{"gene":"PF3D7_0624600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2009,"finding":"ISWI (PF3D7_0624600) was identified as a phosphorylated protein in P. falciparum-infected erythrocytes, detected by affinity enrichment of phosphoproteins combined with LC/MS/MS from trophozoite-stage parasites.","method":"Affinity chromatography enrichment of phosphoproteins followed by nano-flow LC/MS/MS mass spectrometry","journal":"Malaria journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single phosphoproteomic screen, no functional follow-up, single lab, single method","pmids":["19450262"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"ItG"}]},{"year":2009,"finding":"ISWI (PF3D7_0624600) localizes to a distinct nuclear sub-compartment in P. falciparum, as determined by GFP or HA epitope tagging and fluorescence localization analysis.","method":"GFP/HA epitope tagging and fluorescence microscopy localization","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment with epitope tagging, reported in context of broader nuclear architecture study, single lab","pmids":["19765590"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"ISWI (PF3D7_0624600) was co-immunoprecipitated with both PfCK2β1 and PfCK2β2 regulatory subunits of protein kinase CK2, placing it in chromatin assembly/remodeling complexes associated with CK2 in P. falciparum.","method":"Immunoprecipitation of HA-tagged PfCK2β1 and PfCK2β2 followed by mass spectrometry identification","journal":"BMC biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment, no reciprocal pull-down of ISWI itself, single lab","pmids":["22293287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Human ISWI-type remodeler Snf2H moved P. falciparum nucleosomes less efficiently than human nucleosomes in an in vitro remodeling assay, attributable partly to a V21I substitution in the plasmodium histone H4 tail that affects recognition by ISWI-type enzymes. This establishes that the plasmodium nucleosome is a suboptimal substrate for ISWI-type remodeling, though it is a property of the substrate rather than a direct finding about PF3D7_0624600 itself.","method":"In vitro nucleosome remodeling assay using recombinant Snf2H (human ISWI-type) on fluorescently labeled P. falciparum vs. human nucleosomes; competitive bandshift and hybrid octamer experiments","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 1 method but finding concerns the substrate (P. falciparum nucleosome) and human Snf2H, not PF3D7_0624600 itself; Weak relevance to the query gene","pmids":["28033404"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"ISWI (PF3D7_0624600) was validated by chromatin immunoprecipitation (using catalytically inactive dCas9) to be associated with active var gene promoter regions in P. falciparum, placing it in a chromatin complex at var gene loci.","method":"Catalytically inactive Cas9 (dCas9)-based chromatin isolation followed by protein identification (referenced as Bryant et al., 2020 in corpus papers)","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct chromatin occupancy experiment at var promoters, but described only secondarily in PMID:36379669; single lab, single method","pmids":["36379669"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"ISWI (PF3D7_0624600) was identified as a co-immunoprecipitated partner of PfMORC (PF3D7_1468100) by immunoprecipitation followed by mass spectrometry, placing it in the PfMORC chromatin complex associated with heterochromatin and subtelomeric var gene regulation in P. falciparum.","method":"Immunoprecipitation of HA-tagged PfMORC followed by mass spectrometry (IP-MS) with QPROT statistical framework","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/MS from two independent PfMORC-HA replicate pull-downs, corroborated by prior literature on the same interaction; single lab","pmids":["39636094"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"ISWI (PF3D7_0624600) was identified as an interactor of PfSET10 by TurboID proximity labeling coupled with mass spectrometry, placing it in a broader chromatin modulation network in P. falciparum blood stages.","method":"TurboID proximity labeling fused to PfSET10 followed by mass spectrometry","journal":"mSphere","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labeling (not direct binding), single lab, single method; ISWI is one of many proteins detected","pmids":["39445823"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"ISWI (PF3D7_0624600) was co-immunoprecipitated with PfEAF2 (a shared subunit of PfNuA4 and PfSWR1 complexes) by reciprocal pulldown mass spectrometry, indicating ISWI associates with the PfSWR1/NuA4 chromatin remodeling network in P. falciparum.","method":"Affinity pulldown of HA-tagged PfEAF2 followed by mass spectrometry","journal":"mSphere","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown/MS experiment with ISWI as a secondary hit, single lab, single method","pmids":["38564734"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"ISWI (PBANKA_1123500, P. berghei ortholog of PF3D7_0624600) was co-identified by RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins) with both PbAP2-TR and PbMORC, indicating it is a component of the PbAP2-TR/PbMORC transcriptional repressor complex during the intraerythrocytic cycle of P. berghei.","method":"RIME (chromatin-directed immunoprecipitation mass spectrometry) of PbAP2-TR and PbMORC","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — RIME identification with relatively low aveQV scores for ISWI compared to core complex members; single lab, single method","pmids":["41484140"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2024,"finding":"ISWI (PBANKA_1123500, P. berghei ortholog of PF3D7_0624600) was detected with low aveQV in co-immunoprecipitation of PbARID (a SWI/SNF subunit), suggesting a possible association with the PbARID complex during gametocyte development, though at low confidence.","method":"Co-immunoprecipitation of PbARID followed by mass spectrometry (RIME)","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — very low aveQV score (3.0) for ISWI in the PbARID IP; authors explicitly note low confidence; single lab, single method","pmids":["38554111"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"ISWI (PF3D7_0624600) phosphorylation status was altered in PfPPM2-depleted P. falciparum parasites, identifying it as a potential substrate (directly or indirectly) of the protein phosphatase PfPPM2 in chromatin remodeling regulation during asexual blood stage development.","method":"Quantitative phosphoproteomic profiling of PfPPM2-knockdown parasites by mass spectrometry","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — phosphoproteomic screen identifies differential phosphorylation but does not establish direct dephosphorylation of ISWI by PfPPM2; single lab, single method","pmids":["40410154"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"ISWI (PF3D7_0624600) transcript is upregulated specifically during gametocyte commitment (not during subsequent gametocyte development), and its expression is correlated with ap2-g de-repression, placing ISWI upstream of or coincident with PfAP2-G activation in the sexual commitment cascade.","method":"Time-course transcriptomics (RNA-seq) across gametocytogenesis stages; comparison of commitment-stage vs. development-stage transcriptomes","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — transcriptomic expression correlation only, no direct functional experiment on ISWI; single study","pmids":["31795940"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0624600 (ISWI) is a nuclear chromatin-remodeling ATPase in P. falciparum that physically associates with PfMORC, PfSET10, PfCK2 regulatory subunits, and PfEAF2-containing complexes (PfSWR1/NuA4), and is recruited to active var gene promoter regions; its phosphorylation state is regulated downstream of PfPPM2; transcript levels peak during sexual commitment upstream of PfAP2-G, but direct enzymatic activity, substrate specificity, or loss-of-function phenotypes for PF3D7_0624600 itself have not yet been established in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_0624600 (ISWI) is a nuclear chromatin-associated ATPase of Plasmodium falciparum that localizes to a distinct nuclear sub-compartment [PMID:19765590] and participates in chromatin-remodeling and transcriptional-regulatory networks in the parasite [PMID:36379669, PMID:39636094]. It is recruited to active var gene promoter regions [PMID:36379669] and physically associates with the PfMORC chromatin complex linked to heterochromatin and subtelomeric var gene regulation [PMID:39636094]; in the P. berghei ortholog (PBANKA_1123500), ISWI is co-identified within the AP2-TR/MORC transcriptional repressor complex during the intraerythrocytic cycle [PMID:41484140]. Its regulatory context is further defined by phosphorylation: ISWI is a phosphoprotein in blood-stage parasites [PMID:19450262] whose phosphorylation status changes upon depletion of the phosphatase PfPPM2 [PMID:40410154]. Beyond membership in these chromatin complexes and its regulated phosphorylation, the direct enzymatic activity, substrate specificity, and loss-of-function phenotype of PF3D7_0624600 itself have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Establishing that ISWI is post-translationally modified addressed whether the remodeler is subject to signaling control in blood-stage parasites.","evidence":"Phosphoprotein affinity enrichment with LC/MS/MS from trophozoite-stage P. falciparum","pmids":["19450262"],"confidence":"Low","gaps":["Phosphosites and their functional consequence not defined","No kinase assigned","Single screen without functional follow-up"],"attribution":[{"species":"Plasmodium falciparum","strain":"ItG"}]},{"year":2009,"claim":"Defining where ISWI resides addressed whether the ATPase occupies a specialized nuclear territory consistent with a chromatin role.","evidence":"GFP/HA epitope tagging with fluorescence microscopy in P. falciparum","pmids":["19765590"],"confidence":"Medium","gaps":["The specific chromatin loci occupied were not resolved here","No link to a defined remodeling activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Co-purification with CK2 regulatory subunits placed ISWI within CK2-associated chromatin assembly/remodeling complexes, connecting the remodeler to a kinase network.","evidence":"IP of HA-tagged PfCK2β1/PfCK2β2 followed by mass spectrometry","pmids":["22293287"],"confidence":"Low","gaps":["No reciprocal pulldown of ISWI","Direct binding vs. shared complex membership not distinguished","Functional consequence of the association unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Testing plasmodium nucleosomes as substrates for a human ISWI-type enzyme addressed whether parasite chromatin is intrinsically remodelable, though it concerns the substrate rather than PF3D7_0624600 itself.","evidence":"In vitro remodeling assays with recombinant human Snf2H on P. falciparum vs. human nucleosomes; hybrid octamer and bandshift experiments","pmids":["28033404"],"confidence":"Low","gaps":["Not performed with PF3D7_0624600 protein","Enzymatic parameters of the parasite ISWI itself unmeasured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Correlating ISWI transcript timing with ap2-g de-repression addressed whether the remodeler is deployed at the point of sexual commitment.","evidence":"Time-course RNA-seq across gametocytogenesis stages in P. falciparum","pmids":["31795940"],"confidence":"Low","gaps":["Transcript correlation only, no functional test","Causal relationship to ap2-g activation not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Direct chromatin occupancy mapping addressed whether ISWI is physically present at var gene regulatory DNA, linking it to antigenic variation control.","evidence":"dCas9-based chromatin isolation and protein identification at active var promoters in P. falciparum","pmids":["36379669"],"confidence":"Medium","gaps":["Whether ISWI recruitment activates or maintains var expression not shown","Direct vs. complex-mediated occupancy unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Co-purification studies across multiple chromatin machineries addressed which complexes ISWI belongs to, defining its interaction landscape.","evidence":"IP-MS of PfMORC, TurboID proximity labeling of PfSET10, and reciprocal pulldown of PfEAF2 (PfSWR1/NuA4) in P. falciparum; RIME of PbAP2-TR/PbMORC and PbARID in P. berghei","pmids":["39636094","39445823","38564734","41484140","38554111"],"confidence":"Medium","gaps":["Most interactions are single Co-IP/proximity hits without reciprocal validation for ISWI","P. berghei associations (AP2-TR/MORC, ARID) reported at low confidence scores","Whether ISWI is a stable core subunit or transient associate of these complexes unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2025,"claim":"Perturbing a phosphatase addressed how ISWI phosphorylation is controlled, placing it downstream of PfPPM2 signaling in blood-stage chromatin regulation.","evidence":"Quantitative phosphoproteomics of PfPPM2-knockdown P. falciparum parasites","pmids":["40410154"],"confidence":"Low","gaps":["Direct dephosphorylation of ISWI by PfPPM2 not demonstrated","Functional consequence of altered phosphorylation on remodeling activity unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic ATPase/remodeling activity, substrate specificity, and loss-of-function phenotype of PF3D7_0624600 itself remain undefined.","evidence":"No direct enzymatic or genetic characterization of the gene product in the corpus","pmids":[],"confidence":"Low","gaps":["No knockout/knockdown phenotype for ISWI","No demonstration of nucleosome remodeling by the parasite protein","Role at var promoters vs. sexual commitment vs. heterochromatin not functionally dissected"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfMORC chromatin complex [#5]","PfEAF2-containing PfSWR1/NuA4 network [#7]","PbAP2-TR/PbMORC transcriptional repressor complex (P. berghei) [#8]","PbARID/SWI-SNF complex, low confidence (P. berghei) [#9]","PfCK2-associated chromatin remodeling complex [#2]"],"partners":["PFMORC (PF3D7_1468100) [#5]","PFSET10 [#6]","PFEAF2 [#7]","PFCK2Β1 / PFCK2Β2 [#2]","PBAP2-TR (P. BERGHEI) [#8]","PBMORC (P. BERGHEI) [#8]","PBARID (P. BERGHEI) [#9]"],"other_free_text":["Phosphoprotein whose phosphorylation status is altered upon PfPPM2 depletion [#0, #10]","Occupies active var gene promoter regions [#4]","Transcript upregulated specifically during gametocyte commitment, correlated with ap2-g de-repression [#11]","P. falciparum nucleosomes are a suboptimal substrate for ISWI-type remodeling due to a histone H4 V21I substitution (shown with human Snf2H, not the parasite protein) [#3]"]}},"prefetch_data":{},"corpus_meta":[{"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 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microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41130920","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISWI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41484140","id":"","title":"Precise gene regulation through transcriptional repression is essential for Plasmodium berghei asexual blood stage development.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41484140","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISWI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39412522","id":"","title":"A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with 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parasites.\",\n      \"method\": \"Affinity chromatography enrichment of phosphoproteins followed by nano-flow LC/MS/MS mass spectrometry\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single phosphoproteomic screen, no functional follow-up, single lab, single method\",\n      \"pmids\": [\"19450262\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"ItG\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"ISWI (PF3D7_0624600) localizes to a distinct nuclear sub-compartment in P. falciparum, as determined by GFP or HA epitope tagging and fluorescence localization analysis.\",\n      \"method\": \"GFP/HA epitope tagging and fluorescence microscopy localization\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment with epitope tagging, reported in context of broader nuclear architecture study, single lab\",\n      \"pmids\": [\"19765590\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ISWI (PF3D7_0624600) was co-immunoprecipitated with both PfCK2β1 and PfCK2β2 regulatory subunits of protein kinase CK2, placing it in chromatin assembly/remodeling complexes associated with CK2 in P. falciparum.\",\n      \"method\": \"Immunoprecipitation of HA-tagged PfCK2β1 and PfCK2β2 followed by mass spectrometry identification\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment, no reciprocal pull-down of ISWI itself, single lab\",\n      \"pmids\": [\"22293287\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Human ISWI-type remodeler Snf2H moved P. falciparum nucleosomes less efficiently than human nucleosomes in an in vitro remodeling assay, attributable partly to a V21I substitution in the plasmodium histone H4 tail that affects recognition by ISWI-type enzymes. This establishes that the plasmodium nucleosome is a suboptimal substrate for ISWI-type remodeling, though it is a property of the substrate rather than a direct finding about PF3D7_0624600 itself.\",\n      \"method\": \"In vitro nucleosome remodeling assay using recombinant Snf2H (human ISWI-type) on fluorescently labeled P. falciparum vs. human nucleosomes; competitive bandshift and hybrid octamer experiments\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 method but finding concerns the substrate (P. falciparum nucleosome) and human Snf2H, not PF3D7_0624600 itself; Weak relevance to the query gene\",\n      \"pmids\": [\"28033404\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ISWI (PF3D7_0624600) was validated by chromatin immunoprecipitation (using catalytically inactive dCas9) to be associated with active var gene promoter regions in P. falciparum, placing it in a chromatin complex at var gene loci.\",\n      \"method\": \"Catalytically inactive Cas9 (dCas9)-based chromatin isolation followed by protein identification (referenced as Bryant et al., 2020 in corpus papers)\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct chromatin occupancy experiment at var promoters, but described only secondarily in PMID:36379669; single lab, single method\",\n      \"pmids\": [\"36379669\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ISWI (PF3D7_0624600) was identified as a co-immunoprecipitated partner of PfMORC (PF3D7_1468100) by immunoprecipitation followed by mass spectrometry, placing it in the PfMORC chromatin complex associated with heterochromatin and subtelomeric var gene regulation in P. falciparum.\",\n      \"method\": \"Immunoprecipitation of HA-tagged PfMORC followed by mass spectrometry (IP-MS) with QPROT statistical framework\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/MS from two independent PfMORC-HA replicate pull-downs, corroborated by prior literature on the same interaction; single lab\",\n      \"pmids\": [\"39636094\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ISWI (PF3D7_0624600) was identified as an interactor of PfSET10 by TurboID proximity labeling coupled with mass spectrometry, placing it in a broader chromatin modulation network in P. falciparum blood stages.\",\n      \"method\": \"TurboID proximity labeling fused to PfSET10 followed by mass spectrometry\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labeling (not direct binding), single lab, single method; ISWI is one of many proteins detected\",\n      \"pmids\": [\"39445823\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ISWI (PF3D7_0624600) was co-immunoprecipitated with PfEAF2 (a shared subunit of PfNuA4 and PfSWR1 complexes) by reciprocal pulldown mass spectrometry, indicating ISWI associates with the PfSWR1/NuA4 chromatin remodeling network in P. falciparum.\",\n      \"method\": \"Affinity pulldown of HA-tagged PfEAF2 followed by mass spectrometry\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown/MS experiment with ISWI as a secondary hit, single lab, single method\",\n      \"pmids\": [\"38564734\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ISWI (PBANKA_1123500, P. berghei ortholog of PF3D7_0624600) was co-identified by RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins) with both PbAP2-TR and PbMORC, indicating it is a component of the PbAP2-TR/PbMORC transcriptional repressor complex during the intraerythrocytic cycle of P. berghei.\",\n      \"method\": \"RIME (chromatin-directed immunoprecipitation mass spectrometry) of PbAP2-TR and PbMORC\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — RIME identification with relatively low aveQV scores for ISWI compared to core complex members; single lab, single method\",\n      \"pmids\": [\"41484140\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ISWI (PBANKA_1123500, P. berghei ortholog of PF3D7_0624600) was detected with low aveQV in co-immunoprecipitation of PbARID (a SWI/SNF subunit), suggesting a possible association with the PbARID complex during gametocyte development, though at low confidence.\",\n      \"method\": \"Co-immunoprecipitation of PbARID followed by mass spectrometry (RIME)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — very low aveQV score (3.0) for ISWI in the PbARID IP; authors explicitly note low confidence; single lab, single method\",\n      \"pmids\": [\"38554111\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ISWI (PF3D7_0624600) phosphorylation status was altered in PfPPM2-depleted P. falciparum parasites, identifying it as a potential substrate (directly or indirectly) of the protein phosphatase PfPPM2 in chromatin remodeling regulation during asexual blood stage development.\",\n      \"method\": \"Quantitative phosphoproteomic profiling of PfPPM2-knockdown parasites by mass spectrometry\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — phosphoproteomic screen identifies differential phosphorylation but does not establish direct dephosphorylation of ISWI by PfPPM2; single lab, single method\",\n      \"pmids\": [\"40410154\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ISWI (PF3D7_0624600) transcript is upregulated specifically during gametocyte commitment (not during subsequent gametocyte development), and its expression is correlated with ap2-g de-repression, placing ISWI upstream of or coincident with PfAP2-G activation in the sexual commitment cascade.\",\n      \"method\": \"Time-course transcriptomics (RNA-seq) across gametocytogenesis stages; comparison of commitment-stage vs. development-stage transcriptomes\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — transcriptomic expression correlation only, no direct functional experiment on ISWI; single study\",\n      \"pmids\": [\"31795940\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0624600 (ISWI) is a nuclear chromatin-remodeling ATPase in P. falciparum that physically associates with PfMORC, PfSET10, PfCK2 regulatory subunits, and PfEAF2-containing complexes (PfSWR1/NuA4), and is recruited to active var gene promoter regions; its phosphorylation state is regulated downstream of PfPPM2; transcript levels peak during sexual commitment upstream of PfAP2-G, but direct enzymatic activity, substrate specificity, or loss-of-function phenotypes for PF3D7_0624600 itself have not yet been established in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0624600 (ISWI) is a nuclear chromatin-associated ATPase of Plasmodium falciparum that localizes to a distinct nuclear sub-compartment [#1] and participates in chromatin-remodeling and transcriptional-regulatory networks in the parasite [#4, #5]. It is recruited to active var gene promoter regions [#4] and physically associates with the PfMORC chromatin complex linked to heterochromatin and subtelomeric var gene regulation [#5]; in the P. berghei ortholog (PBANKA_1123500), ISWI is co-identified within the AP2-TR/MORC transcriptional repressor complex during the intraerythrocytic cycle [#8]. Its regulatory context is further defined by phosphorylation: ISWI is a phosphoprotein in blood-stage parasites [#0] whose phosphorylation status changes upon depletion of the phosphatase PfPPM2 [#10]. Beyond membership in these chromatin complexes and its regulated phosphorylation, the direct enzymatic activity, substrate specificity, and loss-of-function phenotype of PF3D7_0624600 itself have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing that ISWI is post-translationally modified addressed whether the remodeler is subject to signaling control in blood-stage parasites.\",\n      \"evidence\": \"Phosphoprotein affinity enrichment with LC/MS/MS from trophozoite-stage P. falciparum\",\n      \"pmids\": [\"19450262\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Phosphosites and their functional consequence not defined\", \"No kinase assigned\", \"Single screen without functional follow-up\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"ItG\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Defining where ISWI resides addressed whether the ATPase occupies a specialized nuclear territory consistent with a chromatin role.\",\n      \"evidence\": \"GFP/HA epitope tagging with fluorescence microscopy in P. falciparum\",\n      \"pmids\": [\"19765590\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The specific chromatin loci occupied were not resolved here\", \"No link to a defined remodeling activity\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Co-purification with CK2 regulatory subunits placed ISWI within CK2-associated chromatin assembly/remodeling complexes, connecting the remodeler to a kinase network.\",\n      \"evidence\": \"IP of HA-tagged PfCK2\\u03b21/PfCK2\\u03b22 followed by mass spectrometry\",\n      \"pmids\": [\"22293287\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reciprocal pulldown of ISWI\", \"Direct binding vs. shared complex membership not distinguished\", \"Functional consequence of the association unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Testing plasmodium nucleosomes as substrates for a human ISWI-type enzyme addressed whether parasite chromatin is intrinsically remodelable, though it concerns the substrate rather than PF3D7_0624600 itself.\",\n      \"evidence\": \"In vitro remodeling assays with recombinant human Snf2H on P. falciparum vs. human nucleosomes; hybrid octamer and bandshift experiments\",\n      \"pmids\": [\"28033404\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Not performed with PF3D7_0624600 protein\", \"Enzymatic parameters of the parasite ISWI itself unmeasured\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Correlating ISWI transcript timing with ap2-g de-repression addressed whether the remodeler is deployed at the point of sexual commitment.\",\n      \"evidence\": \"Time-course RNA-seq across gametocytogenesis stages in P. falciparum\",\n      \"pmids\": [\"31795940\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Transcript correlation only, no functional test\", \"Causal relationship to ap2-g activation not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Direct chromatin occupancy mapping addressed whether ISWI is physically present at var gene regulatory DNA, linking it to antigenic variation control.\",\n      \"evidence\": \"dCas9-based chromatin isolation and protein identification at active var promoters in P. falciparum\",\n      \"pmids\": [\"36379669\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether ISWI recruitment activates or maintains var expression not shown\", \"Direct vs. complex-mediated occupancy unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Co-purification studies across multiple chromatin machineries addressed which complexes ISWI belongs to, defining its interaction landscape.\",\n      \"evidence\": \"IP-MS of PfMORC, TurboID proximity labeling of PfSET10, and reciprocal pulldown of PfEAF2 (PfSWR1/NuA4) in P. falciparum; RIME of PbAP2-TR/PbMORC and PbARID in P. berghei\",\n      \"pmids\": [\"39636094\", \"39445823\", \"38564734\", \"41484140\", \"38554111\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Most interactions are single Co-IP/proximity hits without reciprocal validation for ISWI\", \"P. berghei associations (AP2-TR/MORC, ARID) reported at low confidence scores\", \"Whether ISWI is a stable core subunit or transient associate of these complexes unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Perturbing a phosphatase addressed how ISWI phosphorylation is controlled, placing it downstream of PfPPM2 signaling in blood-stage chromatin regulation.\",\n      \"evidence\": \"Quantitative phosphoproteomics of PfPPM2-knockdown P. falciparum parasites\",\n      \"pmids\": [\"40410154\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Direct dephosphorylation of ISWI by PfPPM2 not demonstrated\", \"Functional consequence of altered phosphorylation on remodeling activity unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic ATPase/remodeling activity, substrate specificity, and loss-of-function phenotype of PF3D7_0624600 itself remain undefined.\",\n      \"evidence\": \"No direct enzymatic or genetic characterization of the gene product in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No knockout/knockdown phenotype for ISWI\", \"No demonstration of nucleosome remodeling by the parasite protein\", \"Role at var promoters vs. sexual commitment vs. heterochromatin not functionally dissected\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140658\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006338\", \"supporting_discovery_ids\": [4, 5, 7]},\n      {\"term_id\": \"GO:0045892\", \"supporting_discovery_ids\": [5, 8]},\n      {\"term_id\": \"GO:0060968\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"PfMORC chromatin complex [#5]\",\n      \"PfEAF2-containing PfSWR1/NuA4 network [#7]\",\n      \"PbAP2-TR/PbMORC transcriptional repressor complex (P. berghei) [#8]\",\n      \"PbARID/SWI-SNF complex, low confidence (P. berghei) [#9]\",\n      \"PfCK2-associated chromatin remodeling complex [#2]\"\n    ],\n    \"partners\": [\n      \"PfMORC (PF3D7_1468100) [#5]\",\n      \"PfSET10 [#6]\",\n      \"PfEAF2 [#7]\",\n      \"PfCK2\\u03b21 / PfCK2\\u03b22 [#2]\",\n      \"PbAP2-TR (P. berghei) [#8]\",\n      \"PbMORC (P. berghei) [#8]\",\n      \"PbARID (P. berghei) [#9]\"\n    ],\n    \"other_free_text\": [\n      \"Phosphoprotein whose phosphorylation status is altered upon PfPPM2 depletion [#0, #10]\",\n      \"Occupies active var gene promoter regions [#4]\",\n      \"Transcript upregulated specifically during gametocyte commitment, correlated with ap2-g de-repression [#11]\",\n      \"P. falciparum nucleosomes are a suboptimal substrate for ISWI-type remodeling due to a histone H4 V21I substitution (shown with human Snf2H, not the parasite protein) [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0624600","name":null,"product":"ISWI chromatin-remodeling complex ATPase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1123500","name":null,"product":"ISWI chromatin-remodeling complex ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1125600","name":null,"product":"ISWI chromatin-remodeling complex ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ISWI","evaluation":null}