{"gene":"PF3D7_0518400","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2015,"finding":"CYC3 (PF3D7_0518400), the single Plant (P)-type cyclin in Plasmodium, localizes to both the cytoplasm and nucleus (GFP-tagged protein) throughout the lifecycle in P. berghei. Deletion of cyc3 caused defects in oocyst size, number, and growth, with abnormalities in budding and sporozoite formation, establishing a role for CYC3 in endomitotic development during sporogony.","method":"GFP-tagging for subcellular localization; reverse genetics (gene deletion) with phenotypic analysis of oocyst development; global transcript analysis comparing cyc3-deleted vs. wild-type parasites at gametocyte and ookinete stages","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout with defined cellular phenotype, direct live-imaging localization, and transcriptomic follow-up, all in a single focused study on this specific gene","pmids":["26565797"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"Transcriptional profiling showed that pfcyc3 (PF3D7_0518400) is down-regulated during DHA-induced dormancy in P. falciparum and up-regulated when parasites enter the recovery phase, correlating with cell-cycle arrest and resumption.","method":"Transcription profiling of CDK/cyclin genes before and after dihydroartemisinin (DHA) treatment in three P. falciparum parasite lines","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 4 / Weak — expression-level correlation only; no direct functional experiment on CYC3 protein itself","pmids":["27326764"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"CYC3 (PF3D7_0518400) is the sole Plant (P)-type cyclin in Plasmodium; in P. berghei it localizes to both cytoplasm and nucleus throughout the lifecycle, and its deletion specifically impairs oocyst endomitotic growth, budding, and sporozoite formation during mosquito-stage development, while its transcriptional down-regulation in P. falciparum correlates with artemisinin-induced dormancy."},"narrative":{"mechanistic_narrative":"CYC3 (PF3D7_0518400) is the single Plant (P)-type cyclin in Plasmodium and functions in the endomitotic development that drives mosquito-stage sporogony [PMID:26565797]. In P. berghei, GFP-tagged CYC3 localizes to both the cytoplasm and nucleus throughout the lifecycle, and deletion of the gene specifically impairs oocyst size, number, and growth, with abnormal budding and defective sporozoite formation, establishing CYC3 as a regulator of endomitotic growth during oocyst maturation [PMID:26565797]. Beyond this role in sporogony and a correlative link between CYC3 transcript down-regulation and artemisinin-induced dormancy in P. falciparum [PMID:27326764], no direct cyclin partner, cyclin-dependent kinase, or biochemical activity for CYC3 has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Whether Plasmodium's sole P-type cyclin had a defined cellular role was unknown; live imaging and gene deletion assigned CYC3 to endomitotic oocyst development, showing which lifecycle stage depends on it.","evidence":"GFP-tagging localization plus reverse-genetics knockout with oocyst phenotyping and stage transcriptomics in P. berghei","pmids":["26565797"],"confidence":"High","gaps":["No CDK or cyclin-binding partner identified for CYC3","No biochemical demonstration of cyclin activity or kinase association","Mechanism linking CYC3 to budding and sporozoite formation not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Whether CYC3 expression tracks with parasite cell-cycle arrest was untested; transcriptional profiling showed pfcyc3 is down-regulated during dormancy and up-regulated on recovery, correlating it with cell-cycle exit and re-entry.","evidence":"Transcription profiling of CDK/cyclin genes before and after DHA treatment across three P. falciparum lines","pmids":["27326764"],"confidence":"Low","gaps":["Expression-level correlation only; no functional test of CYC3 protein in dormancy","Does not establish whether CYC3 is a driver or a consequence of cell-cycle arrest","No P. falciparum knockout to test asexual/dormancy requirement"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular mechanism of CYC3 — its partner CDK, substrate specificity, and how it directs endomitotic budding — remains uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No identified cyclin-dependent kinase partner","No structural model or biochemical reconstitution","No mechanistic link between localization and oocyst budding defect"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Single Plant (P)-type cyclin in Plasmodium [#0]","Required for endomitotic oocyst growth, budding, and sporozoite formation during sporogony in P. berghei [#0]","Transcript down-regulated during DHA-induced dormancy and up-regulated on recovery in P. falciparum (correlative only) [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26565797","id":"PMC_26565797","title":"Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.","date":"2015","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/26565797","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CYC3","cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28611247","id":"PMC_28611247","title":"The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.","date":"2017","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/28611247","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27326764","id":"PMC_27326764","title":"Correlation between Cyclin Dependent Kinases and Artemisinin-Induced Dormancy in Plasmodium falciparum In Vitro.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27326764","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin","PfCYC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19519480","id":"PMC_19519480","title":"Evolutionary divergence of Plasmodium falciparum: sequences, protein-protein interactions, pathways and processes.","date":"2009","source":"Infectious disorders drug targets","url":"https://pubmed.ncbi.nlm.nih.gov/19519480","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25879664","id":"PMC_25879664","title":"Effects of cyclin-dependent kinase inhibitor Purvalanol B application on protein expression and developmental progression in intra-erythrocytic Plasmodium falciparum parasites.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/25879664","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41173748","id":"PMC_41173748","title":"A guide to the apicomplexan cell cycle: endodyogeny and schizogony.","date":"2025","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/41173748","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23998890","id":"PMC_23998890","title":"In silico characterization and molecular dynamics simulation of Pfcyc-1, a cyclin homolog of Plasmodium falciparum.","date":"2013","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/23998890","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6480,"output_tokens":694,"usd":0.014925,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5307,"output_tokens":1480,"usd":0.031767,"stage2_stop_reason":"end_turn"},"total_usd":0.046692,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"CYC3 (PF3D7_0518400), the single Plant (P)-type cyclin in Plasmodium, localizes to both the cytoplasm and nucleus (GFP-tagged protein) throughout the lifecycle in P. berghei. Deletion of cyc3 caused defects in oocyst size, number, and growth, with abnormalities in budding and sporozoite formation, establishing a role for CYC3 in endomitotic development during sporogony.\",\n      \"method\": \"GFP-tagging for subcellular localization; reverse genetics (gene deletion) with phenotypic analysis of oocyst development; global transcript analysis comparing cyc3-deleted vs. wild-type parasites at gametocyte and ookinete stages\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout with defined cellular phenotype, direct live-imaging localization, and transcriptomic follow-up, all in a single focused study on this specific gene\",\n      \"pmids\": [\"26565797\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Transcriptional profiling showed that pfcyc3 (PF3D7_0518400) is down-regulated during DHA-induced dormancy in P. falciparum and up-regulated when parasites enter the recovery phase, correlating with cell-cycle arrest and resumption.\",\n      \"method\": \"Transcription profiling of CDK/cyclin genes before and after dihydroartemisinin (DHA) treatment in three P. falciparum parasite lines\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — expression-level correlation only; no direct functional experiment on CYC3 protein itself\",\n      \"pmids\": [\"27326764\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CYC3 (PF3D7_0518400) is the sole Plant (P)-type cyclin in Plasmodium; in P. berghei it localizes to both cytoplasm and nucleus throughout the lifecycle, and its deletion specifically impairs oocyst endomitotic growth, budding, and sporozoite formation during mosquito-stage development, while its transcriptional down-regulation in P. falciparum correlates with artemisinin-induced dormancy.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CYC3 (PF3D7_0518400) is the single Plant (P)-type cyclin in Plasmodium and functions in the endomitotic development that drives mosquito-stage sporogony [#0]. In P. berghei, GFP-tagged CYC3 localizes to both the cytoplasm and nucleus throughout the lifecycle, and deletion of the gene specifically impairs oocyst size, number, and growth, with abnormal budding and defective sporozoite formation, establishing CYC3 as a regulator of endomitotic growth during oocyst maturation [#0]. Beyond this role in sporogony and a correlative link between CYC3 transcript down-regulation and artemisinin-induced dormancy in P. falciparum [#1], no direct cyclin partner, cyclin-dependent kinase, or biochemical activity for CYC3 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether Plasmodium's sole P-type cyclin had a defined cellular role was unknown; live imaging and gene deletion assigned CYC3 to endomitotic oocyst development, showing which lifecycle stage depends on it.\",\n      \"evidence\": \"GFP-tagging localization plus reverse-genetics knockout with oocyst phenotyping and stage transcriptomics in P. berghei\",\n      \"pmids\": [\"26565797\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No CDK or cyclin-binding partner identified for CYC3\",\n        \"No biochemical demonstration of cyclin activity or kinase association\",\n        \"Mechanism linking CYC3 to budding and sporozoite formation not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether CYC3 expression tracks with parasite cell-cycle arrest was untested; transcriptional profiling showed pfcyc3 is down-regulated during dormancy and up-regulated on recovery, correlating it with cell-cycle exit and re-entry.\",\n      \"evidence\": \"Transcription profiling of CDK/cyclin genes before and after DHA treatment across three P. falciparum lines\",\n      \"pmids\": [\"27326764\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Expression-level correlation only; no functional test of CYC3 protein in dormancy\",\n        \"Does not establish whether CYC3 is a driver or a consequence of cell-cycle arrest\",\n        \"No P. falciparum knockout to test asexual/dormancy requirement\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular mechanism of CYC3 — its partner CDK, substrate specificity, and how it directs endomitotic budding — remains uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No identified cyclin-dependent kinase partner\",\n        \"No structural model or biochemical reconstitution\",\n        \"No mechanistic link between localization and oocyst budding defect\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016538\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Single Plant (P)-type cyclin in Plasmodium [#0]\",\n      \"Required for endomitotic oocyst growth, budding, and sporozoite formation during sporogony in P. berghei [#0]\",\n      \"Transcript down-regulated during DHA-induced dormancy and up-regulated on recovery in P. falciparum (correlative only) [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0518400","name":null,"product":"cyclin, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1233200","name":null,"product":"cyclin","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1014800","name":null,"product":"cyclin, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CYC3","evaluation":null}