{"gene":"PF3D7_0919000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2005,"finding":"NAPS (PfNAPS / PF3D7_0919000) exists as a dimer in solution, as shown by biophysical characterization. ELISA-based binding assays demonstrated that NAPS preferentially interacts with H3-H4 tetramer histones over H2A and H2B histones, establishing histone chaperone activity. Immunofluorescence showed NAPS is expressed in all erythrocytic stages and is more intimately associated with the parasite nucleus compared to PfNAPL, most strikingly in gametocytes. NAPS did not co-localize with PfNAPL, indicating spatial segregation. Unlike PfNAPL, NAPS was not phosphorylated by parasite lysate, indicating differential post-translational regulation.","method":"Size-exclusion chromatography / biophysical characterization (dimerization); ELISA-based histone binding assay; immunofluorescence microscopy; in-parasite-lysate phosphorylation assay","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — multiple orthogonal methods (biophysical, binding assay, immunofluorescence, phosphorylation assay) in a single lab; no independent replication reported","pmids":["15899528"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"NAPS (nucleosome assembly proteins / Naps) is phosphorylated in vitro by the P. falciparum CK2 catalytic subunit (PfCK2α), implicating PfCK2 as a kinase that writes phosphorylation on NAPS. NAPS-containing complexes were recovered in both PfCK2β1 and PfCK2β2 immunoprecipitates analyzed by mass spectrometry, placing NAPS within the PfCK2-associated chromatin assembly pathway interactome.","method":"In vitro kinase assay (PfCK2α phosphorylation of recombinant Naps); immunoprecipitation followed by mass spectrometry (interactome of PfCK2β1 and PfCK2β2 complexes)","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — in vitro kinase assay plus mass spectrometry interactome from two independent regulatory subunit pull-downs; single lab, no independent replication","pmids":["22293287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"NAPS (PF3D7_0919000) is a dimeric histone chaperone that preferentially binds H3-H4 tetramers over H2A-H2B, localizes predominantly to the parasite nucleus (especially in gametocytes), is not phosphorylated by parasite lysate (unlike its paralog PfNAPL), and serves as an in vitro substrate and interactome component of the P. falciparum CK2 kinase complex, implicating it in chromatin assembly regulation during the erythrocytic cycle."},"narrative":{"mechanistic_narrative":"NAPS (PF3D7_0919000) is a histone chaperone of P. falciparum that operates in chromatin assembly during the erythrocytic cycle [PMID:15899528]. It exists as a dimer in solution and preferentially binds H3-H4 tetramers over H2A-H2B, the biochemical signature of nucleosome assembly chaperone activity [PMID:15899528]. NAPS is expressed across all erythrocytic stages and is more intimately associated with the parasite nucleus than its paralog PfNAPL, most strikingly in gametocytes, and does not co-localize with PfNAPL, indicating spatial segregation between the two chaperones [PMID:15899528]. NAPS is differentially regulated post-translationally: unlike PfNAPL it is not phosphorylated by parasite lysate [PMID:15899528], yet it is a direct in vitro substrate of the P. falciparum CK2 catalytic subunit (PfCK2α) and is recovered in both PfCK2β1 and PfCK2β2 immunoprecipitates, placing it within the PfCK2-associated chromatin assembly interactome [PMID:22293287]. Beyond this dimerization, histone-binding, localization, and CK2 relationship, no further mechanistic detail for NAPS has been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Establishing whether PF3D7_0919000 is a functional histone chaperone was the first question; biophysical and binding assays showed it is a dimer that preferentially engages H3-H4, defining its core molecular activity and distinguishing it spatially and post-translationally from its paralog PfNAPL.","evidence":"Size-exclusion chromatography/biophysical characterization, ELISA histone-binding assay, immunofluorescence, and in-lysate phosphorylation assay in P. falciparum","pmids":["15899528"],"confidence":"Medium","gaps":["No cellular knockout or knockdown to test whether NAPS is required for nucleosome assembly in vivo","Structural basis of H3-H4 preference over H2A-H2B not resolved","Findings from a single lab without independent replication"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"How NAPS is regulated and what pathway it belongs to was addressed by identifying it as a direct in vitro substrate of PfCK2α and a component of PfCK2β1/β2 complexes, connecting the chaperone to a defined kinase-associated chromatin assembly interactome.","evidence":"In vitro kinase assay with recombinant NAPS and PfCK2α, plus immunoprecipitation-mass spectrometry of PfCK2β1 and PfCK2β2 complexes in P. falciparum","pmids":["22293287"],"confidence":"Medium","gaps":["Specific NAPS residues phosphorylated by PfCK2α not mapped","Functional consequence of PfCK2 phosphorylation on NAPS chaperone activity unknown","In vitro/mass-spec association not validated by reciprocal or in vivo interaction assays"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether NAPS is essential for parasite viability and how its histone chaperone activity is deployed at specific loci or developmental stages (notably the gametocyte-enriched nuclear localization) remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic loss-of-function data for NAPS","No in vivo demonstration of nucleosome assembly activity","Biological significance of gametocyte-specific nuclear enrichment uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfCK2β1-associated complex (NAPS recovered by IP-MS)","PfCK2β2-associated complex (NAPS recovered by IP-MS)"],"partners":["H3-H4 HISTONES (PREFERENTIAL BINDING)","PFCK2Α (KINASE; PHOSPHORYLATES NAPS IN VITRO)"],"other_free_text":["Exists as a dimer in solution","Expressed in all erythrocytic stages; more nuclear-associated than paralog PfNAPL, most strikingly in gametocytes","Does not co-localize with PfNAPL and is not phosphorylated by parasite lysate, unlike PfNAPL"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12368870","id":"PMC_12368870","title":"Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry.","date":"2002","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12368870","citation_count":511,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SET"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18299133","id":"PMC_18299133","title":"Histone lysine methyltransferases and demethylases in Plasmodium falciparum.","date":"2008","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/18299133","citation_count":106,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SET"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19765590","id":"PMC_19765590","title":"Potential epigenetic regulatory proteins localise to distinct nuclear sub-compartments in Plasmodium falciparum.","date":"2009","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19765590","citation_count":65,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15899528","id":"PMC_15899528","title":"Biochemical characterization of the two nucleosome assembly proteins from Plasmodium falciparum.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15899528","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16677299","id":"PMC_16677299","title":"Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage-specific expression.","date":"2006","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16677299","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SET"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20955606","id":"PMC_20955606","title":"Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum.","date":"2010","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/20955606","citation_count":39,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["nucleosome assembly protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22293287","id":"PMC_22293287","title":"Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway.","date":"2012","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/22293287","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NAPS"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19176479","id":"PMC_19176479","title":"Crystal structure of malaria parasite nucleosome assembly protein: distinct modes of protein localization and histone recognition.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19176479","citation_count":34,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NAPS","nucleosome assembly protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41083279","id":"PMC_41083279","title":"Yet to SET: Plasmodium falciparum Histone Lysine Methyltransferases.","date":"2025","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/41083279","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SET"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7276,"output_tokens":886,"usd":0.017559,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5567,"output_tokens":1892,"usd":0.037567,"stage2_stop_reason":"end_turn"},"total_usd":0.055126,"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\": 2005,\n      \"finding\": \"NAPS (PfNAPS / PF3D7_0919000) exists as a dimer in solution, as shown by biophysical characterization. ELISA-based binding assays demonstrated that NAPS preferentially interacts with H3-H4 tetramer histones over H2A and H2B histones, establishing histone chaperone activity. Immunofluorescence showed NAPS is expressed in all erythrocytic stages and is more intimately associated with the parasite nucleus compared to PfNAPL, most strikingly in gametocytes. NAPS did not co-localize with PfNAPL, indicating spatial segregation. Unlike PfNAPL, NAPS was not phosphorylated by parasite lysate, indicating differential post-translational regulation.\",\n      \"method\": \"Size-exclusion chromatography / biophysical characterization (dimerization); ELISA-based histone binding assay; immunofluorescence microscopy; in-parasite-lysate phosphorylation assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — multiple orthogonal methods (biophysical, binding assay, immunofluorescence, phosphorylation assay) in a single lab; no independent replication reported\",\n      \"pmids\": [\"15899528\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"NAPS (nucleosome assembly proteins / Naps) is phosphorylated in vitro by the P. falciparum CK2 catalytic subunit (PfCK2α), implicating PfCK2 as a kinase that writes phosphorylation on NAPS. NAPS-containing complexes were recovered in both PfCK2β1 and PfCK2β2 immunoprecipitates analyzed by mass spectrometry, placing NAPS within the PfCK2-associated chromatin assembly pathway interactome.\",\n      \"method\": \"In vitro kinase assay (PfCK2α phosphorylation of recombinant Naps); immunoprecipitation followed by mass spectrometry (interactome of PfCK2β1 and PfCK2β2 complexes)\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — in vitro kinase assay plus mass spectrometry interactome from two independent regulatory subunit pull-downs; single lab, no independent replication\",\n      \"pmids\": [\"22293287\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"NAPS (PF3D7_0919000) is a dimeric histone chaperone that preferentially binds H3-H4 tetramers over H2A-H2B, localizes predominantly to the parasite nucleus (especially in gametocytes), is not phosphorylated by parasite lysate (unlike its paralog PfNAPL), and serves as an in vitro substrate and interactome component of the P. falciparum CK2 kinase complex, implicating it in chromatin assembly regulation during the erythrocytic cycle.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NAPS (PF3D7_0919000) is a histone chaperone of P. falciparum that operates in chromatin assembly during the erythrocytic cycle [#0]. It exists as a dimer in solution and preferentially binds H3-H4 tetramers over H2A-H2B, the biochemical signature of nucleosome assembly chaperone activity [#0]. NAPS is expressed across all erythrocytic stages and is more intimately associated with the parasite nucleus than its paralog PfNAPL, most strikingly in gametocytes, and does not co-localize with PfNAPL, indicating spatial segregation between the two chaperones [#0]. NAPS is differentially regulated post-translationally: unlike PfNAPL it is not phosphorylated by parasite lysate [#0], yet it is a direct in vitro substrate of the P. falciparum CK2 catalytic subunit (PfCK2\\u03b1) and is recovered in both PfCK2\\u03b21 and PfCK2\\u03b22 immunoprecipitates, placing it within the PfCK2-associated chromatin assembly interactome [#1]. Beyond this dimerization, histone-binding, localization, and CK2 relationship, no further mechanistic detail for NAPS has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing whether PF3D7_0919000 is a functional histone chaperone was the first question; biophysical and binding assays showed it is a dimer that preferentially engages H3-H4, defining its core molecular activity and distinguishing it spatially and post-translationally from its paralog PfNAPL.\",\n      \"evidence\": \"Size-exclusion chromatography/biophysical characterization, ELISA histone-binding assay, immunofluorescence, and in-lysate phosphorylation assay in P. falciparum\",\n      \"pmids\": [\"15899528\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No cellular knockout or knockdown to test whether NAPS is required for nucleosome assembly in vivo\",\n        \"Structural basis of H3-H4 preference over H2A-H2B not resolved\",\n        \"Findings from a single lab without independent replication\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"How NAPS is regulated and what pathway it belongs to was addressed by identifying it as a direct in vitro substrate of PfCK2\\u03b1 and a component of PfCK2\\u03b21/\\u03b22 complexes, connecting the chaperone to a defined kinase-associated chromatin assembly interactome.\",\n      \"evidence\": \"In vitro kinase assay with recombinant NAPS and PfCK2\\u03b1, plus immunoprecipitation-mass spectrometry of PfCK2\\u03b21 and PfCK2\\u03b22 complexes in P. falciparum\",\n      \"pmids\": [\"22293287\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific NAPS residues phosphorylated by PfCK2\\u03b1 not mapped\",\n        \"Functional consequence of PfCK2 phosphorylation on NAPS chaperone activity unknown\",\n        \"In vitro/mass-spec association not validated by reciprocal or in vivo interaction assays\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether NAPS is essential for parasite viability and how its histone chaperone activity is deployed at specific loci or developmental stages (notably the gametocyte-enriched nuclear localization) remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic loss-of-function data for NAPS\",\n        \"No in vivo demonstration of nucleosome assembly activity\",\n        \"Biological significance of gametocyte-specific nuclear enrichment uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140713\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006334\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"PfCK2\\u03b21-associated complex (NAPS recovered by IP-MS)\",\n      \"PfCK2\\u03b22-associated complex (NAPS recovered by IP-MS)\"\n    ],\n    \"partners\": [\n      \"H3-H4 histones (preferential binding)\",\n      \"PfCK2\\u03b1 (kinase; phosphorylates NAPS in vitro)\"\n    ],\n    \"other_free_text\": [\n      \"Exists as a dimer in solution\",\n      \"Expressed in all erythrocytic stages; more nuclear-associated than paralog PfNAPL, most strikingly in gametocytes\",\n      \"Does not co-localize with PfNAPL and is not phosphorylated by parasite lysate, unlike PfNAPL\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0919000","name":null,"product":"nucleosome assembly protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0819900","name":null,"product":"nucleosome assembly protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0717000","name":null,"product":"nucleosome assembly protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SET","evaluation":null}