{"gene":"PF3D7_1445900","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2021,"finding":"PfDDX17 (PF3D7_1445900) exhibits DNA- and RNA-dependent ATPase activity in vitro, but only RNA helicase activity (not DNA helicase activity), and preferentially uses ATP as the nucleotide cofactor for its RNA unwinding function.","method":"In vitro biochemical assays using purified recombinant protein (ATPase assay, time-dependent helicase activity assay with RNA and DNA substrates)","journal":"Biochemistry and biophysics reports","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic reconstitution with recombinant protein, single lab, single study","pmids":["33981864"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PfDDX17 (PF3D7_1445900) is predominantly expressed at the trophozoite stage of intraerythrocytic development, as determined by qRT-PCR.","method":"qRT-PCR across intraerythrocytic stages","journal":"Biochemistry and biophysics reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (qRT-PCR), expression measurement without direct functional manipulation","pmids":["33981864"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PfDDX17 (PF3D7_1445900) localizes predominantly to the cytoplasm and to the infected red blood cell (iRBC) membrane, mainly in the trophozoite stage, as shown by immunofluorescence.","method":"Immunofluorescence microscopy of trophozoite-stage parasites","journal":"Biochemistry and biophysics reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (immunofluorescence), no functional validation of localization consequence","pmids":["33981864"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"dsRNA-mediated knockdown of PfDDX17 (PF3D7_1445900) impairs cell cycle progression in P. falciparum, indicating a functional role in parasite cell cycle.","method":"dsRNA knockdown with cell cycle progression phenotype readout","journal":"Biochemistry and biophysics reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single knockdown approach, no molecular epistasis or pathway placement established","pmids":["33981864"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"DDX17 (PF3D7_1445900) was identified as a proximity-labelled interactor of the male-determining protein Md1 in P. falciparum gametocytes, placing it in the vicinity of cytoplasmic RNP granule-like structures associated with translational repression.","method":"TurboID proximity labelling followed by mass spectrometry (Md1-TurboID strain vs. untagged WT control)","journal":"Nature","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labelling (not direct Co-IP), single study, no direct functional characterization of DDX17 in this context","pmids":["36477538"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1445900 (DDX17) is an ATP-dependent RNA helicase in P. falciparum that displays DNA- and RNA-stimulated ATPase activity but exclusively RNA unwinding activity in vitro, is most highly expressed and localizes to the cytoplasm and iRBC membrane at the trophozoite stage, is required for normal cell cycle progression (dsRNA knockdown), and associates by proximity labelling with cytoplasmic RNP granule components near the male-fate determinant Md1 during gametocytogenesis."},"narrative":{"mechanistic_narrative":"PF3D7_1445900 (DDX17) is an ATP-dependent RNA helicase of Plasmodium falciparum implicated in RNA metabolism during intraerythrocytic development [PMID:33981864]. Biochemical reconstitution of the purified recombinant protein shows DNA- and RNA-stimulated ATPase activity but strictly RNA-directed unwinding, with ATP as the preferred cofactor, defining it as an RNA-specific helicase [PMID:33981864]. The protein is most highly expressed at the trophozoite stage, where it localizes to the cytoplasm and the infected red blood cell membrane, and dsRNA-mediated knockdown impairs cell cycle progression, indicating a functional requirement for normal intraerythrocytic proliferation [PMID:33981864]. Independently, DDX17 was captured by proximity labelling near the male-fate determinant Md1 within cytoplasmic RNP granule-like structures during gametocytogenesis, placing it adjacent to the translational-repression machinery [PMID:36477538]. Beyond these observations, the direct RNA substrates, molecular partners, and the mechanism linking its helicase activity to cell cycle progression have not been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Establishing whether PF3D7_1445900 is a genuine helicase and on which nucleic-acid substrate it acts was needed to assign a molecular activity; in vitro reconstitution showed it is an ATP-dependent, RNA-specific unwinding enzyme.","evidence":"ATPase and time-dependent helicase assays with purified recombinant protein on RNA and DNA substrates","pmids":["33981864"],"confidence":"Medium","gaps":["No physiological RNA substrate identified","No structural model of the helicase core","In vitro activity not linked to a cellular process"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Defining when and where the enzyme acts during the blood stage was needed to place its activity in a developmental context; expression and localization data pointed to a trophozoite-stage cytoplasmic and iRBC-membrane role.","evidence":"qRT-PCR across intraerythrocytic stages and immunofluorescence microscopy of trophozoites","pmids":["33981864"],"confidence":"Low","gaps":["Single method for each readout with no orthogonal confirmation","Functional consequence of iRBC-membrane localization unknown","No quantitative or dynamic localization across the full cycle"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether the helicase is functionally required in the parasite was addressed by depletion; dsRNA knockdown impaired cell cycle progression, establishing a physiological role in intraerythrocytic proliferation.","evidence":"dsRNA-mediated knockdown with cell cycle progression phenotype readout","pmids":["33981864"],"confidence":"Low","gaps":["No molecular epistasis or pathway placement","Downstream RNA targets mediating the phenotype unknown","Knockdown specificity and degree not molecularly validated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Whether PF3D7_1445900 participates in sexual-stage RNA regulation was addressed by mapping the neighborhood of the male-fate determinant Md1; proximity labelling placed DDX17 near cytoplasmic RNP granules associated with translational repression.","evidence":"TurboID proximity labelling with mass spectrometry (Md1-TurboID vs untagged WT) in gametocytes","pmids":["36477538"],"confidence":"Low","gaps":["Proximity labelling does not establish direct interaction","No functional characterization of DDX17 in gametocytes","Reciprocal validation and role within the RNP granule not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct RNA substrates of DDX17, its molecular partners, and the mechanistic link between its unwinding activity and both cell cycle progression and RNP-granule-associated translational repression remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No physiological RNA targets identified","No validated direct protein partners","Mechanism connecting helicase activity to cell cycle and gametocyte RNP granules unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MD1 (PROXIMITY-LABELLED NEIGHBOR, NOT DIRECT INTERACTION) [#4]"],"other_free_text":["Peak expression at the trophozoite stage of intraerythrocytic development [#1]","Localizes to cytoplasm and the infected red blood cell membrane at the trophozoite stage [#2]","Associated with cytoplasmic RNP granule-like structures near Md1 during gametocytogenesis [#4]"]}},"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":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33981864","id":"","title":"Plasmodium falciparum DDX17 is an RNA helicase crucial for parasite development.","date":"2021","source":"Biochemistry and biophysics reports","url":"https://pubmed.ncbi.nlm.nih.gov/33981864","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DDX17"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36477538","id":"","title":"A transcriptional switch controls sex determination in Plasmodium falciparum.","date":"2022","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/36477538","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DDX17"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36548245","id":"","title":"Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation.","date":"2022","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/36548245","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DDX17"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6264,"output_tokens":1230,"usd":0.018621,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6111,"output_tokens":2178,"usd":0.042502,"stage2_stop_reason":"end_turn"},"total_usd":0.061123,"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\": 2021,\n      \"finding\": \"PfDDX17 (PF3D7_1445900) exhibits DNA- and RNA-dependent ATPase activity in vitro, but only RNA helicase activity (not DNA helicase activity), and preferentially uses ATP as the nucleotide cofactor for its RNA unwinding function.\",\n      \"method\": \"In vitro biochemical assays using purified recombinant protein (ATPase assay, time-dependent helicase activity assay with RNA and DNA substrates)\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic reconstitution with recombinant protein, single lab, single study\",\n      \"pmids\": [\"33981864\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PfDDX17 (PF3D7_1445900) is predominantly expressed at the trophozoite stage of intraerythrocytic development, as determined by qRT-PCR.\",\n      \"method\": \"qRT-PCR across intraerythrocytic stages\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (qRT-PCR), expression measurement without direct functional manipulation\",\n      \"pmids\": [\"33981864\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PfDDX17 (PF3D7_1445900) localizes predominantly to the cytoplasm and to the infected red blood cell (iRBC) membrane, mainly in the trophozoite stage, as shown by immunofluorescence.\",\n      \"method\": \"Immunofluorescence microscopy of trophozoite-stage parasites\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (immunofluorescence), no functional validation of localization consequence\",\n      \"pmids\": [\"33981864\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"dsRNA-mediated knockdown of PfDDX17 (PF3D7_1445900) impairs cell cycle progression in P. falciparum, indicating a functional role in parasite cell cycle.\",\n      \"method\": \"dsRNA knockdown with cell cycle progression phenotype readout\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single knockdown approach, no molecular epistasis or pathway placement established\",\n      \"pmids\": [\"33981864\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX17 (PF3D7_1445900) was identified as a proximity-labelled interactor of the male-determining protein Md1 in P. falciparum gametocytes, placing it in the vicinity of cytoplasmic RNP granule-like structures associated with translational repression.\",\n      \"method\": \"TurboID proximity labelling followed by mass spectrometry (Md1-TurboID strain vs. untagged WT control)\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labelling (not direct Co-IP), single study, no direct functional characterization of DDX17 in this context\",\n      \"pmids\": [\"36477538\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1445900 (DDX17) is an ATP-dependent RNA helicase in P. falciparum that displays DNA- and RNA-stimulated ATPase activity but exclusively RNA unwinding activity in vitro, is most highly expressed and localizes to the cytoplasm and iRBC membrane at the trophozoite stage, is required for normal cell cycle progression (dsRNA knockdown), and associates by proximity labelling with cytoplasmic RNP granule components near the male-fate determinant Md1 during gametocytogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1445900 (DDX17) is an ATP-dependent RNA helicase of Plasmodium falciparum implicated in RNA metabolism during intraerythrocytic development [#0]. Biochemical reconstitution of the purified recombinant protein shows DNA- and RNA-stimulated ATPase activity but strictly RNA-directed unwinding, with ATP as the preferred cofactor, defining it as an RNA-specific helicase [#0]. The protein is most highly expressed at the trophozoite stage, where it localizes to the cytoplasm and the infected red blood cell membrane, and dsRNA-mediated knockdown impairs cell cycle progression, indicating a functional requirement for normal intraerythrocytic proliferation [#1, #2, #3]. Independently, DDX17 was captured by proximity labelling near the male-fate determinant Md1 within cytoplasmic RNP granule-like structures during gametocytogenesis, placing it adjacent to the translational-repression machinery [#4]. Beyond these observations, the direct RNA substrates, molecular partners, and the mechanism linking its helicase activity to cell cycle progression have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Establishing whether PF3D7_1445900 is a genuine helicase and on which nucleic-acid substrate it acts was needed to assign a molecular activity; in vitro reconstitution showed it is an ATP-dependent, RNA-specific unwinding enzyme.\",\n      \"evidence\": \"ATPase and time-dependent helicase assays with purified recombinant protein on RNA and DNA substrates\",\n      \"pmids\": [\"33981864\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No physiological RNA substrate identified\", \"No structural model of the helicase core\", \"In vitro activity not linked to a cellular process\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defining when and where the enzyme acts during the blood stage was needed to place its activity in a developmental context; expression and localization data pointed to a trophozoite-stage cytoplasmic and iRBC-membrane role.\",\n      \"evidence\": \"qRT-PCR across intraerythrocytic stages and immunofluorescence microscopy of trophozoites\",\n      \"pmids\": [\"33981864\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method for each readout with no orthogonal confirmation\", \"Functional consequence of iRBC-membrane localization unknown\", \"No quantitative or dynamic localization across the full cycle\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether the helicase is functionally required in the parasite was addressed by depletion; dsRNA knockdown impaired cell cycle progression, establishing a physiological role in intraerythrocytic proliferation.\",\n      \"evidence\": \"dsRNA-mediated knockdown with cell cycle progression phenotype readout\",\n      \"pmids\": [\"33981864\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No molecular epistasis or pathway placement\", \"Downstream RNA targets mediating the phenotype unknown\", \"Knockdown specificity and degree not molecularly validated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether PF3D7_1445900 participates in sexual-stage RNA regulation was addressed by mapping the neighborhood of the male-fate determinant Md1; proximity labelling placed DDX17 near cytoplasmic RNP granules associated with translational repression.\",\n      \"evidence\": \"TurboID proximity labelling with mass spectrometry (Md1-TurboID vs untagged WT) in gametocytes\",\n      \"pmids\": [\"36477538\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Proximity labelling does not establish direct interaction\", \"No functional characterization of DDX17 in gametocytes\", \"Reciprocal validation and role within the RNP granule not shown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct RNA substrates of DDX17, its molecular partners, and the mechanistic link between its unwinding activity and both cell cycle progression and RNP-granule-associated translational repression remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No physiological RNA targets identified\", \"No validated direct protein partners\", \"Mechanism connecting helicase activity to cell cycle and gametocyte RNP granules unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004004\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003724\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0036464\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0022402\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Md1 (proximity-labelled neighbor, not direct interaction) [#4]\"],\n    \"other_free_text\": [\n      \"Peak expression at the trophozoite stage of intraerythrocytic development [#1]\",\n      \"Localizes to cytoplasm and the infected red blood cell membrane at the trophozoite stage [#2]\",\n      \"Associated with cytoplasmic RNP granule-like structures near Md1 during gametocytogenesis [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1445900","name":null,"product":"ATP-dependent RNA helicase DDX17","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1309700","name":null,"product":"ATP-dependent RNA helicase DDX17, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1236300","name":null,"product":"ATP-dependent RNA helicase DDX17, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DDX17","evaluation":null}