{"gene":"PF3D7_0811000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2024,"finding":"P. falciparum CUL1 (PfCullin-1) is predominantly expressed in erythrocytic trophozoite and schizont stages with nucleocytoplasmic localization and chromatin association, and forms a functional SCF complex (PfSCF) comprising PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein, confirmed by immunoprecipitation, in vitro protein-protein interaction, and ubiquitination assay.","method":"Tagged-protein expression in P. falciparum, immunoprecipitation, in vitro protein-protein interaction assay, in vitro ubiquitination assay, subcellular localization by microscopy","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — multiple orthogonal methods (Co-IP, in vitro interaction, functional ubiquitination assay) in a single study with tagged endogenous proteins in P. falciparum","pmids":["38416790"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"P. falciparum CUL1 is a physiological substrate of PfNEDD8: immunoprecipitation of wild-type PfNEDD8 from P. falciparum followed by mass spectrometry identified two putative cullins (including CUL1) as neddylation substrates; complementary experiments in S. cerevisiae rub1Δ and ubc12Δ mutant strains confirmed that PfNEDD8 targets cullin (cdc53), supporting CUL1 as a NEDD8 substrate.","method":"Immunoprecipitation followed by mass spectrometry from P. falciparum expressing tagged PfNEDD8; heterologous complementation in S. cerevisiae mutant strains","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal approaches (IP-MS in parasite, heterologous yeast complementation), single lab","pmids":["33214620"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"In P. berghei, CUL1 forms a conserved SKP1/CUL1/RBX1 complex with at least two adaptor proteins (FBXO1 and FBXL2), confirmed by affinity purification coupled to mass spectrometry of HA-tagged RBX1, SKP1, FBXO1, and FBXL2; CUL1, Nedd8, and polyubiquitin co-purified with RBX1-HA and SKP1-HA. The SCFFBXO1 complex is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress, and integrity of the apical and inner membrane complexes.","method":"Affinity purification of HA-tagged components from synchronised gametocytes followed by label-free semi-quantitative mass spectrometry; genetic disruption with loss-of-function phenotypic analysis; ubiquitinomic survey","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal AP-MS across multiple tagged subunits plus genetic knockouts with defined phenotypic readouts, single lab with multiple orthogonal methods","pmids":["36898988"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"finding":"P. falciparum deubiquitylase PfUCHL3 can cleave HsNedd8 from human Cullin-1 in vitro, as demonstrated using a reconstituted SCF complex (Skp1, Cul1, Myc-Rbx1) and recombinant PfUCHL3; this establishes that a P. falciparum enzyme has deneddylase activity toward CUL1. (Note: the SCF complex used was human/heterologous, not the P. falciparum CUL1 directly.)","method":"In vitro deneddylation assay with purified recombinant PfUCHL3 and heterologous human SCF complex (Cul1-Skp1-Rbx1), Western blot with anti-Cul1 and anti-Nedd8 antibodies","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 2 / Weak — in vitro assay but performed on human CUL1, not directly on PfCUL1; single lab, single method for this specific finding","pmids":["31658303"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum CUL1 (PfCullin-1, PF3D7_0811000) is a scaffold subunit of a functional SCF E3 ubiquitin ligase complex (comprising PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein) that is expressed predominantly in trophozoite and schizont stages with nucleocytoplasmic and chromatin-associated localization; it is neddylated by PfNEDD8 at a conserved lysine residue, and its ortholog in P. berghei assembles with SKP1, RBX1, and F-box adaptors (FBXO1/FBXL2) into a conserved SCFFBXO1 complex required for nuclear segregation, centrosome partitioning, gamete egress, and integrity of the inner membrane complex."},"narrative":{"mechanistic_narrative":"PF3D7_0811000 (CUL1) is the cullin scaffold subunit of a Plasmodium SCF (Skp1–Cullin–F-box) E3 ubiquitin ligase, and in P. falciparum it assembles a functional SCF complex (PfSCF) comprising CUL1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein that is competent for ubiquitination in vitro [PMID:38416790]. The protein is expressed predominantly in erythrocytic trophozoite and schizont stages and shows nucleocytoplasmic localization with chromatin association [PMID:38416790]. CUL1 activity is regulated by neddylation: it is a physiological substrate of PfNEDD8, identified as a cullin neddylation target by IP–mass spectrometry in P. falciparum and corroborated by heterologous complementation in S. cerevisiae cullin (cdc53) [PMID:33214620]. In P. berghei, the CUL1 ortholog assembles a conserved SKP1/CUL1/RBX1 complex with FBXO1 and FBXL2 adaptors, co-purifying with Nedd8 and polyubiquitin, and this SCF^FBXO1 complex is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress, and integrity of the apical and inner membrane complexes [PMID:36898988]. Beyond its role as an SCF scaffold and NEDD8 target, the direct substrates ubiquitinated through CUL1 in P. falciparum have not been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Before this work it was unknown whether any Plasmodium enzyme could reverse cullin neddylation; showing that a parasite deubiquitylase acts on a neddylated cullin established that the neddylation cycle relevant to CUL1 regulation is enzymatically tractable in this system.","evidence":"In vitro deneddylation assay with recombinant PfUCHL3 acting on a reconstituted heterologous human SCF complex (Cul1–Skp1–Rbx1), read out by anti-Cul1/anti-Nedd8 Western blot","pmids":["31658303"],"confidence":"Low","gaps":["The SCF substrate used was human Cul1, not P. falciparum CUL1, so activity on the native parasite protein was not tested","Single in vitro assay from a single lab","Does not establish that PfUCHL3 regulates CUL1 in vivo"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"It was unknown which parasite proteins are neddylated; identifying CUL1 as a PfNEDD8 substrate placed CUL1 within a regulated ubiquitin-ligase cycle and connected the NEDD8 pathway to cullin function.","evidence":"IP–mass spectrometry of tagged PfNEDD8 from P. falciparum identifying cullins as substrates, plus heterologous complementation in S. cerevisiae rub1Δ/ubc12Δ mutants confirming NEDD8 targeting of cullin (cdc53)","pmids":["33214620"],"confidence":"Medium","gaps":["The specific neddylation lysine on CUL1 was not mapped in this study","Functional consequence of CUL1 neddylation for SCF activity not directly measured","IP-MS cannot distinguish direct from indirect neddylation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"The composition and biological requirement of a CUL1-based SCF in Plasmodium was undefined; reciprocal AP-MS and knockouts in P. berghei defined a SKP1/CUL1/RBX1 complex with FBXO1/FBXL2 adaptors and tied it to specific cell-division and egress events.","evidence":"Affinity purification of HA-tagged RBX1, SKP1, FBXO1, FBXL2 from synchronised gametocytes with label-free MS (CUL1, Nedd8, polyubiquitin co-purifying), plus genetic disruption with phenotypic analysis and ubiquitinomic survey","pmids":["36898988"],"confidence":"High","gaps":["Phenotypes were assigned to the complex/FBXO1; the individual contribution of CUL1 was not isolated by CUL1-specific knockout","Substrates ubiquitinated during nuclear segregation or IMC assembly not identified","Shown in P. berghei, not P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"Whether P. falciparum CUL1 forms an intact, catalytically active SCF was unresolved; direct reconstitution and in-parasite characterization established a functional PfSCF and defined CUL1's expression and localization.","evidence":"Tagged-protein expression in P. falciparum, immunoprecipitation, in vitro protein–protein interaction and ubiquitination assays, and subcellular localization microscopy","pmids":["38416790"],"confidence":"High","gaps":["Physiological substrates ubiquitinated by PfSCF not identified","Requirement of CUL1 for parasite viability/stage progression not tested by knockdown/knockout","Role of calcyclin binding protein within the complex not mechanistically defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct substrates targeted for ubiquitination by the CUL1-containing SCF in P. falciparum, and how substrate selection is controlled across the erythrocytic and sexual stages, remain unknown.","evidence":"","pmids":[],"confidence":"High","gaps":["No P. falciparum SCF substrate identified","No structural model of the parasite CUL1–Rbx1–Skp1–FBXO1 assembly","Consequence of blocking CUL1 neddylation for parasite growth untested"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase: CUL1, PfRbx1, PfSkp1, PfFBXO1, calcyclin binding protein (P. falciparum) [#0]","SKP1/CUL1/RBX1 SCF^FBXO1/FBXL2 complex (P. berghei) [#2]"],"partners":["PFRBX1 / RBX1 [#0, #2]","PFSKP1 / SKP1 [#0, #2]","PFFBXO1 / FBXO1 [#0, #2]","FBXL2 [#2]","CALCYCLIN BINDING PROTEIN [#0]","PFNEDD8 [#1, #2]","PFUCHL3 (DENEDDYLASE, ACTIVITY SHOWN ON HETEROLOGOUS HUMAN CUL1) [#3]"],"other_free_text":["CUL1 is a neddylation substrate of PfNEDD8 in P. falciparum [#1].","In P. berghei, the CUL1-containing SCF^FBXO1 is required for nuclear segregation, centrosome partitioning, gamete egress, and inner membrane complex integrity [#2].","Direct ubiquitination substrates of the P. falciparum CUL1 SCF are not identified in the available 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":["cullin-1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33214620","id":"PMC_33214620","title":"Characterization of Plasmodium falciparum NEDD8 and identification of cullins as its substrates.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33214620","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42115185","id":"","title":"Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42115185","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CUL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40281042","id":"","title":"CSP ubiquitylation favours Plasmodium berghei survival during early liver stage infection.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40281042","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CUL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36898988","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CUL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39207167","id":"","title":"A multistage Plasmodium CRL4WIG1 ubiquitin ligase is critical for the formation of functional microtubule organization centers in microgametocytes.","date":"2024","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/39207167","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CUL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31658303","id":"","title":"Nedd8 hydrolysis by UCH proteases in Plasmodium parasites.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/31658303","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CUL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18545708","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CUL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11512,"output_tokens":1609,"usd":0.029336,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6502,"output_tokens":3090,"usd":0.05488,"stage2_stop_reason":"end_turn"},"total_usd":0.084216,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"P. falciparum CUL1 (PfCullin-1) is predominantly expressed in erythrocytic trophozoite and schizont stages with nucleocytoplasmic localization and chromatin association, and forms a functional SCF complex (PfSCF) comprising PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein, confirmed by immunoprecipitation, in vitro protein-protein interaction, and ubiquitination assay.\",\n      \"method\": \"Tagged-protein expression in P. falciparum, immunoprecipitation, in vitro protein-protein interaction assay, in vitro ubiquitination assay, subcellular localization by microscopy\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — multiple orthogonal methods (Co-IP, in vitro interaction, functional ubiquitination assay) in a single study with tagged endogenous proteins in P. falciparum\",\n      \"pmids\": [\"38416790\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"P. falciparum CUL1 is a physiological substrate of PfNEDD8: immunoprecipitation of wild-type PfNEDD8 from P. falciparum followed by mass spectrometry identified two putative cullins (including CUL1) as neddylation substrates; complementary experiments in S. cerevisiae rub1Δ and ubc12Δ mutant strains confirmed that PfNEDD8 targets cullin (cdc53), supporting CUL1 as a NEDD8 substrate.\",\n      \"method\": \"Immunoprecipitation followed by mass spectrometry from P. falciparum expressing tagged PfNEDD8; heterologous complementation in S. cerevisiae mutant strains\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal approaches (IP-MS in parasite, heterologous yeast complementation), single lab\",\n      \"pmids\": [\"33214620\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In P. berghei, CUL1 forms a conserved SKP1/CUL1/RBX1 complex with at least two adaptor proteins (FBXO1 and FBXL2), confirmed by affinity purification coupled to mass spectrometry of HA-tagged RBX1, SKP1, FBXO1, and FBXL2; CUL1, Nedd8, and polyubiquitin co-purified with RBX1-HA and SKP1-HA. The SCFFBXO1 complex is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress, and integrity of the apical and inner membrane complexes.\",\n      \"method\": \"Affinity purification of HA-tagged components from synchronised gametocytes followed by label-free semi-quantitative mass spectrometry; genetic disruption with loss-of-function phenotypic analysis; ubiquitinomic survey\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal AP-MS across multiple tagged subunits plus genetic knockouts with defined phenotypic readouts, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"36898988\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"P. falciparum deubiquitylase PfUCHL3 can cleave HsNedd8 from human Cullin-1 in vitro, as demonstrated using a reconstituted SCF complex (Skp1, Cul1, Myc-Rbx1) and recombinant PfUCHL3; this establishes that a P. falciparum enzyme has deneddylase activity toward CUL1. (Note: the SCF complex used was human/heterologous, not the P. falciparum CUL1 directly.)\",\n      \"method\": \"In vitro deneddylation assay with purified recombinant PfUCHL3 and heterologous human SCF complex (Cul1-Skp1-Rbx1), Western blot with anti-Cul1 and anti-Nedd8 antibodies\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — in vitro assay but performed on human CUL1, not directly on PfCUL1; single lab, single method for this specific finding\",\n      \"pmids\": [\"31658303\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum CUL1 (PfCullin-1, PF3D7_0811000) is a scaffold subunit of a functional SCF E3 ubiquitin ligase complex (comprising PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein) that is expressed predominantly in trophozoite and schizont stages with nucleocytoplasmic and chromatin-associated localization; it is neddylated by PfNEDD8 at a conserved lysine residue, and its ortholog in P. berghei assembles with SKP1, RBX1, and F-box adaptors (FBXO1/FBXL2) into a conserved SCFFBXO1 complex required for nuclear segregation, centrosome partitioning, gamete egress, and integrity of the inner membrane complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0811000 (CUL1) is the cullin scaffold subunit of a Plasmodium SCF (Skp1–Cullin–F-box) E3 ubiquitin ligase, and in P. falciparum it assembles a functional SCF complex (PfSCF) comprising CUL1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein that is competent for ubiquitination in vitro [#0]. The protein is expressed predominantly in erythrocytic trophozoite and schizont stages and shows nucleocytoplasmic localization with chromatin association [#0]. CUL1 activity is regulated by neddylation: it is a physiological substrate of PfNEDD8, identified as a cullin neddylation target by IP–mass spectrometry in P. falciparum and corroborated by heterologous complementation in S. cerevisiae cullin (cdc53) [#1]. In P. berghei, the CUL1 ortholog assembles a conserved SKP1/CUL1/RBX1 complex with FBXO1 and FBXL2 adaptors, co-purifying with Nedd8 and polyubiquitin, and this SCF^FBXO1 complex is required for nuclear segregation during schizogony, centrosome partitioning during microgametogenesis, gamete egress, and integrity of the apical and inner membrane complexes [#2]. Beyond its role as an SCF scaffold and NEDD8 target, the direct substrates ubiquitinated through CUL1 in P. falciparum have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Before this work it was unknown whether any Plasmodium enzyme could reverse cullin neddylation; showing that a parasite deubiquitylase acts on a neddylated cullin established that the neddylation cycle relevant to CUL1 regulation is enzymatically tractable in this system.\",\n      \"evidence\": \"In vitro deneddylation assay with recombinant PfUCHL3 acting on a reconstituted heterologous human SCF complex (Cul1–Skp1–Rbx1), read out by anti-Cul1/anti-Nedd8 Western blot\",\n      \"pmids\": [\"31658303\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"The SCF substrate used was human Cul1, not P. falciparum CUL1, so activity on the native parasite protein was not tested\",\n        \"Single in vitro assay from a single lab\",\n        \"Does not establish that PfUCHL3 regulates CUL1 in vivo\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"It was unknown which parasite proteins are neddylated; identifying CUL1 as a PfNEDD8 substrate placed CUL1 within a regulated ubiquitin-ligase cycle and connected the NEDD8 pathway to cullin function.\",\n      \"evidence\": \"IP–mass spectrometry of tagged PfNEDD8 from P. falciparum identifying cullins as substrates, plus heterologous complementation in S. cerevisiae rub1Δ/ubc12Δ mutants confirming NEDD8 targeting of cullin (cdc53)\",\n      \"pmids\": [\"33214620\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific neddylation lysine on CUL1 was not mapped in this study\",\n        \"Functional consequence of CUL1 neddylation for SCF activity not directly measured\",\n        \"IP-MS cannot distinguish direct from indirect neddylation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The composition and biological requirement of a CUL1-based SCF in Plasmodium was undefined; reciprocal AP-MS and knockouts in P. berghei defined a SKP1/CUL1/RBX1 complex with FBXO1/FBXL2 adaptors and tied it to specific cell-division and egress events.\",\n      \"evidence\": \"Affinity purification of HA-tagged RBX1, SKP1, FBXO1, FBXL2 from synchronised gametocytes with label-free MS (CUL1, Nedd8, polyubiquitin co-purifying), plus genetic disruption with phenotypic analysis and ubiquitinomic survey\",\n      \"pmids\": [\"36898988\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Phenotypes were assigned to the complex/FBXO1; the individual contribution of CUL1 was not isolated by CUL1-specific knockout\",\n        \"Substrates ubiquitinated during nuclear segregation or IMC assembly not identified\",\n        \"Shown in P. berghei, not P. falciparum\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether P. falciparum CUL1 forms an intact, catalytically active SCF was unresolved; direct reconstitution and in-parasite characterization established a functional PfSCF and defined CUL1's expression and localization.\",\n      \"evidence\": \"Tagged-protein expression in P. falciparum, immunoprecipitation, in vitro protein–protein interaction and ubiquitination assays, and subcellular localization microscopy\",\n      \"pmids\": [\"38416790\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Physiological substrates ubiquitinated by PfSCF not identified\",\n        \"Requirement of CUL1 for parasite viability/stage progression not tested by knockdown/knockout\",\n        \"Role of calcyclin binding protein within the complex not mechanistically defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct substrates targeted for ubiquitination by the CUL1-containing SCF in P. falciparum, and how substrate selection is controlled across the erythrocytic and sexual stages, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No P. falciparum SCF substrate identified\",\n        \"No structural model of the parasite CUL1–Rbx1–Skp1–FBXO1 assembly\",\n        \"Consequence of blocking CUL1 neddylation for parasite growth untested\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0031625\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0061630\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0097602\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016567\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0045116\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase: CUL1, PfRbx1, PfSkp1, PfFBXO1, calcyclin binding protein (P. falciparum) [#0]\",\n      \"SKP1/CUL1/RBX1 SCF^FBXO1/FBXL2 complex (P. berghei) [#2]\"\n    ],\n    \"partners\": [\n      \"PfRbx1 / RBX1 [#0, #2]\",\n      \"PfSkp1 / SKP1 [#0, #2]\",\n      \"PfFBXO1 / FBXO1 [#0, #2]\",\n      \"FBXL2 [#2]\",\n      \"calcyclin binding protein [#0]\",\n      \"PfNEDD8 [#1, #2]\",\n      \"PfUCHL3 (deneddylase, activity shown on heterologous human Cul1) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"CUL1 is a neddylation substrate of PfNEDD8 in P. falciparum [#1].\",\n      \"In P. berghei, the CUL1-containing SCF^FBXO1 is required for nuclear segregation, centrosome partitioning, gamete egress, and inner membrane complex integrity [#2].\",\n      \"Direct ubiquitination substrates of the P. falciparum CUL1 SCF are not identified in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0811000","name":null,"product":"cullin-1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1426500","name":null,"product":"cullin-1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1429700","name":null,"product":"cullin-1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CUL1","evaluation":null}