{"gene":"PF3D7_0719300","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2020,"finding":"ARP6 (PF3D7_0719300) co-localizes with PfArp4 in the nucleus of P. falciparum blood-stage parasites, as demonstrated by co-immunofluorescence assay (co-IFA) and co-immunoprecipitation (co-IP), establishing a direct physical interaction between these two nuclear actin-related proteins.","method":"Co-immunofluorescence assay (co-IFA) and co-immunoprecipitation (co-IP) in transgenic P. falciparum parasites generated by CRISPR-Cas9 tagging","journal":"Parasites & vectors","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and co-IFA performed in a single lab, two orthogonal methods confirming nuclear co-localization and interaction","pmids":["32552779"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"ARP6 (PF3D7_0719300) was identified as a subunit of the PfSWR1 complex in P. falciparum via affinity pulldown of the shared NuA4/SWR1 subunit PfEAF2::GFP followed by LC-MS/MS, placing ARP6 within a histone H2A.Z/H2B.Z deposition chromatin-remodeling complex.","method":"GFP-trap affinity pulldown of PfEAF2::GFP followed by LC-MS/MS (three biological replicates, SAINT filtering)","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal pulldown with mass spectrometry, three replicates, single lab; membership in complex established but no direct functional assay of ARP6 itself","pmids":["38564734"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, ARP6 (PF3D7_0719300) is a nuclear actin-related protein that physically interacts with PfArp4 (co-IP/co-IFA) and is a subunit of the PfSWR1 chromatin-remodeling complex (identified by PfEAF2 affinity pulldown/LC-MS/MS), consistent with a role in histone H2A.Z/H2B.Z deposition, but no direct functional assay of ARP6 itself has been reported beyond its complex membership."},"narrative":{"mechanistic_narrative":"ARP6 (PF3D7_0719300) is a nuclear actin-related protein of P. falciparum implicated in chromatin remodeling through its participation in a conserved histone-variant deposition machinery [PMID:32552779, PMID:38564734]. It physically interacts with the nuclear actin-related protein PfArp4, with which it co-localizes in the nucleus of blood-stage parasites by reciprocal co-IP and co-IFA [PMID:32552779]. ARP6 is a subunit of the PfSWR1 complex, identified through affinity pulldown of the shared NuA4/SWR1 subunit PfEAF2 followed by LC-MS/MS, placing it within a complex associated with H2A.Z/H2B.Z deposition [PMID:38564734]. Beyond this complex membership and the PfArp4 interaction, no direct functional assay of ARP6 itself has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Establishing whether ARP6 partners with other nuclear actin-related proteins addressed whether it operates within a nuclear protein assembly rather than acting alone.","evidence":"Co-IFA and reciprocal co-IP in CRISPR-Cas9-tagged transgenic P. falciparum blood-stage parasites","pmids":["32552779"],"confidence":"Medium","gaps":["Does not define the functional consequence of the ARP6-PfArp4 interaction","Does not resolve which larger complex, if any, these proteins belong to","No direct assay of ARP6 activity or essentiality"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Determining the complex membership of ARP6 addressed which chromatin-remodeling machinery it contributes to, linking it to histone-variant deposition.","evidence":"GFP-trap affinity pulldown of PfEAF2::GFP with LC-MS/MS across three biological replicates and SAINT filtering in P. falciparum","pmids":["38564734"],"confidence":"Medium","gaps":["Complex membership established but no direct functional assay of ARP6 within PfSWR1","ARP6's specific contribution to H2A.Z/H2B.Z deposition is not demonstrated","No structural or stoichiometric definition of ARP6 in the complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct molecular function of ARP6 within the PfSWR1 complex and its requirement for parasite chromatin state remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No knockdown/knockout phenotype for ARP6 itself reported","No demonstration that ARP6 is required for histone variant deposition","No mapping of ARP6 genomic occupancy or binding partners beyond PfArp4 and complex co-members"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfSWR1 chromatin-remodeling complex"],"partners":["PFARP4","PFEAF2"],"other_free_text":["Nuclear actin-related protein of P. falciparum blood-stage parasites; complex association linked to histone H2A.Z/H2B.Z deposition [#1], but no direct functional assay of ARP6 itself reported in the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32552779","id":"PMC_32552779","title":"Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum.","date":"2020","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/32552779","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfARP6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38564734","id":"","title":"MYST regulates DNA repair and forms a NuA4-like complex in the malaria parasite Plasmodium falciparum.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/38564734","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33488567","id":"","title":"Optimization of CRISPR/Cas System for Improving Genome Editing Efficiency in Plasmodium falciparum.","date":"2021","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33488567","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34630528","id":"","title":"FnCas12a/crRNA-Mediated Genome Editing in Eimeria tenella.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34630528","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP6"],"competing_organism_flag":true,"competing_organism_match":"Eimeria","competing_organism_only":true},{"pmid":"23060959","id":"","title":"Plasmodium falciparum RuvB proteins: Emerging importance and expectations beyond cell cycle progression.","date":"2012","source":"Communicative & integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/23060959","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ARP6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8204,"output_tokens":744,"usd":0.017886,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5336,"output_tokens":1477,"usd":0.031802,"stage2_stop_reason":"end_turn"},"total_usd":0.049688,"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\": 2020,\n      \"finding\": \"ARP6 (PF3D7_0719300) co-localizes with PfArp4 in the nucleus of P. falciparum blood-stage parasites, as demonstrated by co-immunofluorescence assay (co-IFA) and co-immunoprecipitation (co-IP), establishing a direct physical interaction between these two nuclear actin-related proteins.\",\n      \"method\": \"Co-immunofluorescence assay (co-IFA) and co-immunoprecipitation (co-IP) in transgenic P. falciparum parasites generated by CRISPR-Cas9 tagging\",\n      \"journal\": \"Parasites & vectors\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and co-IFA performed in a single lab, two orthogonal methods confirming nuclear co-localization and interaction\",\n      \"pmids\": [\"32552779\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ARP6 (PF3D7_0719300) was identified as a subunit of the PfSWR1 complex in P. falciparum via affinity pulldown of the shared NuA4/SWR1 subunit PfEAF2::GFP followed by LC-MS/MS, placing ARP6 within a histone H2A.Z/H2B.Z deposition chromatin-remodeling complex.\",\n      \"method\": \"GFP-trap affinity pulldown of PfEAF2::GFP followed by LC-MS/MS (three biological replicates, SAINT filtering)\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pulldown with mass spectrometry, three replicates, single lab; membership in complex established but no direct functional assay of ARP6 itself\",\n      \"pmids\": [\"38564734\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, ARP6 (PF3D7_0719300) is a nuclear actin-related protein that physically interacts with PfArp4 (co-IP/co-IFA) and is a subunit of the PfSWR1 chromatin-remodeling complex (identified by PfEAF2 affinity pulldown/LC-MS/MS), consistent with a role in histone H2A.Z/H2B.Z deposition, but no direct functional assay of ARP6 itself has been reported beyond its complex membership.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ARP6 (PF3D7_0719300) is a nuclear actin-related protein of P. falciparum implicated in chromatin remodeling through its participation in a conserved histone-variant deposition machinery [#0, #1]. It physically interacts with the nuclear actin-related protein PfArp4, with which it co-localizes in the nucleus of blood-stage parasites by reciprocal co-IP and co-IFA [#0]. ARP6 is a subunit of the PfSWR1 complex, identified through affinity pulldown of the shared NuA4/SWR1 subunit PfEAF2 followed by LC-MS/MS, placing it within a complex associated with H2A.Z/H2B.Z deposition [#1]. Beyond this complex membership and the PfArp4 interaction, no direct functional assay of ARP6 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing whether ARP6 partners with other nuclear actin-related proteins addressed whether it operates within a nuclear protein assembly rather than acting alone.\",\n      \"evidence\": \"Co-IFA and reciprocal co-IP in CRISPR-Cas9-tagged transgenic P. falciparum blood-stage parasites\",\n      \"pmids\": [\n        \"32552779\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not define the functional consequence of the ARP6-PfArp4 interaction\",\n        \"Does not resolve which larger complex, if any, these proteins belong to\",\n        \"No direct assay of ARP6 activity or essentiality\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Determining the complex membership of ARP6 addressed which chromatin-remodeling machinery it contributes to, linking it to histone-variant deposition.\",\n      \"evidence\": \"GFP-trap affinity pulldown of PfEAF2::GFP with LC-MS/MS across three biological replicates and SAINT filtering in P. falciparum\",\n      \"pmids\": [\n        \"38564734\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Complex membership established but no direct functional assay of ARP6 within PfSWR1\",\n        \"ARP6's specific contribution to H2A.Z/H2B.Z deposition is not demonstrated\",\n        \"No structural or stoichiometric definition of ARP6 in the complex\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of ARP6 within the PfSWR1 complex and its requirement for parasite chromatin state remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No knockdown/knockout phenotype for ARP6 itself reported\",\n        \"No demonstration that ARP6 is required for histone variant deposition\",\n        \"No mapping of ARP6 genomic occupancy or binding partners beyond PfArp4 and complex co-members\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005634\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006338\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"PfSWR1 chromatin-remodeling complex\"\n    ],\n    \"partners\": [\n      \"PfArp4\",\n      \"PfEAF2\"\n    ],\n    \"other_free_text\": [\n      \"Nuclear actin-related protein of P. falciparum blood-stage parasites; complex association linked to histone H2A.Z/H2B.Z deposition [#1], but no direct functional assay of ARP6 itself reported in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0719300","name":null,"product":"actin-related protein ARP6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0616800","name":null,"product":"actin-related protein ARP6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0314700","name":null,"product":"actin-related protein ARP6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ARP6","evaluation":null}