{"gene":"PF3D7_1238100","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2024,"finding":"CACYBP (PF3D7_1238100) was identified as a component of the functional P. falciparum SCF (PfSCF) ubiquitin E3 ligase complex, comprising PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein (CACYBP), as confirmed by immunoprecipitation and in vitro protein-protein interaction assays.","method":"Immunoprecipitation, in vitro protein-protein interaction assay, and ubiquitination assay","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and in vitro interaction assay with functional ubiquitination assay confirming complex activity, single lab","pmids":["38416790"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"CACYBP (ortholog PyCacyBP) in Plasmodium yoelii nigeriensis is expressed as an approximately 27 kDa protein across all blood stages and exists in both monomer and dimer forms, as determined by molecular characterization of the recombinant protein in parasite lysate.","method":"Cloning, recombinant protein purification, SDS-PAGE/Western blot of parasite lysate, biophysical characterization","journal":"Experimental parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single set of methods establishing basic molecular properties (size, oligomeric state, stage expression); no functional mechanism established","pmids":["36707015"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii nigeriensis","strain":""}]}],"current_model":"CACYBP (PF3D7_1238100) functions as a component of the P. falciparum SCF ubiquitin E3 ligase complex (together with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1), and its ortholog in P. yoelii nigeriensis is expressed across all blood stages as a ~27 kDa protein capable of forming dimers, but beyond complex membership no further mechanistic detail about its specific molecular function has been established."},"narrative":{"mechanistic_narrative":"CACYBP (PF3D7_1238100) is a component of the Plasmodium falciparum SCF (PfSCF) ubiquitin E3 ligase complex, associating with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1, as established by immunoprecipitation and in vitro interaction assays coupled with a functional ubiquitination assay [PMID:38416790]. In P. yoelii nigeriensis, the ortholog is a ~27 kDa protein expressed across all blood stages that adopts both monomer and dimer forms [PMID:36707015]. Beyond its membership in the PfSCF complex [PMID:38416790] and these basic molecular properties of the P. yoelii nigeriensis ortholog [PMID:36707015], no substrate, catalytic contribution, or specific molecular function of CACYBP itself has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"To provide any biochemical footing for an uncharacterized parasite protein, the basic molecular properties of the CACYBP ortholog were defined, establishing its expression pattern and oligomeric behavior.","evidence":"Cloning, recombinant protein purification, and Western blot of parasite lysate in P. yoelii nigeriensis","pmids":["36707015"],"confidence":"Low","gaps":["Single lab establishing only size, oligomeric state, and stage expression; no functional mechanism established","No binding partners or complex context defined for the ortholog","Functional significance of monomer/dimer interconversion unknown"],"attribution":[{"species":"Plasmodium yoelii nigeriensis","strain":""}]},{"year":2024,"claim":"To place CACYBP in a defined molecular pathway, it was tested for association with a candidate ubiquitin ligase, establishing it as a member of a functional SCF E3 ligase complex.","evidence":"Immunoprecipitation, in vitro protein-protein interaction assay, and ubiquitination assay in P. falciparum","pmids":["38416790"],"confidence":"Medium","gaps":["The specific role of CACYBP within the PfSCF complex (e.g. substrate recognition, scaffolding, or regulation) is not defined","No CACYBP-dependent ubiquitination substrate identified","Single-lab characterization without reciprocal in vivo validation of CACYBP's requirement for complex activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"What distinct molecular function CACYBP contributes to the PfSCF complex, and whether it targets specific substrates for ubiquitination, remains unestablished.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate or CACYBP-specific catalytic/adaptor role defined","No structural model of CACYBP within the complex","No genetic loss-of-function phenotype for CACYBP itself"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfSCF ubiquitin E3 ligase complex (PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, CACYBP)"],"partners":["PFCULLIN-1","PFRBX1","PFSKP1","PFFBXO1"],"other_free_text":["P. yoelii nigeriensis ortholog is a ~27 kDa protein expressed across all blood stages and exists in monomer and dimer forms [#1]","Beyond membership in the PfSCF complex, no CACYBP-specific molecular function or substrate has been established in the corpus"]}},"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":["CACYBP","calcyclin binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4189,"output_tokens":682,"usd":0.011399,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5272,"output_tokens":1432,"usd":0.03108,"stage2_stop_reason":"end_turn"},"total_usd":0.042479,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"CACYBP (PF3D7_1238100) was identified as a component of the functional P. falciparum SCF (PfSCF) ubiquitin E3 ligase complex, comprising PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein (CACYBP), as confirmed by immunoprecipitation and in vitro protein-protein interaction assays.\",\n      \"method\": \"Immunoprecipitation, in vitro protein-protein interaction assay, and ubiquitination assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and in vitro interaction assay with functional ubiquitination assay confirming complex activity, single lab\",\n      \"pmids\": [\"38416790\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CACYBP (ortholog PyCacyBP) in Plasmodium yoelii nigeriensis is expressed as an approximately 27 kDa protein across all blood stages and exists in both monomer and dimer forms, as determined by molecular characterization of the recombinant protein in parasite lysate.\",\n      \"method\": \"Cloning, recombinant protein 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 set of methods establishing basic molecular properties (size, oligomeric state, stage expression); no functional mechanism established\",\n      \"pmids\": [\"36707015\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii nigeriensis\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CACYBP (PF3D7_1238100) functions as a component of the P. falciparum SCF ubiquitin E3 ligase complex (together with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1), and its ortholog in P. yoelii nigeriensis is expressed across all blood stages as a ~27 kDa protein capable of forming dimers, but beyond complex membership no further mechanistic detail about its specific molecular function has been established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CACYBP (PF3D7_1238100) is a component of the Plasmodium falciparum SCF (PfSCF) ubiquitin E3 ligase complex, associating with PfCullin-1, PfRbx1, PfSkp1, and PfFBXO1, as established by immunoprecipitation and in vitro interaction assays coupled with a functional ubiquitination assay [#0]. In P. yoelii nigeriensis, the ortholog is a ~27 kDa protein expressed across all blood stages that adopts both monomer and dimer forms [#1]. Beyond its membership in the PfSCF complex [#0] and these basic molecular properties of the P. yoelii nigeriensis ortholog [#1], no substrate, catalytic contribution, or specific molecular function of CACYBP itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"To provide any biochemical footing for an uncharacterized parasite protein, the basic molecular properties of the CACYBP ortholog were defined, establishing its expression pattern and oligomeric behavior.\",\n      \"evidence\": \"Cloning, recombinant protein purification, and Western blot of parasite lysate in P. yoelii nigeriensis\",\n      \"pmids\": [\"36707015\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab establishing only size, oligomeric state, and stage expression; no functional mechanism established\",\n        \"No binding partners or complex context defined for the ortholog\",\n        \"Functional significance of monomer/dimer interconversion unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii nigeriensis\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To place CACYBP in a defined molecular pathway, it was tested for association with a candidate ubiquitin ligase, establishing it as a member of a functional SCF E3 ligase complex.\",\n      \"evidence\": \"Immunoprecipitation, in vitro protein-protein interaction assay, and ubiquitination assay in P. falciparum\",\n      \"pmids\": [\"38416790\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific role of CACYBP within the PfSCF complex (e.g. substrate recognition, scaffolding, or regulation) is not defined\",\n        \"No CACYBP-dependent ubiquitination substrate identified\",\n        \"Single-lab characterization without reciprocal in vivo validation of CACYBP's requirement for complex activity\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"What distinct molecular function CACYBP contributes to the PfSCF complex, and whether it targets specific substrates for ubiquitination, remains unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate or CACYBP-specific catalytic/adaptor role defined\",\n        \"No structural model of CACYBP within the complex\",\n        \"No genetic loss-of-function phenotype for CACYBP itself\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016567\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"PfSCF ubiquitin E3 ligase complex (PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, CACYBP)\"],\n    \"partners\": [\"PfCullin-1\", \"PfRbx1\", \"PfSkp1\", \"PfFBXO1\"],\n    \"other_free_text\": [\n      \"P. yoelii nigeriensis ortholog is a ~27 kDa protein expressed across all blood stages and exists in monomer and dimer forms [#1]\",\n      \"Beyond membership in the PfSCF complex, no CACYBP-specific molecular function or substrate has been established in the corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1238100","name":null,"product":"calcyclin binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1452600","name":null,"product":"calcyclin binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1457900","name":null,"product":"calcyclin binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CACYBP","evaluation":null}