{"gene":"PF3D7_1417000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2018,"finding":"PfIMC1l (PF3D7_1417000) directly binds actin and myosin (identified as novel binding partners by biochemical pulldown assays), with actin and myosin competing for interaction with PfIMC1l. Additionally, PfIMC1l simultaneously binds actin and either cholesterol or PIP2 (phosphatidylinositol 4,5-bisphosphate). PfIMC1l also binds calcium directly, and its interaction with actin is enhanced in the presence of calcium ions.","method":"Biochemical binding/pulldown assays; in silico structural analysis; calcium-binding assays","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — biochemical pulldown assays with multiple binding partners tested in a single lab; two orthogonal readouts (protein-protein and protein-lipid interactions) but no reciprocal Co-IP or in vivo functional rescue reported in the abstract","pmids":["30599160"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfIMC1l (PF3D7_1417000) is expressed in vivo and localizes to the IMC in P. falciparum, consistent with a proposed role in anchoring the IMC membrane to the parasite gliding apparatus.","method":"In vivo expression analysis and subcellular localization (implied by biochemical fractionation/imaging described as 'in vivo expression and localization')","journal":"International journal of biological macromolecules","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization described in a single study without explicit functional rescue or independent replication; abstract does not detail the specific imaging/fractionation method used","pmids":["30599160"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1417000 (IMC1l) is an IMC-localized alveolin in P. falciparum that directly binds the cytoskeletal proteins actin and myosin (which compete for the same site), the lipids cholesterol and PIP2 (which can bind simultaneously with actin), and calcium (which enhances actin binding), suggesting it functions as a membrane-cytoskeleton linker that couples the IMC lipid bilayer to the actin-myosin glideosome in a calcium-dependent manner."},"narrative":{"mechanistic_narrative":"PF3D7_1417000 (IMC1l) is an alveolin of Plasmodium falciparum that functions as a candidate membrane-cytoskeleton linker coupling the inner membrane complex (IMC) to the parasite gliding apparatus [PMID:30599160]. Biochemical pulldown assays established that IMC1l directly binds both actin and myosin, with the two cytoskeletal proteins competing for the same site, and that it simultaneously binds actin together with either cholesterol or PIP2, positioning it to bridge the IMC lipid bilayer to the actin-myosin machinery [PMID:30599160]. IMC1l also binds calcium directly, and calcium enhances its interaction with actin, indicating a calcium-dependent regulation of this membrane-cytoskeleton coupling [PMID:30599160]. Consistent with this bridging role, IMC1l is expressed in vivo and localizes to the IMC [PMID:30599160]. Beyond these binding and localization observations, no in vivo functional, genetic, or structural characterization of IMC1l has been established in the available corpus.","teleology":[{"year":2018,"claim":"To define whether IMC1l could physically link the IMC to the gliding machinery, its direct binding partners were tested, revealing simultaneous protein-protein and protein-lipid interactions consistent with a membrane-cytoskeleton bridge.","evidence":"Biochemical binding/pulldown assays, in silico structural analysis, and calcium-binding assays in P. falciparum","pmids":["30599160"],"confidence":"Medium","gaps":["No reciprocal Co-IP or in vivo functional rescue confirms the interactions","Stoichiometry and physiological relevance of actin/myosin competition unresolved","No structural model of the actin/lipid/calcium binding sites experimentally determined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To place IMC1l in a subcellular context, its expression and localization were examined, showing IMC residence consistent with the proposed anchoring role.","evidence":"In vivo expression analysis and subcellular localization in P. falciparum","pmids":["30599160"],"confidence":"Low","gaps":["Localization reported in a single study without independent replication or detailed imaging method","No functional rescue or knockdown links localization to the anchoring function","Stage-specific expression dynamics not characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether IMC1l is genetically required for gliding motility, IMC integrity, or parasite invasion, and how its calcium-dependent actin binding is regulated in vivo, remain unknown.","evidence":"No genetic knockout, conditional knockdown, or in vivo functional assay is present in the corpus","pmids":[],"confidence":"Low","gaps":["No loss-of-function phenotype established","No demonstration that binding partners engage IMC1l in living parasites","No mechanistic link between calcium binding and gliding motility in vivo"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ACTIN","MYOSIN","CHOLESTEROL","PIP2 (PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE)","CALCIUM"],"other_free_text":["Actin and myosin compete for binding to IMC1l, whereas actin can bind simultaneously with cholesterol or PIP2 [#0].","Calcium binds IMC1l directly and enhances its actin interaction, implying calcium-dependent regulation [#0].","IMC1l is described as an IMC-localized alveolin proposed to anchor the IMC membrane to the gliding apparatus [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30599160","id":"PMC_30599160","title":"Inner membrane complex 1l protein of Plasmodium falciparum links membrane lipids with cytoskeletal element 'actin' and its associated motor 'myosin'.","date":"2018","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/30599160","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfIMC1l"],"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 transmission.","date":"2024","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/39576115","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1l"],"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":["IMC1l"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34395314","id":"","title":"Calcium in the Backstage of Malaria Parasite Biology.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34395314","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1l"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31372645","id":"","title":"Malaria.tools-comparative genomic and transcriptomic database for Plasmodium species.","date":"2020","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31372645","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1l"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33930021","id":"","title":"Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies.","date":"2021","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/33930021","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1l"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33489940","id":"","title":"The Dynamic Roles of the Inner Membrane Complex in the Multiple Stages of the Malaria Parasite.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33489940","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1l"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9481,"output_tokens":713,"usd":0.019569,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5334,"output_tokens":1722,"usd":0.03486,"stage2_stop_reason":"end_turn"},"total_usd":0.054429,"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\": 2018,\n      \"finding\": \"PfIMC1l (PF3D7_1417000) directly binds actin and myosin (identified as novel binding partners by biochemical pulldown assays), with actin and myosin competing for interaction with PfIMC1l. Additionally, PfIMC1l simultaneously binds actin and either cholesterol or PIP2 (phosphatidylinositol 4,5-bisphosphate). PfIMC1l also binds calcium directly, and its interaction with actin is enhanced in the presence of calcium ions.\",\n      \"method\": \"Biochemical binding/pulldown assays; in silico structural analysis; calcium-binding assays\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — biochemical pulldown assays with multiple binding partners tested in a single lab; two orthogonal readouts (protein-protein and protein-lipid interactions) but no reciprocal Co-IP or in vivo functional rescue reported in the abstract\",\n      \"pmids\": [\"30599160\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfIMC1l (PF3D7_1417000) is expressed in vivo and localizes to the IMC in P. falciparum, consistent with a proposed role in anchoring the IMC membrane to the parasite gliding apparatus.\",\n      \"method\": \"In vivo expression analysis and subcellular localization (implied by biochemical fractionation/imaging described as 'in vivo expression and localization')\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization described in a single study without explicit functional rescue or independent replication; abstract does not detail the specific imaging/fractionation method used\",\n      \"pmids\": [\"30599160\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1417000 (IMC1l) is an IMC-localized alveolin in P. falciparum that directly binds the cytoskeletal proteins actin and myosin (which compete for the same site), the lipids cholesterol and PIP2 (which can bind simultaneously with actin), and calcium (which enhances actin binding), suggesting it functions as a membrane-cytoskeleton linker that couples the IMC lipid bilayer to the actin-myosin glideosome in a calcium-dependent manner.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_1417000 (IMC1l) is an alveolin of Plasmodium falciparum that functions as a candidate membrane-cytoskeleton linker coupling the inner membrane complex (IMC) to the parasite gliding apparatus [#0, #1]. Biochemical pulldown assays established that IMC1l directly binds both actin and myosin, with the two cytoskeletal proteins competing for the same site, and that it simultaneously binds actin together with either cholesterol or PIP2, positioning it to bridge the IMC lipid bilayer to the actin-myosin machinery [#0]. IMC1l also binds calcium directly, and calcium enhances its interaction with actin, indicating a calcium-dependent regulation of this membrane-cytoskeleton coupling [#0]. Consistent with this bridging role, IMC1l is expressed in vivo and localizes to the IMC [#1]. Beyond these binding and localization observations, no in vivo functional, genetic, or structural characterization of IMC1l has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"To define whether IMC1l could physically link the IMC to the gliding machinery, its direct binding partners were tested, revealing simultaneous protein-protein and protein-lipid interactions consistent with a membrane-cytoskeleton bridge.\",\n      \"evidence\": \"Biochemical binding/pulldown assays, in silico structural analysis, and calcium-binding assays in P. falciparum\",\n      \"pmids\": [\"30599160\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal Co-IP or in vivo functional rescue confirms the interactions\",\n        \"Stoichiometry and physiological relevance of actin/myosin competition unresolved\",\n        \"No structural model of the actin/lipid/calcium binding sites experimentally determined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To place IMC1l in a subcellular context, its expression and localization were examined, showing IMC residence consistent with the proposed anchoring role.\",\n      \"evidence\": \"In vivo expression analysis and subcellular localization in P. falciparum\",\n      \"pmids\": [\"30599160\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Localization reported in a single study without independent replication or detailed imaging method\",\n        \"No functional rescue or knockdown links localization to the anchoring function\",\n        \"Stage-specific expression dynamics not characterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether IMC1l is genetically required for gliding motility, IMC integrity, or parasite invasion, and how its calcium-dependent actin binding is regulated in vivo, remain unknown.\",\n      \"evidence\": \"No genetic knockout, conditional knockdown, or in vivo functional assay is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype established\",\n        \"No demonstration that binding partners engage IMC1l in living parasites\",\n        \"No mechanistic link between calcium binding and gliding motility in vivo\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003779\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0017022\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005509\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0015485\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005546\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071693\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"actin\", \"myosin\", \"cholesterol\", \"PIP2 (phosphatidylinositol 4,5-bisphosphate)\", \"calcium\"],\n    \"other_free_text\": [\n      \"Actin and myosin compete for binding to IMC1l, whereas actin can bind simultaneously with cholesterol or PIP2 [#0].\",\n      \"Calcium binds IMC1l directly and enhances its actin interaction, implying calcium-dependent regulation [#0].\",\n      \"IMC1l is described as an IMC-localized alveolin proposed to anchor the IMC membrane to the gliding apparatus [#1].\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1417000","name":null,"product":"inner membrane complex protein 1l","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1025700","name":null,"product":"inner membrane complex protein 1l, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1341100","name":null,"product":"inner membrane complex protein 1l, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IMC1l","evaluation":null}