{"gene":"PF3D7_0304100","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2014,"finding":"IMC1e (PbIMC1e) is assembled into the subpellicular network (SPN) concurrent with pellicle development in all three zoite stages (merozoite, ookinete, sporozoite) of P. berghei, as shown by GFP tagging. In sexual stages, PbIMC1e is expressed exclusively from the maternal allele. Recurrent failure to disrupt the gene by double-crossover homologous recombination provides genetic evidence that IMC1e is necessary for asexual blood-stage parasite development.","method":"GFP tagging in P. berghei, allelic replacement by double-crossover homologous recombination (attempted gene disruption), live imaging","journal":"Parasitology research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — GFP tagging with live imaging for localization/timing, plus genetic evidence from repeated failed gene disruption attempts; single lab but two orthogonal approaches","pmids":["25185663"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"In P. falciparum, IMC1e (PfIMC1e) requires PfIMC1f for its sequential recruitment to the basal complex; the alveolin domain of IMC1e alone is insufficient, and a region outside the alveolin domain is important for basal complex recruitment. Alveolin domains mediate alveolin-alveolin interactions and compartment-specific localization, but these domains are not interchangeable between family members.","method":"Fluorescence microscopy of domain-swap and truncation mutants, alveolin-alveolin interaction assays in P. falciparum","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional dissection with domain mutants and reciprocal localization readouts in a single lab using multiple constructs","pmids":["41019501"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"The alveolin domain of PbIMC1e contains tandem 12-amino acid repeat sequences (type 1 domain), as predicted by HHrepID structural repeat analysis, consistent with its classification as a structural intermediate filament-like component of the subpellicular network.","method":"Computational repeat-structure prediction (HHrepID) validated against known alveolin family members","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of the repeat's function","pmids":["25475193"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"IMC1e is listed as a known component of the inner membrane complex (IMC) in the schizont stage of P. yoelii, identified as part of an IMC proteome compiled by TurboID-based proximity labeling.","method":"TurboID proximity labeling proteomics","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proteome-level identification without specific functional characterization of IMC1e itself","pmids":["35775739"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"IMC1e (PF3D7_0304100) is an alveolin-family intermediate filament-like protein that assembles into the subpellicular network concurrent with pellicle development in all zoite stages; in P. falciparum it is recruited to the basal complex in a sequential, IMC1f-dependent manner, with a region outside its alveolin domain being critical for this recruitment, and genetic evidence indicates it is essential for asexual blood-stage development."},"narrative":{"mechanistic_narrative":"IMC1e (PF3D7_0304100) is an alveolin-family, intermediate filament-like structural protein of the Plasmodium inner membrane complex (IMC) that is assembled into the subpellicular network (SPN) concurrent with pellicle development across the zoite stages of the parasite [PMID:25185663]. In P. berghei, GFP-tagged PbIMC1e localizes to the SPN in merozoites, ookinetes, and sporozoites, is expressed exclusively from the maternal allele in sexual stages, and repeated failure to disrupt the gene by double-crossover recombination indicates it is essential for asexual blood-stage development [PMID:25185663]. In P. falciparum, PfIMC1e is recruited to the basal complex in a sequential, PfIMC1f-dependent manner; its alveolin domain alone is insufficient for this recruitment, and a region outside the alveolin domain is critical, while alveolin domains mediate compartment-specific alveolin-alveolin interactions but are not interchangeable between family members [PMID:41019501]. Beyond its structural role in the SPN and basal complex, no catalytic activity or additional mechanistic detail for IMC1e has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing when and where IMC1e acts required localizing the protein and testing its necessity; GFP tagging placed it in the subpellicular network at the time of pellicle formation across zoite stages and identified it as essential for asexual growth.","evidence":"GFP tagging with live imaging and attempted double-crossover gene disruption in P. berghei","pmids":["25185663"],"confidence":"Medium","gaps":["Essentiality is inferred from repeated failed disruption rather than a conditional knockdown/knockout phenotype","The molecular consequence of IMC1e loss on SPN integrity was not measured","Maternal-allele-only expression in sexual stages was described but its functional significance was not tested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"claim":"Classifying IMC1e as a genuine SPN structural component required identifying its defining sequence architecture; repeat analysis found the tandem 12-amino-acid alveolin repeats characteristic of intermediate filament-like family members.","evidence":"Computational structural-repeat prediction (HHrepID) benchmarked against known alveolins, P. berghei","pmids":["25475193"],"confidence":"Low","gaps":["Purely computational — no experimental validation that the predicted repeats form filaments or mediate assembly","Does not link the repeat to any specific interaction or localization determinant"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"Confirming IMC1e as part of the IMC proteome in an independent species and stage placed it within the broader IMC compartment beyond single-lab imaging.","evidence":"TurboID proximity-labeling proteomics of the schizont-stage IMC in P. yoelii","pmids":["35775739"],"confidence":"Low","gaps":["Proteome-level identification only — no IMC1e-specific functional or interaction data","Proximity labeling does not distinguish direct partners from compartment neighbors"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"claim":"How IMC1e is targeted to a specific IMC sub-compartment was unresolved; domain-swap and truncation dissection showed its recruitment to the basal complex is sequential and depends on IMC1f, with a determinant lying outside the alveolin domain.","evidence":"Fluorescence microscopy of domain-swap and truncation mutants plus alveolin-alveolin interaction assays in P. falciparum","pmids":["41019501"],"confidence":"Medium","gaps":["The specific non-alveolin region and its binding partner at the basal complex are not defined","The functional consequence of mislocalizing IMC1e was not assessed","Whether IMC1e-IMC1f interaction is direct is not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The catalytic or structural mechanism by which IMC1e contributes to SPN and basal complex architecture, and the identity of the non-alveolin recruitment determinant and its direct partners, remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct binding partner of IMC1e has been biochemically defined","No structural model of IMC1e filament assembly","No conditional loss-of-function phenotype quantifying its contribution to pellicle integrity"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Subpellicular network (SPN) of the inner membrane complex","Basal complex (P. falciparum)"],"partners":["IMC1F (REQUIRED FOR IMC1E BASAL COMPLEX RECRUITMENT, P. FALCIPARUM)"],"other_free_text":["Alveolin-family intermediate filament-like protein with tandem 12-aa (type 1) alveolin repeats [#2].","Assembled into the SPN concurrent with pellicle formation in merozoites, ookinetes, and sporozoites [#0].","Maternal-allele-only expression in sexual stages of P. berghei [#0].","Genetically refractory to disruption, indicating essentiality for asexual blood-stage development [#0].","Basal complex recruitment requires a region outside the alveolin domain; alveolin domains are compartment-specific and not interchangeable [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25185663","id":"PMC_25185663","title":"Distinct temporal recruitment of Plasmodium alveolins to the subpellicular network.","date":"2014","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/25185663","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PbIMC1e"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41019501","id":"PMC_41019501","title":"Malaria Cytoskeletal Proteins Require Alveolin-Alveolin Interactions for Differential Localization: Recruitment and Organization of Alveolin Proteins.","date":"2025","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41019501","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfIMC1e"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40117352","id":"","title":"SIP2 is the master transcription factor of Plasmodium merozoite formation.","date":"2025","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/40117352","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1e"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35775739","id":"","title":"Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35775739","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1e"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25475193","id":"","title":"Plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.","date":"2014","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/25475193","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1e"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29580379","id":"","title":"Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites.","date":"2018","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/29580379","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1e"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7748,"output_tokens":1126,"usd":0.020067,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5923,"output_tokens":2298,"usd":0.043533,"stage2_stop_reason":"end_turn"},"total_usd":0.0636,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"IMC1e (PbIMC1e) is assembled into the subpellicular network (SPN) concurrent with pellicle development in all three zoite stages (merozoite, ookinete, sporozoite) of P. berghei, as shown by GFP tagging. In sexual stages, PbIMC1e is expressed exclusively from the maternal allele. Recurrent failure to disrupt the gene by double-crossover homologous recombination provides genetic evidence that IMC1e is necessary for asexual blood-stage parasite development.\",\n      \"method\": \"GFP tagging in P. berghei, allelic replacement by double-crossover homologous recombination (attempted gene disruption), live imaging\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — GFP tagging with live imaging for localization/timing, plus genetic evidence from repeated failed gene disruption attempts; single lab but two orthogonal approaches\",\n      \"pmids\": [\"25185663\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In P. falciparum, IMC1e (PfIMC1e) requires PfIMC1f for its sequential recruitment to the basal complex; the alveolin domain of IMC1e alone is insufficient, and a region outside the alveolin domain is important for basal complex recruitment. Alveolin domains mediate alveolin-alveolin interactions and compartment-specific localization, but these domains are not interchangeable between family members.\",\n      \"method\": \"Fluorescence microscopy of domain-swap and truncation mutants, alveolin-alveolin interaction assays in P. falciparum\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional dissection with domain mutants and reciprocal localization readouts in a single lab using multiple constructs\",\n      \"pmids\": [\"41019501\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The alveolin domain of PbIMC1e contains tandem 12-amino acid repeat sequences (type 1 domain), as predicted by HHrepID structural repeat analysis, consistent with its classification as a structural intermediate filament-like component of the subpellicular network.\",\n      \"method\": \"Computational repeat-structure prediction (HHrepID) validated against known alveolin family members\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct experimental validation of the repeat's function\",\n      \"pmids\": [\"25475193\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"IMC1e is listed as a known component of the inner membrane complex (IMC) in the schizont stage of P. yoelii, identified as part of an IMC proteome compiled by TurboID-based proximity labeling.\",\n      \"method\": \"TurboID proximity labeling proteomics\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proteome-level identification without specific functional characterization of IMC1e itself\",\n      \"pmids\": [\"35775739\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"IMC1e (PF3D7_0304100) is an alveolin-family intermediate filament-like protein that assembles into the subpellicular network concurrent with pellicle development in all zoite stages; in P. falciparum it is recruited to the basal complex in a sequential, IMC1f-dependent manner, with a region outside its alveolin domain being critical for this recruitment, and genetic evidence indicates it is essential for asexual blood-stage development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IMC1e (PF3D7_0304100) is an alveolin-family, intermediate filament-like structural protein of the Plasmodium inner membrane complex (IMC) that is assembled into the subpellicular network (SPN) concurrent with pellicle development across the zoite stages of the parasite [#0]. In P. berghei, GFP-tagged PbIMC1e localizes to the SPN in merozoites, ookinetes, and sporozoites, is expressed exclusively from the maternal allele in sexual stages, and repeated failure to disrupt the gene by double-crossover recombination indicates it is essential for asexual blood-stage development [#0]. In P. falciparum, PfIMC1e is recruited to the basal complex in a sequential, PfIMC1f-dependent manner; its alveolin domain alone is insufficient for this recruitment, and a region outside the alveolin domain is critical, while alveolin domains mediate compartment-specific alveolin-alveolin interactions but are not interchangeable between family members [#1]. Beyond its structural role in the SPN and basal complex, no catalytic activity or additional mechanistic detail for IMC1e has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing when and where IMC1e acts required localizing the protein and testing its necessity; GFP tagging placed it in the subpellicular network at the time of pellicle formation across zoite stages and identified it as essential for asexual growth.\",\n      \"evidence\": \"GFP tagging with live imaging and attempted double-crossover gene disruption in P. berghei\",\n      \"pmids\": [\"25185663\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}],\n      \"gaps\": [\n        \"Essentiality is inferred from repeated failed disruption rather than a conditional knockdown/knockout phenotype\",\n        \"The molecular consequence of IMC1e loss on SPN integrity was not measured\",\n        \"Maternal-allele-only expression in sexual stages was described but its functional significance was not tested\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Classifying IMC1e as a genuine SPN structural component required identifying its defining sequence architecture; repeat analysis found the tandem 12-amino-acid alveolin repeats characteristic of intermediate filament-like family members.\",\n      \"evidence\": \"Computational structural-repeat prediction (HHrepID) benchmarked against known alveolins, P. berghei\",\n      \"pmids\": [\"25475193\"],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}],\n      \"gaps\": [\n        \"Purely computational — no experimental validation that the predicted repeats form filaments or mediate assembly\",\n        \"Does not link the repeat to any specific interaction or localization determinant\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirming IMC1e as part of the IMC proteome in an independent species and stage placed it within the broader IMC compartment beyond single-lab imaging.\",\n      \"evidence\": \"TurboID proximity-labeling proteomics of the schizont-stage IMC in P. yoelii\",\n      \"pmids\": [\"35775739\"],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}],\n      \"gaps\": [\n        \"Proteome-level identification only — no IMC1e-specific functional or interaction data\",\n        \"Proximity labeling does not distinguish direct partners from compartment neighbors\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"How IMC1e is targeted to a specific IMC sub-compartment was unresolved; domain-swap and truncation dissection showed its recruitment to the basal complex is sequential and depends on IMC1f, with a determinant lying outside the alveolin domain.\",\n      \"evidence\": \"Fluorescence microscopy of domain-swap and truncation mutants plus alveolin-alveolin interaction assays in P. falciparum\",\n      \"pmids\": [\"41019501\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\n        \"The specific non-alveolin region and its binding partner at the basal complex are not defined\",\n        \"The functional consequence of mislocalizing IMC1e was not assessed\",\n        \"Whether IMC1e-IMC1f interaction is direct is not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic or structural mechanism by which IMC1e contributes to SPN and basal complex architecture, and the identity of the non-alveolin recruitment determinant and its direct partners, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"attribution\": [],\n      \"gaps\": [\n        \"No direct binding partner of IMC1e has been biochemically defined\",\n        \"No structural model of IMC1e filament assembly\",\n        \"No conditional loss-of-function phenotype quantifying its contribution to pellicle integrity\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005200\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007029\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"Subpellicular network (SPN) of the inner membrane complex\",\n      \"Basal complex (P. falciparum)\"\n    ],\n    \"partners\": [\n      \"IMC1f (required for IMC1e basal complex recruitment, P. falciparum)\"\n    ],\n    \"other_free_text\": [\n      \"Alveolin-family intermediate filament-like protein with tandem 12-aa (type 1) alveolin repeats [#2].\",\n      \"Assembled into the SPN concurrent with pellicle formation in merozoites, ookinetes, and sporozoites [#0].\",\n      \"Maternal-allele-only expression in sexual stages of P. berghei [#0].\",\n      \"Genetically refractory to disruption, indicating essentiality for asexual blood-stage development [#0].\",\n      \"Basal complex recruitment requires a region outside the alveolin domain; alveolin domains are compartment-specific and not interchangeable [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0304100","name":null,"product":"inner membrane complex protein 1e","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0402700","name":null,"product":"inner membrane complex protein 1e","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0839000","name":null,"product":"inner membrane complex protein 1e, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IMC1e","evaluation":null}