{"gene":"PF3D7_0905100","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2018,"finding":"NUP221 (PF3D7_0905100) was identified as a nucleoporin component of the nuclear pore complex (NPC) in Plasmodium parasites using bioinformatic and genetic methods; the P. falciparum ortholog was recognized from the P. berghei characterization, establishing NUP221 as part of the NPC macromolecular assembly.","method":"Bioinformatic identification combined with genetic tagging and localization experiments; cryo electron tomography of Plasmodium NPCs","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization by genetic tagging established NPC membership, but NUP221-specific functional data are minimal; single study","pmids":["30050042"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"NUP221 (PF3D7_0905100 ortholog in P. berghei) localizes around nuclei and is organized in a rosette structure around the centriolar plaque during blood-stage asexual replication; using the recombination-induced tag exchange (RITE) system, NUP221 was shown to undergo turnover (exchange) within intact nuclear pore complexes during asexual replication, demonstrating NPC formation/homeostasis dynamics without nuclear envelope breakdown.","method":"Ultrastructure expansion microscopy (U-ExM) for localization; recombination-induced tag exchange (RITE) system adapted to P. berghei via a single plasmid tagging system including Cre recombinase, to demonstrate Nup221 turnover","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization by U-ExM combined with orthogonal RITE-based turnover assay in a single rigorous study; peer-reviewed publication","pmids":["39526784"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"NUP221 (PF3D7_0905100) is a nucleoporin component of the nuclear pore complex in Plasmodium parasites that localizes in a rosette arrangement around the centriolar plaque during blood-stage asexual replication and undergoes dynamic turnover/exchange within intact NPCs during closed mitosis, contributing to NPC homeostasis without nuclear envelope breakdown."},"narrative":{"mechanistic_narrative":"NUP221 (PF3D7_0905100) is a nucleoporin component of the nuclear pore complex (NPC) in Plasmodium parasites, identified as part of the NPC macromolecular assembly through bioinformatic and genetic characterization, with the P. falciparum protein recognized from its P. berghei ortholog [PMID:30050042]. In P. berghei, NUP221 localizes around the nucleus and is arranged in a rosette structure around the centriolar plaque during blood-stage asexual replication, and it undergoes turnover/exchange within intact NPCs during this replication, indicating that NPC formation and homeostasis proceed without nuclear envelope breakdown [PMID:39526784]. Beyond its membership in the NPC and this replication-associated turnover behavior, no NUP221-specific molecular function, binding partners, or structural detail have been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing which parasite proteins build the NPC was the first step; identifying NUP221 as a nucleoporin placed it within the NPC macromolecular assembly.","evidence":"Bioinformatic identification with genetic tagging and localization, plus cryo electron tomography of Plasmodium NPCs, with the P. falciparum ortholog inferred from P. berghei","pmids":["30050042"],"confidence":"Medium","gaps":["No NUP221-specific molecular activity or binding partners defined","Functional role of NUP221 within the NPC not tested","Assignment of the P. falciparum gene rests on orthology to P. berghei"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Whether NPCs are static or remodeled during closed mitosis was unresolved; showing NUP221 turnover within intact pores established that NPC homeostasis occurs without nuclear envelope breakdown during asexual replication.","evidence":"U-ExM localization plus a RITE (recombination-induced tag exchange) turnover assay adapted to P. berghei via a single-plasmid Cre-recombinase tagging system","pmids":["39526784"],"confidence":"High","gaps":["Not demonstrated in P. falciparum","Molecular mechanism and machinery driving NUP221 exchange unknown","Functional consequence of blocking NUP221 turnover not tested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The molecular function of NUP221 beyond NPC membership and its turnover behavior remains undefined, including its interaction partners, structural placement within the pore, and any phenotype upon loss of function.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct binding partners or subcomplex assignment for NUP221","No loss-of-function or essentiality data","No P. falciparum-specific functional characterization"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Nuclear pore complex (NPC)"],"partners":[],"other_free_text":["In P. berghei, NUP221 is arranged in a rosette around the centriolar plaque during blood-stage asexual replication [#1].","NUP221 undergoes turnover/exchange within intact NPCs during closed mitosis, consistent with NPC homeostasis without nuclear envelope breakdown [#1].","The P. falciparum gene (PF3D7_0905100) assignment derives from orthology to the characterized P. berghei protein [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30050042","id":"PMC_30050042","title":"Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30050042","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39526784","id":"PMC_39526784","title":"Nuclear pore complexes undergo Nup221 exchange during blood-stage asexual replication of Plasmodium parasites.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/39526784","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUP221"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38405843","id":"PMC_38405843","title":"Nuclear pore complexes undergo Nup221 exchange during blood stage asexual replication of Plasmodium parasites.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38405843","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUP221"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4475,"output_tokens":720,"usd":0.012113,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5355,"output_tokens":1548,"usd":0.032738,"stage2_stop_reason":"end_turn"},"total_usd":0.044851,"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\": 2018,\n      \"finding\": \"NUP221 (PF3D7_0905100) was identified as a nucleoporin component of the nuclear pore complex (NPC) in Plasmodium parasites using bioinformatic and genetic methods; the P. falciparum ortholog was recognized from the P. berghei characterization, establishing NUP221 as part of the NPC macromolecular assembly.\",\n      \"method\": \"Bioinformatic identification combined with genetic tagging and localization experiments; cryo electron tomography of Plasmodium NPCs\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization by genetic tagging established NPC membership, but NUP221-specific functional data are minimal; single study\",\n      \"pmids\": [\"30050042\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NUP221 (PF3D7_0905100 ortholog in P. berghei) localizes around nuclei and is organized in a rosette structure around the centriolar plaque during blood-stage asexual replication; using the recombination-induced tag exchange (RITE) system, NUP221 was shown to undergo turnover (exchange) within intact nuclear pore complexes during asexual replication, demonstrating NPC formation/homeostasis dynamics without nuclear envelope breakdown.\",\n      \"method\": \"Ultrastructure expansion microscopy (U-ExM) for localization; recombination-induced tag exchange (RITE) system adapted to P. berghei via a single plasmid tagging system including Cre recombinase, to demonstrate Nup221 turnover\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by U-ExM combined with orthogonal RITE-based turnover assay in a single rigorous study; peer-reviewed publication\",\n      \"pmids\": [\"39526784\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"NUP221 (PF3D7_0905100) is a nucleoporin component of the nuclear pore complex in Plasmodium parasites that localizes in a rosette arrangement around the centriolar plaque during blood-stage asexual replication and undergoes dynamic turnover/exchange within intact NPCs during closed mitosis, contributing to NPC homeostasis without nuclear envelope breakdown.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP221 (PF3D7_0905100) is a nucleoporin component of the nuclear pore complex (NPC) in Plasmodium parasites, identified as part of the NPC macromolecular assembly through bioinformatic and genetic characterization, with the P. falciparum protein recognized from its P. berghei ortholog [#0]. In P. berghei, NUP221 localizes around the nucleus and is arranged in a rosette structure around the centriolar plaque during blood-stage asexual replication, and it undergoes turnover/exchange within intact NPCs during this replication, indicating that NPC formation and homeostasis proceed without nuclear envelope breakdown [#1]. Beyond its membership in the NPC and this replication-associated turnover behavior, no NUP221-specific molecular function, binding partners, or structural detail have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing which parasite proteins build the NPC was the first step; identifying NUP221 as a nucleoporin placed it within the NPC macromolecular assembly.\",\n      \"evidence\": \"Bioinformatic identification with genetic tagging and localization, plus cryo electron tomography of Plasmodium NPCs, with the P. falciparum ortholog inferred from P. berghei\",\n      \"pmids\": [\"30050042\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No NUP221-specific molecular activity or binding partners defined\",\n        \"Functional role of NUP221 within the NPC not tested\",\n        \"Assignment of the P. falciparum gene rests on orthology to P. berghei\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether NPCs are static or remodeled during closed mitosis was unresolved; showing NUP221 turnover within intact pores established that NPC homeostasis occurs without nuclear envelope breakdown during asexual replication.\",\n      \"evidence\": \"U-ExM localization plus a RITE (recombination-induced tag exchange) turnover assay adapted to P. berghei via a single-plasmid Cre-recombinase tagging system\",\n      \"pmids\": [\"39526784\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Not demonstrated in P. falciparum\",\n        \"Molecular mechanism and machinery driving NUP221 exchange unknown\",\n        \"Functional consequence of blocking NUP221 turnover not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of NUP221 beyond NPC membership and its turnover behavior remains undefined, including its interaction partners, structural placement within the pore, and any phenotype upon loss of function.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct binding partners or subcomplex assignment for NUP221\",\n        \"No loss-of-function or essentiality data\",\n        \"No P. falciparum-specific functional characterization\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0017056\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0051292\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"Nuclear pore complex (NPC)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"In P. berghei, NUP221 is arranged in a rosette around the centriolar plaque during blood-stage asexual replication [#1].\",\n      \"NUP221 undergoes turnover/exchange within intact NPCs during closed mitosis, consistent with NPC homeostasis without nuclear envelope breakdown [#1].\",\n      \"The P. falciparum gene (PF3D7_0905100) assignment derives from orthology to the characterized P. berghei protein [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0905100","name":null,"product":"nucleoporin NUP221, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0416300","name":null,"product":"nucleoporin NUP221","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0702800","name":null,"product":"nucleoporin NUP221, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NUP221","evaluation":null}