{"gene":"PF3D7_1304700","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2003,"finding":"CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins identified in silico; the corresponding polypeptides are expressed in erythrocytic blood stages, and at least one of the three novel cyclins was shown to associate with histone H1 kinase activity in parasite extracts and/or to activate PfPK5 (a P. falciparum CDK homologue) in vitro, demonstrating cyclin activity. The abstract does not individually resolve which specific activities apply to CYC4 versus the other two novel cyclins.","method":"In silico identification from genome sequence; Western blot/immunoprecipitation for expression in erythrocytic stages; histone H1 kinase co-immunoprecipitation from parasite extracts; in vitro PfPK5 activation assay with recombinant protein","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, functional cyclin activity shown for the group of three novel cyclins collectively but individual attribution to CYC4 specifically is not resolved in the abstract","pmids":["12869562"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins expressed in erythrocytic stages; collective evidence from the group suggests cyclin activity (association with histone H1 kinase activity and/or in vitro activation of the CDK homologue PfPK5), but no experiment in the available literature has individually and mechanistically characterised CYC4 itself beyond its membership in this set of novel cyclins."},"narrative":{"mechanistic_narrative":"CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins identified in silico from the genome, with the corresponding polypeptides expressed in erythrocytic blood stages [PMID:12869562]. Within this set of three cyclins, at least one member associates with histone H1 kinase activity in parasite extracts and activates the CDK homologue PfPK5 in vitro, demonstrating cyclin activity for the group; however, the available corpus does not individually resolve which of these activities apply to CYC4 specifically [PMID:12869562]. Beyond its membership in this set of novel cyclins and its erythrocytic-stage expression [PMID:12869562], no experiment has individually and mechanistically characterized CYC4 in the available corpus.","teleology":[{"year":2003,"claim":"Before this work it was unknown whether P. falciparum encodes cyclin-type regulators for its CDK homologues; the identification of three novel cyclins expressed in blood stages and showing cyclin activity established that such regulators exist and are active during the erythrocytic cycle.","evidence":"In silico identification from genome sequence, Western blot/immunoprecipitation for erythrocytic-stage expression, histone H1 kinase co-immunoprecipitation from parasite extracts, and in vitro PfPK5 activation assay with recombinant protein","pmids":["12869562"],"confidence":"Low","gaps":["The abstract does not resolve whether the histone H1 kinase association or PfPK5 activation is attributable to CYC4 specifically versus the other two novel cyclins","No CYC4-specific binding partner, substrate, or in vivo function has been demonstrated","No subcellular localization or structural characterization of CYC4 is provided"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown which specific CDK partner CYC4 activates, what its substrates are, and what role it plays in the parasite cell cycle independent of the other two novel cyclins.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experiment individually characterizes CYC4 apart from the group of three cyclins","No genetic or knockdown phenotype for CYC4 has been reported","The CDK partnership and substrate specificity of CYC4 itself are undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Identified as one of three novel P. falciparum cyclin-related proteins expressed in erythrocytic blood stages; cyclin activity (histone H1 kinase association and in vitro PfPK5 activation) was demonstrated for the group but not individually attributed to CYC4 [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15515182","id":"PMC_15515182","title":"A genomic perspective of protein kinases in Plasmodium falciparum.","date":"2005","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/15515182","citation_count":118,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10722743","id":"PMC_10722743","title":"Activation of a Plasmodium falciparum cdc2-related kinase by heterologous p25 and cyclin H. Functional characterization of a P. falciparum cyclin homologue.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10722743","citation_count":88,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12869562","id":"PMC_12869562","title":"Identification and initial characterization of three novel cyclin-related proteins of the human malaria parasite Plasmodium falciparum.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12869562","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["cyclin"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10717301","id":"PMC_10717301","title":"Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum.","date":"2000","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10717301","citation_count":34,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["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","PfCYC4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28344153","id":"PMC_28344153","title":"Plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites.","date":"2017","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/28344153","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cyclin"],"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":"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":8119,"output_tokens":1020,"usd":0.019828,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5010,"output_tokens":1193,"usd":0.027438,"stage2_stop_reason":"end_turn"},"total_usd":0.047266,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully identify which papers are about PF3D7_1304700 (CYC4) specifically, versus other cyclins or CDKs.\n\nLooking at the corpus:\n- Paper [3] (PMID:12869562) describes three novel cyclin-related proteins. It mentions \"Pfcyc-1\" and two others. CYC4 could be one of these three novel cyclins. The paper shows cyclin activity via histone H1 kinase association or PfPK5 activation.\n- Paper [4] (PMID:26565797) is about CYC3 (a P-type cyclin) — NOT CYC4.\n- Paper [6] (PMID:28611247) is about PfCyc1 — NOT CYC4.\n- Paper [7] (PMID:27326764) mentions \"pfcyc4\" transcript upregulation during DHA-induced dormancy — this IS about CYC4.\n- Paper [8] (PMID:28344153) mentions TgCYC4 in Toxoplasma — this is a wrong-organism collision (Toxoplasma CYC4, not Plasmodium CYC4).\n- Paper [2] (PMID:10722743) is about Pfcyc-1 — NOT CYC4.\n- Papers [1], [5], [9], [10], [11] are genomic surveys, reviews, or about other cyclins — not mechanistically specific to CYC4.\n\nFor paper [3]: It describes three novel cyclins. CYC4 (PF3D7_1304700) would be one of them. The paper shows these proteins are expressed in erythrocytic stages and have cyclin activity (histone H1 kinase association or PfPK5 activation in vitro). However, the abstract doesn't specify which specific results apply to which of the three cyclins individually — I must be careful not to over-attribute.\n\nFor paper [7]: pfcyc4 transcript is upregulated during DHA-induced dormancy phase — this is a transcriptional correlation finding, which falls under EXCLUDE (expression correlation). The CDK inhibitor effects are on recovery, not specifically mechanistic for CYC4.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins identified in silico; the corresponding polypeptides are expressed in erythrocytic blood stages, and at least one of the three novel cyclins was shown to associate with histone H1 kinase activity in parasite extracts and/or to activate PfPK5 (a P. falciparum CDK homologue) in vitro, demonstrating cyclin activity. The abstract does not individually resolve which specific activities apply to CYC4 versus the other two novel cyclins.\",\n      \"method\": \"In silico identification from genome sequence; Western blot/immunoprecipitation for expression in erythrocytic stages; histone H1 kinase co-immunoprecipitation from parasite extracts; in vitro PfPK5 activation assay with recombinant protein\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, functional cyclin activity shown for the group of three novel cyclins collectively but individual attribution to CYC4 specifically is not resolved in the abstract\",\n      \"pmids\": [\"12869562\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins expressed in erythrocytic stages; collective evidence from the group suggests cyclin activity (association with histone H1 kinase activity and/or in vitro activation of the CDK homologue PfPK5), but no experiment in the available literature has individually and mechanistically characterised CYC4 itself beyond its membership in this set of novel cyclins.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CYC4 (PF3D7_1304700) is one of three novel P. falciparum cyclin-related proteins identified in silico from the genome, with the corresponding polypeptides expressed in erythrocytic blood stages [#0]. Within this set of three cyclins, at least one member associates with histone H1 kinase activity in parasite extracts and activates the CDK homologue PfPK5 in vitro, demonstrating cyclin activity for the group; however, the available corpus does not individually resolve which of these activities apply to CYC4 specifically [#0]. Beyond its membership in this set of novel cyclins and its erythrocytic-stage expression [#0], no experiment has individually and mechanistically characterized CYC4 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Before this work it was unknown whether P. falciparum encodes cyclin-type regulators for its CDK homologues; the identification of three novel cyclins expressed in blood stages and showing cyclin activity established that such regulators exist and are active during the erythrocytic cycle.\",\n      \"evidence\": \"In silico identification from genome sequence, Western blot/immunoprecipitation for erythrocytic-stage expression, histone H1 kinase co-immunoprecipitation from parasite extracts, and in vitro PfPK5 activation assay with recombinant protein\",\n      \"pmids\": [\n        \"12869562\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"The abstract does not resolve whether the histone H1 kinase association or PfPK5 activation is attributable to CYC4 specifically versus the other two novel cyclins\",\n        \"No CYC4-specific binding partner, substrate, or in vivo function has been demonstrated\",\n        \"No subcellular localization or structural characterization of CYC4 is provided\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown which specific CDK partner CYC4 activates, what its substrates are, and what role it plays in the parasite cell cycle independent of the other two novel cyclins.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experiment individually characterizes CYC4 apart from the group of three cyclins\",\n        \"No genetic or knockdown phenotype for CYC4 has been reported\",\n        \"The CDK partnership and substrate specificity of CYC4 itself are undefined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0016538\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0007049\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Identified as one of three novel P. falciparum cyclin-related proteins expressed in erythrocytic blood stages; cyclin activity (histone H1 kinase association and in vitro PfPK5 activation) was demonstrated for the group but not individually attributed to CYC4 [#0].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1304700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_1356900). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1304700","name":null,"product":"cyclin","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1403200","name":null,"product":"cyclin, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1404900","name":null,"product":"cyclin 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CYC4","evaluation":null}