasites, single lab, single method\",\n      \"pmids\": [\"11897124\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"TgCYC1 functionally rescues the G1/S cyclin cell cycle defect in S. cerevisiae strain DL1, demonstrating it can substitute for a canonical G1/S cyclin function in a heterologous system.\",\n      \"method\": \"Heterologous complementation in S. cerevisiae cyclin-deficient strain DL1\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — functional complementation assay in an established heterologous model, single lab, single method\",\n      \"pmids\": [\"11897124\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgCyc1 forms a complex with the atypical Cdk-related kinase TgCrk6; loss of either TgCrk6 or TgCyc1 causes identical mitotic defects, indicating cooperative action of both complex components during endodyogeny.\",\n      \"method\": \"Protein complex identification (proteomics/co-immunoprecipitation), conditional expression knockdown models, quantitative fluorescence microscopy\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal genetic and proteomic evidence, conditional knockdowns of both components yielding identical phenotypes, quantitative microscopy, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"35130726\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The TgCrk6/TgCyc1 complex regulates metaphase and controls the spindle assembly checkpoint (SAC) in T. gondii, specifically governing the centromere-associated network during mitosis coupled to cytokinesis (endodyogeny).\",\n      \"method\": \"Conditional expression knockdown, quantitative fluorescence microscopy of mitotic structures, global proteomics and phosphoproteomics\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdowns with defined mitotic phenotype, phosphoproteomics revealing pathway-level regulation, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"35130726\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgCyc1 is a parasite-specific cyclin H-class protein that forms a functional complex with the atypical Cdk-related kinase TgCrk6 (and was originally identified as an interactor of TgCRK2), is not regulated at the mRNA level through the cell cycle, and cooperatively with TgCrk6 controls metaphase and the spindle assembly checkpoint—specifically the centromere-associated network—during Toxoplasma gondii endodyogeny.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgCyc1 is a parasite cyclin H-class protein that functions as the activating partner of a Cdk-related kinase to control mitotic progression during Toxoplasma gondii endodyogeny [#3, #4]. It was first identified as an interactor of the cdc2-related kinase TgCRK2 and can functionally substitute for a canonical G1/S cyclin, rescuing a cyclin-deficient S. cerevisiae strain [#0, #2]. Its expression is constitutive rather than periodic, as TgCYC1 mRNA levels do not vary across the tachyzoite cell cycle [#1]. In its characterized cellular role, TgCyc1 forms a complex with the atypical kinase TgCrk6, and loss of either component produces identical mitotic defects, establishing that the two act cooperatively [#3]. The TgCrk6/TgCyc1 complex regulates metaphase and the spindle assembly checkpoint, specifically governing the centromere-associated network during mitosis coupled to cytokinesis [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Establishing which kinase TgCyc1 partners with was the first step in assigning it a cell-cycle role; a yeast two-hybrid screen identified TgCRK2 as its interactor, placing TgCyc1 within the parasite Cdk-cyclin machinery.\",\n      \"evidence\": \"GAL4-based yeast two-hybrid screen of 3.2 million transformants\",\n      \"pmids\": [\"11897124\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Y2H interaction without reciprocal validation\", \"Functional consequence of the TgCRK2 interaction not tested\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"To ask whether TgCyc1 acts as a periodic cell-cycle timer, its transcript was measured across synchronized parasites; mRNA levels were invariant, indicating regulation is not achieved at the transcript level.\",\n      \"evidence\": \"mRNA quantification in synchronized tachyzoite populations\",\n      \"pmids\": [\"11897124\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address protein-level or activity-level cell-cycle regulation\", \"Single method, single lab\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"To test whether TgCyc1 retains genuine cyclin function, it was expressed in a cyclin-deficient yeast; it rescued the G1/S defect, demonstrating conserved cyclin activity in a heterologous system.\",\n      \"evidence\": \"Heterologous complementation in S. cerevisiae cyclin-deficient strain DL1\",\n      \"pmids\": [\"11897124\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Heterologous rescue does not establish the native G1/S role in Toxoplasma\", \"Does not identify the native cognate kinase\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defining TgCyc1's native functional partner and phenotype resolved its endogenous role: it forms a complex with TgCrk6, and knockdown of either produces identical mitotic defects, establishing cooperative kinase-cyclin action in endodyogeny.\",\n      \"evidence\": \"Co-immunoprecipitation/proteomics with conditional knockdowns of both components and quantitative fluorescence microscopy\",\n      \"pmids\": [\"35130726\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct kinase-activation mechanism by TgCyc1 not biochemically dissected\", \"Relationship to the earlier TgCRK2 interaction unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placing the complex in a pathway showed that TgCrk6/TgCyc1 governs metaphase and the spindle assembly checkpoint, specifically the centromere-associated network during mitosis coupled to cytokinesis.\",\n      \"evidence\": \"Conditional knockdown, quantitative microscopy of mitotic structures, global proteomics and phosphoproteomics\",\n      \"pmids\": [\"35130726\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct substrates phosphorylated by the complex not individually validated\", \"How the complex is activated at metaphase onset is unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgCyc1's two reported kinase associations (TgCRK2 and TgCrk6) are reconciled, and the mechanism by which the cyclin activates its kinase to enforce the spindle checkpoint, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the cyclin-kinase complex\", \"Direct catalytic substrates unmapped\", \"Relationship between TgCRK2 and TgCrk6 associations unexplained\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016538\", \"supporting_discovery_ids\": [2, 3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}, {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007094\", \"supporting_discovery_ids\": [4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000278\", \"supporting_discovery_ids\": [3, 4], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"TgCrk6/TgCyc1 Cdk-cyclin complex\"],\n    \"partners\": [\"TgCrk6 (atypical Cdk-related kinase)\", \"TgCRK2 (cdc2-related kinase)\"],\n    \"other_free_text\": [\n      \"Cyclin H-class protein that functionally complements a G1/S cyclin defect in S. cerevisiae strain DL1 [#2].\",\n      \"TgCYC1 mRNA is not cell-cycle regulated across synchronized tachyzoites [#1].\",\n      \"The TgCrk6/TgCyc1 complex governs the centromere-associated network during endodyogeny (mitosis coupled to cytokinesis) [#4].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_229200","name":"CYC1","product":"cyclin CYC1","uniprot_acc":"S8F375","chromosome":"TGME49_chrVIII","start_pos":88172},{"strain":"GT1","gene_id":"TGGT1_229200","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":88548},{"strain":"RH88","gene_id":"TGRH88_073930","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":5199958},{"strain":"VEG","gene_id":"TGVEG_229200","name":null,"product":"carboxy-terminal domain cyclin","uniprot_acc":"A0A0F7UWV8","chromosome":"TGVEG_chrVIII","start_pos":93907}]}