{"gene":"PF3D7_1105600","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2009,"finding":"PTEX88 was identified as a component of the Plasmodium translocon of exported proteins (PTEX), a complex located in the parasitophorous vacuole membrane that is ATP-powered and mediates export of parasite proteins into the host erythrocyte cytosol.","method":"Biochemical complex purification and identification of PTEX components","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — original discovery by complex purification, replicated and validated by multiple subsequent independent labs","pmids":["19536257"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PTEX88 is a genuine member of PTEX (validated by genetic tagging); PTEX88 could not be genetically deleted in P. berghei, consistent with an important role in blood-stage growth.","method":"Genetic tagging and attempted gene deletion in P. berghei","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic tagging and deletion attempts in two independent studies, but essentiality inferred from failed knockouts rather than direct functional assay","pmids":["23869529"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2013,"finding":"P. berghei parasites lacking PTEX88 show strongly reduced blood-stage multiplication rates and are outcompeted by wild-type parasites in vivo; endogenous tagging revealed PTEX88::tag displays a diffuse intraparasitic pattern in blood-stage parasites and also localizes to extensions reaching from the parasite surface into the erythrocyte cytoplasm in trophozoites.","method":"Gene deletion (null-mutant generation), flow cytometry-assisted intravital competition assay, endogenous fluorescent tagging and live imaging","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockout with specific phenotypic readout and direct localization imaging, single lab","pmids":["24076174"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"finding":"Endogenous fluorescent tagging of PTEX88 in P. berghei revealed its presence in motile, tubular extensions of the parasitophorous vacuole that protrude from the parasite far into the red blood cell; these tubular structures are most prominent during trophozoite growth and distinct spatiotemporal expression of PTEX88 was observed during sporogony and liver-stage development.","method":"Endogenous fluorescent tagging, live cell imaging, correlative light and electron microscopy","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by live imaging with correlative EM, single lab, multiple imaging methods","pmids":["26219962"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"finding":"PTEX88-deficient P. berghei parasites no longer sequester in the brain, abolishing cerebral malaria complications in infected mice, and show reduced sequestration in pulmonary, adipose, and brain tissue vasculature; however, general protein export is unaffected in PTEX88-deficient mutants that mature normally in vitro, indicating PTEX88 function in sequestration is independent of general protein export.","method":"Gene deletion (null-mutant), mouse infection model, in vitro growth assay, sequestration assay","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockout with multiple defined in vivo phenotypic readouts and explicit test of export function, single lab","pmids":["25820521"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"Inducible knockdown of PTEX88 in P. falciparum and P. berghei hindered in vivo parasite growth but did not produce a general defect in export of known parasite proteins; PTEX88-deficient P. berghei could not cause cerebral malaria and showed reduced peripheral tissue sequestration, while PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial receptor CD36, suggesting PTEX88 plays a specific role in mediating parasite sequestration rather than universal protein trafficking.","method":"Inducible knockdown in P. falciparum and P. berghei, in vivo mouse infection model, protein export assays, CD36 binding assay","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — inducible knockdown in two Plasmodium species with multiple orthogonal phenotypic readouts, export assays and receptor-binding assay, corroborating prior knockout studies","pmids":["26886275"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2018,"finding":"Proteomic analysis of the PTEX88 interactome showed that PTEX88 interacts most closely with HSP101 and has weaker affinity with other core PTEX constituents (PTEX150, EXP2); PTEX88 also associates with other parasitophorous vacuole-resident proteins including chaperones and members of the exported protein-interacting complex (EPIC) that interacts with the virulence factor PfEMP1. PTEX88 is only discretely observed at the parasitophorous vacuole membrane during ring stages and cannot always be detected in the major high molecular weight complex containing other core PTEX components, indicating its interaction with PTEX is dynamic.","method":"Co-immunoprecipitation, mass spectrometry (proteomic interactome analysis), live imaging/localization","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal proteomic interactome with direct localization data, single lab","pmids":["29637707"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PTEX88 is an auxiliary component of the P. falciparum/P. berghei PTEX translocon complex located at the parasitophorous vacuole membrane; it interacts most closely with HSP101 (and more weakly with other core components) in a dynamic manner, localizes to tubular extensions of the vacuole in trophozoites, is required for efficient parasite sequestration in host tissues and virulence (including cerebral malaria), but its knockdown does not impair general protein export to the host erythrocyte, distinguishing its function from that of the core translocon components."},"narrative":{"mechanistic_narrative":"PTEX88 (PF3D7_1105600) is an auxiliary component of the Plasmodium translocon of exported proteins (PTEX), the ATP-powered parasitophorous vacuole membrane complex that mediates export of parasite proteins into the host erythrocyte cytosol [PMID:19536257]. Within this complex, PTEX88 associates most closely with the HSP101 core motor and more weakly with the other core constituents PTEX150 and EXP2, and it also engages other vacuole-resident chaperones and members of the exported protein-interacting complex (EPIC); its incorporation into the high molecular weight PTEX assembly is dynamic rather than constitutive [PMID:29637707]. Beyond its diffuse intraparasitic distribution, PTEX88 localizes to motile tubular extensions of the parasitophorous vacuole that protrude from the parasite into the erythrocyte cytoplasm, most prominently during trophozoite growth [PMID:24076174, PMID:26219962]. Functionally, PTEX88 is required for efficient blood-stage growth and for parasite sequestration in host tissue vasculature: its loss or knockdown abolishes brain sequestration and cerebral malaria in P. berghei and reduces CD36-dependent adhesion of P. falciparum-infected erythrocytes, yet does not impair general protein export, distinguishing its role from that of the core translocon components [PMID:24076174, PMID:25820521, PMID:26886275]. In P. berghei the gene could not be deleted in some settings, consistent with an important blood-stage role [PMID:23869529].","teleology":[{"year":2009,"claim":"Establishing that a dedicated machine exports parasite proteins across the parasitophorous vacuole membrane required defining its components; identifying PTEX88 as part of PTEX placed it within the protein-export translocon.","evidence":"Biochemical complex purification and identification of PTEX components in P. falciparum","pmids":["19536257"],"confidence":"High","gaps":["Does not define PTEX88's specific molecular role versus core components","No stoichiometry or structural placement within the complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"To test whether PTEX88 is a bona fide, functionally important complex member, genetic tagging confirmed its PTEX membership and failed deletion attempts implied an important blood-stage role.","evidence":"Genetic tagging and attempted gene deletion in P. berghei","pmids":["23869529"],"confidence":"Medium","gaps":["Essentiality inferred from failed knockout, not a direct functional assay","Species-specific: deletion outcome differs from later knockout reports"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2013,"claim":"Determining the functional consequence and subcellular distribution of PTEX88 showed a growth defect and revealed localization to extensions reaching into the erythrocyte cytoplasm.","evidence":"Null-mutant generation, intravital competition assay, and endogenous fluorescent tagging with live imaging in P. berghei","pmids":["24076174"],"confidence":"Medium","gaps":["Molecular basis of the growth defect not resolved","Single lab; does not distinguish direct versus indirect effects on growth"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"claim":"Refining the localization further, correlative imaging identified PTEX88 in motile tubular parasitophorous vacuole extensions and revealed distinct expression across sporogony and liver-stage development.","evidence":"Endogenous fluorescent tagging, live cell imaging, and correlative light and electron microscopy in P. berghei","pmids":["26219962"],"confidence":"Medium","gaps":["Function of the tubular extensions not defined","Link between extension localization and export or sequestration not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"claim":"To separate PTEX88's role from general protein export, knockout parasites were tested for sequestration and export, showing loss of brain and peripheral tissue sequestration and abolition of cerebral malaria while export remained intact.","evidence":"Null-mutant, mouse infection model, in vitro growth and sequestration assays in P. berghei","pmids":["25820521"],"confidence":"Medium","gaps":["Mechanism linking PTEX88 to sequestration not identified","Single lab; molecular adhesion pathway not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Extending the sequestration phenotype across species, inducible knockdown confirmed a specific role in adhesion, including reduced CD36 binding in P. falciparum, decoupling PTEX88 from universal protein trafficking.","evidence":"Inducible knockdown in P. falciparum and P. berghei, in vivo infection, protein export assays, and CD36 binding assay","pmids":["26886275"],"confidence":"High","gaps":["Direct molecular mechanism connecting PTEX88 to CD36 adhesion not defined","Whether PTEX88 acts through PfEMP1 trafficking or another route unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2018,"claim":"Mapping the PTEX88 interactome defined its closest partner as HSP101 with weaker association to PTEX150 and EXP2, plus contacts with vacuolar chaperones and EPIC, and showed its PTEX incorporation is dynamic and stage-restricted.","evidence":"Co-immunoprecipitation, mass spectrometry interactome, and live imaging in P. falciparum","pmids":["29637707"],"confidence":"Medium","gaps":["Functional consequence of the dynamic HSP101 interaction not resolved","How EPIC association relates to the sequestration phenotype not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular mechanism by which PTEX88 promotes parasite sequestration and adhesion, and how this relates to its dynamic association with the PTEX core, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined substrate or adhesion-effector pathway for PTEX88","No structural model of PTEX88 within PTEX","Reason for dynamic/stage-restricted PTEX incorporation unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PTEX (Plasmodium translocon of exported proteins)"],"partners":["HSP101","PTEX150","EXP2","EPIC (EXPORTED PROTEIN-INTERACTING COMPLEX) MEMBERS"],"other_free_text":["Auxiliary/non-core PTEX component with dynamic, stage-restricted association to the translocon [#6]","Required for parasite sequestration and virulence (cerebral malaria) but dispensable for general protein export [#4, #5]","Mediates CD36-dependent adhesion of P. falciparum-infected erythrocytes [#5]","Localizes to motile tubular extensions of the parasitophorous vacuole in trophozoites [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19536257","id":"PMC_19536257","title":"A newly discovered protein export machine in malaria parasites.","date":"2009","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/19536257","citation_count":381,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27374802","id":"PMC_27374802","title":"Plasmodium species: master renovators of their host cells.","date":"2016","source":"Nature reviews. Microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27374802","citation_count":137,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23869529","id":"PMC_23869529","title":"The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth.","date":"2013","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23869529","citation_count":72,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24076174","id":"PMC_24076174","title":"Two putative protein export regulators promote Plasmodium blood stage development in vivo.","date":"2013","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/24076174","citation_count":66,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26219962","id":"PMC_26219962","title":"The Plasmodium berghei translocon of exported proteins reveals spatiotemporal dynamics of tubular extensions.","date":"2015","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26219962","citation_count":39,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25820521","id":"PMC_25820521","title":"In Vivo Function of PTEX88 in Malaria Parasite Sequestration and Virulence.","date":"2015","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/25820521","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26886275","id":"PMC_26886275","title":"Contrasting Inducible Knockdown of the Auxiliary PTEX Component PTEX88 in P. falciparum and P. berghei Unmasks a Role in Parasite Virulence.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26886275","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27865834","id":"PMC_27865834","title":"Expression and characterization of the Plasmodium translocon of the exported proteins component EXP2.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/27865834","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29637707","id":"PMC_29637707","title":"The malaria PTEX component PTEX88 interacts most closely with HSP101 at the host-parasite interface.","date":"2018","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/29637707","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PTEX88"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6947,"output_tokens":1984,"usd":0.025301,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7201,"output_tokens":2940,"usd":0.054753,"stage2_stop_reason":"end_turn"},"total_usd":0.080054,"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\": 2009,\n      \"finding\": \"PTEX88 was identified as a component of the Plasmodium translocon of exported proteins (PTEX), a complex located in the parasitophorous vacuole membrane that is ATP-powered and mediates export of parasite proteins into the host erythrocyte cytosol.\",\n      \"method\": \"Biochemical complex purification and identification of PTEX components\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — original discovery by complex purification, replicated and validated by multiple subsequent independent labs\",\n      \"pmids\": [\"19536257\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PTEX88 is a genuine member of PTEX (validated by genetic tagging); PTEX88 could not be genetically deleted in P. berghei, consistent with an important role in blood-stage growth.\",\n      \"method\": \"Genetic tagging and attempted gene deletion in P. berghei\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic tagging and deletion attempts in two independent studies, but essentiality inferred from failed knockouts rather than direct functional assay\",\n      \"pmids\": [\"23869529\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"P. berghei parasites lacking PTEX88 show strongly reduced blood-stage multiplication rates and are outcompeted by wild-type parasites in vivo; endogenous tagging revealed PTEX88::tag displays a diffuse intraparasitic pattern in blood-stage parasites and also localizes to extensions reaching from the parasite surface into the erythrocyte cytoplasm in trophozoites.\",\n      \"method\": \"Gene deletion (null-mutant generation), flow cytometry-assisted intravital competition assay, endogenous fluorescent tagging and live imaging\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with specific phenotypic readout and direct localization imaging, single lab\",\n      \"pmids\": [\"24076174\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Endogenous fluorescent tagging of PTEX88 in P. berghei revealed its presence in motile, tubular extensions of the parasitophorous vacuole that protrude from the parasite far into the red blood cell; these tubular structures are most prominent during trophozoite growth and distinct spatiotemporal expression of PTEX88 was observed during sporogony and liver-stage development.\",\n      \"method\": \"Endogenous fluorescent tagging, live cell imaging, correlative light and electron microscopy\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by live imaging with correlative EM, single lab, multiple imaging methods\",\n      \"pmids\": [\"26219962\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PTEX88-deficient P. berghei parasites no longer sequester in the brain, abolishing cerebral malaria complications in infected mice, and show reduced sequestration in pulmonary, adipose, and brain tissue vasculature; however, general protein export is unaffected in PTEX88-deficient mutants that mature normally in vitro, indicating PTEX88 function in sequestration is independent of general protein export.\",\n      \"method\": \"Gene deletion (null-mutant), mouse infection model, in vitro growth assay, sequestration assay\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with multiple defined in vivo phenotypic readouts and explicit test of export function, single lab\",\n      \"pmids\": [\"25820521\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Inducible knockdown of PTEX88 in P. falciparum and P. berghei hindered in vivo parasite growth but did not produce a general defect in export of known parasite proteins; PTEX88-deficient P. berghei could not cause cerebral malaria and showed reduced peripheral tissue sequestration, while PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial receptor CD36, suggesting PTEX88 plays a specific role in mediating parasite sequestration rather than universal protein trafficking.\",\n      \"method\": \"Inducible knockdown in P. falciparum and P. berghei, in vivo mouse infection model, protein export assays, CD36 binding assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — inducible knockdown in two Plasmodium species with multiple orthogonal phenotypic readouts, export assays and receptor-binding assay, corroborating prior knockout studies\",\n      \"pmids\": [\"26886275\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Proteomic analysis of the PTEX88 interactome showed that PTEX88 interacts most closely with HSP101 and has weaker affinity with other core PTEX constituents (PTEX150, EXP2); PTEX88 also associates with other parasitophorous vacuole-resident proteins including chaperones and members of the exported protein-interacting complex (EPIC) that interacts with the virulence factor PfEMP1. PTEX88 is only discretely observed at the parasitophorous vacuole membrane during ring stages and cannot always be detected in the major high molecular weight complex containing other core PTEX components, indicating its interaction with PTEX is dynamic.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry (proteomic interactome analysis), live imaging/localization\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal proteomic interactome with direct localization data, single lab\",\n      \"pmids\": [\"29637707\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PTEX88 is an auxiliary component of the P. falciparum/P. berghei PTEX translocon complex located at the parasitophorous vacuole membrane; it interacts most closely with HSP101 (and more weakly with other core components) in a dynamic manner, localizes to tubular extensions of the vacuole in trophozoites, is required for efficient parasite sequestration in host tissues and virulence (including cerebral malaria), but its knockdown does not impair general protein export to the host erythrocyte, distinguishing its function from that of the core translocon components.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PTEX88 (PF3D7_1105600) is an auxiliary component of the Plasmodium translocon of exported proteins (PTEX), the ATP-powered parasitophorous vacuole membrane complex that mediates export of parasite proteins into the host erythrocyte cytosol [#0]. Within this complex, PTEX88 associates most closely with the HSP101 core motor and more weakly with the other core constituents PTEX150 and EXP2, and it also engages other vacuole-resident chaperones and members of the exported protein-interacting complex (EPIC); its incorporation into the high molecular weight PTEX assembly is dynamic rather than constitutive [#6]. Beyond its diffuse intraparasitic distribution, PTEX88 localizes to motile tubular extensions of the parasitophorous vacuole that protrude from the parasite into the erythrocyte cytoplasm, most prominently during trophozoite growth [#2, #3]. Functionally, PTEX88 is required for efficient blood-stage growth and for parasite sequestration in host tissue vasculature: its loss or knockdown abolishes brain sequestration and cerebral malaria in P. berghei and reduces CD36-dependent adhesion of P. falciparum-infected erythrocytes, yet does not impair general protein export, distinguishing its role from that of the core translocon components [#2, #4, #5]. In P. berghei the gene could not be deleted in some settings, consistent with an important blood-stage role [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing that a dedicated machine exports parasite proteins across the parasitophorous vacuole membrane required defining its components; identifying PTEX88 as part of PTEX placed it within the protein-export translocon.\",\n      \"evidence\": \"Biochemical complex purification and identification of PTEX components in P. falciparum\",\n      \"pmids\": [\"19536257\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define PTEX88's specific molecular role versus core components\", \"No stoichiometry or structural placement within the complex\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"To test whether PTEX88 is a bona fide, functionally important complex member, genetic tagging confirmed its PTEX membership and failed deletion attempts implied an important blood-stage role.\",\n      \"evidence\": \"Genetic tagging and attempted gene deletion in P. berghei\",\n      \"pmids\": [\"23869529\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Essentiality inferred from failed knockout, not a direct functional assay\", \"Species-specific: deletion outcome differs from later knockout reports\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Determining the functional consequence and subcellular distribution of PTEX88 showed a growth defect and revealed localization to extensions reaching into the erythrocyte cytoplasm.\",\n      \"evidence\": \"Null-mutant generation, intravital competition assay, and endogenous fluorescent tagging with live imaging in P. berghei\",\n      \"pmids\": [\"24076174\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of the growth defect not resolved\", \"Single lab; does not distinguish direct versus indirect effects on growth\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Refining the localization further, correlative imaging identified PTEX88 in motile tubular parasitophorous vacuole extensions and revealed distinct expression across sporogony and liver-stage development.\",\n      \"evidence\": \"Endogenous fluorescent tagging, live cell imaging, and correlative light and electron microscopy in P. berghei\",\n      \"pmids\": [\"26219962\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Function of the tubular extensions not defined\", \"Link between extension localization and export or sequestration not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To separate PTEX88's role from general protein export, knockout parasites were tested for sequestration and export, showing loss of brain and peripheral tissue sequestration and abolition of cerebral malaria while export remained intact.\",\n      \"evidence\": \"Null-mutant, mouse infection model, in vitro growth and sequestration assays in P. berghei\",\n      \"pmids\": [\"25820521\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking PTEX88 to sequestration not identified\", \"Single lab; molecular adhesion pathway not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extending the sequestration phenotype across species, inducible knockdown confirmed a specific role in adhesion, including reduced CD36 binding in P. falciparum, decoupling PTEX88 from universal protein trafficking.\",\n      \"evidence\": \"Inducible knockdown in P. falciparum and P. berghei, in vivo infection, protein export assays, and CD36 binding assay\",\n      \"pmids\": [\"26886275\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct molecular mechanism connecting PTEX88 to CD36 adhesion not defined\", \"Whether PTEX88 acts through PfEMP1 trafficking or another route unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapping the PTEX88 interactome defined its closest partner as HSP101 with weaker association to PTEX150 and EXP2, plus contacts with vacuolar chaperones and EPIC, and showed its PTEX incorporation is dynamic and stage-restricted.\",\n      \"evidence\": \"Co-immunoprecipitation, mass spectrometry interactome, and live imaging in P. falciparum\",\n      \"pmids\": [\"29637707\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the dynamic HSP101 interaction not resolved\", \"How EPIC association relates to the sequestration phenotype not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular mechanism by which PTEX88 promotes parasite sequestration and adhesion, and how this relates to its dynamic association with the PTEX core, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No defined substrate or adhesion-effector pathway for PTEX88\", \"No structural model of PTEX88 within PTEX\", \"Reason for dynamic/stage-restricted PTEX incorporation unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0020002\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0020036\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046短\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"PTEX (Plasmodium translocon of exported proteins)\"],\n    \"partners\": [\"HSP101\", \"PTEX150\", \"EXP2\", \"EPIC (exported protein-interacting complex) members\"],\n    \"other_free_text\": [\n      \"Auxiliary/non-core PTEX component with dynamic, stage-restricted association to the translocon [#6]\",\n      \"Required for parasite sequestration and virulence (cerebral malaria) but dispensable for general protein export [#4, #5]\",\n      \"Mediates CD36-dependent adhesion of P. falciparum-infected erythrocytes [#5]\",\n      \"Localizes to motile tubular extensions of the parasitophorous vacuole in trophozoites [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1105600","name":null,"product":"translocon component PTEX88","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0941300","name":null,"product":"translocon component PTEX88","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0903200","name":null,"product":"translocon component PTEX88, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PTEX88","evaluation":null}