{"gene":"PF3D7_1011000","run_date":"2026-09-08T15:29:19+00:00","timeline":{"discoveries":[{"year":2013,"finding":"ISP1 localizes to the anterior apical end of Plasmodium berghei parasites where IMC organisation is initiated, and is expressed at all developmental stages, especially invasive ones. Gene disruption studies suggest ISP1 is likely essential for parasite development. ISP1 is N-myristoylated, phosphorylated, and membrane-bound.","method":"Live cell imaging, reverse genetics (gene disruption), biochemical characterization (N-myristoylation, phosphorylation assays) in P. berghei","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging and gene disruption with phenotypic readout, two orthogonal methods, single lab","pmids":["24244852"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2013,"finding":"Absence of ISP3 alters the apical localisation of ISP1 in all invasive stages including ookinetes and sporozoites, indicating a coordinated function between ISP1 and ISP3 in organising apical polarity.","method":"Live cell imaging of ISP3 gene-disruption parasites in P. berghei","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via gene disruption with direct localization readout, single lab","pmids":["24244852"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"finding":"PfISP1 is a dual-acylated (N-myristoylated and palmitoylated) IMC-localized protein in P. falciparum. PfDHHC1, a palmitoyl acyltransferase exclusively localized to the IMC, co-distributes with PfISP1 during schizogony, implicating it in ISP1 palmitoylation and IMC membrane recruitment.","method":"Systematic phylogenetic analysis, localization studies (fluorescence microscopy), biochemical acylation assays in P. falciparum","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-localization and biochemical characterization, single lab, multiple methods","pmids":["25425642"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"ISP1 anchors the GCβ/CDC50A complex at the ookinete extrados site (OES) of mature Plasmodium yoelii ookinetes. Screening of inner membrane complex proteins identified ISP1 as the key molecule mediating this polarized anchoring, which initiates ookinete gliding motility.","method":"Real-time imaging, protein–protein interaction screening of IMC proteins, genetic and cell biological experiments in P. yoelii","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging plus interaction screening with functional (gliding) readout, single lab","pmids":["30146157"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2020,"finding":"Palmitoylation of N-terminal cysteines of ISP1 (and ISP3) by the IMC-residing palmitoyl-S-acyl-transferase DHHC2 regulates ISP1 localization to the IMC and is required for zygote-to-ookinete differentiation. IMC-anchored ISP1 physically interacts with microtubule component β-tubulin, functioning as a tether to maintain proper subpellicular microtubule (SPM) structure during zygote elongation.","method":"Palmitoylation assays, PAT-substrate interaction experiments, co-immunoprecipitation with β-tubulin, genetic disruption with morphological/functional phenotype readout in Plasmodium","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro palmitoylation assays, reciprocal Co-IP, genetic disruption, and multiple orthogonal methods establishing mechanism in a single rigorous study","pmids":["32395856"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium yoelii","strain":""}]},{"year":2012,"finding":"ISP1 is one of eight structurally distinct IMC proteins in Plasmodium that display differential spatial-temporal expression patterns across the parasite life cycle, with the IMC serving as an essential structural compartment for sexual stage development and morphogenesis.","method":"Colocalization studies, evolutionary/phylogenetic analysis, fluorescence microscopy across life-cycle stages in P. falciparum","journal":"Molecular biology and evolution","confidence":"Low","confidence_rationale":"Tier 3 / Weak — colocalization and comparative analysis, ISP1-specific mechanistic detail minimal in this broad study","pmids":["22389454"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"ISP1 (PF3D7_1011000) is a dual-acylated (N-myristoylated and palmitoylated) inner membrane complex protein whose palmitoylation by the IMC-resident PAT DHHC2 controls its IMC localization; once anchored at the IMC, ISP1 physically interacts with β-tubulin to tether subpellicular microtubules, anchors the GCβ/CDC50A complex at the apical ookinete extrados site to initiate cGMP-dependent gliding motility, and—together with ISP3—organises apical polarity in invasive stages, with gene disruption evidence suggesting it is essential for parasite development."},"narrative":{"mechanistic_narrative":"ISP1 (PF3D7_1011000) is a dual-acylated inner membrane complex (IMC) protein that organises apical polarity and cytoskeletal architecture in invasive and sexual stages of Plasmodium [PMID:24244852, PMID:32395856]. In P. berghei it localizes to the anterior apical end where IMC assembly is initiated, is expressed across developmental stages with a bias toward invasive stages, and is N-myristoylated, phosphorylated, and membrane-bound; gene disruption indicates it is likely essential for parasite development [PMID:24244852]. Its apical positioning is coordinated with ISP3, whose loss mislocalizes ISP1 in ookinetes and sporozoites [PMID:24244852]. Beyond N-myristoylation, ISP1 is palmitoylated on N-terminal cysteines by the IMC-resident palmitoyl-S-acyltransferase DHHC2, and this acylation controls its recruitment to the IMC and is required for zygote-to-ookinete differentiation [PMID:32395856]; in P. falciparum an IMC-restricted acyltransferase, DHHC1, co-distributes with ISP1 during schizogony, consistent with a role in its palmitoylation and membrane targeting [PMID:25425642]. Once IMC-anchored, ISP1 acts as a structural and organizing hub: it physically interacts with β-tubulin to tether and maintain subpellicular microtubules during zygote elongation [PMID:32395856], and in P. yoelii ookinetes it anchors the GCβ/CDC50A complex at the ookinete extrados site to initiate gliding motility [PMID:30146157]. No structural model or higher-resolution mechanism of ISP1's tethering interactions has been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Establishing that ISP1 is a distinct member of a small family of IMC proteins with stage-specific expression framed it as a candidate structural component of the parasite pellicle rather than a diffuse cytoplasmic factor.","evidence":"Colocalization and comparative phylogenetic analysis across life-cycle stages in P. falciparum","pmids":["22389454"],"confidence":"Low","gaps":["This broad survey provides minimal ISP1-specific mechanistic detail","No function or binding partner assigned to ISP1 individually","Life-cycle expression not tied to any phenotype"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Localization and gene-disruption work answered where ISP1 sits and whether it matters, showing apical anterior positioning at the site of IMC initiation and likely essentiality, and revealing coordination with ISP3 in setting apical polarity.","evidence":"Live cell imaging, reverse genetics, and biochemical acylation/phosphorylation assays in P. berghei, plus imaging of ISP3-disruption parasites","pmids":["24244852"],"confidence":"Medium","gaps":["Essentiality inferred from disruption difficulty rather than conditional knockout","Molecular basis of ISP1–ISP3 coordination not defined","No direct binding partners identified"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"claim":"Identifying ISP1 as dual-acylated and co-distributing with the IMC-restricted acyltransferase DHHC1 addressed how it is targeted to the IMC membrane, linking its localization to palmitoylation machinery.","evidence":"Phylogenetic analysis, fluorescence colocalization, and biochemical acylation assays in P. falciparum","pmids":["25425642"],"confidence":"Medium","gaps":["DHHC1-mediated palmitoylation of ISP1 shown by co-distribution, not direct enzymatic assay","Functional consequence of acylation not yet tested","Relationship between myristoylation and palmitoylation in targeting unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"An interaction screen defined a downstream function of IMC-anchored ISP1: it anchors the GCβ/CDC50A complex at the ookinete extrados site to initiate gliding motility, connecting ISP1 to signalling that drives motility.","evidence":"Real-time imaging, protein–protein interaction screening of IMC proteins, and genetic/cell-biological experiments in P. yoelii","pmids":["30146157"],"confidence":"Medium","gaps":["Direct binding interface between ISP1 and GCβ/CDC50A not mapped","How ISP1 achieves polarized (extrados-only) anchoring unknown","Single lab, single species"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2020,"claim":"Reciprocal biochemistry and genetics unified acylation, localization, and cytoskeletal function, showing DHHC2 palmitoylates N-terminal cysteines of ISP1 to drive IMC localization and zygote-to-ookinete differentiation, and that IMC-anchored ISP1 binds β-tubulin to tether subpellicular microtubules.","evidence":"In vitro palmitoylation assays, PAT-substrate experiments, reciprocal co-immunoprecipitation with β-tubulin, and genetic disruption with morphological readout in P. falciparum and P. yoelii","pmids":["32395856"],"confidence":"High","gaps":["Structural basis of the ISP1–β-tubulin tethering interaction not resolved","Reconciliation of DHHC2 (this study) versus DHHC1 (2014 co-distribution) as the relevant acyltransferase not addressed","Whether β-tubulin tethering and GCβ/CDC50A anchoring are mechanistically linked is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"It remains unresolved how ISP1's two documented downstream functions—microtubule tethering via β-tubulin and polarized anchoring of the GCβ/CDC50A gliding-motility complex—are structurally and mechanistically integrated at the apical IMC.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of ISP1 or its binding interfaces","Mechanism of polarized apical/extrados restriction unexplained","Interplay between myristoylation, palmitoylation, and phosphorylation in regulating ISP1 not defined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["BETA-TUBULIN (VIA DIRECT CO-IP INTERACTION) [#4]","GCBETA/CDC50A COMPLEX (ANCHORED BY ISP1) [#3]","DHHC2 PALMITOYL-S-ACYLTRANSFERASE (ENZYME ACTING ON ISP1) [#4]","DHHC1 PALMITOYL ACYLTRANSFERASE (CO-DISTRIBUTES WITH ISP1) [#2]","ISP3 (FUNCTIONAL COORDINATION IN APICAL POLARITY) [#1]"],"other_free_text":["ISP1 is N-myristoylated, palmitoylated on N-terminal cysteines, and phosphorylated [#0, #2, #4]","Palmitoylation by DHHC2 is required for IMC localization and zygote-to-ookinete differentiation [#4]","Gene disruption indicates ISP1 is likely essential for parasite development [#0]","Species evidence spans P. berghei [#0, #1], P. falciparum [#2, #4, #5], and P. yoelii [#3, #4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"22389454","id":"PMC_22389454","title":"Evolution and architecture of the inner membrane complex in asexual and sexual stages of the malaria parasite.","date":"2012","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/22389454","citation_count":105,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30146157","id":"PMC_30146157","title":"ISP1-Anchored Polarization of GCβ/CDC50A Complex Initiates Malaria Ookinete Gliding Motility.","date":"2018","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/30146157","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24244852","id":"PMC_24244852","title":"Unique apicomplexan IMC sub-compartment proteins are early markers for apical polarity in the malaria parasite.","date":"2013","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/24244852","citation_count":45,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32395856","id":"PMC_32395856","title":"A protein palmitoylation cascade regulates microtubule cytoskeleton integrity in Plasmodium.","date":"2020","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/32395856","citation_count":43,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25425642","id":"PMC_25425642","title":"The role of palmitoylation for protein recruitment to the inner membrane complex of the malaria parasite.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25425642","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfISP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5239,"output_tokens":1709,"usd":0.020676,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6807,"output_tokens":3340,"usd":0.058768,"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\": 2013,\n      \"finding\": \"ISP1 localizes to the anterior apical end of Plasmodium berghei parasites where IMC organisation is initiated, and is expressed at all developmental stages, especially invasive ones. Gene disruption studies suggest ISP1 is likely essential for parasite development. ISP1 is N-myristoylated, phosphorylated, and membrane-bound.\",\n      \"method\": \"Live cell imaging, reverse genetics (gene disruption), biochemical characterization (N-myristoylation, phosphorylation assays) in P. berghei\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging and gene disruption with phenotypic readout, two orthogonal methods, single lab\",\n      \"pmids\": [\"24244852\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Absence of ISP3 alters the apical localisation of ISP1 in all invasive stages including ookinetes and sporozoites, indicating a coordinated function between ISP1 and ISP3 in organising apical polarity.\",\n      \"method\": \"Live cell imaging of ISP3 gene-disruption parasites in P. berghei\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via gene disruption with direct localization readout, single lab\",\n      \"pmids\": [\"24244852\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PfISP1 is a dual-acylated (N-myristoylated and palmitoylated) IMC-localized protein in P. falciparum. PfDHHC1, a palmitoyl acyltransferase exclusively localized to the IMC, co-distributes with PfISP1 during schizogony, implicating it in ISP1 palmitoylation and IMC membrane recruitment.\",\n      \"method\": \"Systematic phylogenetic analysis, localization studies (fluorescence microscopy), biochemical acylation assays in P. falciparum\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-localization and biochemical characterization, single lab, multiple methods\",\n      \"pmids\": [\"25425642\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ISP1 anchors the GCβ/CDC50A complex at the ookinete extrados site (OES) of mature Plasmodium yoelii ookinetes. Screening of inner membrane complex proteins identified ISP1 as the key molecule mediating this polarized anchoring, which initiates ookinete gliding motility.\",\n      \"method\": \"Real-time imaging, protein–protein interaction screening of IMC proteins, genetic and cell biological experiments in P. yoelii\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging plus interaction screening with functional (gliding) readout, single lab\",\n      \"pmids\": [\"30146157\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Palmitoylation of N-terminal cysteines of ISP1 (and ISP3) by the IMC-residing palmitoyl-S-acyl-transferase DHHC2 regulates ISP1 localization to the IMC and is required for zygote-to-ookinete differentiation. IMC-anchored ISP1 physically interacts with microtubule component β-tubulin, functioning as a tether to maintain proper subpellicular microtubule (SPM) structure during zygote elongation.\",\n      \"method\": \"Palmitoylation assays, PAT-substrate interaction experiments, co-immunoprecipitation with β-tubulin, genetic disruption with morphological/functional phenotype readout in Plasmodium\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro palmitoylation assays, reciprocal Co-IP, genetic disruption, and multiple orthogonal methods establishing mechanism in a single rigorous study\",\n      \"pmids\": [\"32395856\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ISP1 is one of eight structurally distinct IMC proteins in Plasmodium that display differential spatial-temporal expression patterns across the parasite life cycle, with the IMC serving as an essential structural compartment for sexual stage development and morphogenesis.\",\n      \"method\": \"Colocalization studies, evolutionary/phylogenetic analysis, fluorescence microscopy across life-cycle stages in P. falciparum\",\n      \"journal\": \"Molecular biology and evolution\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — colocalization and comparative analysis, ISP1-specific mechanistic detail minimal in this broad study\",\n      \"pmids\": [\"22389454\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"ISP1 (PF3D7_1011000) is a dual-acylated (N-myristoylated and palmitoylated) inner membrane complex protein whose palmitoylation by the IMC-resident PAT DHHC2 controls its IMC localization; once anchored at the IMC, ISP1 physically interacts with β-tubulin to tether subpellicular microtubules, anchors the GCβ/CDC50A complex at the apical ookinete extrados site to initiate cGMP-dependent gliding motility, and—together with ISP3—organises apical polarity in invasive stages, with gene disruption evidence suggesting it is essential for parasite development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ISP1 (PF3D7_1011000) is a dual-acylated inner membrane complex (IMC) protein that organises apical polarity and cytoskeletal architecture in invasive and sexual stages of Plasmodium [#0, #4]. In P. berghei it localizes to the anterior apical end where IMC assembly is initiated, is expressed across developmental stages with a bias toward invasive stages, and is N-myristoylated, phosphorylated, and membrane-bound; gene disruption indicates it is likely essential for parasite development [#0]. Its apical positioning is coordinated with ISP3, whose loss mislocalizes ISP1 in ookinetes and sporozoites [#1]. Beyond N-myristoylation, ISP1 is palmitoylated on N-terminal cysteines by the IMC-resident palmitoyl-S-acyltransferase DHHC2, and this acylation controls its recruitment to the IMC and is required for zygote-to-ookinete differentiation [#4]; in P. falciparum an IMC-restricted acyltransferase, DHHC1, co-distributes with ISP1 during schizogony, consistent with a role in its palmitoylation and membrane targeting [#2]. Once IMC-anchored, ISP1 acts as a structural and organizing hub: it physically interacts with \\u03b2-tubulin to tether and maintain subpellicular microtubules during zygote elongation [#4], and in P. yoelii ookinetes it anchors the GC\\u03b2/CDC50A complex at the ookinete extrados site to initiate gliding motility [#3]. No structural model or higher-resolution mechanism of ISP1's tethering interactions has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing that ISP1 is a distinct member of a small family of IMC proteins with stage-specific expression framed it as a candidate structural component of the parasite pellicle rather than a diffuse cytoplasmic factor.\",\n      \"evidence\": \"Colocalization and comparative phylogenetic analysis across life-cycle stages in P. falciparum\",\n      \"pmids\": [\n        \"22389454\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"This broad survey provides minimal ISP1-specific mechanistic detail\",\n        \"No function or binding partner assigned to ISP1 individually\",\n        \"Life-cycle expression not tied to any phenotype\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Localization and gene-disruption work answered where ISP1 sits and whether it matters, showing apical anterior positioning at the site of IMC initiation and likely essentiality, and revealing coordination with ISP3 in setting apical polarity.\",\n      \"evidence\": \"Live cell imaging, reverse genetics, and biochemical acylation/phosphorylation assays in P. berghei, plus imaging of ISP3-disruption parasites\",\n      \"pmids\": [\n        \"24244852\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Essentiality inferred from disruption difficulty rather than conditional knockout\",\n        \"Molecular basis of ISP1\\u2013ISP3 coordination not defined\",\n        \"No direct binding partners identified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identifying ISP1 as dual-acylated and co-distributing with the IMC-restricted acyltransferase DHHC1 addressed how it is targeted to the IMC membrane, linking its localization to palmitoylation machinery.\",\n      \"evidence\": \"Phylogenetic analysis, fluorescence colocalization, and biochemical acylation assays in P. falciparum\",\n      \"pmids\": [\n        \"25425642\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"DHHC1-mediated palmitoylation of ISP1 shown by co-distribution, not direct enzymatic assay\",\n        \"Functional consequence of acylation not yet tested\",\n        \"Relationship between myristoylation and palmitoylation in targeting unresolved\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"An interaction screen defined a downstream function of IMC-anchored ISP1: it anchors the GC\\u03b2/CDC50A complex at the ookinete extrados site to initiate gliding motility, connecting ISP1 to signalling that drives motility.\",\n      \"evidence\": \"Real-time imaging, protein\\u2013protein interaction screening of IMC proteins, and genetic/cell-biological experiments in P. yoelii\",\n      \"pmids\": [\n        \"30146157\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct binding interface between ISP1 and GC\\u03b2/CDC50A not mapped\",\n        \"How ISP1 achieves polarized (extrados-only) anchoring unknown\",\n        \"Single lab, single species\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium yoelii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Reciprocal biochemistry and genetics unified acylation, localization, and cytoskeletal function, showing DHHC2 palmitoylates N-terminal cysteines of ISP1 to drive IMC localization and zygote-to-ookinete differentiation, and that IMC-anchored ISP1 binds \\u03b2-tubulin to tether subpellicular microtubules.\",\n      \"evidence\": \"In vitro palmitoylation assays, PAT-substrate experiments, reciprocal co-immunoprecipitation with \\u03b2-tubulin, and genetic disruption with morphological readout in P. falciparum and P. yoelii\",\n      \"pmids\": [\n        \"32395856\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the ISP1\\u2013\\u03b2-tubulin tethering interaction not resolved\",\n        \"Reconciliation of DHHC2 (this study) versus DHHC1 (2014 co-distribution) as the relevant acyltransferase not addressed\",\n        \"Whether \\u03b2-tubulin tethering and GC\\u03b2/CDC50A anchoring are mechanistically linked is unknown\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        },\n        {\n          \"species\": \"Plasmodium yoelii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how ISP1's two documented downstream functions\\u2014microtubule tethering via \\u03b2-tubulin and polarized anchoring of the GC\\u03b2/CDC50A gliding-motility complex\\u2014are structurally and mechanistically integrated at the apical IMC.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of ISP1 or its binding interfaces\",\n        \"Mechanism of polarized apical/extrados restriction unexplained\",\n        \"Interplay between myristoylation, palmitoylation, and phosphorylation in regulating ISP1 not defined\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0008017\",\n        \"supporting_discovery_ids\": [\n          4\n        ]\n      },\n      {\n        \"term_id\": \"GO:0005198\",\n        \"supporting_discovery_ids\": [\n          4,\n          3\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0070258\",\n        \"supporting_discovery_ids\": [\n          0,\n          2,\n          4,\n          5\n        ]\n      },\n      {\n        \"term_id\": \"GO:0020015\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0071973\",\n        \"supporting_discovery_ids\": [\n          3\n        ]\n      },\n      {\n        \"term_id\": \"GO:0018345\",\n        \"supporting_discovery_ids\": [\n          4,\n          2\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"beta-tubulin (via direct co-IP interaction) [#4]\",\n      \"GCbeta/CDC50A complex (anchored by ISP1) [#3]\",\n      \"DHHC2 palmitoyl-S-acyltransferase (enzyme acting on ISP1) [#4]\",\n      \"DHHC1 palmitoyl acyltransferase (co-distributes with ISP1) [#2]\",\n      \"ISP3 (functional coordination in apical polarity) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"ISP1 is N-myristoylated, palmitoylated on N-terminal cysteines, and phosphorylated [#0, #2, #4]\",\n      \"Palmitoylation by DHHC2 is required for IMC localization and zygote-to-ookinete differentiation [#4]\",\n      \"Gene disruption indicates ISP1 is likely essential for parasite development [#0]\",\n      \"Species evidence spans P. berghei [#0, #1], P. falciparum [#2, #4, #5], and P. yoelii [#3, #4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1011000","name":null,"product":"inner membrane complex sub-compartment protein 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1209400","name":null,"product":"inner membrane complex sub-compartment protein 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0810800","name":null,"product":"inner membrane complex sub-compartment protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ISP1","evaluation":null}