{"gene":"PF3D7_1367000","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2024,"finding":"PfSKP1 (PF3D7_1367000) physically associates with PfCullin-1, PfRbx1, and PfFBXO1 to form a functional SCF (Skp1-Cullin-1-Fbox) ubiquitin E3 ligase complex in P. falciparum, as confirmed by immunoprecipitation and in vitro protein-protein interaction assays; the complex also contains calcyclin binding protein and possesses in vitro ubiquitination activity.","method":"Immunoprecipitation, in vitro protein-protein interaction assay, in vitro ubiquitination assay","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — reciprocal IP plus in vitro ubiquitination assay plus protein-interaction assay, single lab but three orthogonal methods","pmids":["38416790"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"In P. berghei, SKP1 forms a conserved SCF^FBXO1 (Skp1/Cullin1/FBXO1) complex whose expression and localisation are tightly regulated across multiple developmental stages; the complex is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress from the host erythrocyte, and integrity of the apical complex and inner membrane complex in merozoites and ookinetes.","method":"Genetic tagging and co-immunoprecipitation to define complex membership; conditional knockouts with phenotypic analysis (nuclear segregation, centrosome partitioning, egress, IMC integrity); ubiquitinomic profiling (mass spectrometry) to identify FBXO1-dependent ubiquitination substrates; epistasis with calcium-dependent protein kinase 1 signalling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP defining complex, conditional KO with multiple defined cellular phenotypes, ubiquitinomic substrate mapping, and epistasis with CDPK1, all in one study with replicated phenotypes","pmids":["36898988"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Proteomic analysis of PfFBXO1 interactors identified PfSKP1 (PF3D7_1367000) as one of PfFBXO1's stable binding partners in P. falciparum, consistent with its membership in the SCF complex.","method":"Proteomic co-immunoprecipitation / affinity purification–mass spectrometry","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS pulldown from one lab; no orthogonal validation of the PfSKP1 interaction reported in the abstract","pmids":["39915671"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"Bioinformatic HMM/Pfam domain analysis predicted SKP1 orthologues in apicomplexan parasites, including P. falciparum, as components of ubiquitin E3 ligase complexes; no direct biochemical or genetic experiment was performed on the P. falciparum protein in this study.","method":"HMM profile search of Pfam domains across apicomplexan genomes","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of PfSKP1 function","pmids":["18545708"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfSKP1 (PF3D7_1367000) is the adaptor subunit of a functional SCF ubiquitin E3 ligase complex (together with PfCullin-1, PfRbx1, and PfFBXO1) in P. falciparum, and the orthologous complex in P. berghei is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress, and integrity of the inner membrane complex in motile stages."},"narrative":{"mechanistic_narrative":"SKP1 (PF3D7_1367000) is the adaptor subunit of a functional SCF (Skp1–Cullin-1–Fbox) ubiquitin E3 ligase complex in Plasmodium falciparum, where it physically associates with PfCullin-1, PfRbx1, PfFBXO1, and calcyclin binding protein to form a complex with in vitro ubiquitination activity [PMID:38416790]. Its stable partnership with PfFBXO1 has been independently confirmed by affinity purification–mass spectrometry [PMID:39915671]. In the rodent malaria model P. berghei, the orthologous SKP1-containing SCF^FBXO1 complex is developmentally regulated and required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress from the host erythrocyte, and integrity of the apical and inner membrane complexes, with function coupled to calcium-dependent protein kinase 1 signalling [PMID:36898988]. Beyond its role as the SCF adaptor subunit, no SKP1-specific molecular mechanism (e.g. substrate-recruitment determinants or a dedicated cellular phenotype attributable to SKP1 alone rather than the complex) has been characterized in the available corpus.","teleology":[{"year":2008,"claim":"Before any experimental work, it was unknown whether apicomplexan parasites encode SCF ubiquitin ligase machinery; genome-wide domain analysis predicted a SKP1 orthologue in P. falciparum, framing it as a candidate E3 ligase component.","evidence":"HMM/Pfam domain profile search across apicomplexan genomes","pmids":["18545708"],"confidence":"Low","gaps":["Computational prediction only, with no biochemical or genetic validation of the P. falciparum protein","Complex membership, activity, and cellular role all left unaddressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"To establish what the SKP1-containing complex actually does in vivo, the P. berghei ortholog was studied genetically, showing it assembles a conserved SCF^FBXO1 complex essential for nuclear segregation, centrosome partitioning, gamete egress, and IMC/apical complex integrity across development.","evidence":"Genetic tagging with reciprocal Co-IP, conditional knockouts with phenotypic analysis, ubiquitinomic substrate mapping, and epistasis with CDPK1 signalling in P. berghei","pmids":["36898988"],"confidence":"High","gaps":["Phenotypes are ascribed to the SCF^FBXO1 complex, not to SKP1's own adaptor function in isolation","SKP1-specific substrate-recruitment contribution not separated from FBXO1","Findings are in P. berghei and not directly demonstrated for PF3D7_1367000"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"It remained unproven that the predicted P. falciparum SKP1 forms a catalytically active E3 ligase; reconstitution and interaction assays confirmed PF3D7_1367000 associates with PfCullin-1, PfRbx1, PfFBXO1, and calcyclin binding protein in a complex with in vitro ubiquitination activity.","evidence":"Immunoprecipitation, in vitro protein-protein interaction assay, and in vitro ubiquitination assay in P. falciparum","pmids":["38416790"],"confidence":"High","gaps":["In vitro ubiquitination does not identify physiological substrates in P. falciparum","No structural basis for how SKP1 bridges Cullin-1 and the F-box protein is defined","Cellular phenotype of SKP1 loss in P. falciparum not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"An independent proteomic survey of PfFBXO1 interactors was needed to corroborate the SCF membership; it recovered PF3D7_1367000 as a stable PfFBXO1 partner, reinforcing SKP1's role as the SCF adaptor.","evidence":"Affinity purification–mass spectrometry of PfFBXO1 interactors in P. falciparum","pmids":["39915671"],"confidence":"Medium","gaps":["Single Co-IP/MS pulldown without orthogonal validation of the specific SKP1 interaction","Does not add functional or substrate information for SKP1"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether SKP1 (PF3D7_1367000) has any function or phenotype in P. falciparum distinct from its role as the SCF adaptor, and which physiological substrates the complex ubiquitinates through SKP1-mediated F-box recruitment.","evidence":"No discovery in the corpus addresses SKP1-specific substrate selection or a P. falciparum loss-of-function phenotype","pmids":[],"confidence":"Low","gaps":["No conditional knockout of PF3D7_1367000 in P. falciparum reported","No substrate attributable specifically to SKP1's adaptor activity","No structural model of the P. falciparum SCF assembly"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SCF (Skp1-Cullin-1-Fbox) ubiquitin E3 ligase complex","SCF^FBXO1 complex (P. berghei ortholog)"],"partners":["PFCULLIN-1","PFRBX1","PFFBXO1","CALCYCLIN BINDING PROTEIN"],"other_free_text":["P. berghei ortholog function couples to calcium-dependent protein kinase 1 (CDPK1) signalling [#1]","SKP1 (PF3D7_1367000) is characterized in the corpus principally as the adaptor subunit of the SCF complex; developmental phenotypes are established for the P. berghei complex, not for SKP1 in isolation [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18545708","id":"PMC_18545708","title":"Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence.","date":"2008","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/18545708","citation_count":85,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36898988","id":"PMC_36898988","title":"The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/36898988","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SKP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["SKP1","PfSKP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39915671","id":"PMC_39915671","title":"PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages.","date":"2025","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39915671","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSKP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5230,"output_tokens":1280,"usd":0.017445,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6099,"output_tokens":2633,"usd":0.04816,"stage2_stop_reason":"end_turn"},"total_usd":0.065605,"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\": \"PfSKP1 (PF3D7_1367000) physically associates with PfCullin-1, PfRbx1, and PfFBXO1 to form a functional SCF (Skp1-Cullin-1-Fbox) ubiquitin E3 ligase complex in P. falciparum, as confirmed by immunoprecipitation and in vitro protein-protein interaction assays; the complex also contains calcyclin binding protein and possesses in vitro ubiquitination activity.\",\n      \"method\": \"Immunoprecipitation, in vitro protein-protein interaction assay, in vitro ubiquitination assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — reciprocal IP plus in vitro ubiquitination assay plus protein-interaction assay, single lab but three orthogonal methods\",\n      \"pmids\": [\"38416790\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In P. berghei, SKP1 forms a conserved SCF^FBXO1 (Skp1/Cullin1/FBXO1) complex whose expression and localisation are tightly regulated across multiple developmental stages; the complex is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress from the host erythrocyte, and integrity of the apical complex and inner membrane complex in merozoites and ookinetes.\",\n      \"method\": \"Genetic tagging and co-immunoprecipitation to define complex membership; conditional knockouts with phenotypic analysis (nuclear segregation, centrosome partitioning, egress, IMC integrity); ubiquitinomic profiling (mass spectrometry) to identify FBXO1-dependent ubiquitination substrates; epistasis with calcium-dependent protein kinase 1 signalling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP defining complex, conditional KO with multiple defined cellular phenotypes, ubiquitinomic substrate mapping, and epistasis with CDPK1, all in one study with replicated phenotypes\",\n      \"pmids\": [\"36898988\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Proteomic analysis of PfFBXO1 interactors identified PfSKP1 (PF3D7_1367000) as one of PfFBXO1's stable binding partners in P. falciparum, consistent with its membership in the SCF complex.\",\n      \"method\": \"Proteomic co-immunoprecipitation / affinity purification–mass spectrometry\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS pulldown from one lab; no orthogonal validation of the PfSKP1 interaction reported in the abstract\",\n      \"pmids\": [\"39915671\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Bioinformatic HMM/Pfam domain analysis predicted SKP1 orthologues in apicomplexan parasites, including P. falciparum, as components of ubiquitin E3 ligase complexes; no direct biochemical or genetic experiment was performed on the P. falciparum protein in this study.\",\n      \"method\": \"HMM profile search of Pfam domains across apicomplexan genomes\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct experimental validation of PfSKP1 function\",\n      \"pmids\": [\"18545708\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfSKP1 (PF3D7_1367000) is the adaptor subunit of a functional SCF ubiquitin E3 ligase complex (together with PfCullin-1, PfRbx1, and PfFBXO1) in P. falciparum, and the orthologous complex in P. berghei is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress, and integrity of the inner membrane complex in motile stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SKP1 (PF3D7_1367000) is the adaptor subunit of a functional SCF (Skp1–Cullin-1–Fbox) ubiquitin E3 ligase complex in Plasmodium falciparum, where it physically associates with PfCullin-1, PfRbx1, PfFBXO1, and calcyclin binding protein to form a complex with in vitro ubiquitination activity [#0]. Its stable partnership with PfFBXO1 has been independently confirmed by affinity purification–mass spectrometry [#2]. In the rodent malaria model P. berghei, the orthologous SKP1-containing SCF^FBXO1 complex is developmentally regulated and required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress from the host erythrocyte, and integrity of the apical and inner membrane complexes, with function coupled to calcium-dependent protein kinase 1 signalling [#1]. Beyond its role as the SCF adaptor subunit, no SKP1-specific molecular mechanism (e.g. substrate-recruitment determinants or a dedicated cellular phenotype attributable to SKP1 alone rather than the complex) has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Before any experimental work, it was unknown whether apicomplexan parasites encode SCF ubiquitin ligase machinery; genome-wide domain analysis predicted a SKP1 orthologue in P. falciparum, framing it as a candidate E3 ligase component.\",\n      \"evidence\": \"HMM/Pfam domain profile search across apicomplexan genomes\",\n      \"pmids\": [\n        \"18545708\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, with no biochemical or genetic validation of the P. falciparum protein\",\n        \"Complex membership, activity, and cellular role all left unaddressed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To establish what the SKP1-containing complex actually does in vivo, the P. berghei ortholog was studied genetically, showing it assembles a conserved SCF^FBXO1 complex essential for nuclear segregation, centrosome partitioning, gamete egress, and IMC/apical complex integrity across development.\",\n      \"evidence\": \"Genetic tagging with reciprocal Co-IP, conditional knockouts with phenotypic analysis, ubiquitinomic substrate mapping, and epistasis with CDPK1 signalling in P. berghei\",\n      \"pmids\": [\n        \"36898988\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Phenotypes are ascribed to the SCF^FBXO1 complex, not to SKP1's own adaptor function in isolation\",\n        \"SKP1-specific substrate-recruitment contribution not separated from FBXO1\",\n        \"Findings are in P. berghei and not directly demonstrated for PF3D7_1367000\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It remained unproven that the predicted P. falciparum SKP1 forms a catalytically active E3 ligase; reconstitution and interaction assays confirmed PF3D7_1367000 associates with PfCullin-1, PfRbx1, PfFBXO1, and calcyclin binding protein in a complex with in vitro ubiquitination activity.\",\n      \"evidence\": \"Immunoprecipitation, in vitro protein-protein interaction assay, and in vitro ubiquitination assay in P. falciparum\",\n      \"pmids\": [\n        \"38416790\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"In vitro ubiquitination does not identify physiological substrates in P. falciparum\",\n        \"No structural basis for how SKP1 bridges Cullin-1 and the F-box protein is defined\",\n        \"Cellular phenotype of SKP1 loss in P. falciparum not tested\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"An independent proteomic survey of PfFBXO1 interactors was needed to corroborate the SCF membership; it recovered PF3D7_1367000 as a stable PfFBXO1 partner, reinforcing SKP1's role as the SCF adaptor.\",\n      \"evidence\": \"Affinity purification–mass spectrometry of PfFBXO1 interactors in P. falciparum\",\n      \"pmids\": [\n        \"39915671\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP/MS pulldown without orthogonal validation of the specific SKP1 interaction\",\n        \"Does not add functional or substrate information for SKP1\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether SKP1 (PF3D7_1367000) has any function or phenotype in P. falciparum distinct from its role as the SCF adaptor, and which physiological substrates the complex ubiquitinates through SKP1-mediated F-box recruitment.\",\n      \"evidence\": \"No discovery in the corpus addresses SKP1-specific substrate selection or a P. falciparum loss-of-function phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No conditional knockout of PF3D7_1367000 in P. falciparum reported\",\n        \"No substrate attributable specifically to SKP1's adaptor activity\",\n        \"No structural model of the P. falciparum SCF assembly\"\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:0019005\",\n        \"supporting_discovery_ids\": [\n          0,\n          1,\n          2\n        ]\n      },\n      {\n        \"term_id\": \"GO:0061630\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0016567\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ]\n      },\n      {\n        \"term_id\": \"GO:0007049\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"SCF (Skp1-Cullin-1-Fbox) ubiquitin E3 ligase complex\",\n      \"SCF^FBXO1 complex (P. berghei ortholog)\"\n    ],\n    \"partners\": [\n      \"PfCullin-1\",\n      \"PfRbx1\",\n      \"PfFBXO1\",\n      \"calcyclin binding protein\"\n    ],\n    \"other_free_text\": [\n      \"P. berghei ortholog function couples to calcium-dependent protein kinase 1 (CDPK1) signalling [#1]\",\n      \"SKP1 (PF3D7_1367000) is characterized in the corpus principally as the adaptor subunit of the SCF complex; developmental phenotypes are established for the P. berghei complex, not for SKP1 in isolation [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1367000","name":null,"product":"suppressor of kinetochore protein 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1142900","name":null,"product":"suppressor of kinetochore protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1104200","name":null,"product":"suppressor of kinetochore protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SKP1","evaluation":null}