{"gene":"PF3D7_1021800","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2014,"finding":"SEA1 (PF3D7_1021800) is a 244-kilodalton antigen expressed in schizont-infected red blood cells; antibodies to SEA1 decreased parasite replication by arresting schizont rupture, and conditional disruption of SEA1 resulted in a profound parasite replication defect.","method":"Differential whole-proteome screening for antigen identification; conditional genetic disruption of SEA1 in P. falciparum with replication assay readout; antibody inhibition assay","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional disruption with defined replication phenotype combined with antibody inhibition assay, replicated in P. berghei vaccination model","pmids":["24855263"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2021,"finding":"SEA1 (PF3D7_1021800) localizes in proximity to centromeres within dividing nuclei of schizonts; conditional disruption of SEA1 severely impairs DNA distribution and merozoite formation, with a proportion of SEA1-null merozoites completely lacking nuclei, demonstrating that SEA1 acts as an essential regulator of nuclear segregation during schizogony rather than a direct mediator of egress.","method":"Conditional disruption (DiCre-based) of SEA1 in P. falciparum; fluorescence microscopy for nuclear localization relative to centromere markers; flow cytometry and electron microscopy for merozoite morphology; egress efficiency assay","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional genetic disruption with multiple orthogonal readouts (fluorescence microscopy, electron microscopy, flow cytometry, egress assay) in a single rigorous study","pmids":["33688001"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"SEA1-null schizonts rupture (albeit with low efficiency), indicating that SEA1 function and normal nuclear segmentation are not prerequisites for egress itself; this result is inconsistent with a direct mechanistic role for SEA1 in egress.","method":"Conditional disruption of SEA1 with egress efficiency assay","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with specific egress phenotype readout; finding explicitly reported as a negative result for direct egress function","pmids":["33688001"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"SEA1 undergoes phosphorylation in a manner dependent upon the parasite cGMP-dependent protein kinase PKG (which triggers egress); this PKG-dependent phosphorylation of SEA1 was noted as a prior finding cited in the study.","method":"Phosphoproteomic analysis (cited prior finding referenced within the mBio study)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single prior dataset cited (not independently replicated in this paper), phosphoproteomic identification without mutagenesis validation","pmids":["33688001"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Vaccination of mice with recombinant P. berghei SEA1 (PbSEA-1) significantly reduced parasitemia and delayed mortality after lethal P. berghei ANKA challenge, establishing in vivo functional relevance of the SEA1 ortholog.","method":"Mouse vaccination with recombinant PbSEA-1 followed by lethal P. berghei ANKA challenge; parasitemia measurement and survival analysis","journal":"Science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo vaccination/challenge model with two readouts (parasitemia and survival), single lab","pmids":["24855263"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]}],"current_model":"SEA1 (PF3D7_1021800) is a 244-kDa schizont-stage protein that localizes near centromeres in dividing parasite nuclei and is essential for correct nuclear segregation during schizogony, ensuring proper packaging of replicated DNA into daughter merozoites; it undergoes PKG-dependent phosphorylation, but conditional disruption experiments demonstrate it does not play a direct mechanistic role in schizont egress, instead acting upstream of egress to enable normal merozoite formation."},"narrative":{"mechanistic_narrative":"SEA1 (PF3D7_1021800) is a 244-kDa schizont-stage antigen of Plasmodium falciparum that is essential for the correct partitioning of replicated DNA into forming daughter merozoites during schizogony [PMID:24855263, PMID:33688001]. It localizes near centromeres within dividing schizont nuclei, and conditional disruption severely impairs DNA distribution and merozoite formation, producing a proportion of merozoites entirely lacking nuclei — establishing SEA1 as a regulator of nuclear segregation rather than a direct effector of any single downstream event [PMID:33688001]. Although SEA1 was originally identified through its impact on schizont rupture and undergoes phosphorylation dependent on the egress-triggering kinase PKG [PMID:24855263, PMID:33688001], conditional-null schizonts still rupture, albeit inefficiently, showing that SEA1 acts upstream of egress to enable normal merozoite production rather than mediating egress itself [PMID:33688001]. Its in vivo functional relevance is supported by the P. berghei ortholog, whose recombinant form reduces parasitemia and delays mortality when used as a vaccine in the ANKA lethal-challenge model [PMID:24855263]. Beyond nuclear segregation, no molecular partners, structural determinants, or biochemical activities of SEA1 have been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing that SEA1 is an antigen whose targeting blocks parasite replication answered whether it is functionally required during the blood stage and a candidate protective antigen.","evidence":"Whole-proteome antigen screen, conditional genetic disruption with replication readout, and antibody inhibition in P. falciparum","pmids":["24855263"],"confidence":"High","gaps":["The step at which replication was arrested (rupture vs. an earlier event) was not resolved","No molecular mechanism or interacting partners identified","Whether the antibody phenotype reflects a direct SEA1 function or blockade of a complex was not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2014,"claim":"Vaccination with the recombinant P. berghei ortholog tested whether SEA1 protein exposure confers in vivo protection, supporting its vaccine relevance.","evidence":"Mouse vaccination with recombinant PbSEA-1 and lethal P. berghei ANKA challenge with parasitemia and survival readouts","pmids":["24855263"],"confidence":"Medium","gaps":["Single-lab in vivo result","Mechanism of protection (which SEA1 function the antibodies interfere with) not defined","Cross-species applicability to P. falciparum immunity not established"],"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2021,"claim":"Localization near centromeres plus conditional disruption reassigned SEA1's essential role from egress to nuclear segregation, resolving what cellular process it actually controls.","evidence":"DiCre conditional disruption in P. falciparum with fluorescence microscopy relative to centromere markers, electron microscopy, and flow cytometry of merozoite morphology","pmids":["33688001"],"confidence":"High","gaps":["Molecular basis of centromere-proximal localization is unknown","No binding partners at the centromere/kinetochore identified","How SEA1 mechanistically drives DNA distribution is undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Demonstrating that SEA1-null schizonts still rupture established that SEA1 acts upstream of egress rather than serving as a direct egress effector, correcting the initial interpretation.","evidence":"Conditional disruption with quantitative egress efficiency assay in P. falciparum","pmids":["33688001"],"confidence":"High","gaps":["The reduced egress efficiency may be an indirect consequence of defective merozoite formation rather than a residual direct role","Relationship between nuclear segregation failure and egress timing not dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Noting PKG-dependent phosphorylation of SEA1 linked it to the egress signaling cascade, raising the question of how a segregation factor is regulated by the egress kinase.","evidence":"Phosphoproteomic dataset cited as a prior finding within the mBio study","pmids":["33688001"],"confidence":"Medium","gaps":["Phosphosite identification without mutagenesis validation; functional consequence unknown","Not independently replicated within the citing study","Whether phosphorylation regulates SEA1 localization or activity is undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How SEA1 is recruited to centromere-proximal regions and mechanistically directs DNA partitioning — and whether its PKG phosphorylation regulates that activity — remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No binding partners, structural model, or biochemical activity defined","Functional role of PKG-dependent phosphorylation not tested by mutagenesis","Molecular link between centromere localization and daughter-nucleus packaging unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["244-kDa schizont-stage antigen expressed in schizont-infected red blood cells [#0]","Essential regulator of nuclear segregation during schizogony; conditional disruption causes anucleate merozoites and impaired DNA distribution [#1]","Acts upstream of egress rather than as a direct egress mediator; SEA1-null schizonts still rupture at reduced efficiency [#2]","Undergoes PKG-dependent phosphorylation (cited phosphoproteomic finding, not validated by mutagenesis) [#3]","P. berghei ortholog (PbSEA-1) confers vaccine protection in the ANKA lethal-challenge model [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24855263","id":"PMC_24855263","title":"Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection.","date":"2014","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/24855263","citation_count":99,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1","PfSEA1","PbSEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27130708","id":"PMC_27130708","title":"Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27130708","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33688001","id":"PMC_33688001","title":"Malaria Parasite Schizont Egress Antigen-1 Plays an Essential Role in Nuclear Segregation during Schizogony.","date":"2021","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/33688001","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEA1","schizont egress antigen-1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30165569","id":"PMC_30165569","title":"Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.","date":"2019","source":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","url":"https://pubmed.ncbi.nlm.nih.gov/30165569","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1","PfSEA1","PbSEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28033393","id":"PMC_28033393","title":"Regulatory T Cells in Endemic Burkitt Lymphoma Patients Are Associated with Poor Outcomes: A Prospective, Longitudinal Study.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/28033393","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28468980","id":"PMC_28468980","title":"Identification of Protective B-Cell Epitopes within the Novel Malaria Vaccine Candidate Plasmodium falciparum Schizont Egress Antigen 1.","date":"2017","source":"Clinical and vaccine immunology : CVI","url":"https://pubmed.ncbi.nlm.nih.gov/28468980","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35711005","id":"PMC_35711005","title":"Factors Associated With Human IgG Antibody Response to Anopheles albimanus Salivary Gland Extract, Artibonite Department, Haiti, 2017.","date":"2022","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/35711005","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40006050","id":"PMC_40006050","title":"Targeting Plasmodium falciparum Schizont Egress Antigen-1 in Infected Red Blood Cells: Docking-Based Fingerprinting, Density Functional Theory, Molecular Dynamics Simulations, and Binding Free Energy Analysis.","date":"2025","source":"Pharmaceuticals (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/40006050","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1","PfSEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31288996","id":"PMC_31288996","title":"Impact of maternally derived antibodies to Plasmodium falciparum Schizont Egress Antigen-1 on the endogenous production of anti-PfSEA-1 in offspring.","date":"2019","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/31288996","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1","PfSEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40402846","id":"PMC_40402846","title":"T-follicular helper cell profiles differ by malaria antigen and for children compared to adults.","date":"2025","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/40402846","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41295464","id":"PMC_41295464","title":"A Multiplex Serological Assay to Evaluate the Antibody Responses to a Set of Plasmodium falciparum Antigens and Their Protective Role Against Malaria in Children Aged 1.5 to 12 Years Living in a Highly Seasonal Malaria Transmission Area of Burkina Faso.","date":"2025","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/41295464","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38659768","id":"PMC_38659768","title":"T follicular helper cell profiles differ by malaria antigen and for children compared to adults.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38659768","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["schizont egress antigen-1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42695673","id":"PMC_42695673","title":"Antibodies targeting blood stage antigens of Plasmodium falciparum are associated with resistance to malaria infection and disease.","date":"2026","source":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","url":"https://pubmed.ncbi.nlm.nih.gov/42695673","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSEA1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10327,"output_tokens":1400,"usd":0.02599,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6355,"output_tokens":2535,"usd":0.047575,"stage2_stop_reason":"end_turn"},"total_usd":0.073565,"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\": 2014,\n      \"finding\": \"SEA1 (PF3D7_1021800) is a 244-kilodalton antigen expressed in schizont-infected red blood cells; antibodies to SEA1 decreased parasite replication by arresting schizont rupture, and conditional disruption of SEA1 resulted in a profound parasite replication defect.\",\n      \"method\": \"Differential whole-proteome screening for antigen identification; conditional genetic disruption of SEA1 in P. falciparum with replication assay readout; antibody inhibition assay\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional disruption with defined replication phenotype combined with antibody inhibition assay, replicated in P. berghei vaccination model\",\n      \"pmids\": [\"24855263\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SEA1 (PF3D7_1021800) localizes in proximity to centromeres within dividing nuclei of schizonts; conditional disruption of SEA1 severely impairs DNA distribution and merozoite formation, with a proportion of SEA1-null merozoites completely lacking nuclei, demonstrating that SEA1 acts as an essential regulator of nuclear segregation during schizogony rather than a direct mediator of egress.\",\n      \"method\": \"Conditional disruption (DiCre-based) of SEA1 in P. falciparum; fluorescence microscopy for nuclear localization relative to centromere markers; flow cytometry and electron microscopy for merozoite morphology; egress efficiency assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional genetic disruption with multiple orthogonal readouts (fluorescence microscopy, electron microscopy, flow cytometry, egress assay) in a single rigorous study\",\n      \"pmids\": [\"33688001\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SEA1-null schizonts rupture (albeit with low efficiency), indicating that SEA1 function and normal nuclear segmentation are not prerequisites for egress itself; this result is inconsistent with a direct mechanistic role for SEA1 in egress.\",\n      \"method\": \"Conditional disruption of SEA1 with egress efficiency assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with specific egress phenotype readout; finding explicitly reported as a negative result for direct egress function\",\n      \"pmids\": [\"33688001\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SEA1 undergoes phosphorylation in a manner dependent upon the parasite cGMP-dependent protein kinase PKG (which triggers egress); this PKG-dependent phosphorylation of SEA1 was noted as a prior finding cited in the study.\",\n      \"method\": \"Phosphoproteomic analysis (cited prior finding referenced within the mBio study)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single prior dataset cited (not independently replicated in this paper), phosphoproteomic identification without mutagenesis validation\",\n      \"pmids\": [\"33688001\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Vaccination of mice with recombinant P. berghei SEA1 (PbSEA-1) significantly reduced parasitemia and delayed mortality after lethal P. berghei ANKA challenge, establishing in vivo functional relevance of the SEA1 ortholog.\",\n      \"method\": \"Mouse vaccination with recombinant PbSEA-1 followed by lethal P. berghei ANKA challenge; parasitemia measurement and survival analysis\",\n      \"journal\": \"Science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo vaccination/challenge model with two readouts (parasitemia and survival), single lab\",\n      \"pmids\": [\"24855263\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SEA1 (PF3D7_1021800) is a 244-kDa schizont-stage protein that localizes near centromeres in dividing parasite nuclei and is essential for correct nuclear segregation during schizogony, ensuring proper packaging of replicated DNA into daughter merozoites; it undergoes PKG-dependent phosphorylation, but conditional disruption experiments demonstrate it does not play a direct mechanistic role in schizont egress, instead acting upstream of egress to enable normal merozoite formation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SEA1 (PF3D7_1021800) is a 244-kDa schizont-stage antigen of Plasmodium falciparum that is essential for the correct partitioning of replicated DNA into forming daughter merozoites during schizogony [#0, #1]. It localizes near centromeres within dividing schizont nuclei, and conditional disruption severely impairs DNA distribution and merozoite formation, producing a proportion of merozoites entirely lacking nuclei — establishing SEA1 as a regulator of nuclear segregation rather than a direct effector of any single downstream event [#1]. Although SEA1 was originally identified through its impact on schizont rupture and undergoes phosphorylation dependent on the egress-triggering kinase PKG [#0, #3], conditional-null schizonts still rupture, albeit inefficiently, showing that SEA1 acts upstream of egress to enable normal merozoite production rather than mediating egress itself [#2]. Its in vivo functional relevance is supported by the P. berghei ortholog, whose recombinant form reduces parasitemia and delays mortality when used as a vaccine in the ANKA lethal-challenge model [#4]. Beyond nuclear segregation, no molecular partners, structural determinants, or biochemical activities of SEA1 have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that SEA1 is an antigen whose targeting blocks parasite replication answered whether it is functionally required during the blood stage and a candidate protective antigen.\",\n      \"evidence\": \"Whole-proteome antigen screen, conditional genetic disruption with replication readout, and antibody inhibition in P. falciparum\",\n      \"pmids\": [\"24855263\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The step at which replication was arrested (rupture vs. an earlier event) was not resolved\",\n        \"No molecular mechanism or interacting partners identified\",\n        \"Whether the antibody phenotype reflects a direct SEA1 function or blockade of a complex was not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Vaccination with the recombinant P. berghei ortholog tested whether SEA1 protein exposure confers in vivo protection, supporting its vaccine relevance.\",\n      \"evidence\": \"Mouse vaccination with recombinant PbSEA-1 and lethal P. berghei ANKA challenge with parasitemia and survival readouts\",\n      \"pmids\": [\"24855263\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab in vivo result\",\n        \"Mechanism of protection (which SEA1 function the antibodies interfere with) not defined\",\n        \"Cross-species applicability to P. falciparum immunity not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Localization near centromeres plus conditional disruption reassigned SEA1's essential role from egress to nuclear segregation, resolving what cellular process it actually controls.\",\n      \"evidence\": \"DiCre conditional disruption in P. falciparum with fluorescence microscopy relative to centromere markers, electron microscopy, and flow cytometry of merozoite morphology\",\n      \"pmids\": [\"33688001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis of centromere-proximal localization is unknown\",\n        \"No binding partners at the centromere/kinetochore identified\",\n        \"How SEA1 mechanistically drives DNA distribution is undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrating that SEA1-null schizonts still rupture established that SEA1 acts upstream of egress rather than serving as a direct egress effector, correcting the initial interpretation.\",\n      \"evidence\": \"Conditional disruption with quantitative egress efficiency assay in P. falciparum\",\n      \"pmids\": [\"33688001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The reduced egress efficiency may be an indirect consequence of defective merozoite formation rather than a residual direct role\",\n        \"Relationship between nuclear segregation failure and egress timing not dissected\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Noting PKG-dependent phosphorylation of SEA1 linked it to the egress signaling cascade, raising the question of how a segregation factor is regulated by the egress kinase.\",\n      \"evidence\": \"Phosphoproteomic dataset cited as a prior finding within the mBio study\",\n      \"pmids\": [\"33688001\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phosphosite identification without mutagenesis validation; functional consequence unknown\",\n        \"Not independently replicated within the citing study\",\n        \"Whether phosphorylation regulates SEA1 localization or activity is undetermined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SEA1 is recruited to centromere-proximal regions and mechanistically directs DNA partitioning — and whether its PKG phosphorylation regulates that activity — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No binding partners, structural model, or biochemical activity defined\",\n        \"Functional role of PKG-dependent phosphorylation not tested by mutagenesis\",\n        \"Molecular link between centromere localization and daughter-nucleus packaging unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0000775\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"244-kDa schizont-stage antigen expressed in schizont-infected red blood cells [#0]\",\n      \"Essential regulator of nuclear segregation during schizogony; conditional disruption causes anucleate merozoites and impaired DNA distribution [#1]\",\n      \"Acts upstream of egress rather than as a direct egress mediator; SEA1-null schizonts still rupture at reduced efficiency [#2]\",\n      \"Undergoes PKG-dependent phosphorylation (cited phosphoproteomic finding, not validated by mutagenesis) [#3]\",\n      \"P. berghei ortholog (PbSEA-1) confers vaccine protection in the ANKA lethal-challenge model [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1021800","name":null,"product":"schizont egress antigen-1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0506000","name":null,"product":"schizont egress antigen-1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0606100","name":null,"product":"schizont egress antigen-1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SEA1","evaluation":null}