{"gene":"PF3D7_1417200","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2021,"finding":"In Plasmodium, the NOT1 scaffold protein of the CAF1/CCR4/NOT complex is duplicated into two paralogues; one paralogue (NOT1-G) is dedicated to essential transmission functions, while the canonical NOT1 (PF3D7_1417200) represents the other paralogue. PyNOT1-G localizes to cytosolic puncta throughout much of the life cycle, and deletion of not1-g leads to arrest phenotypes in both male and female parasites, implicating the two NOT1 paralogues in distinct but intertwined roles within the complex.","method":"Genetic deletion (not1-g knockout in Plasmodium yoelii), comparative transcriptomics, live imaging of cytosolic localization, domain-deletion analysis of TTP-binding domain","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined phenotypic readout and comparative transcriptomics in a single lab; establishes that canonical NOT1 (PF3D7_1417200) is distinct from NOT1-G, but mechanistic detail about PF3D7_1417200 itself is inferred from the paralogue study rather than directly tested","pmids":["34673764"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2024,"finding":"TurboID-based proximity proteomics revealed that DOZI (DDX6 orthologue) exchanges its interaction from NOT1-G in female gametocytes to the canonical NOT1 (PF3D7_1417200) in zygotes, providing a molecular model in which this switch acts as a trigger for the release of mRNAs from translational repression upon host-to-vector transmission.","method":"TurboID-based proximity proteomics (DIA-MS) of the DOZI/CITH/ALBA complex in female gametocytes versus zygotes of Plasmodium yoelii; cross-validated by ultrastructure expansion microscopy and structured illumination microscopy for selected protein colocalizations","journal":"bioRxiv : the preprint server for biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — proximity proteomics with microscopy cross-validation in a single lab, single study; preprint not yet peer-reviewed at time of corpus assembly","pmids":["38352447"],"is_preprint":true,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"finding":"Peer-reviewed publication of the same proximity proteomics dataset confirmed that DOZI exchanges its interaction partner from NOT1-G in female gametocytes to the canonical NOT1 (PF3D7_1417200) in zygotes, consistent with the canonical NOT1 functioning in the release of translational repression following fertilization.","method":"TurboID-based proximity proteomics (DIA-MS), comparative transcriptomics, and imaging across the host-to-vector transmission event in Plasmodium yoelii","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — peer-reviewed version of proximity proteomics study; single lab but orthogonal methods (proteomics + imaging); canonical NOT1 interaction established by proximity labelling rather than direct co-IP","pmids":["39777415"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2015,"finding":"Bioinformatic and comparative interactome analysis identified PF3D7_1417200 (NOT1) as a component of the conserved PfCaf1-CCR4-NOT complex in Plasmodium falciparum, predicting it functions as the scaffold subunit of this post-transcriptional regulatory complex.","method":"Bioinformatic analysis of P. falciparum genome; comparative protein-protein interaction network analysis using human and Plasmodium datasets; Cytoscape network visualization","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of NOT1 itself","pmids":["26525978"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1417200 (NOT1) is the canonical scaffold subunit of the CAF1/CCR4/NOT complex in Plasmodium; it is distinct from a gametocyte/transmission-specific paralogue (NOT1-G), and proximity proteomics in P. yoelii shows that DOZI shifts its interaction from NOT1-G in female gametocytes to canonical NOT1 in zygotes, suggesting that NOT1 plays a role in releasing mRNAs from translational repression following host-to-vector transmission."},"narrative":{"mechanistic_narrative":"PF3D7_1417200 (NOT1) is the canonical scaffold subunit of the Plasmodium CAF1/CCR4/NOT complex, a post-transcriptional regulatory machine, and in Plasmodium the NOT1 scaffold is duplicated into two paralogues: PF3D7_1417200 and a transmission-dedicated paralogue, NOT1-G [PMID:34673764]. The distinct role of PF3D7_1417200 is defined chiefly by its behaviour across the host-to-vector transmission event: in P. yoelii, proximity proteomics shows that DOZI (a DDX6 orthologue) exchanges its interaction from NOT1-G in female gametocytes to canonical NOT1 in zygotes, positioning PF3D7_1417200 as a molecular trigger for the release of mRNAs from translational repression following fertilization [PMID:38352447, PMID:39777415]. Beyond its identification as the scaffold component of the PfCaf1-CCR4-NOT complex [PMID:26525978] and this DOZI-exchange model, no direct biochemical or structural characterization of PF3D7_1417200 itself has been established in the available corpus; much of its mechanistic role is inferred from studies of its paralogue and interacting partners rather than tested directly on PF3D7_1417200.","teleology":[{"year":2015,"claim":"Before any experimental work, it was unknown whether Plasmodium encodes a NOT1 scaffold; comparative interactome analysis assigned PF3D7_1417200 to the conserved Caf1-CCR4-NOT complex, establishing a candidate post-transcriptional regulatory role.","evidence":"Bioinformatic genome analysis and comparative protein-protein interaction network reconstruction in P. falciparum","pmids":["26525978"],"confidence":"Low","gaps":["Computational prediction only, with no direct experimental validation of PF3D7_1417200","No demonstration of physical association with complex members","No functional assay of the predicted scaffold activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"It was unknown how one NOT1 scaffold could serve both housekeeping and transmission needs; discovery of a paralogue duplication showed that a dedicated NOT1-G handles essential transmission functions while PF3D7_1417200 represents the canonical, distinct paralogue.","evidence":"Genetic deletion of not1-g, comparative transcriptomics, live imaging, and domain-deletion analysis in P. yoelii","pmids":["34673764"],"confidence":"Medium","gaps":["Mechanistic detail about PF3D7_1417200 itself is inferred from the paralogue knockout rather than directly tested","No phenotype from direct perturbation of canonical NOT1","Division of labour between the two paralogues within the complex not biochemically resolved"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"claim":"The functional trigger distinguishing PF3D7_1417200 from its paralogue was unresolved; proximity proteomics showed that DOZI switches from NOT1-G in female gametocytes to canonical NOT1 in zygotes, providing a model in which PF3D7_1417200 mediates release of repressed mRNAs after transmission.","evidence":"TurboID proximity proteomics (DIA-MS) of the DOZI/CITH/ALBA complex across gametocyte-to-zygote transition, with expansion and structured-illumination microscopy cross-validation in P. yoelii (peer-reviewed following a 2024 preprint)","pmids":["39777415","38352447"],"confidence":"Medium","gaps":["Canonical NOT1 interaction established by proximity labelling rather than direct co-IP or reciprocal validation","Single lab, single study","The mRNA-release model is inferred from the interaction switch, not directly demonstrated by measuring translational activation"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"Direct biochemical, structural, and functional characterization of PF3D7_1417200 as a scaffold — its assembled complex composition, deadenylation activity, and the mechanism by which the DOZI switch releases translational repression — remains unestablished.","evidence":"No direct experimental study of PF3D7_1417200 function in the available corpus","pmids":[],"confidence":"Low","gaps":["No direct co-IP or reconstitution confirming PF3D7_1417200 scaffold interactions","No structural model of PF3D7_1417200 or its subunit-binding surfaces","No loss-of-function phenotype from direct perturbation of PF3D7_1417200"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CAF1/CCR4-NOT complex (PfCaf1-CCR4-NOT)"],"partners":["DOZI (DDX6 ORTHOLOGUE)"],"other_free_text":["PF3D7_1417200 is the canonical NOT1 scaffold paralogue, distinct from the transmission-dedicated paralogue NOT1-G [#0].","In P. yoelii zygotes, DOZI shifts its association from NOT1-G to canonical NOT1 (PF3D7_1417200) across the host-to-vector transmission event [#1, #2].","Complex membership was originally inferred computationally in P. falciparum [#3]; direct biochemical characterization of PF3D7_1417200 is absent from the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26525978","id":"PMC_26525978","title":"A bioinformatic survey of RNA-binding proteins in Plasmodium.","date":"2015","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/26525978","citation_count":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21803864","id":"PMC_21803864","title":"CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins.","date":"2011","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/21803864","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30703164","id":"PMC_30703164","title":"Plasmodium male gametocyte development and transmission are critically regulated by the two putative deadenylases of the CAF1/CCR4/NOT complex.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/30703164","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4","NOT","PyCCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31531994","id":"PMC_31531994","title":"The molecular machinery of translational control in malaria parasites.","date":"2019","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31531994","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCR4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34673764","id":"PMC_34673764","title":"The Plasmodium NOT1-G paralogue is an essential regulator of sexual stage maturation and parasite transmission.","date":"2021","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/34673764","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NOT1","CCR4","PyNOT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39777415","id":"PMC_39777415","title":"Widespread release of translational repression across Plasmodium's host-to-vector transmission event.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/39777415","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NOT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39913602","id":"PMC_39913602","title":"Not just monkey business.","date":"2025","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39913602","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NOT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38352447","id":"PMC_38352447","title":"Global Release of Translational Repression Across Plasmodium's Host-to-Vector Transmission Event.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38352447","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NOT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6511,"output_tokens":1343,"usd":0.019839,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6309,"output_tokens":2166,"usd":0.042847,"stage2_stop_reason":"end_turn"},"total_usd":0.062686,"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\": 2021,\n      \"finding\": \"In Plasmodium, the NOT1 scaffold protein of the CAF1/CCR4/NOT complex is duplicated into two paralogues; one paralogue (NOT1-G) is dedicated to essential transmission functions, while the canonical NOT1 (PF3D7_1417200) represents the other paralogue. PyNOT1-G localizes to cytosolic puncta throughout much of the life cycle, and deletion of not1-g leads to arrest phenotypes in both male and female parasites, implicating the two NOT1 paralogues in distinct but intertwined roles within the complex.\",\n      \"method\": \"Genetic deletion (not1-g knockout in Plasmodium yoelii), comparative transcriptomics, live imaging of cytosolic localization, domain-deletion analysis of TTP-binding domain\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined phenotypic readout and comparative transcriptomics in a single lab; establishes that canonical NOT1 (PF3D7_1417200) is distinct from NOT1-G, but mechanistic detail about PF3D7_1417200 itself is inferred from the paralogue study rather than directly tested\",\n      \"pmids\": [\"34673764\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TurboID-based proximity proteomics revealed that DOZI (DDX6 orthologue) exchanges its interaction from NOT1-G in female gametocytes to the canonical NOT1 (PF3D7_1417200) in zygotes, providing a molecular model in which this switch acts as a trigger for the release of mRNAs from translational repression upon host-to-vector transmission.\",\n      \"method\": \"TurboID-based proximity proteomics (DIA-MS) of the DOZI/CITH/ALBA complex in female gametocytes versus zygotes of Plasmodium yoelii; cross-validated by ultrastructure expansion microscopy and structured illumination microscopy for selected protein colocalizations\",\n      \"journal\": \"bioRxiv : the preprint server for biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — proximity proteomics with microscopy cross-validation in a single lab, single study; preprint not yet peer-reviewed at time of corpus assembly\",\n      \"pmids\": [\"38352447\"],\n      \"is_preprint\": true,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Peer-reviewed publication of the same proximity proteomics dataset confirmed that DOZI exchanges its interaction partner from NOT1-G in female gametocytes to the canonical NOT1 (PF3D7_1417200) in zygotes, consistent with the canonical NOT1 functioning in the release of translational repression following fertilization.\",\n      \"method\": \"TurboID-based proximity proteomics (DIA-MS), comparative transcriptomics, and imaging across the host-to-vector transmission event in Plasmodium yoelii\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — peer-reviewed version of proximity proteomics study; single lab but orthogonal methods (proteomics + imaging); canonical NOT1 interaction established by proximity labelling rather than direct co-IP\",\n      \"pmids\": [\"39777415\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Bioinformatic and comparative interactome analysis identified PF3D7_1417200 (NOT1) as a component of the conserved PfCaf1-CCR4-NOT complex in Plasmodium falciparum, predicting it functions as the scaffold subunit of this post-transcriptional regulatory complex.\",\n      \"method\": \"Bioinformatic analysis of P. falciparum genome; comparative protein-protein interaction network analysis using human and Plasmodium datasets; Cytoscape network visualization\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct experimental validation of NOT1 itself\",\n      \"pmids\": [\"26525978\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1417200 (NOT1) is the canonical scaffold subunit of the CAF1/CCR4/NOT complex in Plasmodium; it is distinct from a gametocyte/transmission-specific paralogue (NOT1-G), and proximity proteomics in P. yoelii shows that DOZI shifts its interaction from NOT1-G in female gametocytes to canonical NOT1 in zygotes, suggesting that NOT1 plays a role in releasing mRNAs from translational repression following host-to-vector transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1417200 (NOT1) is the canonical scaffold subunit of the Plasmodium CAF1/CCR4/NOT complex, a post-transcriptional regulatory machine, and in Plasmodium the NOT1 scaffold is duplicated into two paralogues: PF3D7_1417200 and a transmission-dedicated paralogue, NOT1-G [#0]. The distinct role of PF3D7_1417200 is defined chiefly by its behaviour across the host-to-vector transmission event: in P. yoelii, proximity proteomics shows that DOZI (a DDX6 orthologue) exchanges its interaction from NOT1-G in female gametocytes to canonical NOT1 in zygotes, positioning PF3D7_1417200 as a molecular trigger for the release of mRNAs from translational repression following fertilization [#1, #2]. Beyond its identification as the scaffold component of the PfCaf1-CCR4-NOT complex [#3] and this DOZI-exchange model, no direct biochemical or structural characterization of PF3D7_1417200 itself has been established in the available corpus; much of its mechanistic role is inferred from studies of its paralogue and interacting partners rather than tested directly on PF3D7_1417200.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Before any experimental work, it was unknown whether Plasmodium encodes a NOT1 scaffold; comparative interactome analysis assigned PF3D7_1417200 to the conserved Caf1-CCR4-NOT complex, establishing a candidate post-transcriptional regulatory role.\",\n      \"evidence\": \"Bioinformatic genome analysis and comparative protein-protein interaction network reconstruction in P. falciparum\",\n      \"pmids\": [\"26525978\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, with no direct experimental validation of PF3D7_1417200\",\n        \"No demonstration of physical association with complex members\",\n        \"No functional assay of the predicted scaffold activity\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown how one NOT1 scaffold could serve both housekeeping and transmission needs; discovery of a paralogue duplication showed that a dedicated NOT1-G handles essential transmission functions while PF3D7_1417200 represents the canonical, distinct paralogue.\",\n      \"evidence\": \"Genetic deletion of not1-g, comparative transcriptomics, live imaging, and domain-deletion analysis in P. yoelii\",\n      \"pmids\": [\"34673764\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanistic detail about PF3D7_1417200 itself is inferred from the paralogue knockout rather than directly tested\",\n        \"No phenotype from direct perturbation of canonical NOT1\",\n        \"Division of labour between the two paralogues within the complex not biochemically resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The functional trigger distinguishing PF3D7_1417200 from its paralogue was unresolved; proximity proteomics showed that DOZI switches from NOT1-G in female gametocytes to canonical NOT1 in zygotes, providing a model in which PF3D7_1417200 mediates release of repressed mRNAs after transmission.\",\n      \"evidence\": \"TurboID proximity proteomics (DIA-MS) of the DOZI/CITH/ALBA complex across gametocyte-to-zygote transition, with expansion and structured-illumination microscopy cross-validation in P. yoelii (peer-reviewed following a 2024 preprint)\",\n      \"pmids\": [\"39777415\", \"38352447\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Canonical NOT1 interaction established by proximity labelling rather than direct co-IP or reciprocal validation\",\n        \"Single lab, single study\",\n        \"The mRNA-release model is inferred from the interaction switch, not directly demonstrated by measuring translational activation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Direct biochemical, structural, and functional characterization of PF3D7_1417200 as a scaffold — its assembled complex composition, deadenylation activity, and the mechanism by which the DOZI switch releases translational repression — remains unestablished.\",\n      \"evidence\": \"No direct experimental study of PF3D7_1417200 function in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct co-IP or reconstitution confirming PF3D7_1417200 scaffold interactions\",\n        \"No structural model of PF3D7_1417200 or its subunit-binding surfaces\",\n        \"No loss-of-function phenotype from direct perturbation of PF3D7_1417200\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000932\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\"CAF1/CCR4-NOT complex (PfCaf1-CCR4-NOT)\"],\n    \"partners\": [\"DOZI (DDX6 orthologue)\"],\n    \"other_free_text\": [\n      \"PF3D7_1417200 is the canonical NOT1 scaffold paralogue, distinct from the transmission-dedicated paralogue NOT1-G [#0].\",\n      \"In P. yoelii zygotes, DOZI shifts its association from NOT1-G to canonical NOT1 (PF3D7_1417200) across the host-to-vector transmission event [#1, #2].\",\n      \"Complex membership was originally inferred computationally in P. falciparum [#3]; direct biochemical characterization of PF3D7_1417200 is absent from the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1417200","name":null,"product":"CCR4-NOT transcription complex subunit NOT1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1025500","name":null,"product":"NOT family protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1340900","name":null,"product":"CCR4-NOT transcription complex subunit NOT1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NOT1","evaluation":null}