{"gene":"PF3D7_0501800","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2017,"finding":"PF3D7_0501800 (CAF1A/PfCAF1) interacts with PfCAF2, histones, and PfHP1, and is present at telomeric repeat regions, central and subtelomeric var gene loci together with PfHP1, consistent with a role in heterochromatin maintenance and nucleosome assembly as a histone chaperone.","method":"Co-immunoprecipitation/protein interaction assays; chromatin immunoprecipitation (ChIP) at telomeric and var gene loci; functional characterization including treatment with genotoxic agents MMS and HU","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple interaction partners identified and ChIP localization shown in a single lab study; orthogonal methods (Co-IP + ChIP + genotoxic stress), but no in vitro reconstitution or mutagenesis","pmids":["29183721"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PF3D7_0501800 (CAF1A/PfCAF1) is upregulated after treatment with genotoxic agents methyl methanesulfonate (MMS) and hydroxyurea (HU), implicating it in the DNA damage repair response.","method":"Western blot / protein expression analysis after genotoxic stress treatment","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (expression upregulation after drug treatment), no direct functional rescue or pathway placement experiment","pmids":["29183721"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"PF3D7_0501800 (CAF1A) was identified as an interactor of the histone methyltransferase PfSET10 by TurboID proximity-labeling coupled with mass spectrometry, placing it within the chromatin remodeling interaction network of PfSET10 in blood-stage parasites.","method":"TurboID proximity-labeling coupled with mass spectrometry","journal":"mSphere","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proximity-labeling experiment, no reciprocal validation or functional follow-up specific to CAF1A","pmids":["39445823"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"PF3D7_0501800 (CAF1A) was identified as an interaction partner of the gametocyte transcription factor AP2-G2 by chromatin proteomics, placing it within a gametocyte-specific SAGA-like effector complex associated with the histone code H3K18acK23ac.","method":"Chromatin proteomics / co-purification mass spectrometry","journal":"Molecular & cellular proteomics : MCP","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single chromatin proteomics experiment identifying CAF1A as a co-purifying protein; no direct functional validation specific to CAF1A","pmids":["35051657"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0501800 (CAF1A) is a P. falciparum chromatin assembly factor 1 subunit that functions as a histone chaperone involved in nucleosome assembly, heterochromatin maintenance at telomeric and var gene loci (co-localizing with PfHP1), and DNA damage repair responses; it physically associates with PfCAF2, histones, PfHP1, the histone methyltransferase PfSET10, and the gametocyte transcription factor AP2-G2, placing it within broader chromatin remodeling and gene-regulatory networks during both asexual and sexual blood stages."},"narrative":{"mechanistic_narrative":"PF3D7_0501800 (CAF1A) is a Plasmodium falciparum chromatin assembly factor 1 subunit that acts as a histone chaperone in nucleosome assembly and heterochromatin maintenance [PMID:29183721]. It physically associates with PfCAF2 and histones and co-localizes with the heterochromatin protein PfHP1 at telomeric repeat regions and at central and subtelomeric var gene loci, consistent with a role in maintaining silenced chromatin at these loci [PMID:29183721]. CAF1A is also embedded in broader chromatin-regulatory networks in blood-stage parasites, having been captured as a proximity interactor of the histone methyltransferase PfSET10 [PMID:39445823] and as a co-purifying partner of the gametocyte transcription factor AP2-G2 within a SAGA-like effector complex linked to the H3K18acK23ac histone code [PMID:35051657]. Beyond these interaction and localization data, the enzymatic and mechanistic details of CAF1A's chaperone activity have not been characterized in the available corpus, and its associations with PfSET10 and AP2-G2 rest on single proximity/proteomics experiments without reciprocal validation.","teleology":[{"year":2017,"claim":"Establishing whether CAF1A operates in heterochromatin biology required identifying its physical partners and genomic occupancy; co-IP and ChIP placed it with PfCAF2, histones, and PfHP1 at telomeric and var loci, defining it as a histone chaperone for nucleosome assembly and heterochromatin maintenance.","evidence":"Co-immunoprecipitation and ChIP at telomeric and var gene loci in P. falciparum","pmids":["29183721"],"confidence":"Medium","gaps":["No in vitro reconstitution of chaperone or nucleosome-assembly activity","No mutagenesis to define which interactions are direct versus complex-mediated","Functional consequence of CAF1A loss on var gene silencing not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"To test a role in genome maintenance, CAF1A protein levels were monitored after genotoxic stress; upregulation following MMS and HU treatment implicated it in the DNA damage repair response.","evidence":"Western blot / expression analysis after MMS and HU treatment in P. falciparum","pmids":["29183721"],"confidence":"Low","gaps":["Single method (expression change) without functional rescue or pathway placement","Does not identify which repair pathway CAF1A participates in","No demonstration that upregulation is required for survival under stress"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Whether CAF1A contributes to sexual-stage gene regulation was addressed by chromatin proteomics of AP2-G2, which co-purified CAF1A within a gametocyte-specific SAGA-like effector complex associated with H3K18acK23ac.","evidence":"Chromatin proteomics / co-purification mass spectrometry in P. falciparum","pmids":["35051657"],"confidence":"Low","gaps":["Single co-purification experiment without reciprocal validation specific to CAF1A","Direct versus indirect association with AP2-G2 unresolved","No functional role of CAF1A in gametocyte gene regulation demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Proximity labeling of the histone methyltransferase PfSET10 identified CAF1A as a network member, extending its associations into blood-stage chromatin-remodeling machinery.","evidence":"TurboID proximity-labeling coupled with mass spectrometry in blood-stage P. falciparum","pmids":["39445823"],"confidence":"Low","gaps":["Single proximity-labeling experiment with no reciprocal validation or functional follow-up for CAF1A","Proximity does not establish a direct or stable interaction","Functional consequence of the CAF1A–PfSET10 association untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic biochemical activity of CAF1A as a histone chaperone and its causal requirement for nucleosome assembly, var gene silencing, DNA repair, and gametocyte gene regulation remain undefined.","evidence":"No reconstitution, genetic knockout/knockdown, or mutagenesis of CAF1A reported in the corpus","pmids":[],"confidence":"Low","gaps":["No in vitro histone-chaperone assay","No loss-of-function phenotype for CAF1A","Direction of interactions (direct vs complex-mediated) with PfHP1, PfSET10, and AP2-G2 not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CAF-1 complex (with PfCAF2) [#0]","AP2-G2-associated SAGA-like effector complex [#3]"],"partners":["PFCAF2 [#0]","HISTONES [#0]","PFHP1 [#0]","PFSET10 [#2]","AP2-G2 [#3]"],"other_free_text":["Co-localizes with PfHP1 at telomeric repeat regions and central/subtelomeric var gene loci [#0]","Protein upregulated after MMS and HU genotoxic stress [#1]","Associated histone code H3K18acK23ac within the AP2-G2 complex [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29183721","id":"PMC_29183721","title":"Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum.","date":"2017","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/29183721","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"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":["CAF1A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35051657","id":"","title":"A Dynamic and Combinatorial Histone Code Drives Malaria Parasite Asexual and Sexual Development.","date":"2022","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/35051657","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CAF1A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5612,"output_tokens":1184,"usd":0.017298,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5990,"output_tokens":2340,"usd":0.044225,"stage2_stop_reason":"end_turn"},"total_usd":0.061523,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"PF3D7_0501800 (CAF1A/PfCAF1) interacts with PfCAF2, histones, and PfHP1, and is present at telomeric repeat regions, central and subtelomeric var gene loci together with PfHP1, consistent with a role in heterochromatin maintenance and nucleosome assembly as a histone chaperone.\",\n      \"method\": \"Co-immunoprecipitation/protein interaction assays; chromatin immunoprecipitation (ChIP) at telomeric and var gene loci; functional characterization including treatment with genotoxic agents MMS and HU\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple interaction partners identified and ChIP localization shown in a single lab study; orthogonal methods (Co-IP + ChIP + genotoxic stress), but no in vitro reconstitution or mutagenesis\",\n      \"pmids\": [\"29183721\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PF3D7_0501800 (CAF1A/PfCAF1) is upregulated after treatment with genotoxic agents methyl methanesulfonate (MMS) and hydroxyurea (HU), implicating it in the DNA damage repair response.\",\n      \"method\": \"Western blot / protein expression analysis after genotoxic stress treatment\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (expression upregulation after drug treatment), no direct functional rescue or pathway placement experiment\",\n      \"pmids\": [\"29183721\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PF3D7_0501800 (CAF1A) was identified as an interactor of the histone methyltransferase PfSET10 by TurboID proximity-labeling coupled with mass spectrometry, placing it within the chromatin remodeling interaction network of PfSET10 in blood-stage parasites.\",\n      \"method\": \"TurboID proximity-labeling coupled with mass spectrometry\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proximity-labeling experiment, no reciprocal validation or functional follow-up specific to CAF1A\",\n      \"pmids\": [\"39445823\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PF3D7_0501800 (CAF1A) was identified as an interaction partner of the gametocyte transcription factor AP2-G2 by chromatin proteomics, placing it within a gametocyte-specific SAGA-like effector complex associated with the histone code H3K18acK23ac.\",\n      \"method\": \"Chromatin proteomics / co-purification mass spectrometry\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single chromatin proteomics experiment identifying CAF1A as a co-purifying protein; no direct functional validation specific to CAF1A\",\n      \"pmids\": [\"35051657\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0501800 (CAF1A) is a P. falciparum chromatin assembly factor 1 subunit that functions as a histone chaperone involved in nucleosome assembly, heterochromatin maintenance at telomeric and var gene loci (co-localizing with PfHP1), and DNA damage repair responses; it physically associates with PfCAF2, histones, PfHP1, the histone methyltransferase PfSET10, and the gametocyte transcription factor AP2-G2, placing it within broader chromatin remodeling and gene-regulatory networks during both asexual and sexual blood stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0501800 (CAF1A) is a Plasmodium falciparum chromatin assembly factor 1 subunit that acts as a histone chaperone in nucleosome assembly and heterochromatin maintenance [#0]. It physically associates with PfCAF2 and histones and co-localizes with the heterochromatin protein PfHP1 at telomeric repeat regions and at central and subtelomeric var gene loci, consistent with a role in maintaining silenced chromatin at these loci [#0]. CAF1A is also embedded in broader chromatin-regulatory networks in blood-stage parasites, having been captured as a proximity interactor of the histone methyltransferase PfSET10 [#2] and as a co-purifying partner of the gametocyte transcription factor AP2-G2 within a SAGA-like effector complex linked to the H3K18acK23ac histone code [#3]. Beyond these interaction and localization data, the enzymatic and mechanistic details of CAF1A's chaperone activity have not been characterized in the available corpus, and its associations with PfSET10 and AP2-G2 rest on single proximity/proteomics experiments without reciprocal validation.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing whether CAF1A operates in heterochromatin biology required identifying its physical partners and genomic occupancy; co-IP and ChIP placed it with PfCAF2, histones, and PfHP1 at telomeric and var loci, defining it as a histone chaperone for nucleosome assembly and heterochromatin maintenance.\",\n      \"evidence\": \"Co-immunoprecipitation and ChIP at telomeric and var gene loci in P. falciparum\",\n      \"pmids\": [\"29183721\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution of chaperone or nucleosome-assembly activity\",\n        \"No mutagenesis to define which interactions are direct versus complex-mediated\",\n        \"Functional consequence of CAF1A loss on var gene silencing not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"To test a role in genome maintenance, CAF1A protein levels were monitored after genotoxic stress; upregulation following MMS and HU treatment implicated it in the DNA damage repair response.\",\n      \"evidence\": \"Western blot / expression analysis after MMS and HU treatment in P. falciparum\",\n      \"pmids\": [\"29183721\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (expression change) without functional rescue or pathway placement\",\n        \"Does not identify which repair pathway CAF1A participates in\",\n        \"No demonstration that upregulation is required for survival under stress\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether CAF1A contributes to sexual-stage gene regulation was addressed by chromatin proteomics of AP2-G2, which co-purified CAF1A within a gametocyte-specific SAGA-like effector complex associated with H3K18acK23ac.\",\n      \"evidence\": \"Chromatin proteomics / co-purification mass spectrometry in P. falciparum\",\n      \"pmids\": [\"35051657\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single co-purification experiment without reciprocal validation specific to CAF1A\",\n        \"Direct versus indirect association with AP2-G2 unresolved\",\n        \"No functional role of CAF1A in gametocyte gene regulation demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Proximity labeling of the histone methyltransferase PfSET10 identified CAF1A as a network member, extending its associations into blood-stage chromatin-remodeling machinery.\",\n      \"evidence\": \"TurboID proximity-labeling coupled with mass spectrometry in blood-stage P. falciparum\",\n      \"pmids\": [\"39445823\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single proximity-labeling experiment with no reciprocal validation or functional follow-up for CAF1A\",\n        \"Proximity does not establish a direct or stable interaction\",\n        \"Functional consequence of the CAF1A–PfSET10 association untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic biochemical activity of CAF1A as a histone chaperone and its causal requirement for nucleosome assembly, var gene silencing, DNA repair, and gametocyte gene regulation remain undefined.\",\n      \"evidence\": \"No reconstitution, genetic knockout/knockdown, or mutagenesis of CAF1A reported in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vitro histone-chaperone assay\",\n        \"No loss-of-function phenotype for CAF1A\",\n        \"Direction of interactions (direct vs complex-mediated) with PfHP1, PfSET10, and AP2-G2 not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140713\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005721\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006335\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006281\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"CAF-1 complex (with PfCAF2) [#0]\",\n      \"AP2-G2-associated SAGA-like effector complex [#3]\"\n    ],\n    \"partners\": [\n      \"PfCAF2 [#0]\",\n      \"histones [#0]\",\n      \"PfHP1 [#0]\",\n      \"PfSET10 [#2]\",\n      \"AP2-G2 [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Co-localizes with PfHP1 at telomeric repeat regions and central/subtelomeric var gene loci [#0]\",\n      \"Protein upregulated after MMS and HU genotoxic stress [#1]\",\n      \"Associated histone code H3K18acK23ac within the AP2-G2 complex [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0501800","name":null,"product":"chromatin assembly factor 1 subunit A","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1101600","name":null,"product":"chromatin assembly factor 1 subunit A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1032100","name":null,"product":"chromatin assembly factor 1 subunit A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CAF1A","evaluation":null}