{"gene":"PF3D7_0524000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2003,"finding":"PF3D7_0524000 (KASbeta) was cloned and characterized as a Plasmodium falciparum homolog of nuclear import factor karyopherin beta, establishing its identity as a nuclear import factor in the parasite.","method":"Cloning and molecular characterization","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — cloning and characterization study; abstract not fully available but referenced by subsequent work confirming the gene identity","pmids":["12672529"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"KASbeta (PF3D7_0524000) protein (~110 kDa) was localized to the cytoplasm at ring and trophozoite stages, and to the parasitophorous vacuole at the schizont stage, as determined by immunolocalization with antisera against recombinant N- and C-terminal fragments expressed in E. coli.","method":"Immunolocalization with recombinant protein-derived antisera; RT-PCR and Northern blot to confirm expression in blood stages","journal":"Parasite immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single-lab immunolocalization study with recombinant antigen-derived antisera; no functional consequence linked to localization","pmids":["15987343"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"KASbeta (PF3D7_0524000) is a transcriptional target of PfGCN5: under stress conditions (heat shock, low glucose, and dihydroartemisinin treatment), PfGCN5 is enriched at the 5′ UTR promoter region of KASbeta, and knockdown of PfGCN5 reduces this enrichment, indicating that PfGCN5-dependent histone acetyltransferase activity directly regulates KASbeta transcription during stress responses.","method":"Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) in TetR-DOZI conditional PfGCN5 knockdown parasites","journal":"Antimicrobial agents and chemotherapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct ChIP-qPCR evidence of PfGCN5 binding to KASbeta 5′ UTR under multiple stress conditions with conditional KD controls, single lab","pmids":["37702516"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"KASbeta (PF3D7_0524000) is a ~110 kDa karyopherin beta homolog in P. falciparum that localizes to the cytoplasm during ring and trophozoite stages and to the parasitophorous vacuole at the schizont stage; its transcription during stress conditions (heat shock, nutrient starvation, and artemisinin exposure) is directly regulated by PfGCN5, which binds its 5′ UTR promoter region in a stress-dependent manner."},"narrative":{"mechanistic_narrative":"KASbeta (PF3D7_0524000) is a Plasmodium falciparum homolog of the nuclear import factor karyopherin beta, cloned and characterized as a parasite nuclear import factor [PMID:12672529]. The ~110 kDa protein displays stage-dependent localization across the intraerythrocytic cycle, occupying the cytoplasm at ring and trophozoite stages and the parasitophorous vacuole at the schizont stage [PMID:15987343]. Its transcription is embedded in the parasite's stress response: under heat shock, low glucose, and dihydroartemisinin treatment, the histone acetyltransferase PfGCN5 is enriched at the KASbeta 5′ UTR promoter, and PfGCN5 knockdown reduces this enrichment, establishing KASbeta as a direct PfGCN5 transcriptional target during stress [PMID:37702516]. Beyond this identity, localization, and transcriptional regulation, the specific import cargoes, receptor interactions, and functional consequences of KASbeta activity have not been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing whether P. falciparum encodes a dedicated nuclear import machinery, the gene was cloned and identified as a karyopherin beta homolog, defining KASbeta as a candidate nuclear import factor in the parasite.","evidence":"Cloning and molecular characterization","pmids":["12672529"],"confidence":"Medium","gaps":["No direct demonstration of nuclear import activity or cargo binding","No identification of interacting importin-alpha or Ran partners","Functional role in parasite biology not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"To place KASbeta in the parasite cell, immunolocalization resolved its distribution across blood stages, unexpectedly revealing stage-specific relocation from cytoplasm to the parasitophorous vacuole rather than a purely nuclear-envelope pattern.","evidence":"Immunolocalization with recombinant antigen-derived antisera, plus RT-PCR and Northern blot confirming blood-stage expression","pmids":["15987343"],"confidence":"Medium","gaps":["No functional consequence linked to the stage-dependent localization","The parasitophorous vacuole localization at schizont stage is unexplained mechanistically","Single-lab study with antisera against recombinant fragments"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Addressing how KASbeta expression is controlled, ChIP-qPCR showed its 5′ UTR is a direct binding target of the acetyltransferase PfGCN5 under multiple stresses, embedding KASbeta transcription within a stress-responsive chromatin regulatory program.","evidence":"ChIP-qPCR in TetR-DOZI conditional PfGCN5 knockdown parasites under heat shock, low glucose, and dihydroartemisinin","pmids":["37702516"],"confidence":"Medium","gaps":["Whether KASbeta protein levels or import activity actually change under stress is not shown","Functional contribution of KASbeta to stress survival not tested","Single-lab correlative promoter-binding evidence"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct import cargoes, receptor/adapter partners, and the functional role of KASbeta in nuclear transport and stress adaptation remain unestablished.","evidence":"No direct evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No cargo or importin-alpha/Ran interaction identified","No loss-of-function phenotype for KASbeta itself","No structural or biochemical demonstration of transport activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFGCN5 (REGULATES KASBETA TRANSCRIPTION BY BINDING ITS 5′ UTR PROMOTER UNDER STRESS) [#2]"],"other_free_text":["KASbeta transcription is directly regulated by PfGCN5-dependent histone acetyltransferase activity during heat shock, nutrient starvation, and artemisinin (dihydroartemisinin) exposure [#2].","The corpus establishes KASbeta identity as a karyopherin beta homolog, stage-specific localization, and its status as a PfGCN5 transcriptional target, but does not characterize its import cargoes or functional partners beyond this."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12672529","id":"PMC_12672529","title":"Cloning and characterization of Plasmodium falciparum homologs of nuclear import factors, karyopherin alpha and karyopherin beta.","date":"2003","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/12672529","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["karyopherin beta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15987343","id":"PMC_15987343","title":"Identification of karyopherin beta as an immunogenic antigen of the malaria parasite using immune mice and human sera.","date":"2005","source":"Parasite immunology","url":"https://pubmed.ncbi.nlm.nih.gov/15987343","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["karyopherin beta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37702516","id":"","title":"Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses.","date":"2023","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/37702516","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["KASbeta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4876,"output_tokens":930,"usd":0.014289,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5645,"output_tokens":1980,"usd":0.038863,"stage2_stop_reason":"end_turn"},"total_usd":0.053152,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"PF3D7_0524000 (KASbeta) was cloned and characterized as a Plasmodium falciparum homolog of nuclear import factor karyopherin beta, establishing its identity as a nuclear import factor in the parasite.\",\n      \"method\": \"Cloning and molecular characterization\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — cloning and characterization study; abstract not fully available but referenced by subsequent work confirming the gene identity\",\n      \"pmids\": [\"12672529\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"KASbeta (PF3D7_0524000) protein (~110 kDa) was localized to the cytoplasm at ring and trophozoite stages, and to the parasitophorous vacuole at the schizont stage, as determined by immunolocalization with antisera against recombinant N- and C-terminal fragments expressed in E. coli.\",\n      \"method\": \"Immunolocalization with recombinant protein-derived antisera; RT-PCR and Northern blot to confirm expression in blood stages\",\n      \"journal\": \"Parasite immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab immunolocalization study with recombinant antigen-derived antisera; no functional consequence linked to localization\",\n      \"pmids\": [\"15987343\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KASbeta (PF3D7_0524000) is a transcriptional target of PfGCN5: under stress conditions (heat shock, low glucose, and dihydroartemisinin treatment), PfGCN5 is enriched at the 5′ UTR promoter region of KASbeta, and knockdown of PfGCN5 reduces this enrichment, indicating that PfGCN5-dependent histone acetyltransferase activity directly regulates KASbeta transcription during stress responses.\",\n      \"method\": \"Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) in TetR-DOZI conditional PfGCN5 knockdown parasites\",\n      \"journal\": \"Antimicrobial agents and chemotherapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct ChIP-qPCR evidence of PfGCN5 binding to KASbeta 5′ UTR under multiple stress conditions with conditional KD controls, single lab\",\n      \"pmids\": [\"37702516\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"KASbeta (PF3D7_0524000) is a ~110 kDa karyopherin beta homolog in P. falciparum that localizes to the cytoplasm during ring and trophozoite stages and to the parasitophorous vacuole at the schizont stage; its transcription during stress conditions (heat shock, nutrient starvation, and artemisinin exposure) is directly regulated by PfGCN5, which binds its 5′ UTR promoter region in a stress-dependent manner.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"KASbeta (PF3D7_0524000) is a Plasmodium falciparum homolog of the nuclear import factor karyopherin beta, cloned and characterized as a parasite nuclear import factor [#0]. The ~110 kDa protein displays stage-dependent localization across the intraerythrocytic cycle, occupying the cytoplasm at ring and trophozoite stages and the parasitophorous vacuole at the schizont stage [#1]. Its transcription is embedded in the parasite's stress response: under heat shock, low glucose, and dihydroartemisinin treatment, the histone acetyltransferase PfGCN5 is enriched at the KASbeta 5′ UTR promoter, and PfGCN5 knockdown reduces this enrichment, establishing KASbeta as a direct PfGCN5 transcriptional target during stress [#2]. Beyond this identity, localization, and transcriptional regulation, the specific import cargoes, receptor interactions, and functional consequences of KASbeta activity have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing whether P. falciparum encodes a dedicated nuclear import machinery, the gene was cloned and identified as a karyopherin beta homolog, defining KASbeta as a candidate nuclear import factor in the parasite.\",\n      \"evidence\": \"Cloning and molecular characterization\",\n      \"pmids\": [\"12672529\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct demonstration of nuclear import activity or cargo binding\",\n        \"No identification of interacting importin-alpha or Ran partners\",\n        \"Functional role in parasite biology not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"To place KASbeta in the parasite cell, immunolocalization resolved its distribution across blood stages, unexpectedly revealing stage-specific relocation from cytoplasm to the parasitophorous vacuole rather than a purely nuclear-envelope pattern.\",\n      \"evidence\": \"Immunolocalization with recombinant antigen-derived antisera, plus RT-PCR and Northern blot confirming blood-stage expression\",\n      \"pmids\": [\"15987343\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional consequence linked to the stage-dependent localization\",\n        \"The parasitophorous vacuole localization at schizont stage is unexplained mechanistically\",\n        \"Single-lab study with antisera against recombinant fragments\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Addressing how KASbeta expression is controlled, ChIP-qPCR showed its 5′ UTR is a direct binding target of the acetyltransferase PfGCN5 under multiple stresses, embedding KASbeta transcription within a stress-responsive chromatin regulatory program.\",\n      \"evidence\": \"ChIP-qPCR in TetR-DOZI conditional PfGCN5 knockdown parasites under heat shock, low glucose, and dihydroartemisinin\",\n      \"pmids\": [\"37702516\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether KASbeta protein levels or import activity actually change under stress is not shown\",\n        \"Functional contribution of KASbeta to stress survival not tested\",\n        \"Single-lab correlative promoter-binding evidence\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct import cargoes, receptor/adapter partners, and the functional role of KASbeta in nuclear transport and stress adaptation remain unestablished.\",\n      \"evidence\": \"No direct evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No cargo or importin-alpha/Ran interaction identified\",\n        \"No loss-of-function phenotype for KASbeta itself\",\n        \"No structural or biochemical demonstration of transport activity\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0061608\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006606\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006950\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfGCN5 (regulates KASbeta transcription by binding its 5′ UTR promoter under stress) [#2]\"\n    ],\n    \"other_free_text\": [\n      \"KASbeta transcription is directly regulated by PfGCN5-dependent histone acetyltransferase activity during heat shock, nutrient starvation, and artemisinin (dihydroartemisinin) exposure [#2].\",\n      \"The corpus establishes KASbeta identity as a karyopherin beta homolog, stage-specific localization, and its status as a PfGCN5 transcriptional target, but does not characterize its import cargoes or functional partners beyond this.\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0524000","name":null,"product":"karyopherin beta","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1238800","name":null,"product":"karyopherin beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1008900","name":null,"product":"karyopherin beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"KASbeta","evaluation":null}