{"gene":"PF3D7_0515700","run_date":"2026-09-07T12:57:17+00:00","timeline":{"discoveries":[{"year":2005,"finding":"GAP40 homologues (referred to in this paper as one of the 'glideosome-associated proteins 45 and 50' naming context, but explicitly identified as part of the motor complex) are present in P. falciparum merozoites and appear to function in erythrocyte invasion, as part of a conserved actin-myosin motor complex linking extracellular adhesins to the inner membrane complex.","method":"Protein identification and localization by immunofluorescence/Western blot in merozoites; comparative genomic analysis across Apicomplexan genera","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-lab identification with indirect functional inference; GAP40 is mentioned by name but no direct loss-of-function experiment performed for this specific protein","pmids":["16321976"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"GAP40 is identified as a polytopic (multi-transmembrane) protein of the inner membrane complex (IMC) and an additional component of the glideosome in Toxoplasma; the orthologous P. falciparum GAP40 is noted as part of this conserved complex architecture.","method":"Molecular characterization, subcellular fractionation, and localization studies in Toxoplasma with comparative identification in P. falciparum","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical characterization establishing IMC localization and polytopic membrane topology, but primary functional experiments performed in Toxoplasma with P. falciparum noted as ortholog","pmids":["20951968"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"GAP40 is a component of the P. berghei glideosome complex that co-purifies with MyoA, MTIP, and the newly identified essential light chain (ELC), and is present at the parasite periphery in extracellular merozoites, ookinetes, and sporozoites.","method":"Co-immunoprecipitation/mass spectrometry-based glideosome complex composition analysis; immunofluorescence localization throughout the P. berghei life cycle","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal complex composition by MS and direct localization, single lab, multiple life cycle stages examined","pmids":["28893907"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"PfGAP40 is required for asexual blood-stage replication and efficient merozoite invasion of red blood cells, as demonstrated by conditional knockdown; knockdown did not affect merozoite egress or attachment to RBCs, but impaired invasion.","method":"Conditional knockdown (TetR-DOZI aptamer system) with invasion and egress assays","journal":"Microbiology spectrum","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional knockdown with specific phenotypic readouts (invasion vs. egress vs. attachment dissected), published in peer-reviewed journal, single lab but multiple orthogonal assays","pmids":["37249423"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfGAP40 co-precipitates with PfGAP45 and PfGAP50, and its knockdown reduces the protein levels of PfGAP45 and PfGAP50 in schizonts, indicating that PfGAP40 stabilizes the expression/stability of these glideosome components.","method":"Co-immunoprecipitation and Western blot analysis after conditional knockdown","journal":"Microbiology spectrum","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP combined with KD-Western to show stabilization role, single lab","pmids":["37249423"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfGAP40 is phosphorylated, and alanine substitution mutations blocking phosphorylation at C-terminal serine residues S370, S372, S376, S405, S409, S420, and S445 reduced merozoite invasion efficiency, establishing that phosphorylation at these sites is required for full PfGAP40 function.","method":"Site-directed mutagenesis of phosphoserine residues combined with invasion efficiency assays","journal":"Microbiology spectrum","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — active-site (phosphosite) mutagenesis with functional invasion readout, single lab, no identification of the kinase writer","pmids":["37249423"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfGAP40 knockdown impaired gametocyte maturation, indicating a role for PfGAP40 beyond asexual blood-stage invasion, extending to the sexual stage.","method":"Conditional knockdown with gametocyte development/maturation assay","journal":"Microbiology spectrum","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KD with defined stage-specific phenotypic readout, single lab","pmids":["37249423"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfGAP40 (PF3D7_0515700) is a polytopic inner membrane complex (IMC)-resident protein and essential component of the glideosome that physically associates with PfGAP45 and PfGAP50, stabilizes their expression in schizonts, is required for efficient merozoite invasion of red blood cells (but not egress or attachment), supports gametocyte maturation, and depends on phosphorylation at multiple C-terminal serine residues for full invasion function."},"narrative":{"mechanistic_narrative":"GAP40 (PF3D7_0515700) is an essential, polytopic (multi-transmembrane) inner membrane complex (IMC) protein and a core component of the glideosome, the actin-myosin motor that links extracellular adhesins to the IMC to power host-cell entry [PMID:20951968, PMID:28893907]. Within this complex GAP40 physically associates with PfGAP45 and PfGAP50, and its loss reduces the levels of both partners in schizonts, indicating that GAP40 stabilizes the assembly or steady-state expression of these glideosome components [PMID:37249423]. Functionally, conditional knockdown of GAP40 impairs asexual blood-stage replication by blocking efficient merozoite invasion of red blood cells, while leaving egress and initial attachment intact, defining a specific role in the invasion step [PMID:37249423]. GAP40 function is regulated by phosphorylation: alanine substitution of multiple C-terminal serine residues (S370, S372, S376, S405, S409, S420, S445) reduces invasion efficiency, establishing these phosphosites as required for full activity [PMID:37249423]. Beyond the asexual stage, GAP40 knockdown impairs gametocyte maturation, extending its role into the sexual stage [PMID:37249423]. The kinase(s) writing these phosphorylation marks and the structural basis of GAP40's role in the complex have not been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Established GAP40 as part of the conserved actin-myosin motor complex of the P. falciparum merozoite, placing it within the machinery that couples adhesins to the IMC for erythrocyte invasion.","evidence":"Protein identification and immunolocalization in merozoites with comparative genomic analysis across Apicomplexa","pmids":["16321976"],"confidence":"Low","gaps":["No direct loss-of-function experiment performed for GAP40 itself; functional role inferred indirectly","GAP40's own topology and specific molecular role in the complex not defined here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Defined GAP40 as a polytopic IMC membrane protein and an additional glideosome component, giving a physical/topological basis for its position in the motor complex.","evidence":"Molecular characterization, subcellular fractionation, and localization in Toxoplasma with comparative identification of the P. falciparum ortholog","pmids":["20951968"],"confidence":"Medium","gaps":["Primary functional experiments were performed in Toxoplasma; P. falciparum only noted as ortholog","No functional consequence of GAP40 loss tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Confirmed GAP40 as a co-purifying member of the glideosome present at the parasite periphery across multiple invasive stages, extending its association beyond blood-stage merozoites.","evidence":"Co-immunoprecipitation/mass spectrometry of glideosome composition and immunofluorescence across the P. berghei life cycle","pmids":["28893907"],"confidence":"Medium","gaps":["Shown in P. berghei; direct functional requirement not tested here","Nature of GAP40's interactions with individual motor subunits not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Demonstrated that GAP40 is specifically required for efficient merozoite invasion, dissociating its role from egress and attachment and establishing it as essential for blood-stage replication.","evidence":"Conditional TetR-DOZI knockdown with invasion, egress, and attachment assays in P. falciparum","pmids":["37249423"],"confidence":"High","gaps":["Molecular step of invasion that fails upon GAP40 loss not pinpointed","Single-lab study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Showed that GAP40 stabilizes glideosome partners PfGAP45 and PfGAP50, providing a mechanism by which its loss disrupts motor function.","evidence":"Co-immunoprecipitation and Western blot of partner levels after conditional knockdown in P. falciparum","pmids":["37249423"],"confidence":"Medium","gaps":["Whether stabilization is at the level of assembly, folding, or turnover not distinguished","Reciprocal dependence (whether partners stabilize GAP40) not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Established that phosphorylation of specific C-terminal serine residues is required for full GAP40 invasion function, identifying a regulatory layer on the protein.","evidence":"Site-directed alanine mutagenesis of phosphoserines S370/S372/S376/S405/S409/S420/S445 with invasion efficiency assays in P. falciparum","pmids":["37249423"],"confidence":"Medium","gaps":["The kinase(s) writing these phosphomarks not identified","How phosphorylation affects complex assembly or motor activity not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Extended GAP40's role beyond asexual invasion by showing its knockdown impairs gametocyte maturation, implicating it in the sexual stage.","evidence":"Conditional knockdown with gametocyte development/maturation assay in P. falciparum","pmids":["37249423"],"confidence":"Medium","gaps":["The gametocyte-stage function of GAP40 (whether motor-related or structural) not defined","Single-lab study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The identity of the kinase(s) that phosphorylate GAP40 and the structural basis for how GAP40 organizes and stabilizes the glideosome remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No kinase writer identified for the C-terminal phosphosites","No structural model of GAP40 within the glideosome","Mechanism linking GAP40 loss to invasion failure not resolved at molecular resolution"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["glideosome (with PfGAP45, PfGAP50; co-purifies with MyoA, MTIP, ELC in P. berghei)"],"partners":["PFGAP45","PFGAP50","MYOA (P. BERGHEI GLIDEOSOME CO-PURIFICATION)","MTIP (P. BERGHEI GLIDEOSOME CO-PURIFICATION)","ELC (P. BERGHEI GLIDEOSOME CO-PURIFICATION)"],"other_free_text":["Polytopic multi-transmembrane inner membrane complex protein [#1].","Essential for asexual blood-stage replication and efficient merozoite invasion; dispensable for egress and attachment [#3].","Stabilizes steady-state levels of PfGAP45 and PfGAP50 in schizonts [#4].","Requires C-terminal serine phosphorylation (S370, S372, S376, S405, S409, S420, S445) for full invasion function [#5].","Required for gametocyte maturation [#6].","Localized at parasite periphery across merozoite, ookinete, and sporozoite stages in P. berghei [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16321976","id":"PMC_16321976","title":"A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16321976","citation_count":291,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAP40"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20951968","id":"PMC_20951968","title":"Functional dissection of the apicomplexan glideosome molecular architecture.","date":"2010","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/20951968","citation_count":237,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAP40"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28893907","id":"PMC_28893907","title":"Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28893907","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAP40"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37249423","id":"PMC_37249423","title":"Plasmodium falciparum GAP40 Plays an Essential Role in Merozoite Invasion and Gametocytogenesis.","date":"2023","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/37249423","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAP40","PfGAP40"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5072,"output_tokens":1806,"usd":0.021153,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6922,"output_tokens":3110,"usd":0.05618,"stage2_stop_reason":"end_turn"},"total_usd":0.0,"stage1_batch_id":"msgbatch_01BW7vvc7h5iV39oJ1MHMzXw","stage2_batch_id":"msgbatch_01Kh5HbgbPXepNfNCbktYkSD","note":"batch pricing = 50% of standard","skipped":true},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"GAP40 homologues (referred to in this paper as one of the 'glideosome-associated proteins 45 and 50' naming context, but explicitly identified as part of the motor complex) are present in P. falciparum merozoites and appear to function in erythrocyte invasion, as part of a conserved actin-myosin motor complex linking extracellular adhesins to the inner membrane complex.\",\n      \"method\": \"Protein identification and localization by immunofluorescence/Western blot in merozoites; comparative genomic analysis across Apicomplexan genera\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab identification with indirect functional inference; GAP40 is mentioned by name but no direct loss-of-function experiment performed for this specific protein\",\n      \"pmids\": [\"16321976\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"GAP40 is identified as a polytopic (multi-transmembrane) protein of the inner membrane complex (IMC) and an additional component of the glideosome in Toxoplasma; the orthologous P. falciparum GAP40 is noted as part of this conserved complex architecture.\",\n      \"method\": \"Molecular characterization, subcellular fractionation, and localization studies in Toxoplasma with comparative identification in P. falciparum\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical characterization establishing IMC localization and polytopic membrane topology, but primary functional experiments performed in Toxoplasma with P. falciparum noted as ortholog\",\n      \"pmids\": [\"20951968\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"GAP40 is a component of the P. berghei glideosome complex that co-purifies with MyoA, MTIP, and the newly identified essential light chain (ELC), and is present at the parasite periphery in extracellular merozoites, ookinetes, and sporozoites.\",\n      \"method\": \"Co-immunoprecipitation/mass spectrometry-based glideosome complex composition analysis; immunofluorescence localization throughout the P. berghei life cycle\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal complex composition by MS and direct localization, single lab, multiple life cycle stages examined\",\n      \"pmids\": [\"28893907\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfGAP40 is required for asexual blood-stage replication and efficient merozoite invasion of red blood cells, as demonstrated by conditional knockdown; knockdown did not affect merozoite egress or attachment to RBCs, but impaired invasion.\",\n      \"method\": \"Conditional knockdown (TetR-DOZI aptamer system) with invasion and egress assays\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional knockdown with specific phenotypic readouts (invasion vs. egress vs. attachment dissected), published in peer-reviewed journal, single lab but multiple orthogonal assays\",\n      \"pmids\": [\"37249423\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfGAP40 co-precipitates with PfGAP45 and PfGAP50, and its knockdown reduces the protein levels of PfGAP45 and PfGAP50 in schizonts, indicating that PfGAP40 stabilizes the expression/stability of these glideosome components.\",\n      \"method\": \"Co-immunoprecipitation and Western blot analysis after conditional knockdown\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP combined with KD-Western to show stabilization role, single lab\",\n      \"pmids\": [\"37249423\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfGAP40 is phosphorylated, and alanine substitution mutations blocking phosphorylation at C-terminal serine residues S370, S372, S376, S405, S409, S420, and S445 reduced merozoite invasion efficiency, establishing that phosphorylation at these sites is required for full PfGAP40 function.\",\n      \"method\": \"Site-directed mutagenesis of phosphoserine residues combined with invasion efficiency assays\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site (phosphosite) mutagenesis with functional invasion readout, single lab, no identification of the kinase writer\",\n      \"pmids\": [\"37249423\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfGAP40 knockdown impaired gametocyte maturation, indicating a role for PfGAP40 beyond asexual blood-stage invasion, extending to the sexual stage.\",\n      \"method\": \"Conditional knockdown with gametocyte development/maturation assay\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KD with defined stage-specific phenotypic readout, single lab\",\n      \"pmids\": [\"37249423\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfGAP40 (PF3D7_0515700) is a polytopic inner membrane complex (IMC)-resident protein and essential component of the glideosome that physically associates with PfGAP45 and PfGAP50, stabilizes their expression in schizonts, is required for efficient merozoite invasion of red blood cells (but not egress or attachment), supports gametocyte maturation, and depends on phosphorylation at multiple C-terminal serine residues for full invasion function.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GAP40 (PF3D7_0515700) is an essential, polytopic (multi-transmembrane) inner membrane complex (IMC) protein and a core component of the glideosome, the actin-myosin motor that links extracellular adhesins to the IMC to power host-cell entry [#1, #2]. Within this complex GAP40 physically associates with PfGAP45 and PfGAP50, and its loss reduces the levels of both partners in schizonts, indicating that GAP40 stabilizes the assembly or steady-state expression of these glideosome components [#4]. Functionally, conditional knockdown of GAP40 impairs asexual blood-stage replication by blocking efficient merozoite invasion of red blood cells, while leaving egress and initial attachment intact, defining a specific role in the invasion step [#3]. GAP40 function is regulated by phosphorylation: alanine substitution of multiple C-terminal serine residues (S370, S372, S376, S405, S409, S420, S445) reduces invasion efficiency, establishing these phosphosites as required for full activity [#5]. Beyond the asexual stage, GAP40 knockdown impairs gametocyte maturation, extending its role into the sexual stage [#6]. The kinase(s) writing these phosphorylation marks and the structural basis of GAP40's role in the complex have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established GAP40 as part of the conserved actin-myosin motor complex of the P. falciparum merozoite, placing it within the machinery that couples adhesins to the IMC for erythrocyte invasion.\",\n      \"evidence\": \"Protein identification and immunolocalization in merozoites with comparative genomic analysis across Apicomplexa\",\n      \"pmids\": [\"16321976\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct loss-of-function experiment performed for GAP40 itself; functional role inferred indirectly\",\n        \"GAP40's own topology and specific molecular role in the complex not defined here\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined GAP40 as a polytopic IMC membrane protein and an additional glideosome component, giving a physical/topological basis for its position in the motor complex.\",\n      \"evidence\": \"Molecular characterization, subcellular fractionation, and localization in Toxoplasma with comparative identification of the P. falciparum ortholog\",\n      \"pmids\": [\"20951968\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Primary functional experiments were performed in Toxoplasma; P. falciparum only noted as ortholog\",\n        \"No functional consequence of GAP40 loss tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Confirmed GAP40 as a co-purifying member of the glideosome present at the parasite periphery across multiple invasive stages, extending its association beyond blood-stage merozoites.\",\n      \"evidence\": \"Co-immunoprecipitation/mass spectrometry of glideosome composition and immunofluorescence across the P. berghei life cycle\",\n      \"pmids\": [\"28893907\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Shown in P. berghei; direct functional requirement not tested here\",\n        \"Nature of GAP40's interactions with individual motor subunits not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated that GAP40 is specifically required for efficient merozoite invasion, dissociating its role from egress and attachment and establishing it as essential for blood-stage replication.\",\n      \"evidence\": \"Conditional TetR-DOZI knockdown with invasion, egress, and attachment assays in P. falciparum\",\n      \"pmids\": [\"37249423\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular step of invasion that fails upon GAP40 loss not pinpointed\",\n        \"Single-lab study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed that GAP40 stabilizes glideosome partners PfGAP45 and PfGAP50, providing a mechanism by which its loss disrupts motor function.\",\n      \"evidence\": \"Co-immunoprecipitation and Western blot of partner levels after conditional knockdown in P. falciparum\",\n      \"pmids\": [\"37249423\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether stabilization is at the level of assembly, folding, or turnover not distinguished\",\n        \"Reciprocal dependence (whether partners stabilize GAP40) not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established that phosphorylation of specific C-terminal serine residues is required for full GAP40 invasion function, identifying a regulatory layer on the protein.\",\n      \"evidence\": \"Site-directed alanine mutagenesis of phosphoserines S370/S372/S376/S405/S409/S420/S445 with invasion efficiency assays in P. falciparum\",\n      \"pmids\": [\"37249423\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The kinase(s) writing these phosphomarks not identified\",\n        \"How phosphorylation affects complex assembly or motor activity not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Extended GAP40's role beyond asexual invasion by showing its knockdown impairs gametocyte maturation, implicating it in the sexual stage.\",\n      \"evidence\": \"Conditional knockdown with gametocyte development/maturation assay in P. falciparum\",\n      \"pmids\": [\"37249423\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The gametocyte-stage function of GAP40 (whether motor-related or structural) not defined\",\n        \"Single-lab study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The identity of the kinase(s) that phosphorylate GAP40 and the structural basis for how GAP40 organizes and stabilizes the glideosome remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No kinase writer identified for the C-terminal phosphosites\",\n        \"No structural model of GAP40 within the glideosome\",\n        \"Mechanism linking GAP40 loss to invasion failure not resolved at molecular resolution\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 2, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0071944\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006909\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"glideosome (with PfGAP45, PfGAP50; co-purifies with MyoA, MTIP, ELC in P. berghei)\"\n    ],\n    \"partners\": [\n      \"PfGAP45\",\n      \"PfGAP50\",\n      \"MyoA (P. berghei glideosome co-purification)\",\n      \"MTIP (P. berghei glideosome co-purification)\",\n      \"ELC (P. berghei glideosome co-purification)\"\n    ],\n    \"other_free_text\": [\n      \"Polytopic multi-transmembrane inner membrane complex protein [#1].\",\n      \"Essential for asexual blood-stage replication and efficient merozoite invasion; dispensable for egress and attachment [#3].\",\n      \"Stabilizes steady-state levels of PfGAP45 and PfGAP50 in schizonts [#4].\",\n      \"Requires C-terminal serine phosphorylation (S370, S372, S376, S405, S409, S420, S445) for full invasion function [#5].\",\n      \"Required for gametocyte maturation [#6].\",\n      \"Localized at parasite periphery across merozoite, ookinete, and sporozoite stages in P. berghei [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0515700","name":null,"product":"glideosome-associated protein 40","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1115300","name":null,"product":"glideosome-associated protein 40, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1017500","name":null,"product":"glideosome-associated protein 40, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GAP40","evaluation":null}