{"gene":"PF3D7_1141900","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2008,"finding":"IMC1b (PF3D7_1141900 ortholog in P. berghei) localizes exclusively to the pellicle of ookinetes when tagged with GFP, and its genetic disruption causes abnormal ookinete cell shape, reduced gliding motility, decreased mechanical strength, and reduced infectivity in mosquito midgut, establishing a membrane skeletal role in ookinete biology.","method":"GFP-tagging for subcellular localization (live imaging); targeted gene disruption (knockout) with phenotypic readouts of cell morphology, tensile strength assay, gliding motility assay, and mosquito infectivity","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with multiple orthogonal phenotypic readouts (morphology, mechanical strength, motility, infectivity) plus direct GFP localization, primary mechanistic study of this gene","pmids":["18650444"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"finding":"IMC1b (P. berghei ortholog) functions independently of IMC1h in the ookinete subpellicular network; double knockout of IMC1b and IMC1h exacerbates tensile strength, motility, and infectivity defects beyond those of each single knockout, but does not further affect ookinete morphology, demonstrating that IMC1b contributes to gliding motility independently of its role in cell shape.","method":"Double null mutant generation by targeted gene disruption; phenotypic analysis including tensile strength (hypo-osmotic shock), gliding motility assay, and mosquito infectivity","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis via double-KO with multiple orthogonal phenotypic readouts, clearly separating motility and morphology contributions","pmids":["21098480"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"finding":"IMC1b (P. berghei ortholog) is identified as a phosphorylation target of the cGMP-dependent protein kinase PKG in gliding ookinetes, placing it downstream of the PKG signalling pathway that controls ookinete motility.","method":"Quantitative phosphoproteomics of P. berghei ookinetes comparing PKG inhibitor-treated versus untreated parasites","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — phosphoproteomic identification in a single study; site-specific mutagenesis not performed on IMC1b itself","pmids":["24594931"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"IMC1b (P. berghei ortholog) co-purifies with FBXO1-HA by immunoprecipitation in ookinetes 12 h post-activation, identifying it as part of the FBXO1-associated pellicular protein network in the subpellicular filamentous layer below the IMC.","method":"Immunoprecipitation of FBXO1-HA followed by mass spectrometry in P. berghei ookinetes","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment from one biological replicate; no reciprocal pulldown or functional validation specific to IMC1b","pmids":["36898988"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"IMC1b (PF3D7_1141900), the P. falciparum inner membrane complex protein 1b, functions as a membrane skeletal component of the ookinete pellicle in Plasmodium berghei, where it localizes exclusively to the subpellicular network, provides mechanical strength and normal cell shape to ookinetes, and contributes to gliding motility independently of its morphological role; it is phosphorylated in a PKG-dependent manner and associates with the FBXO1 ubiquitin-ligase complex at the pellicle, but no direct enzymatic activity or atomic-resolution structure has been established."},"narrative":{"mechanistic_narrative":"IMC1b (PF3D7_1141900), characterized through its P. berghei ortholog, is a membrane skeletal component of the ookinete pellicle that localizes exclusively to the subpellicular network and provides mechanical strength, normal cell shape, gliding motility, and mosquito midgut infectivity, as demonstrated by GFP-tagging and targeted gene disruption [PMID:18650444]. Genetic epistasis with IMC1h shows that IMC1b's contribution to gliding motility is separable from its role in maintaining ookinete morphology: double knockout worsens tensile strength, motility, and infectivity defects beyond either single mutant without further altering cell shape [PMID:21098480]. IMC1b is a phosphorylation target of the cGMP-dependent protein kinase PKG in gliding ookinetes, placing it downstream of the PKG signalling pathway that controls motility [PMID:24594931], and it co-purifies with the FBXO1 ubiquitin-ligase complex within the subpellicular filamentous layer beneath the inner membrane complex [PMID:36898988]. No direct enzymatic activity or atomic-resolution structure of IMC1b has been established in the available corpus.","teleology":[{"year":2008,"claim":"Established that IMC1b is a pellicle-associated membrane skeletal protein required for ookinete integrity, answering whether the gene has a structural role in the invasive-stage cytoskeleton.","evidence":"GFP-tagging for localization plus targeted gene knockout with morphology, tensile strength, gliding motility, and mosquito infectivity readouts in P. berghei","pmids":["18650444"],"confidence":"High","gaps":["Molecular partners within the subpellicular network not defined","No structural model of how IMC1b confers mechanical strength","Function assessed only in P. berghei ookinetes, not in P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"claim":"Separated IMC1b's role in gliding motility from its role in cell shape, resolving whether its functions are mechanistically coupled.","evidence":"IMC1b/IMC1h double null mutants generated by targeted disruption with tensile strength, motility, and infectivity assays in P. berghei","pmids":["21098480"],"confidence":"High","gaps":["Molecular basis for the motility-versus-morphology separation unknown","How IMC1b and IMC1h partition within the same network not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"claim":"Placed IMC1b downstream of PKG signalling by identifying it as a phosphorylation target in gliding ookinetes, linking the skeletal protein to a motility-controlling kinase pathway.","evidence":"Quantitative phosphoproteomics of P. berghei ookinetes comparing PKG inhibitor-treated versus untreated parasites","pmids":["24594931"],"confidence":"Medium","gaps":["Site-specific mutagenesis of IMC1b phosphosites not performed","Functional consequence of IMC1b phosphorylation on motility not demonstrated","Whether PKG phosphorylates IMC1b directly or indirectly unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Associated IMC1b with the FBXO1 pellicular protein network, raising the possibility of ubiquitin-ligase-linked regulation at the subpellicular layer.","evidence":"Immunoprecipitation of FBXO1-HA followed by mass spectrometry in P. berghei ookinetes 12 h post-activation","pmids":["36898988"],"confidence":"Low","gaps":["Single Co-IP/MS from one biological replicate without reciprocal pulldown","No functional validation of the FBXO1-IMC1b association specific to IMC1b","Whether IMC1b is a ubiquitination substrate of the FBXO1 complex untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How IMC1b physically integrates into the subpellicular network and whether its phosphorylation or FBXO1 association mechanistically controls gliding motility remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No atomic-resolution structure or defined biochemical activity","Direct binding partners in the subpellicular network not mapped","No characterization of IMC1b in P. falciparum itself"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["FBXO1-associated pellicular protein network (subpellicular filamentous layer)"],"partners":["FBXO1 (CO-PURIFICATION BY IP-MS IN OOKINETES)","IMC1H (FUNCTIONALLY INDEPENDENT WITHIN THE SUBPELLICULAR NETWORK; GENETIC EPISTASIS)"],"other_free_text":["All mechanistic evidence derives from the P. berghei ortholog of IMC1b (PF3D7_1141900); no P. falciparum-specific characterization is present in the corpus.","IMC1b provides ookinete mechanical strength and cell shape, and contributes to gliding motility and mosquito midgut infectivity.","IMC1b's motility contribution is genetically separable from its morphological role.","No direct enzymatic activity or atomic-resolution structure has been established."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18650444","id":"PMC_18650444","title":"IMC1b is a putative membrane skeleton protein involved in cell shape, mechanical strength, motility, and infectivity of malaria ookinetes.","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18650444","citation_count":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21098480","id":"PMC_21098480","title":"Malaria IMC1 membrane skeleton proteins operate autonomously and participate in motility independently of cell shape.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21098480","citation_count":44,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41117539","id":"","title":"Plasmodium berghei IMC1j interacts with δ-tubulin to orchestrate subpellicular microtubule organization in ookinetes.","date":"2025","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/41117539","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39576115","id":"","title":"An inner membrane complex protein IMC1g in Plasmodium berghei is involved in asexual stage schizogony and parasite 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decreased mechanical strength, and reduced infectivity in mosquito midgut, establishing a membrane skeletal role in ookinete biology.\",\n      \"method\": \"GFP-tagging for subcellular localization (live imaging); targeted gene disruption (knockout) with phenotypic readouts of cell morphology, tensile strength assay, gliding motility assay, and mosquito infectivity\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with multiple orthogonal phenotypic readouts (morphology, mechanical strength, motility, infectivity) plus direct GFP localization, primary mechanistic study of this gene\",\n      \"pmids\": [\"18650444\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"IMC1b (P. berghei ortholog) functions independently of IMC1h in the ookinete subpellicular network; double knockout of IMC1b and IMC1h exacerbates tensile strength, motility, and infectivity defects beyond those of each single knockout, but does not further affect ookinete morphology, demonstrating that IMC1b contributes to gliding motility independently of its role in cell shape.\",\n      \"method\": \"Double null mutant generation by targeted gene disruption; phenotypic analysis including tensile strength (hypo-osmotic shock), gliding motility assay, and mosquito infectivity\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis via double-KO with multiple orthogonal phenotypic readouts, clearly separating motility and morphology contributions\",\n      \"pmids\": [\"21098480\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"IMC1b (P. berghei ortholog) is identified as a phosphorylation target of the cGMP-dependent protein kinase PKG in gliding ookinetes, placing it downstream of the PKG signalling pathway that controls ookinete motility.\",\n      \"method\": \"Quantitative phosphoproteomics of P. berghei ookinetes comparing PKG inhibitor-treated versus untreated parasites\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — phosphoproteomic identification in a single study; site-specific mutagenesis not performed on IMC1b itself\",\n      \"pmids\": [\"24594931\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"IMC1b (P. berghei ortholog) co-purifies with FBXO1-HA by immunoprecipitation in ookinetes 12 h post-activation, identifying it as part of the FBXO1-associated pellicular protein network in the subpellicular filamentous layer below the IMC.\",\n      \"method\": \"Immunoprecipitation of FBXO1-HA followed by mass spectrometry in P. berghei ookinetes\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment from one biological replicate; no reciprocal pulldown or functional validation specific to IMC1b\",\n      \"pmids\": [\"36898988\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"IMC1b (PF3D7_1141900), the P. falciparum inner membrane complex protein 1b, functions as a membrane skeletal component of the ookinete pellicle in Plasmodium berghei, where it localizes exclusively to the subpellicular network, provides mechanical strength and normal cell shape to ookinetes, and contributes to gliding motility independently of its morphological role; it is phosphorylated in a PKG-dependent manner and associates with the FBXO1 ubiquitin-ligase complex at the pellicle, but no direct enzymatic activity or atomic-resolution structure has been established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IMC1b (PF3D7_1141900), characterized through its P. berghei ortholog, is a membrane skeletal component of the ookinete pellicle that localizes exclusively to the subpellicular network and provides mechanical strength, normal cell shape, gliding motility, and mosquito midgut infectivity, as demonstrated by GFP-tagging and targeted gene disruption [#0]. Genetic epistasis with IMC1h shows that IMC1b's contribution to gliding motility is separable from its role in maintaining ookinete morphology: double knockout worsens tensile strength, motility, and infectivity defects beyond either single mutant without further altering cell shape [#1]. IMC1b is a phosphorylation target of the cGMP-dependent protein kinase PKG in gliding ookinetes, placing it downstream of the PKG signalling pathway that controls motility [#2], and it co-purifies with the FBXO1 ubiquitin-ligase complex within the subpellicular filamentous layer beneath the inner membrane complex [#3]. No direct enzymatic activity or atomic-resolution structure of IMC1b has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Established that IMC1b is a pellicle-associated membrane skeletal protein required for ookinete integrity, answering whether the gene has a structural role in the invasive-stage cytoskeleton.\",\n      \"evidence\": \"GFP-tagging for localization plus targeted gene knockout with morphology, tensile strength, gliding motility, and mosquito infectivity readouts in P. berghei\",\n      \"pmids\": [\"18650444\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular partners within the subpellicular network not defined\",\n        \"No structural model of how IMC1b confers mechanical strength\",\n        \"Function assessed only in P. berghei ookinetes, not in P. falciparum\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Separated IMC1b's role in gliding motility from its role in cell shape, resolving whether its functions are mechanistically coupled.\",\n      \"evidence\": \"IMC1b/IMC1h double null mutants generated by targeted disruption with tensile strength, motility, and infectivity assays in P. berghei\",\n      \"pmids\": [\"21098480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis for the motility-versus-morphology separation unknown\",\n        \"How IMC1b and IMC1h partition within the same network not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Placed IMC1b downstream of PKG signalling by identifying it as a phosphorylation target in gliding ookinetes, linking the skeletal protein to a motility-controlling kinase pathway.\",\n      \"evidence\": \"Quantitative phosphoproteomics of P. berghei ookinetes comparing PKG inhibitor-treated versus untreated parasites\",\n      \"pmids\": [\"24594931\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Site-specific mutagenesis of IMC1b phosphosites not performed\",\n        \"Functional consequence of IMC1b phosphorylation on motility not demonstrated\",\n        \"Whether PKG phosphorylates IMC1b directly or indirectly unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Associated IMC1b with the FBXO1 pellicular protein network, raising the possibility of ubiquitin-ligase-linked regulation at the subpellicular layer.\",\n      \"evidence\": \"Immunoprecipitation of FBXO1-HA followed by mass spectrometry in P. berghei ookinetes 12 h post-activation\",\n      \"pmids\": [\"36898988\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS from one biological replicate without reciprocal pulldown\",\n        \"No functional validation of the FBXO1-IMC1b association specific to IMC1b\",\n        \"Whether IMC1b is a ubiquitination substrate of the FBXO1 complex untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How IMC1b physically integrates into the subpellicular network and whether its phosphorylation or FBXO1 association mechanistically controls gliding motility remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No atomic-resolution structure or defined biochemical activity\",\n        \"Direct binding partners in the subpellicular network not mapped\",\n        \"No characterization of IMC1b in P. falciparum itself\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005200\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071902\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0035371\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"FBXO1-associated pellicular protein network (subpellicular filamentous layer)\"\n    ],\n    \"partners\": [\n      \"FBXO1 (co-purification by IP-MS in ookinetes)\",\n      \"IMC1h (functionally independent within the subpellicular network; genetic epistasis)\"\n    ],\n    \"other_free_text\": [\n      \"All mechanistic evidence derives from the P. berghei ortholog of IMC1b (PF3D7_1141900); no P. falciparum-specific characterization is present in the corpus.\",\n      \"IMC1b provides ookinete mechanical strength and cell shape, and contributes to gliding motility and mosquito midgut infectivity.\",\n      \"IMC1b's motility contribution is genetically separable from its morphological role.\",\n      \"No direct enzymatic activity or atomic-resolution structure has been established.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1141900","name":null,"product":"inner membrane complex protein 1b, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0907100","name":null,"product":"inner membrane complex protein 1b","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0939700","name":null,"product":"inner membrane complex protein 1b, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IMC1b","evaluation":null}