{"gene":"PF3D7_1426200","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2009,"finding":"PfPRMT1 (PF3D7_1426200) has authentic type I PRMT enzymatic activity, catalyzing formation of monomethylarginines and asymmetric dimethylarginines on substrate arginines.","method":"In vitro methyltransferase assay with recombinant PfPRMT1, MS-based identification of methylation sites","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic reconstitution with recombinant protein, substrate identification by MS, kinetic analysis, multiple orthogonal methods in a single focused study","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Recombinant PfPRMT1 methylates histones H4 and H2A, as well as RNA metabolism-related substrates including fibrillarin, poly(A)-binding protein II, ribosomal protein S2, and a putative splicing factor; in histone H4, only Arg3 is methylated, a mark associated with transcription activation.","method":"In vitro methyltransferase assay with recombinant PfPRMT1 and synthetic peptides; MS-based identification of target arginines","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with defined substrates, MS confirmation of specific methylation sites, enzyme kinetics measured","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"The distinctive N-terminal extension (~50 amino acids longer than mammalian PRMT1) of PfPRMT1 is essential for enzyme activity.","method":"Truncation/deletion analysis of recombinant PfPRMT1 with in vitro methyltransferase assay","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro functional assay with domain deletion, single lab, single study","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"GFP-tagged PfPRMT1 localizes to both the cytoplasm and nucleus of P. falciparum, with the majority of the protein in the cytoplasm; untagged PfPRMT1 shows the same dual distribution.","method":"Live imaging of GFP-tagged PfPRMT1; subcellular fractionation/western blot of untagged PfPRMT1","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by GFP imaging and confirmed with untagged protein, two orthogonal approaches, single lab","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Dynamic asymmetric dimethylation of histone H4-Arg3 was detected during parasite development by western blotting, consistent with a role for PfPRMT1 in chromatin-mediated gene regulation.","method":"Western blotting with dimethyl-H4-Arg3-specific antibody across parasite developmental stages","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — western blot evidence of dynamic H4R3me2a across stages, consistent with PfPRMT1 activity but indirect; single lab","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"PfPRMT1 kinetic parameters on an H4 peptide substrate and S-adenosylmethionine are similar to mammalian PRMT1, but PfPRMT1 exhibits much higher substrate-turnover rates.","method":"Enzyme kinetics (in vitro methyltransferase assay with defined substrates and co-factor)","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — rigorous in vitro kinetic characterization with defined substrates, single focused study","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Several small-molecule inhibitors inhibit recombinant PfPRMT1 activity in vitro with IC50 values in the sub-micromolar range, and most also inhibit parasite growth.","method":"In vitro PRMT inhibition assay with recombinant PfPRMT1; parasite growth inhibition assay","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro enzymatic inhibition corroborated by parasite growth assay, single lab","pmids":["19344311"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"PfPRMT1 was proposed as the most likely cellular target of the PRMT inhibitor TC-E 5003, which shows antiplasmodial activity across multiple parasite life-cycle stages, with a defined structure-activity relationship demonstrated by analog expansion.","method":"Chemical repositioning screen; structure-activity relationship analysis with TC-E 5003 analogs; multistage parasite growth inhibition assays","journal":"ACS infectious diseases","confidence":"Low","confidence_rationale":"Tier 3 / Weak — target assignment is proposed (not directly validated by genetic or biochemical target engagement assay); single lab, indirect pharmacological evidence","pmids":["41914674"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfPRMT1 (PF3D7_1426200) is a type I protein arginine N-methyltransferase that catalyzes monomethylation and asymmetric dimethylation of arginine residues; its distinctive ~50-aa N-terminal extension is essential for activity, it methylates histone H4 specifically at Arg3 (a transcription-activating mark whose levels change dynamically during parasite development) as well as RNA metabolism proteins (fibrillarin, PABP II, ribosomal protein S2, a splicing factor), and it localizes predominantly to the cytoplasm with a nuclear fraction, consistent with substrates in both compartments."},"narrative":{"mechanistic_narrative":"PfPRMT1 (PF3D7_1426200) is a type I protein arginine N-methyltransferase of Plasmodium falciparum that catalyzes formation of monomethylarginine and asymmetric dimethylarginine on substrate arginines, with kinetics comparable to the mammalian enzyme but markedly higher substrate turnover [PMID:19344311]. It methylates histones H4 and H2A—modifying histone H4 exclusively at Arg3, a transcription-activating mark that varies dynamically across parasite developmental stages—as well as RNA-metabolism proteins including fibrillarin, poly(A)-binding protein II, ribosomal protein S2, and a putative splicing factor, consistent with a dual role in chromatin-mediated gene regulation and RNA metabolism [PMID:19344311]. Consistent with substrates in both compartments, PfPRMT1 localizes predominantly to the cytoplasm with a nuclear fraction [PMID:19344311], and its activity depends on a distinctive N-terminal extension roughly 50 residues longer than the mammalian ortholog [PMID:19344311]. Small-molecule PRMT inhibitors block recombinant PfPRMT1 with sub-micromolar potency and impair parasite growth, marking the enzyme as an antiplasmodial target [PMID:19344311].","teleology":[{"year":2009,"claim":"Establishing whether the Plasmodium enzyme was a bona fide type I PRMT was the first question, and in vitro reconstitution showed it generates both monomethyl- and asymmetric dimethylarginine, defining its catalytic type.","evidence":"In vitro methyltransferase assay with recombinant PfPRMT1 and MS identification of methylation products","pmids":["19344311"],"confidence":"High","gaps":["Does not identify which substrates are methylated in vivo","No structural basis for type I product specificity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"To connect the enzyme to biological pathways, its substrate repertoire was mapped, revealing histones (H4 methylated specifically at Arg3) and multiple RNA-metabolism proteins, placing PfPRMT1 at the interface of chromatin regulation and RNA processing.","evidence":"In vitro methyltransferase assays with recombinant enzyme, synthetic peptides, and defined protein substrates; MS site mapping","pmids":["19344311"],"confidence":"High","gaps":["In vitro substrate methylation does not prove these are physiological targets in the parasite","Functional consequence of each substrate methylation not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Whether the parasite-specific N-terminal extension mattered was tested by truncation, showing it is required for catalysis and marking a divergent feature of the parasite enzyme.","evidence":"Domain deletion/truncation of recombinant PfPRMT1 with in vitro methyltransferase assay","pmids":["19344311"],"confidence":"Medium","gaps":["Mechanism by which the extension supports activity unknown","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"To place the enzyme in cellular space relative to its dual substrate classes, localization was determined, showing predominantly cytoplasmic distribution with a nuclear fraction consistent with both histone and RNA-protein substrates.","evidence":"Live GFP imaging and subcellular fractionation/western blot of untagged protein","pmids":["19344311"],"confidence":"Medium","gaps":["Does not resolve stage-dependent shifts in localization","Nuclear vs cytoplasmic substrate engagement not directly demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Whether the H4R3 mark is used dynamically in vivo was addressed by profiling H4R3me2a across development, linking the enzyme's activity to developmentally regulated gene expression.","evidence":"Western blotting with dimethyl-H4-Arg3-specific antibody across parasite stages","pmids":["19344311"],"confidence":"Medium","gaps":["Antibody signal does not directly attribute the mark to PfPRMT1","No genetic knockout to confirm causality"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"To assess druggability, PRMT inhibitors were tested, showing sub-micromolar in vitro inhibition of PfPRMT1 that mostly correlated with parasite growth suppression, nominating the enzyme as an antimalarial target.","evidence":"In vitro PRMT inhibition assay with recombinant enzyme plus parasite growth inhibition assay","pmids":["19344311"],"confidence":"Medium","gaps":["Growth inhibition not proven to act through PfPRMT1 in cells","No target engagement assay"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Extending the druggability question, a chemical repositioning effort nominated PfPRMT1 as the likely cellular target of the multistage-active inhibitor TC-E 5003, supported by a structure-activity relationship.","evidence":"Chemical repositioning screen, SAR analysis of TC-E 5003 analogs, multistage growth inhibition assays","pmids":["41914674"],"confidence":"Low","gaps":["Target assignment is proposed, not validated by genetic or biochemical target engagement","Single lab, indirect pharmacological evidence"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo consequences of PfPRMT1 activity remain open: no genetic loss-of-function study establishes which substrates are physiologically methylated or whether PfPRMT1 is essential for parasite viability or stage progression.","evidence":"","pmids":[],"confidence":"Low","gaps":["No knockout/knockdown phenotype reported","Physiological substrates not confirmed in vivo","No structural model of the parasite enzyme"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["HISTONE H4 (SUBSTRATE, METHYLATED AT ARG3)","HISTONE H2A (SUBSTRATE)","FIBRILLARIN (SUBSTRATE)","POLY(A)-BINDING PROTEIN II (SUBSTRATE)","RIBOSOMAL PROTEIN S2 (SUBSTRATE)","PUTATIVE SPLICING FACTOR (SUBSTRATE)"],"other_free_text":["Type I PRMT producing monomethyl- and asymmetric dimethylarginine [#0]","Kinetics similar to mammalian PRMT1 but higher substrate turnover [#5]","Parasite-specific ~50-aa N-terminal extension required for activity [#2]","Inhibited by small-molecule PRMT inhibitors with sub-micromolar IC50; correlated antiplasmodial activity [#6]","Proposed cellular target of TC-E 5003 (Low confidence, not validated) [#7]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19344311","id":"PMC_19344311","title":"Characterization of PRMT1 from Plasmodium falciparum.","date":"2009","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/19344311","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PRMT1","PfPRMT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41914674","id":"PMC_41914674","title":"Protein Arginine Methyltransferase Inhibitors Target Multiple Stages of Plasmodium falciparum Parasites In Vitro.","date":"2026","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/41914674","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPRMT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3920,"output_tokens":1977,"usd":0.020708,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7169,"output_tokens":3072,"usd":0.056322,"stage2_stop_reason":"end_turn"},"total_usd":0.07703,"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\": 2009,\n      \"finding\": \"PfPRMT1 (PF3D7_1426200) has authentic type I PRMT enzymatic activity, catalyzing formation of monomethylarginines and asymmetric dimethylarginines on substrate arginines.\",\n      \"method\": \"In vitro methyltransferase assay with recombinant PfPRMT1, MS-based identification of methylation sites\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic reconstitution with recombinant protein, substrate identification by MS, kinetic analysis, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Recombinant PfPRMT1 methylates histones H4 and H2A, as well as RNA metabolism-related substrates including fibrillarin, poly(A)-binding protein II, ribosomal protein S2, and a putative splicing factor; in histone H4, only Arg3 is methylated, a mark associated with transcription activation.\",\n      \"method\": \"In vitro methyltransferase assay with recombinant PfPRMT1 and synthetic peptides; MS-based identification of target arginines\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with defined substrates, MS confirmation of specific methylation sites, enzyme kinetics measured\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The distinctive N-terminal extension (~50 amino acids longer than mammalian PRMT1) of PfPRMT1 is essential for enzyme activity.\",\n      \"method\": \"Truncation/deletion analysis of recombinant PfPRMT1 with in vitro methyltransferase assay\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro functional assay with domain deletion, single lab, single study\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"GFP-tagged PfPRMT1 localizes to both the cytoplasm and nucleus of P. falciparum, with the majority of the protein in the cytoplasm; untagged PfPRMT1 shows the same dual distribution.\",\n      \"method\": \"Live imaging of GFP-tagged PfPRMT1; subcellular fractionation/western blot of untagged PfPRMT1\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by GFP imaging and confirmed with untagged protein, two orthogonal approaches, single lab\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Dynamic asymmetric dimethylation of histone H4-Arg3 was detected during parasite development by western blotting, consistent with a role for PfPRMT1 in chromatin-mediated gene regulation.\",\n      \"method\": \"Western blotting with dimethyl-H4-Arg3-specific antibody across parasite developmental stages\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — western blot evidence of dynamic H4R3me2a across stages, consistent with PfPRMT1 activity but indirect; single lab\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PfPRMT1 kinetic parameters on an H4 peptide substrate and S-adenosylmethionine are similar to mammalian PRMT1, but PfPRMT1 exhibits much higher substrate-turnover rates.\",\n      \"method\": \"Enzyme kinetics (in vitro methyltransferase assay with defined substrates and co-factor)\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — rigorous in vitro kinetic characterization with defined substrates, single focused study\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Several small-molecule inhibitors inhibit recombinant PfPRMT1 activity in vitro with IC50 values in the sub-micromolar range, and most also inhibit parasite growth.\",\n      \"method\": \"In vitro PRMT inhibition assay with recombinant PfPRMT1; parasite growth inhibition assay\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro enzymatic inhibition corroborated by parasite growth assay, single lab\",\n      \"pmids\": [\"19344311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"PfPRMT1 was proposed as the most likely cellular target of the PRMT inhibitor TC-E 5003, which shows antiplasmodial activity across multiple parasite life-cycle stages, with a defined structure-activity relationship demonstrated by analog expansion.\",\n      \"method\": \"Chemical repositioning screen; structure-activity relationship analysis with TC-E 5003 analogs; multistage parasite growth inhibition assays\",\n      \"journal\": \"ACS infectious diseases\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — target assignment is proposed (not directly validated by genetic or biochemical target engagement assay); single lab, indirect pharmacological evidence\",\n      \"pmids\": [\"41914674\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfPRMT1 (PF3D7_1426200) is a type I protein arginine N-methyltransferase that catalyzes monomethylation and asymmetric dimethylation of arginine residues; its distinctive ~50-aa N-terminal extension is essential for activity, it methylates histone H4 specifically at Arg3 (a transcription-activating mark whose levels change dynamically during parasite development) as well as RNA metabolism proteins (fibrillarin, PABP II, ribosomal protein S2, a splicing factor), and it localizes predominantly to the cytoplasm with a nuclear fraction, consistent with substrates in both compartments.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PfPRMT1 (PF3D7_1426200) is a type I protein arginine N-methyltransferase of Plasmodium falciparum that catalyzes formation of monomethylarginine and asymmetric dimethylarginine on substrate arginines, with kinetics comparable to the mammalian enzyme but markedly higher substrate turnover [#0, #5]. It methylates histones H4 and H2A—modifying histone H4 exclusively at Arg3, a transcription-activating mark that varies dynamically across parasite developmental stages—as well as RNA-metabolism proteins including fibrillarin, poly(A)-binding protein II, ribosomal protein S2, and a putative splicing factor, consistent with a dual role in chromatin-mediated gene regulation and RNA metabolism [#1, #4]. Consistent with substrates in both compartments, PfPRMT1 localizes predominantly to the cytoplasm with a nuclear fraction [#3], and its activity depends on a distinctive N-terminal extension roughly 50 residues longer than the mammalian ortholog [#2]. Small-molecule PRMT inhibitors block recombinant PfPRMT1 with sub-micromolar potency and impair parasite growth, marking the enzyme as an antiplasmodial target [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing whether the Plasmodium enzyme was a bona fide type I PRMT was the first question, and in vitro reconstitution showed it generates both monomethyl- and asymmetric dimethylarginine, defining its catalytic type.\",\n      \"evidence\": \"In vitro methyltransferase assay with recombinant PfPRMT1 and MS identification of methylation products\",\n      \"pmids\": [\"19344311\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not identify which substrates are methylated in vivo\", \"No structural basis for type I product specificity\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"To connect the enzyme to biological pathways, its substrate repertoire was mapped, revealing histones (H4 methylated specifically at Arg3) and multiple RNA-metabolism proteins, placing PfPRMT1 at the interface of chromatin regulation and RNA processing.\",\n      \"evidence\": \"In vitro methyltransferase assays with recombinant enzyme, synthetic peptides, and defined protein substrates; MS site mapping\",\n      \"pmids\": [\"19344311\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vitro substrate methylation does not prove these are physiological targets in the parasite\", \"Functional consequence of each substrate methylation not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether the parasite-specific N-terminal extension mattered was tested by truncation, showing it is required for catalysis and marking a divergent feature of the parasite enzyme.\",\n      \"evidence\": \"Domain deletion/truncation of recombinant PfPRMT1 with in vitro methyltransferase assay\",\n      \"pmids\": [\"19344311\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which the extension supports activity unknown\", \"Single lab, single study\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"To place the enzyme in cellular space relative to its dual substrate classes, localization was determined, showing predominantly cytoplasmic distribution with a nuclear fraction consistent with both histone and RNA-protein substrates.\",\n      \"evidence\": \"Live GFP imaging and subcellular fractionation/western blot of untagged protein\",\n      \"pmids\": [\"19344311\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not resolve stage-dependent shifts in localization\", \"Nuclear vs cytoplasmic substrate engagement not directly demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether the H4R3 mark is used dynamically in vivo was addressed by profiling H4R3me2a across development, linking the enzyme's activity to developmentally regulated gene expression.\",\n      \"evidence\": \"Western blotting with dimethyl-H4-Arg3-specific antibody across parasite stages\",\n      \"pmids\": [\"19344311\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Antibody signal does not directly attribute the mark to PfPRMT1\", \"No genetic knockout to confirm causality\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"To assess druggability, PRMT inhibitors were tested, showing sub-micromolar in vitro inhibition of PfPRMT1 that mostly correlated with parasite growth suppression, nominating the enzyme as an antimalarial target.\",\n      \"evidence\": \"In vitro PRMT inhibition assay with recombinant enzyme plus parasite growth inhibition assay\",\n      \"pmids\": [\"19344311\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Growth inhibition not proven to act through PfPRMT1 in cells\", \"No target engagement assay\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Extending the druggability question, a chemical repositioning effort nominated PfPRMT1 as the likely cellular target of the multistage-active inhibitor TC-E 5003, supported by a structure-activity relationship.\",\n      \"evidence\": \"Chemical repositioning screen, SAR analysis of TC-E 5003 analogs, multistage growth inhibition assays\",\n      \"pmids\": [\"41914674\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Target assignment is proposed, not validated by genetic or biochemical target engagement\", \"Single lab, indirect pharmacological evidence\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo consequences of PfPRMT1 activity remain open: no genetic loss-of-function study establishes which substrates are physiologically methylated or whether PfPRMT1 is essential for parasite viability or stage progression.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No knockout/knockdown phenotype reported\", \"Physiological substrates not confirmed in vivo\", \"No structural model of the parasite enzyme\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016274\", \"supporting_discovery_ids\": [0, 1, 5]},\n      {\"term_id\": \"GO:0035242\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0044020\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006479\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0034968\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"GO:0016070\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"histone H4 (substrate, methylated at Arg3)\",\n      \"histone H2A (substrate)\",\n      \"fibrillarin (substrate)\",\n      \"poly(A)-binding protein II (substrate)\",\n      \"ribosomal protein S2 (substrate)\",\n      \"putative splicing factor (substrate)\"\n    ],\n    \"other_free_text\": [\n      \"Type I PRMT producing monomethyl- and asymmetric dimethylarginine [#0]\",\n      \"Kinetics similar to mammalian PRMT1 but higher substrate turnover [#5]\",\n      \"Parasite-specific ~50-aa N-terminal extension required for activity [#2]\",\n      \"Inhibited by small-molecule PRMT inhibitors with sub-micromolar IC50; correlated antiplasmodial activity [#6]\",\n      \"Proposed cellular target of TC-E 5003 (Low confidence, not validated) [#7]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1426200","name":null,"product":"protein arginine N-methyltransferase 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1018400","name":null,"product":"protein arginine N-methyltransferase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1332500","name":null,"product":"protein arginine N-methyltransferase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PRMT1","evaluation":null}