{"gene":"PF3D7_1361100","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2008,"finding":"SEC24A (PfSec24a) localizes to distinct foci corresponding to transitional ER (tER) sites in P. falciparum, distinct from PfSec12 which is distributed throughout the ER. These tER foci are closely apposed to cis-Golgi sites marked by PfGRASP-GFP, and upon brefeldin A treatment they accumulate a model cargo protein in a manner dependent on an intact diacidic export motif, establishing that SEC24A functions as a COPII cargo adaptor at tER sites.","method":"Fluorescence microscopy of GFP-tagged proteins, brefeldin A treatment, site-directed mutagenesis of diacidic export motif in cargo protein","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (live imaging, pharmacological treatment, mutagenesis of cargo motif) in a single focused study establishing localization and cargo-adaptor function","pmids":["18410493"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"SEC24A (Sec24a) was co-immunoprecipitated with K13 using K13-specific monoclonal antibodies, suggesting that SEC24A partially associates with K13 at transitional ER sites. Quantitative IFA on a Sec24a-GFP parasite line showed intermediate to high colocalization (median PCC 0.60–0.67) between Sec24a and K13, with no significant change upon dihydroartemisinin treatment.","method":"Co-immunoprecipitation with K13-specific monoclonal antibodies, quantitative immunofluorescence assay (IFA) with PCC analysis on Sec24a-GFP parasite lines","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP plus orthogonal quantitative IFA in the same study, single lab","pmids":["32310999"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, SEC24A (PF3D7_1361100) is a COPII cargo adaptor that concentrates at transitional ER (tER) sites juxtaposed to the cis-Golgi, where it captures cargo bearing diacidic export motifs for packaging into COPII vesicles; it also partially co-localizes and co-immunoprecipitates with the artemisinin-resistance protein K13 at these ER exit sites."},"narrative":{"mechanistic_narrative":"In P. falciparum, SEC24A (PF3D7_1361100) functions as a COPII cargo adaptor at transitional ER (tER) sites, where it concentrates in distinct foci closely apposed to cis-Golgi elements marked by PfGRASP and packages secretory cargo for export from the ER [PMID:18410493]. Its cargo-adaptor role is established by its capacity to accumulate a model cargo protein at these foci in a manner dependent on an intact diacidic export motif, distinguishing it from PfSec12, which is distributed throughout the ER [PMID:18410493]. SEC24A also partially associates with the artemisinin-resistance protein K13 at these sites, as shown by co-immunoprecipitation and intermediate-to-high colocalization by quantitative IFA that is unchanged by dihydroartemisinin treatment [PMID:32310999]. Beyond its localization to tER, its cargo-adaptor activity, and its partial association with K13 [PMID:18410493, PMID:32310999], no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2008,"claim":"Whether P. falciparum organizes ER export at discrete transitional ER sites and which factor selects cargo there was unknown; identifying SEC24A as a focally concentrated cargo adaptor established the molecular basis of COPII-dependent ER export in the parasite.","evidence":"Live fluorescence imaging of GFP-tagged proteins, brefeldin A treatment, and site-directed mutagenesis of a cargo diacidic export motif in P. falciparum","pmids":["18410493"],"confidence":"High","gaps":["The full endogenous cargo repertoire captured by SEC24A is not defined","The composition of the COPII coat complex assembled with SEC24A at tER is not resolved","No structural model of SEC24A cargo-motif recognition is provided"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether SEC24A physically and spatially associates with the artemisinin-resistance protein K13 was unknown; demonstrating co-immunoprecipitation and partial colocalization placed K13 at ER exit sites in proximity to the COPII machinery.","evidence":"Co-immunoprecipitation with K13-specific monoclonal antibodies and quantitative IFA (PCC analysis) on a Sec24a-GFP parasite line, with and without dihydroartemisinin, in P. falciparum","pmids":["32310999"],"confidence":"Medium","gaps":["Single Co-IP plus IFA from one lab; reciprocal pulldown and direct interaction not established","Whether the SEC24A–K13 association is direct or bridged by other proteins is unresolved","Functional consequence of the association for cargo transport or drug resistance is not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The endogenous cargo set, coat-complex partners, and the functional and mechanistic significance of SEC24A's proximity to K13 remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No identified physiological cargo beyond the diacidic-motif model substrate","No direct interaction map of the parasite COPII coat around SEC24A","No test of whether SEC24A is required for K13-associated function or artemisinin resistance"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["COPII coat"],"partners":["K13 (KELCH13)"],"other_free_text":["Concentrates at transitional ER foci juxtaposed to cis-Golgi sites marked by PfGRASP, distinct from the ER-wide distribution of PfSec12 [#0]","Captures a model cargo in a manner dependent on an intact diacidic export motif [#0]","Partial association with K13 by Co-IP and colocalization is unchanged by dihydroartemisinin treatment [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18410493","id":"PMC_18410493","title":"Plasmodium falciparum Sec24 marks transitional ER that exports a model cargo via a diacidic motif.","date":"2008","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/18410493","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSec24A","PfSEC24A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41152982","id":"","title":"The Plasmodium berghei merozoite protein PbGAC is critically involved in erythrocyte binding during invasion.","date":"2025","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/41152982","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC24A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36582189","id":"","title":"Combining IP3 affinity chromatography and bioinformatics reveals a novel protein-IP3 binding site on Plasmodium falciparum MDR1 transporter.","date":"2022","source":"Current research in microbial sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36582189","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC24A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32310999","id":"","title":"Insights into the intracellular localization, protein associations and artemisinin resistance properties of Plasmodium falciparum K13.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32310999","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC24A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30704415","id":"","title":"A genome-wide analysis of coatomer protein (COP) subunits of apicomplexan parasites and their evolutionary relationships.","date":"2019","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/30704415","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC24A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25418785","id":"","title":"Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte.","date":"2014","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/25418785","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC24A"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9601,"output_tokens":746,"usd":0.019997,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5391,"output_tokens":1789,"usd":0.03584,"stage2_stop_reason":"end_turn"},"total_usd":0.055837,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"SEC24A (PfSec24a) localizes to distinct foci corresponding to transitional ER (tER) sites in P. falciparum, distinct from PfSec12 which is distributed throughout the ER. These tER foci are closely apposed to cis-Golgi sites marked by PfGRASP-GFP, and upon brefeldin A treatment they accumulate a model cargo protein in a manner dependent on an intact diacidic export motif, establishing that SEC24A functions as a COPII cargo adaptor at tER sites.\",\n      \"method\": \"Fluorescence microscopy of GFP-tagged proteins, brefeldin A treatment, site-directed mutagenesis of diacidic export motif in cargo protein\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (live imaging, pharmacological treatment, mutagenesis of cargo motif) in a single focused study establishing localization and cargo-adaptor function\",\n      \"pmids\": [\"18410493\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SEC24A (Sec24a) was co-immunoprecipitated with K13 using K13-specific monoclonal antibodies, suggesting that SEC24A partially associates with K13 at transitional ER sites. Quantitative IFA on a Sec24a-GFP parasite line showed intermediate to high colocalization (median PCC 0.60–0.67) between Sec24a and K13, with no significant change upon dihydroartemisinin treatment.\",\n      \"method\": \"Co-immunoprecipitation with K13-specific monoclonal antibodies, quantitative immunofluorescence assay (IFA) with PCC analysis on Sec24a-GFP parasite lines\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP plus orthogonal quantitative IFA in the same study, single lab\",\n      \"pmids\": [\"32310999\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, SEC24A (PF3D7_1361100) is a COPII cargo adaptor that concentrates at transitional ER (tER) sites juxtaposed to the cis-Golgi, where it captures cargo bearing diacidic export motifs for packaging into COPII vesicles; it also partially co-localizes and co-immunoprecipitates with the artemisinin-resistance protein K13 at these ER exit sites.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In P. falciparum, SEC24A (PF3D7_1361100) functions as a COPII cargo adaptor at transitional ER (tER) sites, where it concentrates in distinct foci closely apposed to cis-Golgi elements marked by PfGRASP and packages secretory cargo for export from the ER [#0]. Its cargo-adaptor role is established by its capacity to accumulate a model cargo protein at these foci in a manner dependent on an intact diacidic export motif, distinguishing it from PfSec12, which is distributed throughout the ER [#0]. SEC24A also partially associates with the artemisinin-resistance protein K13 at these sites, as shown by co-immunoprecipitation and intermediate-to-high colocalization by quantitative IFA that is unchanged by dihydroartemisinin treatment [#1]. Beyond its localization to tER, its cargo-adaptor activity, and its partial association with K13 [#0, #1], no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Whether P. falciparum organizes ER export at discrete transitional ER sites and which factor selects cargo there was unknown; identifying SEC24A as a focally concentrated cargo adaptor established the molecular basis of COPII-dependent ER export in the parasite.\",\n      \"evidence\": \"Live fluorescence imaging of GFP-tagged proteins, brefeldin A treatment, and site-directed mutagenesis of a cargo diacidic export motif in P. falciparum\",\n      \"pmids\": [\n        \"18410493\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The full endogenous cargo repertoire captured by SEC24A is not defined\",\n        \"The composition of the COPII coat complex assembled with SEC24A at tER is not resolved\",\n        \"No structural model of SEC24A cargo-motif recognition is provided\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether SEC24A physically and spatially associates with the artemisinin-resistance protein K13 was unknown; demonstrating co-immunoprecipitation and partial colocalization placed K13 at ER exit sites in proximity to the COPII machinery.\",\n      \"evidence\": \"Co-immunoprecipitation with K13-specific monoclonal antibodies and quantitative IFA (PCC analysis) on a Sec24a-GFP parasite line, with and without dihydroartemisinin, in P. falciparum\",\n      \"pmids\": [\n        \"32310999\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP plus IFA from one lab; reciprocal pulldown and direct interaction not established\",\n        \"Whether the SEC24A\\u2013K13 association is direct or bridged by other proteins is unresolved\",\n        \"Functional consequence of the association for cargo transport or drug resistance is not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous cargo set, coat-complex partners, and the functional and mechanistic significance of SEC24A's proximity to K13 remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No identified physiological cargo beyond the diacidic-motif model substrate\",\n        \"No direct interaction map of the parasite COPII coat around SEC24A\",\n        \"No test of whether SEC24A is required for K13-associated function or artemisinin resistance\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0008565\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0070971\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ]\n      },\n      {\n        \"term_id\": \"GO:0005789\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0090110\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"COPII coat\"\n    ],\n    \"partners\": [\n      \"K13 (Kelch13)\"\n    ],\n    \"other_free_text\": [\n      \"Concentrates at transitional ER foci juxtaposed to cis-Golgi sites marked by PfGRASP, distinct from the ER-wide distribution of PfSec12 [#0]\",\n      \"Captures a model cargo in a manner dependent on an intact diacidic export motif [#0]\",\n      \"Partial association with K13 by Co-IP and colocalization is unchanged by dihydroartemisinin treatment [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1361100","name":null,"product":"protein transport protein Sec24A","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1137200","name":null,"product":"protein transport protein Sec24A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1110300","name":null,"product":"protein transport protein Sec24A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SEC24A","evaluation":null}