{"gene":"PF3D7_1459000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2024,"finding":"DBP5 (PF3D7_1459000) was identified as a potential interaction partner of PfMORC (PF3D7_1468100) in P. falciparum asexual blood stages, detected by mass spectrometry-based interactomics (co-immunoprecipitation/pulldown with PfMORC as bait).","method":"Co-immunoprecipitation / mass spectrometry (PfMORC pulldown)","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown (PfMORC as bait), marginal statistical significance (-log10 p-value 0.46), single lab, no reciprocal validation or functional follow-up for DBP5 specifically","pmids":["39412522"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"DBP5 (PF3D7_1459000) was identified among the interaction partners of PfSET10 by TurboID proximity labeling coupled with mass spectrometry, placing it within the nuclear PfSET10 chromatin modulation network involved in mRNA processing.","method":"TurboID proximity labeling coupled with mass spectrometry","journal":"mSphere","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labeling (not direct binding), single lab, no reciprocal validation or functional follow-up for DBP5 specifically","pmids":["39445823"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"The P. falciparum homolog of yeast Dbp5 (referred to as PfD66 in the literature, corresponding to PF3D7_1459000) was functionally characterized as an ATP-dependent RNA helicase with MgCl2- and single-stranded DNA-dependent ATPase activity; it unwinds DNA in both 5′→3′ and 3′→5′ directions in the presence of Mg2+, Mn2+, or Zn2+, and preferentially unwinds poly(A) RNA substrates. The Q motif and helicase motifs I, Ia, Ib, and II were demonstrated to be required for helicase and ATPase activities using truncated derivatives.","method":"In vitro helicase and ATPase assays with recombinant protein; truncation mutagenesis","journal":"The Korean journal of parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay with mutagenesis establishing catalytic mechanism, but reported in a review citing original work (primary source not directly in corpus), single lab","pmids":["26537038"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"DNA intercalating agents DAPI, ethidium bromide, netropsin, and nogalamycin were identified as inhibitors of DBP5 (PfD66/PF3D7_1459000) unwinding and ATPase activities in vitro, likely acting by forming compound-DNA complexes that impede enzyme movement. Netropsin inhibited DBP5 with an IC50 of 3.2 µM.","method":"In vitro helicase and ATPase inhibition assays with recombinant protein","journal":"The Korean journal of parasitology","confidence":"Low","confidence_rationale":"Tier 1 / Weak — in vitro assay result, but reported secondhand in a review (primary source not directly in corpus), single lab","pmids":["26537038"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1459000 (DBP5) is a P. falciparum ATP-dependent RNA helicase (homolog of yeast Dbp5/human DDX19) that exhibits poly(A)-preferring RNA unwinding and ATPase activities requiring divalent cations and conserved helicase motifs (Q, I, Ia, Ib, II); it has been detected as a nuclear interaction partner of chromatin-associated proteins PfMORC and PfSET10 by proximity/affinity proteomics, but its precise role in mRNA export or any other cellular process has not yet been experimentally established in Plasmodium."},"narrative":{"mechanistic_narrative":"PF3D7_1459000 (DBP5) is a Plasmodium falciparum ATP-dependent RNA helicase characterized in vitro as possessing MgCl2- and single-stranded-DNA-dependent ATPase activity, unwinding duplex substrates in both 5′→3′ and 3′→5′ directions in the presence of Mg2+, Mn2+, or Zn2+, and preferentially unwinding poly(A) RNA substrates; its Q motif and helicase motifs I, Ia, Ib, and II are required for both helicase and ATPase activities [PMID:26537038]. These catalytic activities are inhibited in vitro by DNA-intercalating agents including netropsin (IC50 3.2 µM), DAPI, ethidium bromide, and nogalamycin, which are thought to impede enzyme translocation [PMID:26537038]. In asexual blood stages, DBP5 has been detected as a nuclear interaction partner of the chromatin-associated proteins PfMORC [PMID:39412522] and PfSET10 [PMID:39445823], placing it in proximity to chromatin modulation and mRNA-processing machinery. Beyond its in vitro enzymatic properties and these proteomic associations, the cellular role of DBP5 — including any function in mRNA export — has not been experimentally established in Plasmodium in the available corpus.","teleology":[{"year":2015,"claim":"Whether the P. falciparum Dbp5 homolog is a catalytically active helicase was unknown; recombinant enzyme assays established it as an ATP-dependent RNA helicase with defined cofactor requirements and mapped the motifs essential for catalysis.","evidence":"In vitro helicase and ATPase assays with recombinant protein and truncation mutagenesis of conserved motifs","pmids":["26537038"],"confidence":"Medium","gaps":["Enzymatic characterization reported secondhand via a review; primary source not directly in corpus","Physiological RNA substrates and in vivo function not addressed","No cellular localization or knockdown/knockout phenotype established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To probe the enzyme's mechanism and druggability, small-molecule inhibitors were tested, showing that DNA-intercalating agents block DBP5 unwinding and ATPase activity.","evidence":"In vitro helicase and ATPase inhibition assays with recombinant protein using DAPI, ethidium bromide, netropsin, and nogalamycin","pmids":["26537038"],"confidence":"Low","gaps":["Result reported secondhand in a review; primary source not directly in corpus","Inhibition is via nonspecific nucleic-acid intercalation, not selective targeting of DBP5","No cellular or parasite-growth validation of inhibition"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"To situate DBP5 in a cellular pathway, interactomics identified it as a nuclear associate of chromatin-linked proteins, linking the helicase to chromatin/mRNA-processing machinery rather than characterizing it in isolation.","evidence":"Co-immunoprecipitation/mass spectrometry with PfMORC as bait, and TurboID proximity labeling with PfSET10, in asexual blood stages","pmids":["39412522","39445823"],"confidence":"Low","gaps":["Single pulldown with marginal significance and proximity labeling without reciprocal validation or direct-binding confirmation for DBP5","Functional consequence of the PfMORC and PfSET10 associations not tested","Does not establish DBP5's role in mRNA export or chromatin regulation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo cellular function of DBP5 in Plasmodium — whether it acts in mRNA export, chromatin-associated processing, or another process — remains unestablished.","evidence":"No functional genetic or in-cell mechanistic study of DBP5 in the corpus","pmids":[],"confidence":"Low","gaps":["No knockdown/knockout or conditional depletion phenotype","No demonstration of an mRNA export role in Plasmodium","Functional significance of PfMORC/PfSET10 associations untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFMORC (PF3D7_1468100)","PFSET10"],"other_free_text":["In vitro ATPase activity is dependent on MgCl2 and single-stranded DNA; unwinding occurs in both 5′→3′ and 3′→5′ directions with Mg2+, Mn2+, or Zn2+ [#2]","Preferentially unwinds poly(A) RNA substrates [#2]","Q motif and helicase motifs I, Ia, Ib, and II required for helicase and ATPase activities [#2]","Unwinding and ATPase activities inhibited in vitro by DNA-intercalating agents; netropsin IC50 = 3.2 µM [#3]","Referred to in earlier literature as PfD66 [#2]"]}},"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":"39445823","id":"","title":"The Plasmodium falciparum histone methyltransferase SET10 participates in a chromatin modulation network crucial for intraerythrocytic development.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/39445823","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DBP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39412522","id":"","title":"A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/39412522","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DBP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36582189","id":"","title":"Combining IP3 affinity chromatography and bioinformatics reveals a novel protein-IP3 binding site on Plasmodium falciparum MDR1 transporter.","date":"2022","source":"Current research in microbial sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36582189","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DBP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27809838","id":"","title":"Characterization of Plasmodium falciparum ATP-dependent DNA helicase RuvB3.","date":"2016","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/27809838","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DBP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26537038","id":"","title":"DEAD/DExH-Box RNA Helicases in Selected Human Parasites.","date":"2015","source":"The Korean journal of parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/26537038","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DBP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9475,"output_tokens":1268,"usd":0.023723,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6124,"output_tokens":2225,"usd":0.043123,"stage2_stop_reason":"end_turn"},"total_usd":0.066846,"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\": \"DBP5 (PF3D7_1459000) was identified as a potential interaction partner of PfMORC (PF3D7_1468100) in P. falciparum asexual blood stages, detected by mass spectrometry-based interactomics (co-immunoprecipitation/pulldown with PfMORC as bait).\",\n      \"method\": \"Co-immunoprecipitation / mass spectrometry (PfMORC pulldown)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown (PfMORC as bait), marginal statistical significance (-log10 p-value 0.46), single lab, no reciprocal validation or functional follow-up for DBP5 specifically\",\n      \"pmids\": [\"39412522\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DBP5 (PF3D7_1459000) was identified among the interaction partners of PfSET10 by TurboID proximity labeling coupled with mass spectrometry, placing it within the nuclear PfSET10 chromatin modulation network involved in mRNA processing.\",\n      \"method\": \"TurboID proximity labeling coupled with mass spectrometry\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labeling (not direct binding), single lab, no reciprocal validation or functional follow-up for DBP5 specifically\",\n      \"pmids\": [\"39445823\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The P. falciparum homolog of yeast Dbp5 (referred to as PfD66 in the literature, corresponding to PF3D7_1459000) was functionally characterized as an ATP-dependent RNA helicase with MgCl2- and single-stranded DNA-dependent ATPase activity; it unwinds DNA in both 5′→3′ and 3′→5′ directions in the presence of Mg2+, Mn2+, or Zn2+, and preferentially unwinds poly(A) RNA substrates. The Q motif and helicase motifs I, Ia, Ib, and II were demonstrated to be required for helicase and ATPase activities using truncated derivatives.\",\n      \"method\": \"In vitro helicase and ATPase assays with recombinant protein; truncation mutagenesis\",\n      \"journal\": \"The Korean journal of parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay with mutagenesis establishing catalytic mechanism, but reported in a review citing original work (primary source not directly in corpus), single lab\",\n      \"pmids\": [\"26537038\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DNA intercalating agents DAPI, ethidium bromide, netropsin, and nogalamycin were identified as inhibitors of DBP5 (PfD66/PF3D7_1459000) unwinding and ATPase activities in vitro, likely acting by forming compound-DNA complexes that impede enzyme movement. Netropsin inhibited DBP5 with an IC50 of 3.2 µM.\",\n      \"method\": \"In vitro helicase and ATPase inhibition assays with recombinant protein\",\n      \"journal\": \"The Korean journal of parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro assay result, but reported secondhand in a review (primary source not directly in corpus), single lab\",\n      \"pmids\": [\"26537038\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1459000 (DBP5) is a P. falciparum ATP-dependent RNA helicase (homolog of yeast Dbp5/human DDX19) that exhibits poly(A)-preferring RNA unwinding and ATPase activities requiring divalent cations and conserved helicase motifs (Q, I, Ia, Ib, II); it has been detected as a nuclear interaction partner of chromatin-associated proteins PfMORC and PfSET10 by proximity/affinity proteomics, but its precise role in mRNA export or any other cellular process has not yet been experimentally established in Plasmodium.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1459000 (DBP5) is a Plasmodium falciparum ATP-dependent RNA helicase characterized in vitro as possessing MgCl2- and single-stranded-DNA-dependent ATPase activity, unwinding duplex substrates in both 5′→3′ and 3′→5′ directions in the presence of Mg2+, Mn2+, or Zn2+, and preferentially unwinding poly(A) RNA substrates; its Q motif and helicase motifs I, Ia, Ib, and II are required for both helicase and ATPase activities [#2]. These catalytic activities are inhibited in vitro by DNA-intercalating agents including netropsin (IC50 3.2 µM), DAPI, ethidium bromide, and nogalamycin, which are thought to impede enzyme translocation [#3]. In asexual blood stages, DBP5 has been detected as a nuclear interaction partner of the chromatin-associated proteins PfMORC [#0] and PfSET10 [#1], placing it in proximity to chromatin modulation and mRNA-processing machinery. Beyond its in vitro enzymatic properties and these proteomic associations, the cellular role of DBP5 — including any function in mRNA export — has not been experimentally established in Plasmodium in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether the P. falciparum Dbp5 homolog is a catalytically active helicase was unknown; recombinant enzyme assays established it as an ATP-dependent RNA helicase with defined cofactor requirements and mapped the motifs essential for catalysis.\",\n      \"evidence\": \"In vitro helicase and ATPase assays with recombinant protein and truncation mutagenesis of conserved motifs\",\n      \"pmids\": [\"26537038\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Enzymatic characterization reported secondhand via a review; primary source not directly in corpus\",\n        \"Physiological RNA substrates and in vivo function not addressed\",\n        \"No cellular localization or knockdown/knockout phenotype established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To probe the enzyme's mechanism and druggability, small-molecule inhibitors were tested, showing that DNA-intercalating agents block DBP5 unwinding and ATPase activity.\",\n      \"evidence\": \"In vitro helicase and ATPase inhibition assays with recombinant protein using DAPI, ethidium bromide, netropsin, and nogalamycin\",\n      \"pmids\": [\"26537038\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Result reported secondhand in a review; primary source not directly in corpus\",\n        \"Inhibition is via nonspecific nucleic-acid intercalation, not selective targeting of DBP5\",\n        \"No cellular or parasite-growth validation of inhibition\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To situate DBP5 in a cellular pathway, interactomics identified it as a nuclear associate of chromatin-linked proteins, linking the helicase to chromatin/mRNA-processing machinery rather than characterizing it in isolation.\",\n      \"evidence\": \"Co-immunoprecipitation/mass spectrometry with PfMORC as bait, and TurboID proximity labeling with PfSET10, in asexual blood stages\",\n      \"pmids\": [\"39412522\", \"39445823\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single pulldown with marginal significance and proximity labeling without reciprocal validation or direct-binding confirmation for DBP5\",\n        \"Functional consequence of the PfMORC and PfSET10 associations not tested\",\n        \"Does not establish DBP5's role in mRNA export or chromatin regulation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo cellular function of DBP5 in Plasmodium — whether it acts in mRNA export, chromatin-associated processing, or another process — remains unestablished.\",\n      \"evidence\": \"No functional genetic or in-cell mechanistic study of DBP5 in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockdown/knockout or conditional depletion phenotype\",\n        \"No demonstration of an mRNA export role in Plasmodium\",\n        \"Functional significance of PfMORC/PfSET10 associations untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004004\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0003724\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0008026\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006397\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfMORC (PF3D7_1468100)\",\n      \"PfSET10\"\n    ],\n    \"other_free_text\": [\n      \"In vitro ATPase activity is dependent on MgCl2 and single-stranded DNA; unwinding occurs in both 5′→3′ and 3′→5′ directions with Mg2+, Mn2+, or Zn2+ [#2]\",\n      \"Preferentially unwinds poly(A) RNA substrates [#2]\",\n      \"Q motif and helicase motifs I, Ia, Ib, and II required for helicase and ATPase activities [#2]\",\n      \"Unwinding and ATPase activities inhibited in vitro by DNA-intercalating agents; netropsin IC50 = 3.2 µM [#3]\",\n      \"Referred to in earlier literature as PfD66 [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1459000","name":null,"product":"ATP-dependent RNA helicase DBP5","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1322700","name":null,"product":"ATP-dependent RNA helicase DBP5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1222800","name":null,"product":"ATP-dependent RNA helicase DBP5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DBP5","evaluation":null}