{"gene":"PF3D7_0613900","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2019,"finding":"MyoE (PF3D7_0613900), one of two Class XIV myosins alongside MyoB, is expressed in all invasive stages and localises to the basal end of parasites. Gene deletion in Plasmodium berghei revealed that MyoE is functionally required for sporozoite traversal.","method":"Gene deletion (knockout), immunofluorescence/live-imaging for subcellular localisation, sporozoite traversal assay","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with defined phenotypic readout (sporozoite traversal defect) plus direct localization; single lab study with two orthogonal methods","pmids":["31283102"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"MyoE co-immunoprecipitates with CDPK4 in Plasmodium berghei schizonts, placing MyoE within the glideosome/IMC protein network. MyoE-3xHA immunoprecipitates also recovered glideosome and IMC proteins, and protein interactions between MyoE and components such as GAP40 were identified from reciprocal immunoprecipitates.","method":"Endogenous 3xHA tagging, cross-linked co-immunoprecipitation followed by mass spectrometry","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — reciprocal co-IP (both CDPK4-3xHA and MyoE-3xHA IPs recovered the interaction) in a single lab; mass spectrometry identification of partners","pmids":["30315162"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2005,"finding":"MyoE (referred to as Pfmyo-E in this study) transcript is barely detectable in early asexual blood stages but becomes abundant in schizonts, indicating stage-specific transcriptional regulation; protein expression data were not reported for MyoE in this study.","method":"RT-PCR on blood-stage parasite mRNA across developmental stages","journal":"Cell motility and the cytoskeleton","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single method (RT-PCR), single lab, transcriptional data only with no protein-level mechanistic follow-up for MyoE","pmids":["15754360"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"MyoE (PF3D7_0613900) is a Class XIV Plasmodium-specific myosin that localises to the basal end of invasive parasite stages, is transcriptionally upregulated in schizonts, is required for sporozoite traversal in P. berghei (shown by gene deletion), and associates physically with glideosome/IMC components including CDPK4 and GAP40 (shown by co-immunoprecipitation), placing it within the actomyosin motor machinery, though its precise enzymatic mechanism remains uncharacterised."},"narrative":{"mechanistic_narrative":"MyoE (PF3D7_0613900) is one of two Plasmodium Class XIV myosins that operates within the actomyosin motor machinery of invasive parasite stages, expressed across all invasive stages and localised to the basal end of the parasite [PMID:31283102]. Gene deletion in P. berghei establishes that MyoE is functionally required for sporozoite traversal [PMID:31283102]. Consistent with a role in the invasion motor, MyoE physically associates with the glideosome/inner-membrane-complex (IMC) network: endogenously tagged MyoE co-immunoprecipitates with CDPK4 and recovers glideosome and IMC components including GAP40 in P. berghei schizonts [PMID:30315162]. Beyond this localisation, complex membership, and traversal phenotype, the enzymatic and motor mechanism of MyoE itself has not been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Establishing when MyoE is deployed narrowed its likely functional window: the question was whether MyoE acts in early replicating blood stages or in the invasive schizont/merozoite, and stage-resolved transcript profiling placed its expression at the schizont stage.","evidence":"RT-PCR of blood-stage parasite mRNA across developmental stages in P. falciparum","pmids":["15754360"],"confidence":"Low","gaps":["Transcript-only data; no protein-level expression or timing confirmed for MyoE in this study","Single method, single lab","Does not address function or localisation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"It was unknown whether MyoE physically integrates into the invasion motor; reciprocal co-immunoprecipitation placed MyoE within the glideosome/IMC protein network, linking it to CDPK4 and GAP40.","evidence":"Endogenous 3xHA tagging and cross-linked co-immunoprecipitation followed by mass spectrometry in P. berghei ANKA schizonts","pmids":["30315162"],"confidence":"Medium","gaps":["Co-IP demonstrates association, not direct binding or the interface involved","Functional consequence of the CDPK4/GAP40 associations for MyoE activity untested","Interactions defined in schizonts; relevance to other invasive stages not shown"],"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":2019,"claim":"Whether MyoE has a non-redundant biological role was open given the presence of a second Class XIV myosin (MyoB); gene deletion assigned MyoE a specific, non-redundant requirement in sporozoite traversal and defined its basal localisation.","evidence":"Gene deletion, immunofluorescence/live-imaging, and sporozoite traversal assay in P. berghei (expression also assessed in P. falciparum)","pmids":["31283102"],"confidence":"Medium","gaps":["Molecular mechanism connecting basal localisation to the traversal defect not resolved","Whether the traversal role depends on the CDPK4/GAP40 associations untested","No biochemical demonstration of motor/ATPase activity"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The enzymatic and mechanochemical basis of MyoE function — its actin engagement, motor activity, and how basal localisation drives sporozoite traversal — remains unresolved.","evidence":"No discovery in the corpus addresses MyoE motor biochemistry or the causal chain from localisation to phenotype","pmids":[],"confidence":"Low","gaps":["No reconstitution or ATPase/motility assay for MyoE","No structural model of MyoE or its complex","Mechanism of basal recruitment unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["glideosome / inner membrane complex (IMC) protein network [#1]"],"partners":["CDPK4 [#1]","GAP40 [#1]"],"other_free_text":["One of two Class XIV myosins in Plasmodium, alongside MyoB [#0]","Localises to the basal end of invasive parasite stages [#0]","Transcript upregulated in schizonts relative to early asexual blood stages [#2]","Gene deletion in P. berghei causes a sporozoite traversal defect [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"31283102","id":"PMC_31283102","title":"Systematic analysis of Plasmodium myosins reveals differential expression, localisation, and function in invasive and proliferative parasite stages.","date":"2019","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31283102","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15754360","id":"PMC_15754360","title":"Plasmodium falciparum myosins: transcription and translation during asexual parasite development.","date":"2005","source":"Cell motility and the cytoskeleton","url":"https://pubmed.ncbi.nlm.nih.gov/15754360","citation_count":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfMyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41482054","id":"","title":"Defining the Proteome of Sexually Committed Parasites in Plasmodium falciparum.","date":"2025","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/41482054","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33104759","id":"","title":"Actomyosin forces and the energetics of red blood cell invasion by the malaria parasite Plasmodium falciparum.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33104759","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37988347","id":"","title":"Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37988347","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38935780","id":"","title":"Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38935780","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36780562","id":"","title":"PbAP2-FG2 and PbAP2R-2 function together as a transcriptional repressor complex essential for Plasmodium female development.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/36780562","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30315162","id":"","title":"Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30315162","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38039338","id":"","title":"The Kelch13 compartment contains highly divergent vesicle trafficking proteins in malaria parasites.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38039338","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32817103","id":"","title":"Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum Merozoites.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32817103","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31075098","id":"","title":"Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.","date":"2019","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/31075098","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MyoE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13943,"output_tokens":943,"usd":0.027987,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5656,"output_tokens":1875,"usd":0.037577,"stage2_stop_reason":"end_turn"},"total_usd":0.065564,"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\": 2019,\n      \"finding\": \"MyoE (PF3D7_0613900), one of two Class XIV myosins alongside MyoB, is expressed in all invasive stages and localises to the basal end of parasites. Gene deletion in Plasmodium berghei revealed that MyoE is functionally required for sporozoite traversal.\",\n      \"method\": \"Gene deletion (knockout), immunofluorescence/live-imaging for subcellular localisation, sporozoite traversal assay\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with defined phenotypic readout (sporozoite traversal defect) plus direct localization; single lab study with two orthogonal methods\",\n      \"pmids\": [\"31283102\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MyoE co-immunoprecipitates with CDPK4 in Plasmodium berghei schizonts, placing MyoE within the glideosome/IMC protein network. MyoE-3xHA immunoprecipitates also recovered glideosome and IMC proteins, and protein interactions between MyoE and components such as GAP40 were identified from reciprocal immunoprecipitates.\",\n      \"method\": \"Endogenous 3xHA tagging, cross-linked co-immunoprecipitation followed by mass spectrometry\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — reciprocal co-IP (both CDPK4-3xHA and MyoE-3xHA IPs recovered the interaction) in a single lab; mass spectrometry identification of partners\",\n      \"pmids\": [\"30315162\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"MyoE (referred to as Pfmyo-E in this study) transcript is barely detectable in early asexual blood stages but becomes abundant in schizonts, indicating stage-specific transcriptional regulation; protein expression data were not reported for MyoE in this study.\",\n      \"method\": \"RT-PCR on blood-stage parasite mRNA across developmental stages\",\n      \"journal\": \"Cell motility and the cytoskeleton\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single method (RT-PCR), single lab, transcriptional data only with no protein-level mechanistic follow-up for MyoE\",\n      \"pmids\": [\"15754360\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"MyoE (PF3D7_0613900) is a Class XIV Plasmodium-specific myosin that localises to the basal end of invasive parasite stages, is transcriptionally upregulated in schizonts, is required for sporozoite traversal in P. berghei (shown by gene deletion), and associates physically with glideosome/IMC components including CDPK4 and GAP40 (shown by co-immunoprecipitation), placing it within the actomyosin motor machinery, though its precise enzymatic mechanism remains uncharacterised.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MyoE (PF3D7_0613900) is one of two Plasmodium Class XIV myosins that operates within the actomyosin motor machinery of invasive parasite stages, expressed across all invasive stages and localised to the basal end of the parasite [#0]. Gene deletion in P. berghei establishes that MyoE is functionally required for sporozoite traversal [#0]. Consistent with a role in the invasion motor, MyoE physically associates with the glideosome/inner-membrane-complex (IMC) network: endogenously tagged MyoE co-immunoprecipitates with CDPK4 and recovers glideosome and IMC components including GAP40 in P. berghei schizonts [#1]. Beyond this localisation, complex membership, and traversal phenotype, the enzymatic and motor mechanism of MyoE itself has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing when MyoE is deployed narrowed its likely functional window: the question was whether MyoE acts in early replicating blood stages or in the invasive schizont/merozoite, and stage-resolved transcript profiling placed its expression at the schizont stage.\",\n      \"evidence\": \"RT-PCR of blood-stage parasite mRNA across developmental stages in P. falciparum\",\n      \"pmids\": [\"15754360\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcript-only data; no protein-level expression or timing confirmed for MyoE in this study\",\n        \"Single method, single lab\",\n        \"Does not address function or localisation\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unknown whether MyoE physically integrates into the invasion motor; reciprocal co-immunoprecipitation placed MyoE within the glideosome/IMC protein network, linking it to CDPK4 and GAP40.\",\n      \"evidence\": \"Endogenous 3xHA tagging and cross-linked co-immunoprecipitation followed by mass spectrometry in P. berghei ANKA schizonts\",\n      \"pmids\": [\"30315162\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-IP demonstrates association, not direct binding or the interface involved\",\n        \"Functional consequence of the CDPK4/GAP40 associations for MyoE activity untested\",\n        \"Interactions defined in schizonts; relevance to other invasive stages not shown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Whether MyoE has a non-redundant biological role was open given the presence of a second Class XIV myosin (MyoB); gene deletion assigned MyoE a specific, non-redundant requirement in sporozoite traversal and defined its basal localisation.\",\n      \"evidence\": \"Gene deletion, immunofluorescence/live-imaging, and sporozoite traversal assay in P. berghei (expression also assessed in P. falciparum)\",\n      \"pmids\": [\"31283102\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism connecting basal localisation to the traversal defect not resolved\",\n        \"Whether the traversal role depends on the CDPK4/GAP40 associations untested\",\n        \"No biochemical demonstration of motor/ATPase activity\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The enzymatic and mechanochemical basis of MyoE function — its actin engagement, motor activity, and how basal localisation drives sporozoite traversal — remains unresolved.\",\n      \"evidence\": \"No discovery in the corpus addresses MyoE motor biochemistry or the causal chain from localisation to phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution or ATPase/motility assay for MyoE\",\n        \"No structural model of MyoE or its complex\",\n        \"Mechanism of basal recruitment unknown\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0090543\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0009405\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"glideosome / inner membrane complex (IMC) protein network [#1]\"\n    ],\n    \"partners\": [\n      \"CDPK4 [#1]\",\n      \"GAP40 [#1]\"\n    ],\n    \"other_free_text\": [\n      \"One of two Class XIV myosins in Plasmodium, alongside MyoB [#0]\",\n      \"Localises to the basal end of invasive parasite stages [#0]\",\n      \"Transcript upregulated in schizonts relative to early asexual blood stages [#2]\",\n      \"Gene deletion in P. berghei causes a sporozoite traversal defect [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0613900","name":null,"product":"myosin E, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0112200","name":null,"product":"myosin E","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1136100","name":null,"product":"myosin E, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MyoE","evaluation":null}