{"gene":"PF3D7_1008100","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2019,"finding":"PHD1 (PF3D7_1008100) was identified as a reader protein that binds histone H3K4me2/3 marks and may mediate crosstalk between H3K4me2/3 and H3K9ac marks, based on histone peptide pull-down experiments.","method":"Histone peptide pull-down with quantitative proteomics","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — histone peptide pull-down with MS identification, single lab, single method; crosstalk inference is suggestive but not fully validated by orthogonal assay in this paper","pmids":["31728527"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PHD1 (PF3D7_1008100) is a subunit of a divergent PfGCN5 histone acetyltransferase complex that also contains PfPHD2 and PfAP2-LT; deletion of the PHD domain of PHD1 caused significantly reduced merozoite invasion of erythrocytes, elevated sexual conversion, dramatic decreases in H3K9 acetylation and H3K4 trimethylation, and global transcriptional dysregulation including disruption of mutually exclusive var gene expression.","method":"Interaction proteomics identifying complex subunits; conditional genetic deletion of the PHD domain of PHD1 with phenotypic readouts (invasion assays, ChIP for H3K9ac and H3K4me3, transcriptomics)","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction proteomics plus domain-deletion loss-of-function with multiple orthogonal phenotypic readouts (invasion, sexual conversion, histone marks by ChIP, transcriptomics) in a single rigorous study","pmids":["34403450"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PHD1 (PF3D7_1008100) is a PHD-finger subunit of the divergent PfGCN5 histone acetyltransferase complex in P. falciparum; its PHD domain binds H3K4me2/3 marks and is required for normal H3K9 acetylation, H3K4 trimethylation, erythrocyte invasion, suppression of sexual conversion, and mutually exclusive var gene regulation, consistent with a role in mediating crosstalk between active chromatin marks to co-activate invasion and virulence gene programs."},"narrative":{"mechanistic_narrative":"PHD1 (PF3D7_1008100) is a PHD-finger chromatin reader that functions within a divergent PfGCN5 histone acetyltransferase complex to co-activate erythrocyte invasion and virulence gene programs in Plasmodium falciparum [PMID:31728527, PMID:34403450]. Its PHD domain binds the active histone marks H3K4me2/3, positioning PHD1 to mediate crosstalk between H3K4 methylation and H3K9 acetylation [PMID:31728527]. PHD1 is a subunit of a PfGCN5 acetyltransferase complex that also contains PfPHD2 and PfAP2-LT, and deletion of its PHD domain causes dramatic loss of H3K9 acetylation and H3K4 trimethylation together with global transcriptional dysregulation [PMID:34403450]. These chromatin defects manifest phenotypically as reduced merozoite invasion of erythrocytes, elevated sexual conversion, and disruption of mutually exclusive var gene expression, establishing PHD1 as a link between active chromatin marks and the invasion and virulence transcriptional programs [PMID:34403450]. Beyond these findings, no further mechanistic detail for PF3D7_1008100 has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"To determine what chromatin signal PHD1 recognizes, it was tested as a candidate histone mark reader, establishing that its PHD domain engages active H3K4me2/3 and may bridge to H3K9 acetylation.","evidence":"Histone peptide pull-down with quantitative proteomics in P. falciparum","pmids":["31728527"],"confidence":"Medium","gaps":["Crosstalk between H3K4me2/3 and H3K9ac is inferred from binding, not shown by an orthogonal functional assay in this study","No structural basis for the PHD-mark interaction established","Direct binding affinity and specificity across the full mark repertoire not quantified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To place PHD1 in a pathway and test its functional requirement, its complex membership and the consequences of losing its reader domain were resolved, establishing PHD1 as a PfGCN5-complex subunit needed for normal histone acetylation/methylation and for invasion, sexual conversion suppression, and var gene control.","evidence":"Interaction proteomics identifying PfPHD2 and PfAP2-LT as complex subunits, plus conditional deletion of the PHD1 PHD domain with invasion assays, ChIP for H3K9ac/H3K4me3, and transcriptomics in P. falciparum","pmids":["34403450"],"confidence":"High","gaps":["Whether the H3K4me2/3 reading activity is directly responsible for complex recruitment to target loci is not shown mechanistically","The contribution of PHD1 beyond its PHD domain (full-gene knockout vs domain deletion) is not resolved","How loss of PHD1 mechanistically links reduced H3K9ac to specific invasion and var loci is not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PHD1's mark-reading activity is mechanistically coupled to targeted PfGCN5 acetylation at specific invasion and virulence loci remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genome-wide occupancy map of PHD1 itself","No structural model of the PHD domain bound to H3K4me2/3","Individual roles of PfPHD2 and PfAP2-LT relative to PHD1 within the complex not dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Divergent PfGCN5 histone acetyltransferase complex (contains PHD1/PF3D7_1008100, PfPHD2, PfAP2-LT) [#1]"],"partners":["PFPHD2 [#1]","PFAP2-LT [#1]"],"other_free_text":["PHD domain of PHD1 binds active histone marks H3K4me2/3 [#0]","PHD domain deletion reduces H3K9 acetylation and H3K4 trimethylation and dysregulates the transcriptome [#1]","Required for normal merozoite invasion of erythrocytes and for suppression of sexual conversion [#1]","Required for mutually exclusive var gene expression [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"31728527","id":"PMC_31728527","title":"Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31728527","citation_count":48,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PHD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34403450","id":"PMC_34403450","title":"A unique GCN5 histone acetyltransferase complex controls erythrocyte invasion and virulence in the malaria parasite Plasmodium falciparum.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34403450","citation_count":44,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PHD","PfPHD1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34418264","id":"PMC_34418264","title":"Zinc finger proteins of Plasmodium falciparum.","date":"2021","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34418264","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PHD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34389510","id":"PMC_34389510","title":"Plasmodium falciparum SET2 domain is allosterically regulated by its PHD-like domain to methylate at H3K36.","date":"2021","source":"Biochimica et biophysica acta. Gene regulatory mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/34389510","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PHD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4900,"output_tokens":750,"usd":0.012975,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5379,"output_tokens":1928,"usd":0.037547,"stage2_stop_reason":"end_turn"},"total_usd":0.050522,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"PHD1 (PF3D7_1008100) was identified as a reader protein that binds histone H3K4me2/3 marks and may mediate crosstalk between H3K4me2/3 and H3K9ac marks, based on histone peptide pull-down experiments.\",\n      \"method\": \"Histone peptide pull-down with quantitative proteomics\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — histone peptide pull-down with MS identification, single lab, single method; crosstalk inference is suggestive but not fully validated by orthogonal assay in this paper\",\n      \"pmids\": [\"31728527\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PHD1 (PF3D7_1008100) is a subunit of a divergent PfGCN5 histone acetyltransferase complex that also contains PfPHD2 and PfAP2-LT; deletion of the PHD domain of PHD1 caused significantly reduced merozoite invasion of erythrocytes, elevated sexual conversion, dramatic decreases in H3K9 acetylation and H3K4 trimethylation, and global transcriptional dysregulation including disruption of mutually exclusive var gene expression.\",\n      \"method\": \"Interaction proteomics identifying complex subunits; conditional genetic deletion of the PHD domain of PHD1 with phenotypic readouts (invasion assays, ChIP for H3K9ac and H3K4me3, transcriptomics)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction proteomics plus domain-deletion loss-of-function with multiple orthogonal phenotypic readouts (invasion, sexual conversion, histone marks by ChIP, transcriptomics) in a single rigorous study\",\n      \"pmids\": [\"34403450\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PHD1 (PF3D7_1008100) is a PHD-finger subunit of the divergent PfGCN5 histone acetyltransferase complex in P. falciparum; its PHD domain binds H3K4me2/3 marks and is required for normal H3K9 acetylation, H3K4 trimethylation, erythrocyte invasion, suppression of sexual conversion, and mutually exclusive var gene regulation, consistent with a role in mediating crosstalk between active chromatin marks to co-activate invasion and virulence gene programs.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PHD1 (PF3D7_1008100) is a PHD-finger chromatin reader that functions within a divergent PfGCN5 histone acetyltransferase complex to co-activate erythrocyte invasion and virulence gene programs in Plasmodium falciparum [#0, #1]. Its PHD domain binds the active histone marks H3K4me2/3, positioning PHD1 to mediate crosstalk between H3K4 methylation and H3K9 acetylation [#0]. PHD1 is a subunit of a PfGCN5 acetyltransferase complex that also contains PfPHD2 and PfAP2-LT, and deletion of its PHD domain causes dramatic loss of H3K9 acetylation and H3K4 trimethylation together with global transcriptional dysregulation [#1]. These chromatin defects manifest phenotypically as reduced merozoite invasion of erythrocytes, elevated sexual conversion, and disruption of mutually exclusive var gene expression, establishing PHD1 as a link between active chromatin marks and the invasion and virulence transcriptional programs [#1]. Beyond these findings, no further mechanistic detail for PF3D7_1008100 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"To determine what chromatin signal PHD1 recognizes, it was tested as a candidate histone mark reader, establishing that its PHD domain engages active H3K4me2/3 and may bridge to H3K9 acetylation.\",\n      \"evidence\": \"Histone peptide pull-down with quantitative proteomics in P. falciparum\",\n      \"pmids\": [\"31728527\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Crosstalk between H3K4me2/3 and H3K9ac is inferred from binding, not shown by an orthogonal functional assay in this study\",\n        \"No structural basis for the PHD-mark interaction established\",\n        \"Direct binding affinity and specificity across the full mark repertoire not quantified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To place PHD1 in a pathway and test its functional requirement, its complex membership and the consequences of losing its reader domain were resolved, establishing PHD1 as a PfGCN5-complex subunit needed for normal histone acetylation/methylation and for invasion, sexual conversion suppression, and var gene control.\",\n      \"evidence\": \"Interaction proteomics identifying PfPHD2 and PfAP2-LT as complex subunits, plus conditional deletion of the PHD1 PHD domain with invasion assays, ChIP for H3K9ac/H3K4me3, and transcriptomics in P. falciparum\",\n      \"pmids\": [\"34403450\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the H3K4me2/3 reading activity is directly responsible for complex recruitment to target loci is not shown mechanistically\",\n        \"The contribution of PHD1 beyond its PHD domain (full-gene knockout vs domain deletion) is not resolved\",\n        \"How loss of PHD1 mechanistically links reduced H3K9ac to specific invasion and var loci is not mapped\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PHD1's mark-reading activity is mechanistically coupled to targeted PfGCN5 acetylation at specific invasion and virulence loci remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genome-wide occupancy map of PHD1 itself\",\n        \"No structural model of the PHD domain bound to H3K4me2/3\",\n        \"Individual roles of PfPHD2 and PfAP2-LT relative to PHD1 within the complex not dissected\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140002\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140030\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016573\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"Divergent PfGCN5 histone acetyltransferase complex (contains PHD1/PF3D7_1008100, PfPHD2, PfAP2-LT) [#1]\"\n    ],\n    \"partners\": [\n      \"PfPHD2 [#1]\",\n      \"PfAP2-LT [#1]\"\n    ],\n    \"other_free_text\": [\n      \"PHD domain of PHD1 binds active histone marks H3K4me2/3 [#0]\",\n      \"PHD domain deletion reduces H3K9 acetylation and H3K4 trimethylation and dysregulates the transcriptome [#1]\",\n      \"Required for normal merozoite invasion of erythrocytes and for suppression of sexual conversion [#1]\",\n      \"Required for mutually exclusive var gene expression [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1008100","name":null,"product":"PHD finger protein PHD1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1206300","name":null,"product":"PHD finger protein PHD1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0807100","name":null,"product":"PHD finger protein PHD1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PHD1","evaluation":null}