{"gene":"PF3D7_1230700","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2013,"finding":"PF3D7_1230700 (SEC13/PfSec13) is a nucleoporin of P. falciparum that localizes dynamically to nuclear pore complexes (NPCs) during intra-erythrocytic development, and its NPC dynamics are associated with microtubules rather than F-actin, as shown by 3D-SIM super-resolution fluorescence microscopy and in vivo imaging.","method":"3D-SIM super-resolution fluorescence microscopy and in vivo imaging; co-localization with NPC markers and cytoskeletal markers","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiments with multiple imaging methods in a single lab establishing both NPC association and cytoskeletal linkage","pmids":["23687383"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PF3D7_1230700 (SEC13/PfSec13) does not co-localize with heterochromatin markers HP1 and H3K9me3, indicating that NPCs occupy euchromatic regions of the P. falciparum nucleus.","method":"Co-localization fluorescence microscopy with heterochromatin markers HP1 and H3K9me3","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct imaging with established chromatin markers, single lab","pmids":["23687383"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"In addition to NPC localization, PF3D7_1230700 (SEC13/PfSec13) is also found in the nucleoplasm where it is associated with chromatin, as revealed by ultrastructural analysis and chromatin immunoprecipitation (ChIP), indicating an unusual dual nucleoporin/chromatin-associated function.","method":"Chromatin immunoprecipitation (ChIP) and ultrastructural (electron microscopy) analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (ChIP + ultrastructural EM) in a single lab","pmids":["23687383"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PF3D7_1230700 (SEC13/PfSec13) is essential for P. falciparum parasite proliferation in human erythrocytes, as demonstrated by peptide nucleic acid (PNA)-mediated downregulation leading to loss of parasite growth.","method":"Peptide nucleic acid (PNA) knockdown of PfSec13 with parasite proliferation readout","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss-of-function via PNA with defined proliferation phenotype, single lab, single method","pmids":["23687383"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PF3D7_1230700 (SEC13/PfSec13) shows unique structural similarities suggesting it is a fusion protein combining features of Sec13 and Nup145C of yeast, making it an unusual nucleoporin.","method":"Bioinformatic structural similarity analysis","journal":"Journal of cell science","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic prediction only, no mutagenesis or structural validation reported","pmids":["23687383"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"SEC13 in P. berghei carries an extended C-terminal poly-proline extension that is largely restricted to apicomplexans and is essential for parasite survival, as shown by genetic analysis.","method":"Bioinformatic identification of poly-proline extension combined with genetic functional analysis in P. berghei","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with survival phenotype, supported by bioinformatic characterization, single lab","pmids":["30050042"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2018,"finding":"SEC13 is localized to the nuclear pore complex throughout the P. berghei life cycle, as determined by fluorescence imaging of tagged Nup components combined with cryo-electron tomography of Plasmodium NPCs.","method":"Fluorescence imaging of GFP-tagged Nups and cryo-electron tomography","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization across multiple life cycle stages with two complementary imaging methods, single lab","pmids":["30050042"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"A mutation in PF3D7_1230700 (SEC13), which encodes a component of the P. falciparum secretory machinery, reduces parasite susceptibility to the antimalarial compound MED6-189, implicating SEC13 in vesicular trafficking and/or the secretory pathway targeted by this drug.","method":"Genomic/genetic analysis identifying resistance-conferring mutation in SEC13 in drug-treated P. falciparum","journal":"Science (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic mutation identified by genomics with defined drug-resistance phenotype, single study, mechanistic pathway placement is inferential from drug mode-of-action","pmids":["39325875"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1230700 (SEC13) is an essential, structurally unusual nucleoporin of Plasmodium falciparum that localizes dynamically to nuclear pore complexes (associated with microtubules) and is also found in the nucleoplasm associated with chromatin; in P. berghei, an apicomplexan-specific C-terminal poly-proline extension in SEC13 is required for parasite survival, and in P. falciparum, a mutation in SEC13 confers reduced susceptibility to a drug targeting the secretory/vesicular trafficking pathway, indicating SEC13 participates in both nuclear pore function and secretory machinery."},"narrative":{"mechanistic_narrative":"PF3D7_1230700 (SEC13) is an essential nucleoporin of Plasmodium falciparum that localizes dynamically to nuclear pore complexes (NPCs) during intra-erythrocytic development, with NPC movement coupled to microtubules rather than F-actin [PMID:23687383]. It is an unusual nucleoporin in that, beyond its NPC pool, SEC13 also occupies the nucleoplasm in physical association with chromatin, and its NPCs are excluded from HP1/H3K9me3-marked heterochromatin, confining pores to euchromatic territory [PMID:23687383]. NPC localization persists throughout the life cycle in the P. berghei ortholog [PMID:30050042], and in P. berghei an apicomplexan-restricted C-terminal poly-proline extension of SEC13 is required for parasite survival [PMID:30050042]. SEC13 is essential for P. falciparum proliferation in human erythrocytes [PMID:23687383], and a resistance-conferring mutation in SEC13 reduces P. falciparum susceptibility to the antimalarial MED6-189, linking the protein to the secretory/vesicular trafficking pathway in addition to its nuclear pore role [PMID:39325875]. Beyond these observations, the detailed molecular mechanism connecting SEC13's nuclear pore, chromatin, and secretory functions has not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing where SEC13 acts and whether its dynamics depend on cytoskeleton addressed whether this protein is a bona fide nucleoporin with regulated pore behavior; imaging placed it at NPCs moving along microtubules.","evidence":"3D-SIM super-resolution microscopy and in vivo imaging with NPC and cytoskeletal markers in P. falciparum","pmids":["23687383"],"confidence":"Medium","gaps":["Molecular basis of the microtubule coupling is unresolved","Does not identify SEC13's direct NPC binding partners"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Whether NPCs and SEC13 relate to chromatin state was unknown; co-localization and ChIP/EM showed pores avoid heterochromatin and that SEC13 additionally binds chromatin in the nucleoplasm, defining an unusual dual role.","evidence":"Co-localization with HP1/H3K9me3 markers plus ChIP and ultrastructural EM in P. falciparum","pmids":["23687383"],"confidence":"Medium","gaps":["Functional consequence of SEC13 chromatin association is not defined","No genomic loci or gene-regulatory targets identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Whether SEC13 is required for the parasite was tested by knockdown, establishing it as essential for blood-stage proliferation.","evidence":"PNA-mediated knockdown of PfSec13 with parasite proliferation readout in P. falciparum","pmids":["23687383"],"confidence":"Medium","gaps":["Single knockdown method, no genetic complementation","Does not distinguish which SEC13 function (NPC vs chromatin) underlies essentiality"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Sequence/structure analysis addressed why SEC13 behaves unusually, predicting it is a Sec13–Nup145C fusion protein.","evidence":"Bioinformatic structural similarity analysis","pmids":["23687383"],"confidence":"Low","gaps":["Computational prediction only, no structural or mutagenesis validation","Fusion architecture not experimentally confirmed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether SEC13's unusual domain features matter for viability was tested in P. berghei, showing an apicomplexan-specific C-terminal poly-proline extension is essential and confirming NPC localization across the life cycle.","evidence":"Genetic functional analysis, GFP-tagged Nup imaging, and cryo-electron tomography in P. berghei","pmids":["30050042"],"confidence":"Medium","gaps":["Molecular function of the poly-proline extension is unknown","Findings in P. berghei not directly reproduced for the P. falciparum ortholog"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"A drug-resistance screen unexpectedly implicated SEC13 in secretory/vesicular trafficking, extending its role beyond the nuclear pore.","evidence":"Genomic identification of a MED6-189 resistance-conferring SEC13 mutation in P. falciparum","pmids":["39325875"],"confidence":"Medium","gaps":["Pathway placement is inferred from drug mode-of-action, not direct trafficking assay","How a single mutation confers resistance is not mechanistically defined","Relationship between SEC13's nuclear-pore and secretory roles is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown how SEC13's distinct activities — nuclear pore function, chromatin association, and secretory/vesicular trafficking — are mechanistically integrated within a single protein.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct interaction map of SEC13 in either compartment","No structural validation of the predicted fusion architecture","No assay directly connecting the drug-resistance mutation to a trafficking defect"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Nuclear pore complex (NPC)"],"partners":[],"other_free_text":["Essential for P. falciparum blood-stage proliferation (PNA knockdown) [#3]","Apicomplexan-restricted C-terminal poly-proline extension essential in P. berghei [#5]","Predicted Sec13–Nup145C fusion protein (bioinformatic, unvalidated) [#4]","NPC dynamics associated with microtubules, not F-actin [#0]","NPCs excluded from HP1/H3K9me3 heterochromatin, confined to euchromatin [#1]","MED6-189 resistance-conferring mutation implicates SEC13 in secretory/vesicular trafficking [#7]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23687383","id":"PMC_23687383","title":"PfSec13 is an unusual chromatin-associated nucleoporin of Plasmodium falciparum that is essential for parasite proliferation in human erythrocytes.","date":"2013","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/23687383","citation_count":46,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC13","PfSEC13"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["SEC13"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39325875","id":"PMC_39325875","title":"A kalihinol analog disrupts apicoplast function and vesicular trafficking in P. falciparum malaria.","date":"2024","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39325875","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSEC13"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4220,"output_tokens":1945,"usd":0.020917,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7194,"output_tokens":2758,"usd":0.05246,"stage2_stop_reason":"end_turn"},"total_usd":0.073377,"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\": 2013,\n      \"finding\": \"PF3D7_1230700 (SEC13/PfSec13) is a nucleoporin of P. falciparum that localizes dynamically to nuclear pore complexes (NPCs) during intra-erythrocytic development, and its NPC dynamics are associated with microtubules rather than F-actin, as shown by 3D-SIM super-resolution fluorescence microscopy and in vivo imaging.\",\n      \"method\": \"3D-SIM super-resolution fluorescence microscopy and in vivo imaging; co-localization with NPC markers and cytoskeletal markers\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiments with multiple imaging methods in a single lab establishing both NPC association and cytoskeletal linkage\",\n      \"pmids\": [\"23687383\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PF3D7_1230700 (SEC13/PfSec13) does not co-localize with heterochromatin markers HP1 and H3K9me3, indicating that NPCs occupy euchromatic regions of the P. falciparum nucleus.\",\n      \"method\": \"Co-localization fluorescence microscopy with heterochromatin markers HP1 and H3K9me3\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging with established chromatin markers, single lab\",\n      \"pmids\": [\"23687383\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In addition to NPC localization, PF3D7_1230700 (SEC13/PfSec13) is also found in the nucleoplasm where it is associated with chromatin, as revealed by ultrastructural analysis and chromatin immunoprecipitation (ChIP), indicating an unusual dual nucleoporin/chromatin-associated function.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) and ultrastructural (electron microscopy) analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (ChIP + ultrastructural EM) in a single lab\",\n      \"pmids\": [\"23687383\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PF3D7_1230700 (SEC13/PfSec13) is essential for P. falciparum parasite proliferation in human erythrocytes, as demonstrated by peptide nucleic acid (PNA)-mediated downregulation leading to loss of parasite growth.\",\n      \"method\": \"Peptide nucleic acid (PNA) knockdown of PfSec13 with parasite proliferation readout\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss-of-function via PNA with defined proliferation phenotype, single lab, single method\",\n      \"pmids\": [\"23687383\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PF3D7_1230700 (SEC13/PfSec13) shows unique structural similarities suggesting it is a fusion protein combining features of Sec13 and Nup145C of yeast, making it an unusual nucleoporin.\",\n      \"method\": \"Bioinformatic structural similarity analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic prediction only, no mutagenesis or structural validation reported\",\n      \"pmids\": [\"23687383\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SEC13 in P. berghei carries an extended C-terminal poly-proline extension that is largely restricted to apicomplexans and is essential for parasite survival, as shown by genetic analysis.\",\n      \"method\": \"Bioinformatic identification of poly-proline extension combined with genetic functional analysis in P. berghei\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with survival phenotype, supported by bioinformatic characterization, single lab\",\n      \"pmids\": [\"30050042\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SEC13 is localized to the nuclear pore complex throughout the P. berghei life cycle, as determined by fluorescence imaging of tagged Nup components combined with cryo-electron tomography of Plasmodium NPCs.\",\n      \"method\": \"Fluorescence imaging of GFP-tagged Nups and cryo-electron tomography\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization across multiple life cycle stages with two complementary imaging methods, single lab\",\n      \"pmids\": [\"30050042\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A mutation in PF3D7_1230700 (SEC13), which encodes a component of the P. falciparum secretory machinery, reduces parasite susceptibility to the antimalarial compound MED6-189, implicating SEC13 in vesicular trafficking and/or the secretory pathway targeted by this drug.\",\n      \"method\": \"Genomic/genetic analysis identifying resistance-conferring mutation in SEC13 in drug-treated P. falciparum\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic mutation identified by genomics with defined drug-resistance phenotype, single study, mechanistic pathway placement is inferential from drug mode-of-action\",\n      \"pmids\": [\"39325875\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1230700 (SEC13) is an essential, structurally unusual nucleoporin of Plasmodium falciparum that localizes dynamically to nuclear pore complexes (associated with microtubules) and is also found in the nucleoplasm associated with chromatin; in P. berghei, an apicomplexan-specific C-terminal poly-proline extension in SEC13 is required for parasite survival, and in P. falciparum, a mutation in SEC13 confers reduced susceptibility to a drug targeting the secretory/vesicular trafficking pathway, indicating SEC13 participates in both nuclear pore function and secretory machinery.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1230700 (SEC13) is an essential nucleoporin of Plasmodium falciparum that localizes dynamically to nuclear pore complexes (NPCs) during intra-erythrocytic development, with NPC movement coupled to microtubules rather than F-actin [#0]. It is an unusual nucleoporin in that, beyond its NPC pool, SEC13 also occupies the nucleoplasm in physical association with chromatin, and its NPCs are excluded from HP1/H3K9me3-marked heterochromatin, confining pores to euchromatic territory [#1, #2]. NPC localization persists throughout the life cycle in the P. berghei ortholog [#6], and in P. berghei an apicomplexan-restricted C-terminal poly-proline extension of SEC13 is required for parasite survival [#5]. SEC13 is essential for P. falciparum proliferation in human erythrocytes [#3], and a resistance-conferring mutation in SEC13 reduces P. falciparum susceptibility to the antimalarial MED6-189, linking the protein to the secretory/vesicular trafficking pathway in addition to its nuclear pore role [#7]. Beyond these observations, the detailed molecular mechanism connecting SEC13's nuclear pore, chromatin, and secretory functions has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing where SEC13 acts and whether its dynamics depend on cytoskeleton addressed whether this protein is a bona fide nucleoporin with regulated pore behavior; imaging placed it at NPCs moving along microtubules.\",\n      \"evidence\": \"3D-SIM super-resolution microscopy and in vivo imaging with NPC and cytoskeletal markers in P. falciparum\",\n      \"pmids\": [\"23687383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of the microtubule coupling is unresolved\", \"Does not identify SEC13's direct NPC binding partners\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether NPCs and SEC13 relate to chromatin state was unknown; co-localization and ChIP/EM showed pores avoid heterochromatin and that SEC13 additionally binds chromatin in the nucleoplasm, defining an unusual dual role.\",\n      \"evidence\": \"Co-localization with HP1/H3K9me3 markers plus ChIP and ultrastructural EM in P. falciparum\",\n      \"pmids\": [\"23687383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of SEC13 chromatin association is not defined\", \"No genomic loci or gene-regulatory targets identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether SEC13 is required for the parasite was tested by knockdown, establishing it as essential for blood-stage proliferation.\",\n      \"evidence\": \"PNA-mediated knockdown of PfSec13 with parasite proliferation readout in P. falciparum\",\n      \"pmids\": [\"23687383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single knockdown method, no genetic complementation\", \"Does not distinguish which SEC13 function (NPC vs chromatin) underlies essentiality\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Sequence/structure analysis addressed why SEC13 behaves unusually, predicting it is a Sec13–Nup145C fusion protein.\",\n      \"evidence\": \"Bioinformatic structural similarity analysis\",\n      \"pmids\": [\"23687383\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational prediction only, no structural or mutagenesis validation\", \"Fusion architecture not experimentally confirmed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether SEC13's unusual domain features matter for viability was tested in P. berghei, showing an apicomplexan-specific C-terminal poly-proline extension is essential and confirming NPC localization across the life cycle.\",\n      \"evidence\": \"Genetic functional analysis, GFP-tagged Nup imaging, and cryo-electron tomography in P. berghei\",\n      \"pmids\": [\"30050042\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular function of the poly-proline extension is unknown\", \"Findings in P. berghei not directly reproduced for the P. falciparum ortholog\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A drug-resistance screen unexpectedly implicated SEC13 in secretory/vesicular trafficking, extending its role beyond the nuclear pore.\",\n      \"evidence\": \"Genomic identification of a MED6-189 resistance-conferring SEC13 mutation in P. falciparum\",\n      \"pmids\": [\"39325875\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Pathway placement is inferred from drug mode-of-action, not direct trafficking assay\", \"How a single mutation confers resistance is not mechanistically defined\", \"Relationship between SEC13's nuclear-pore and secretory roles is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how SEC13's distinct activities — nuclear pore function, chromatin association, and secretory/vesicular trafficking — are mechanistically integrated within a single protein.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct interaction map of SEC13 in either compartment\", \"No structural validation of the predicted fusion architecture\", \"No assay directly connecting the drug-resistance mutation to a trafficking defect\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0017056\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0003682\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0051028\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [\"Nuclear pore complex (NPC)\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Essential for P. falciparum blood-stage proliferation (PNA knockdown) [#3]\",\n      \"Apicomplexan-restricted C-terminal poly-proline extension essential in P. berghei [#5]\",\n      \"Predicted Sec13–Nup145C fusion protein (bioinformatic, unvalidated) [#4]\",\n      \"NPC dynamics associated with microtubules, not F-actin [#0]\",\n      \"NPCs excluded from HP1/H3K9me3 heterochromatin, confined to euchromatin [#1]\",\n      \"MED6-189 resistance-conferring mutation implicates SEC13 in secretory/vesicular trafficking [#7]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1230700","name":null,"product":"protein transport protein SEC13","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1445400","name":null,"product":"protein transport protein SEC13","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1450100","name":null,"product":"protein transport protein SEC13, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SEC13","evaluation":null}