{"gene":"PF3D7_0933200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2024,"finding":"Calcyclin-binding protein (PF3D7_0933200) was identified as a component of the functional Plasmodium falciparum SCF (PfSCF) E3 ubiquitin ligase complex, together with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1, as confirmed by immunoprecipitation and in vitro protein-protein interaction assays, with the complex also shown to have ubiquitination activity in vitro.","method":"Immunoprecipitation, in vitro protein-protein interaction assay, in vitro ubiquitination assay","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and in vitro ubiquitination assay from a single lab; calcyclin-binding protein membership in the complex is established but its specific functional contribution within the complex is not dissected","pmids":["38416790"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"The P. yoelii nigeriensis ortholog of calcyclin-binding protein (PyCacyBP) is expressed as an ~27 kDa protein in all blood stages of the parasite and exists in both monomer and dimer forms, as determined by cloning, recombinant expression, and parasite lysate analysis.","method":"Molecular cloning, recombinant protein expression and purification, SDS-PAGE/Western blot of parasite lysate, biophysical characterization","journal":"Experimental parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method set; establishes expression and oligomeric state but no functional mechanism","pmids":["36707015"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii nigeriensis","strain":""}]}],"current_model":"PF3D7_0933200 (calcyclin-binding protein) is a subunit of the functional Plasmodium falciparum SCF E3 ubiquitin ligase complex (PfCullin-1/PfRbx1/PfSkp1/PfFBXO1/calcyclin-binding protein); its ortholog in P. yoelii nigeriensis is expressed across all blood stages as a ~27 kDa protein that can form dimers, but the specific biochemical role of this subunit within the complex has not yet been established."},"narrative":{"mechanistic_narrative":"PF3D7_0933200 (calcyclin-binding protein) is a subunit of the functional Plasmodium falciparum SCF E3 ubiquitin ligase complex, in which it associates with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1; this assembled complex has demonstrable in vitro ubiquitination activity [PMID:38416790]. Its specific biochemical contribution to the complex has not been dissected in the available corpus, and beyond complex membership no substrate or catalytic role is assigned to this subunit [PMID:38416790]. In the rodent parasite P. yoelii nigeriensis, the ortholog (PyCacyBP) is expressed as a ~27 kDa protein across all blood stages and exists in both monomeric and dimeric forms [PMID:36707015].","teleology":[{"year":2023,"claim":"Whether the calcyclin-binding protein ortholog is expressed during parasite blood stages and what physical form it adopts was previously undefined; characterizing this established its stage expression and oligomeric behavior.","evidence":"Molecular cloning, recombinant expression, and Western blot of P. yoelii nigeriensis parasite lysate with biophysical characterization","pmids":["36707015"],"confidence":"Low","gaps":["Establishes expression and monomer/dimer state but assigns no functional mechanism","Does not connect the ortholog to any complex or enzymatic activity","Findings are in P. yoelii nigeriensis, not directly in P. falciparum"],"attribution":[{"species":"Plasmodium yoelii nigeriensis","strain":""}]},{"year":2024,"claim":"Whether calcyclin-binding protein participates in a defined P. falciparum ubiquitination machinery was unknown; showing it co-purifies with an SCF complex that is enzymatically active established it as a bona fide subunit of a functional E3 ubiquitin ligase.","evidence":"Immunoprecipitation, in vitro protein-protein interaction assays, and in vitro ubiquitination assay in P. falciparum","pmids":["38416790"],"confidence":"Medium","gaps":["The specific functional contribution of calcyclin-binding protein within the complex is not dissected","No substrate of the complex attributable to this subunit is identified","Reciprocal Co-IP and activity assay are from a single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The precise biochemical role of PF3D7_0933200 within the PfSCF complex — including whether it contributes to substrate recognition, complex assembly, or regulation — remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No substrate or adaptor function assigned to this subunit specifically","No structural model of the subunit within the complex","Functional consequence of its monomer/dimer state is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfSCF E3 ubiquitin ligase complex (PfCullin-1/PfRbx1/PfSkp1/PfFBXO1/calcyclin-binding protein)"],"partners":["PFCULLIN-1","PFRBX1","PFSKP1","PFFBXO1"],"other_free_text":["P. yoelii nigeriensis ortholog PyCacyBP is a ~27 kDa protein expressed across all blood stages, existing in monomer and dimer forms [#1]","Specific biochemical role of PF3D7_0933200 within the SCF complex not established in the corpus [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"38416790","id":"PMC_38416790","title":"Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrity.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38416790","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["calcyclin-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36707015","id":"PMC_36707015","title":"Molecular and immunological characterization of the calcyclin binding protein in rodent malaria parasite.","date":"2023","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/36707015","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["calcyclin-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4146,"output_tokens":722,"usd":0.011634,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5270,"output_tokens":1561,"usd":0.032688,"stage2_stop_reason":"end_turn"},"total_usd":0.044322,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"Calcyclin-binding protein (PF3D7_0933200) was identified as a component of the functional Plasmodium falciparum SCF (PfSCF) E3 ubiquitin ligase complex, together with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1, as confirmed by immunoprecipitation and in vitro protein-protein interaction assays, with the complex also shown to have ubiquitination activity in vitro.\",\n      \"method\": \"Immunoprecipitation, in vitro protein-protein interaction assay, in vitro ubiquitination assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and in vitro ubiquitination assay from a single lab; calcyclin-binding protein membership in the complex is established but its specific functional contribution within the complex is not dissected\",\n      \"pmids\": [\"38416790\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The P. yoelii nigeriensis ortholog of calcyclin-binding protein (PyCacyBP) is expressed as an ~27 kDa protein in all blood stages of the parasite and exists in both monomer and dimer forms, as determined by cloning, recombinant expression, and parasite lysate analysis.\",\n      \"method\": \"Molecular cloning, recombinant protein expression and purification, SDS-PAGE/Western blot of parasite lysate, biophysical characterization\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method set; establishes expression and oligomeric state but no functional mechanism\",\n      \"pmids\": [\"36707015\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii nigeriensis\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0933200 (calcyclin-binding protein) is a subunit of the functional Plasmodium falciparum SCF E3 ubiquitin ligase complex (PfCullin-1/PfRbx1/PfSkp1/PfFBXO1/calcyclin-binding protein); its ortholog in P. yoelii nigeriensis is expressed across all blood stages as a ~27 kDa protein that can form dimers, but the specific biochemical role of this subunit within the complex has not yet been established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0933200 (calcyclin-binding protein) is a subunit of the functional Plasmodium falciparum SCF E3 ubiquitin ligase complex, in which it associates with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1; this assembled complex has demonstrable in vitro ubiquitination activity [#0]. Its specific biochemical contribution to the complex has not been dissected in the available corpus, and beyond complex membership no substrate or catalytic role is assigned to this subunit [#0]. In the rodent parasite P. yoelii nigeriensis, the ortholog (PyCacyBP) is expressed as a ~27 kDa protein across all blood stages and exists in both monomeric and dimeric forms [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether the calcyclin-binding protein ortholog is expressed during parasite blood stages and what physical form it adopts was previously undefined; characterizing this established its stage expression and oligomeric behavior.\",\n      \"evidence\": \"Molecular cloning, recombinant expression, and Western blot of P. yoelii nigeriensis parasite lysate with biophysical characterization\",\n      \"pmids\": [\n        \"36707015\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Establishes expression and monomer/dimer state but assigns no functional mechanism\",\n        \"Does not connect the ortholog to any complex or enzymatic activity\",\n        \"Findings are in P. yoelii nigeriensis, not directly in P. falciparum\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium yoelii nigeriensis\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether calcyclin-binding protein participates in a defined P. falciparum ubiquitination machinery was unknown; showing it co-purifies with an SCF complex that is enzymatically active established it as a bona fide subunit of a functional E3 ubiquitin ligase.\",\n      \"evidence\": \"Immunoprecipitation, in vitro protein-protein interaction assays, and in vitro ubiquitination assay in P. falciparum\",\n      \"pmids\": [\n        \"38416790\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific functional contribution of calcyclin-binding protein within the complex is not dissected\",\n        \"No substrate of the complex attributable to this subunit is identified\",\n        \"Reciprocal Co-IP and activity assay are from a single lab\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise biochemical role of PF3D7_0933200 within the PfSCF complex — including whether it contributes to substrate recognition, complex assembly, or regulation — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No substrate or adaptor function assigned to this subunit specifically\",\n        \"No structural model of the subunit within the complex\",\n        \"Functional consequence of its monomer/dimer state is unknown\"\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:0061630\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0016567\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"complexes\": [\n      \"PfSCF E3 ubiquitin ligase complex (PfCullin-1/PfRbx1/PfSkp1/PfFBXO1/calcyclin-binding protein)\"\n    ],\n    \"partners\": [\n      \"PfCullin-1\",\n      \"PfRbx1\",\n      \"PfSkp1\",\n      \"PfFBXO1\"\n    ],\n    \"other_free_text\": [\n      \"P. yoelii nigeriensis ortholog PyCacyBP is a ~27 kDa protein expressed across all blood stages, existing in monomer and dimer forms [#1]\",\n      \"Specific biochemical role of PF3D7_0933200 within the SCF complex not established in the corpus [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0933200","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0319100, PF3D7_1367000). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0933200","name":null,"product":"calcyclin-binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0834000","name":null,"product":"calcyclin-binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0731900","name":null,"product":"calcyclin-binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}