{"gene":"PF3D7_1203700","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2005,"finding":"NAPL (PfNAPL) exists as a dimer in solution, preferentially binds H3-H4 tetramer histones over H2A and H2B histones in ELISA-based binding assays, and is phosphorylated by parasite lysate in a heparin-inhibitable manner (suggesting casein kinase II involvement). Immunofluorescence showed NAPL is expressed in all erythrocytic stages and is predominantly localised in the cytoplasm in both asexual and sexual stages, while not co-localising with PfNAPS.","method":"ELISA-based histone binding assay, analytical size exclusion/biophysical characterisation, in-cell phosphorylation assay with heparin inhibition, circular dichroism, immunofluorescence microscopy","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple orthogonal biochemical and cell-biology methods in a single lab; no independent replication reported","pmids":["15899528"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"NAPL (PfNAPL) interacts with histone oligomers (including linker histone H1 and core histones H3/H4) but, unlike PfNAPS, is unable to deposit histones onto DNA. NAPL is phosphorylated in vivo and in vitro by casein kinase II (heparin-inhibitable), and phosphorylation increases NAPL's affinity approximately 3-fold for core histones H3, H4, and linker histone H1. PfNAPS can extract histones from both phosphorylated and unphosphorylated NAPL, suggesting NAPL functions as a nucleocytoplasmic histone relay protein rather than a direct chromatin assembly factor.","method":"In vitro histone deposition assay, in vivo and in vitro phosphorylation assays with casein kinase II and heparin inhibition, fluorescence spectroscopy, circular dichroism, chymotrypsin fingerprinting, histone-binding affinity measurements","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal in vitro biochemical assays (deposition, phosphorylation, binding affinity) with specific inhibitor controls, establishing distinct mechanistic role; single lab but rigorous multi-method design","pmids":["16638744"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"The crystal structure of NAPL (PfNapL) was determined at 2.3 Å resolution. NAPL adopts a dimeric fold characteristic of eukaryotic NAPs (related to yeast NAP-1/Vps75 and human SET/TAF-1β/INHAT), composed of a domain I (dimerisation α-helix) and domain II (α-helices plus β-subdomain). Notably, the 'accessory domain' present in yeast NAP-1 and other eukaryotic NAPs is absent in NAPL. GFP-tagging experiments confirmed exclusive cytoplasmic localisation of NAPL. Attempts to disrupt the NAPL gene failed, indicating it is essential for parasite viability.","method":"X-ray crystallography (2.3 Å), GFP-fusion transfection and live fluorescence microscopy, gene disruption attempts","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — atomic-resolution crystal structure with functional validation by GFP localisation and failed gene disruption; single lab but multiple orthogonal methods","pmids":["19176479"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"The crystal structure of NAPL (PfNapL) was solved by iodide-SAD/SIRAS phasing at 2.4 Å resolution (native data), using quick cryo-soaking with 500 mM NaI. Molecular replacement and selenomethionine derivatisation had previously failed. This established the phasing methodology for the NAPL structure.","method":"X-ray crystallography — iodide-SAD, SIR, and SIRAS phasing","journal":"Acta crystallographica. Section D, Biological crystallography","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystallographic structure determination paper; primarily a methodological contribution confirming the structure reported in PMID:19176479; single lab","pmids":["19465776"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Using histone peptide interaction arrays and NMR chemical shift perturbation, NAPL (referred to as Nap in this study, representing both PfNapL and PfNapS) was shown to recognise core histone regions (H2A, H2B, H3, H4) that form a surface-exposed contiguous patch on the histone octamer. Phosphorylation at H3T32 and H3T118 enhanced Nap-peptide interactions, while modifications H3K122, H4K59, and H2AK36 diminished binding. Nap binding sites on H2A-H2B and H3-H4 fall on opposite surfaces of the octamer, allowing two dimeric Nap molecules to bind simultaneously. The interfacial residues overlap with the DNA wrapping path on the octamer, implying mutually exclusive residency of Nap and DNA. NMR identified specific NAPL residues undergoing chemical shift perturbations upon histone peptide binding.","method":"Histone peptide interaction arrays, NMR chemical shift perturbation","journal":"Journal of structural biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — NMR and peptide array are high-quality methods but findings are reported for Nap generally (both PfNapL and PfNapS) in a single lab study; attribution to NAPL specifically is partial","pmids":["22771717"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"NAPL (PF3D7_1203700) is an essential, cytoplasm-localised dimeric histone chaperone in P. falciparum that preferentially binds H3-H4 and linker histone H1 but cannot deposit histones onto DNA; it is phosphorylated by casein kinase II, which increases its histone affinity ~3-fold, and histones can be extracted from it by the nuclear partner PfNAPS, consistent with a role as a nucleocytoplasmic histone shuttle rather than a direct chromatin assembly factor; its 2.3 Å crystal structure reveals a conserved NAP-fold but lacks the 'accessory domain' found in yeast NAP-1."},"narrative":{"mechanistic_narrative":"NAPL (PF3D7_1203700) is an essential, dimeric histone chaperone of Plasmodium falciparum that binds histones in the cytoplasm but does not itself deposit them onto DNA, marking it as a nucleocytoplasmic histone relay rather than a direct chromatin assembly factor [PMID:16638744, PMID:19176479]. It exists as a dimer in solution and preferentially binds the H3-H4 tetramer over H2A-H2B, and also engages linker histone H1 [PMID:15899528, PMID:16638744]. NAPL is phosphorylated by parasite casein kinase II in a heparin-inhibitable manner, and this phosphorylation increases its affinity for H3, H4, and H1 approximately three-fold [PMID:15899528, PMID:16638744]. Its histone cargo can be extracted by the nuclear paralog PfNAPS, consistent with a hand-off role in which NAPL delivers histones toward chromatin without depositing them [PMID:16638744]. The 2.3 Å crystal structure reveals a dimeric NAP-fold comprising a dimerization helix (domain I) and an α-helical/β-subdomain (domain II) but lacks the accessory domain found in yeast NAP-1 [PMID:19176479, PMID:19465776]. Consistent with this shuttling role, NAPL localizes exclusively to the cytoplasm across asexual and sexual erythrocytic stages and does not co-localize with PfNAPS, and gene-disruption attempts failed, establishing it as essential for parasite viability [PMID:15899528, PMID:19176479]. Histone-recognition mapping indicates NAPL contacts a surface-exposed patch on the histone octamer that overlaps the DNA-wrapping path, and this interaction is tuned by histone post-translational modifications [PMID:22771717].","teleology":[{"year":2005,"claim":"Establishing that PF3D7_1203700 is a histone-binding protein defined its candidacy as a chaperone and distinguished it from its nuclear partner by localization.","evidence":"ELISA histone-binding assays, biophysical dimer characterization, in-cell phosphorylation with heparin inhibition, and immunofluorescence across erythrocytic stages in P. falciparum","pmids":["15899528"],"confidence":"Medium","gaps":["ELISA binding does not establish physiological affinity or stoichiometry","casein kinase II involvement inferred from heparin inhibition, not direct identification","cytoplasmic localization from immunofluorescence not corroborated by fractionation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Defining NAPL as unable to deposit histones onto DNA yet capable of handing them to PfNAPS reframed it from an assembly factor to a nucleocytoplasmic histone relay, and linked its function to CKII regulation.","evidence":"In vitro histone deposition assays, in vivo/in vitro CKII phosphorylation with heparin controls, and histone-binding affinity measurements in P. falciparum","pmids":["16638744"],"confidence":"High","gaps":["the in vivo directionality of the NAPL-to-PfNAPS hand-off was not demonstrated in cells","the CKII phosphosites on NAPL and their in vivo occupancy were not mapped","functional consequence of the ~3-fold affinity increase for parasite chromatin dynamics untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Solving the NAPL crystal structure and demonstrating failed gene disruption provided the atomic architecture of a NAP-fold and established the protein as essential.","evidence":"X-ray crystallography at 2.3 Å (iodide-SAD/SIRAS phasing), GFP-fusion live microscopy, and gene-disruption attempts in P. falciparum","pmids":["19176479","19465776"],"confidence":"High","gaps":["the functional significance of the missing accessory domain not tested by mutagenesis","no histone-bound structure to define the interaction interface","essentiality inferred from failed disruption rather than conditional knockdown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Mapping the histone-recognition surface showed NAPL contacts an octamer patch overlapping the DNA path and is modulated by histone PTMs, providing a structural rationale for mutually exclusive NAPL/DNA binding.","evidence":"Histone peptide interaction arrays and NMR chemical shift perturbation in P. falciparum","pmids":["22771717"],"confidence":"Medium","gaps":["findings reported for Nap generally (both PfNapL and PfNapS), so attribution to NAPL specifically is partial","peptide arrays may not recapitulate intact octamer binding","the in vivo relevance of the PTM-tuned binding untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How NAPL's histone cargo is directed toward the nucleus and handed to PfNAPS in vivo, and how CKII phosphorylation is regulated across the parasite life cycle, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["no in vivo demonstration of the proposed nucleocytoplasmic shuttling","CKII phosphosites and their dynamic regulation unmapped","no conditional depletion to define essential function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFNAPS","HISTONE H3","HISTONE H4","LINKER HISTONE H1","CASEIN KINASE II"],"other_free_text":["Dimeric NAP-fold lacking the accessory domain present in yeast NAP-1 [#2].","Phosphorylation by casein kinase II increases histone affinity ~3-fold [#1].","Binds but does not deposit histones onto DNA; PfNAPS extracts histones from NAPL, consistent with a histone-relay role [#1].","Gene disruption attempts failed, indicating essentiality [#2]."]}},"prefetch_data":{},"corpus_meta":[{"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":"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":["PFL0185c","nucleosome assembly protein"],"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":["nucleosome assembly protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16638744","id":"PMC_16638744","title":"The two Plasmodium falciparum nucleosome assembly proteins play distinct roles in histone transport and chromatin assembly.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16638744","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NAPL"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20377878","id":"PMC_20377878","title":"Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum.","date":"2010","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/20377878","citation_count":19,"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":"19465776","id":"PMC_19465776","title":"Iodide-SAD, SIR and SIRAS phasing for structure solution of a nucleosome assembly protein.","date":"2009","source":"Acta crystallographica. Section D, Biological crystallography","url":"https://pubmed.ncbi.nlm.nih.gov/19465776","citation_count":11,"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":"22771717","id":"PMC_22771717","title":"Structural delineation of histone post-translation modifications in histone-nucleosome assembly protein complex.","date":"2012","source":"Journal of structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/22771717","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["nucleosome assembly protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6243,"output_tokens":1929,"usd":0.023832,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7100,"output_tokens":2493,"usd":0.048912,"stage2_stop_reason":"end_turn"},"total_usd":0.072744,"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\": 2005,\n      \"finding\": \"NAPL (PfNAPL) exists as a dimer in solution, preferentially binds H3-H4 tetramer histones over H2A and H2B histones in ELISA-based binding assays, and is phosphorylated by parasite lysate in a heparin-inhibitable manner (suggesting casein kinase II involvement). Immunofluorescence showed NAPL is expressed in all erythrocytic stages and is predominantly localised in the cytoplasm in both asexual and sexual stages, while not co-localising with PfNAPS.\",\n      \"method\": \"ELISA-based histone binding assay, analytical size exclusion/biophysical characterisation, in-cell phosphorylation assay with heparin inhibition, circular dichroism, immunofluorescence microscopy\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple orthogonal biochemical and cell-biology methods 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\": 2006,\n      \"finding\": \"NAPL (PfNAPL) interacts with histone oligomers (including linker histone H1 and core histones H3/H4) but, unlike PfNAPS, is unable to deposit histones onto DNA. NAPL is phosphorylated in vivo and in vitro by casein kinase II (heparin-inhibitable), and phosphorylation increases NAPL's affinity approximately 3-fold for core histones H3, H4, and linker histone H1. PfNAPS can extract histones from both phosphorylated and unphosphorylated NAPL, suggesting NAPL functions as a nucleocytoplasmic histone relay protein rather than a direct chromatin assembly factor.\",\n      \"method\": \"In vitro histone deposition assay, in vivo and in vitro phosphorylation assays with casein kinase II and heparin inhibition, fluorescence spectroscopy, circular dichroism, chymotrypsin fingerprinting, histone-binding affinity measurements\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal in vitro biochemical assays (deposition, phosphorylation, binding affinity) with specific inhibitor controls, establishing distinct mechanistic role; single lab but rigorous multi-method design\",\n      \"pmids\": [\"16638744\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The crystal structure of NAPL (PfNapL) was determined at 2.3 Å resolution. NAPL adopts a dimeric fold characteristic of eukaryotic NAPs (related to yeast NAP-1/Vps75 and human SET/TAF-1β/INHAT), composed of a domain I (dimerisation α-helix) and domain II (α-helices plus β-subdomain). Notably, the 'accessory domain' present in yeast NAP-1 and other eukaryotic NAPs is absent in NAPL. GFP-tagging experiments confirmed exclusive cytoplasmic localisation of NAPL. Attempts to disrupt the NAPL gene failed, indicating it is essential for parasite viability.\",\n      \"method\": \"X-ray crystallography (2.3 Å), GFP-fusion transfection and live fluorescence microscopy, gene disruption attempts\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — atomic-resolution crystal structure with functional validation by GFP localisation and failed gene disruption; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"19176479\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The crystal structure of NAPL (PfNapL) was solved by iodide-SAD/SIRAS phasing at 2.4 Å resolution (native data), using quick cryo-soaking with 500 mM NaI. Molecular replacement and selenomethionine derivatisation had previously failed. This established the phasing methodology for the NAPL structure.\",\n      \"method\": \"X-ray crystallography — iodide-SAD, SIR, and SIRAS phasing\",\n      \"journal\": \"Acta crystallographica. Section D, Biological crystallography\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystallographic structure determination paper; primarily a methodological contribution confirming the structure reported in PMID:19176479; single lab\",\n      \"pmids\": [\"19465776\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Using histone peptide interaction arrays and NMR chemical shift perturbation, NAPL (referred to as Nap in this study, representing both PfNapL and PfNapS) was shown to recognise core histone regions (H2A, H2B, H3, H4) that form a surface-exposed contiguous patch on the histone octamer. Phosphorylation at H3T32 and H3T118 enhanced Nap-peptide interactions, while modifications H3K122, H4K59, and H2AK36 diminished binding. Nap binding sites on H2A-H2B and H3-H4 fall on opposite surfaces of the octamer, allowing two dimeric Nap molecules to bind simultaneously. The interfacial residues overlap with the DNA wrapping path on the octamer, implying mutually exclusive residency of Nap and DNA. NMR identified specific NAPL residues undergoing chemical shift perturbations upon histone peptide binding.\",\n      \"method\": \"Histone peptide interaction arrays, NMR chemical shift perturbation\",\n      \"journal\": \"Journal of structural biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — NMR and peptide array are high-quality methods but findings are reported for Nap generally (both PfNapL and PfNapS) in a single lab study; attribution to NAPL specifically is partial\",\n      \"pmids\": [\"22771717\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"NAPL (PF3D7_1203700) is an essential, cytoplasm-localised dimeric histone chaperone in P. falciparum that preferentially binds H3-H4 and linker histone H1 but cannot deposit histones onto DNA; it is phosphorylated by casein kinase II, which increases its histone affinity ~3-fold, and histones can be extracted from it by the nuclear partner PfNAPS, consistent with a role as a nucleocytoplasmic histone shuttle rather than a direct chromatin assembly factor; its 2.3 Å crystal structure reveals a conserved NAP-fold but lacks the 'accessory domain' found in yeast NAP-1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NAPL (PF3D7_1203700) is an essential, dimeric histone chaperone of Plasmodium falciparum that binds histones in the cytoplasm but does not itself deposit them onto DNA, marking it as a nucleocytoplasmic histone relay rather than a direct chromatin assembly factor [#1, #2]. It exists as a dimer in solution and preferentially binds the H3-H4 tetramer over H2A-H2B, and also engages linker histone H1 [#0, #1]. NAPL is phosphorylated by parasite casein kinase II in a heparin-inhibitable manner, and this phosphorylation increases its affinity for H3, H4, and H1 approximately three-fold [#0, #1]. Its histone cargo can be extracted by the nuclear paralog PfNAPS, consistent with a hand-off role in which NAPL delivers histones toward chromatin without depositing them [#1]. The 2.3 Å crystal structure reveals a dimeric NAP-fold comprising a dimerization helix (domain I) and an α-helical/β-subdomain (domain II) but lacks the accessory domain found in yeast NAP-1 [#2, #3]. Consistent with this shuttling role, NAPL localizes exclusively to the cytoplasm across asexual and sexual erythrocytic stages and does not co-localize with PfNAPS, and gene-disruption attempts failed, establishing it as essential for parasite viability [#0, #2]. Histone-recognition mapping indicates NAPL contacts a surface-exposed patch on the histone octamer that overlaps the DNA-wrapping path, and this interaction is tuned by histone post-translational modifications [#4].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing that PF3D7_1203700 is a histone-binding protein defined its candidacy as a chaperone and distinguished it from its nuclear partner by localization.\",\n      \"evidence\": \"ELISA histone-binding assays, biophysical dimer characterization, in-cell phosphorylation with heparin inhibition, and immunofluorescence across erythrocytic stages in P. falciparum\",\n      \"pmids\": [\"15899528\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ELISA binding does not establish physiological affinity or stoichiometry\", \"casein kinase II involvement inferred from heparin inhibition, not direct identification\", \"cytoplasmic localization from immunofluorescence not corroborated by fractionation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defining NAPL as unable to deposit histones onto DNA yet capable of handing them to PfNAPS reframed it from an assembly factor to a nucleocytoplasmic histone relay, and linked its function to CKII regulation.\",\n      \"evidence\": \"In vitro histone deposition assays, in vivo/in vitro CKII phosphorylation with heparin controls, and histone-binding affinity measurements in P. falciparum\",\n      \"pmids\": [\"16638744\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"the in vivo directionality of the NAPL-to-PfNAPS hand-off was not demonstrated in cells\", \"the CKII phosphosites on NAPL and their in vivo occupancy were not mapped\", \"functional consequence of the ~3-fold affinity increase for parasite chromatin dynamics untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Solving the NAPL crystal structure and demonstrating failed gene disruption provided the atomic architecture of a NAP-fold and established the protein as essential.\",\n      \"evidence\": \"X-ray crystallography at 2.3 Å (iodide-SAD/SIRAS phasing), GFP-fusion live microscopy, and gene-disruption attempts in P. falciparum\",\n      \"pmids\": [\"19176479\", \"19465776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"the functional significance of the missing accessory domain not tested by mutagenesis\", \"no histone-bound structure to define the interaction interface\", \"essentiality inferred from failed disruption rather than conditional knockdown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Mapping the histone-recognition surface showed NAPL contacts an octamer patch overlapping the DNA path and is modulated by histone PTMs, providing a structural rationale for mutually exclusive NAPL/DNA binding.\",\n      \"evidence\": \"Histone peptide interaction arrays and NMR chemical shift perturbation in P. falciparum\",\n      \"pmids\": [\"22771717\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"findings reported for Nap generally (both PfNapL and PfNapS), so attribution to NAPL specifically is partial\", \"peptide arrays may not recapitulate intact octamer binding\", \"the in vivo relevance of the PTM-tuned binding untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NAPL's histone cargo is directed toward the nucleus and handed to PfNAPS in vivo, and how CKII phosphorylation is regulated across the parasite life cycle, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no in vivo demonstration of the proposed nucleocytoplasmic shuttling\", \"CKII phosphosites and their dynamic regulation unmapped\", \"no conditional depletion to define essential function\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0140713\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0042802\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006334\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfNAPS\", \"histone H3\", \"histone H4\", \"linker histone H1\", \"casein kinase II\"],\n    \"other_free_text\": [\n      \"Dimeric NAP-fold lacking the accessory domain present in yeast NAP-1 [#2].\",\n      \"Phosphorylation by casein kinase II increases histone affinity ~3-fold [#1].\",\n      \"Binds but does not deposit histones onto DNA; PfNAPS extracts histones from NAPL, consistent with a histone-relay role [#1].\",\n      \"Gene disruption attempts failed, indicating essentiality [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1203700","name":null,"product":"nucleosome assembly protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0602700","name":null,"product":"nucleosome assembly protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1303500","name":null,"product":"nucleosome assembly protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NAPL","evaluation":null}