{"gene":"PF3D7_0415800","run_date":"2026-09-07T12:57:15+00:00","timeline":{"discoveries":[{"year":2021,"finding":"PIC3 (referred to in the abstract as PfPhIP, an uncharacterized PhIL1-interacting protein, corresponding to PF3D7_0415800) was identified as a component of a novel PhIL1-associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of P. falciparum merozoites. Genetic depletion of PIC3 resulted in defects in merozoite segmentation, abrogation of merozoite reorientation/gliding after initial RBC attachment, and failure to invade host erythrocytes, while initial attachment with host RBCs was not affected.","method":"Experimental genetics (conditional knockdown/disruption), invasion assays, reorientation/gliding assays, immunoprecipitation to define complex membership","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional knockdown with specific phenotypic readouts (segmentation, reorientation, invasion) and complex membership established by co-immunoprecipitation, single lab","pmids":["34324609"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PhIL1 immunoprecipitation coupled with mass spectrometry identified PIC3 (PF3D7_0415800) as one of the interacting/associated proteins of the PhIL1 IMC complex in P. falciparum gametocytes, establishing its membership in the PhIL1-interacting candidate protein set.","method":"Immunoprecipitation and mass spectrometry","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment identifying complex membership, no direct functional characterization of PIC3 itself in this study","pmids":["28985225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"BioID-based proximity proteomics using PhIL1 as bait in asexual blood-stage P. falciparum identified PIC3 (PF3D7_0415800) among enriched candidate proteins of the IMC, and subsequent endogenous GFP-tagging validated its localization to the IMC.","method":"BioID proximity-dependent biotinylation proteomics, mass spectrometry, endogenous GFP-tagging and fluorescence microscopy","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID plus direct GFP-tagging localization validation, two orthogonal methods, single lab","pmids":["33830607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIC3 (PF3D7_0415800) is a component of the PhIL1-associated inner membrane complex in P. falciparum; its loss impairs merozoite segmentation and abolishes reorientation/gliding after initial erythrocyte attachment, blocking RBC invasion, while initial attachment remains intact, placing it specifically in the post-attachment reorientation step required for tight junction formation."},"narrative":{"mechanistic_narrative":"PIC3 (PF3D7_0415800) is a component of the PhIL1-associated protein complex that resides in the inner membrane complex (IMC) of P. falciparum and functions in erythrocyte invasion by the merozoite [PMID:34324609, PMID:33830607]. It was defined as a member of the PhIL1-interacting protein set through PhIL1 immunoprecipitation-mass spectrometry in gametocytes [PMID:28985225] and through BioID proximity proteomics in asexual blood stages, with endogenous GFP-tagging confirming its IMC localization [PMID:33830607]; this PhIL1 complex co-exists with the glideosome motor complex in the merozoite IMC [PMID:34324609]. Conditional depletion of PIC3 impairs merozoite segmentation and abolishes the reorientation/gliding step that follows initial erythrocyte attachment, so that invasion fails while initial RBC attachment is unaffected — placing PIC3 specifically in the post-attachment reorientation step required for productive invasion [PMID:34324609]. Beyond its complex membership and this invasion phenotype, no further biochemical activity, structural detail, or direct binding partner of PIC3 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"To begin defining the composition of the PhIL1 IMC complex, it was necessary to identify its associated proteins; this placed PIC3 within the PhIL1-interacting candidate set.","evidence":"PhIL1 immunoprecipitation coupled with mass spectrometry in P. falciparum gametocytes","pmids":["28985225"],"confidence":"Low","gaps":["Single Co-IP/MS experiment identifying membership only, with no functional characterization of PIC3 itself","Direct versus indirect association with PhIL1 not resolved","Finding was made in gametocytes, leaving the asexual-stage role undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To confirm PIC3 is a genuine IMC-resident protein rather than a Co-IP artifact, orthogonal proximity labeling and direct tagging were needed; this validated both its association with PhIL1 and its subcellular localization.","evidence":"BioID proximity-dependent biotinylation proteomics with PhIL1 as bait plus endogenous GFP-tagging and fluorescence microscopy in asexual blood-stage P. falciparum","pmids":["33830607"],"confidence":"Medium","gaps":["Proximity labeling does not establish direct physical contact between PIC3 and PhIL1","No stoichiometry or architecture of the complex determined","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To move from association to function, PIC3 needed to be genetically depleted; this established that PIC3 is required for merozoite segmentation and for the post-attachment reorientation/gliding step of invasion, pinpointing where in the invasion sequence it acts.","evidence":"Conditional knockdown/disruption with invasion, reorientation/gliding, and segmentation assays, and immunoprecipitation to define complex membership, in P. falciparum merozoites","pmids":["34324609"],"confidence":"Medium","gaps":["The molecular activity of PIC3 that drives reorientation is unknown","How PIC3 mechanistically couples the PhIL1 complex to the glideosome motor is undefined","Whether the segmentation and reorientation defects are separable functions is not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biochemical activity of PIC3, its direct binding partners within the PhIL1 complex, and the mechanism by which it enables merozoite reorientation remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No enzymatic or structural function assigned to PIC3","No direct (versus proximity/co-purifying) interaction partner mapped","Molecular link between PIC3, the PhIL1 complex, and the glideosome motor not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PhIL1-associated inner membrane complex"],"partners":["PHIL1 (ASSOCIATION / PROXIMITY)"],"other_free_text":["PIC3 (PF3D7_0415800) is a member of the PhIL1-interacting candidate protein set; the corpus establishes it as a component of the PhIL1-associated IMC complex that co-exists with the glideosome, not an independently characterized enzyme.","Genetic depletion impairs merozoite segmentation and abolishes post-attachment reorientation/gliding, blocking erythrocyte invasion while leaving initial attachment intact."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28985225","id":"PMC_28985225","title":"Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development.","date":"2017","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/28985225","citation_count":64,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PhIL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33830607","id":"PMC_33830607","title":"Identification of novel inner membrane complex and apical annuli proteins of the malaria parasite Plasmodium falciparum.","date":"2021","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33830607","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PhIL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29138437","id":"PMC_29138437","title":"Photosensitized INA-Labelled protein 1 (PhIL1) is novel component of the inner membrane complex and is required for Plasmodium parasite development.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29138437","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PhIL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34324609","id":"PMC_34324609","title":"Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34324609","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PhIL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39576115","id":"PMC_39576115","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":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PhIL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5490,"output_tokens":939,"usd":0.015277,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5667,"output_tokens":1936,"usd":0.038367,"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\": 2021,\n      \"finding\": \"PIC3 (referred to in the abstract as PfPhIP, an uncharacterized PhIL1-interacting protein, corresponding to PF3D7_0415800) was identified as a component of a novel PhIL1-associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of P. falciparum merozoites. Genetic depletion of PIC3 resulted in defects in merozoite segmentation, abrogation of merozoite reorientation/gliding after initial RBC attachment, and failure to invade host erythrocytes, while initial attachment with host RBCs was not affected.\",\n      \"method\": \"Experimental genetics (conditional knockdown/disruption), invasion assays, reorientation/gliding assays, immunoprecipitation to define complex membership\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional knockdown with specific phenotypic readouts (segmentation, reorientation, invasion) and complex membership established by co-immunoprecipitation, single lab\",\n      \"pmids\": [\"34324609\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PhIL1 immunoprecipitation coupled with mass spectrometry identified PIC3 (PF3D7_0415800) as one of the interacting/associated proteins of the PhIL1 IMC complex in P. falciparum gametocytes, establishing its membership in the PhIL1-interacting candidate protein set.\",\n      \"method\": \"Immunoprecipitation and mass spectrometry\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment identifying complex membership, no direct functional characterization of PIC3 itself in this study\",\n      \"pmids\": [\"28985225\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"BioID-based proximity proteomics using PhIL1 as bait in asexual blood-stage P. falciparum identified PIC3 (PF3D7_0415800) among enriched candidate proteins of the IMC, and subsequent endogenous GFP-tagging validated its localization to the IMC.\",\n      \"method\": \"BioID proximity-dependent biotinylation proteomics, mass spectrometry, endogenous GFP-tagging and fluorescence microscopy\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID plus direct GFP-tagging localization validation, two orthogonal methods, single lab\",\n      \"pmids\": [\"33830607\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PIC3 (PF3D7_0415800) is a component of the PhIL1-associated inner membrane complex in P. falciparum; its loss impairs merozoite segmentation and abolishes reorientation/gliding after initial erythrocyte attachment, blocking RBC invasion, while initial attachment remains intact, placing it specifically in the post-attachment reorientation step required for tight junction formation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIC3 (PF3D7_0415800) is a component of the PhIL1-associated protein complex that resides in the inner membrane complex (IMC) of P. falciparum and functions in erythrocyte invasion by the merozoite [#0, #2]. It was defined as a member of the PhIL1-interacting protein set through PhIL1 immunoprecipitation-mass spectrometry in gametocytes [#1] and through BioID proximity proteomics in asexual blood stages, with endogenous GFP-tagging confirming its IMC localization [#2]; this PhIL1 complex co-exists with the glideosome motor complex in the merozoite IMC [#0]. Conditional depletion of PIC3 impairs merozoite segmentation and abolishes the reorientation/gliding step that follows initial erythrocyte attachment, so that invasion fails while initial RBC attachment is unaffected — placing PIC3 specifically in the post-attachment reorientation step required for productive invasion [#0]. Beyond its complex membership and this invasion phenotype, no further biochemical activity, structural detail, or direct binding partner of PIC3 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"To begin defining the composition of the PhIL1 IMC complex, it was necessary to identify its associated proteins; this placed PIC3 within the PhIL1-interacting candidate set.\",\n      \"evidence\": \"PhIL1 immunoprecipitation coupled with mass spectrometry in P. falciparum gametocytes\",\n      \"pmids\": [\"28985225\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS experiment identifying membership only, with no functional characterization of PIC3 itself\",\n        \"Direct versus indirect association with PhIL1 not resolved\",\n        \"Finding was made in gametocytes, leaving the asexual-stage role undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To confirm PIC3 is a genuine IMC-resident protein rather than a Co-IP artifact, orthogonal proximity labeling and direct tagging were needed; this validated both its association with PhIL1 and its subcellular localization.\",\n      \"evidence\": \"BioID proximity-dependent biotinylation proteomics with PhIL1 as bait plus endogenous GFP-tagging and fluorescence microscopy in asexual blood-stage P. falciparum\",\n      \"pmids\": [\"33830607\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Proximity labeling does not establish direct physical contact between PIC3 and PhIL1\",\n        \"No stoichiometry or architecture of the complex determined\",\n        \"Single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To move from association to function, PIC3 needed to be genetically depleted; this established that PIC3 is required for merozoite segmentation and for the post-attachment reorientation/gliding step of invasion, pinpointing where in the invasion sequence it acts.\",\n      \"evidence\": \"Conditional knockdown/disruption with invasion, reorientation/gliding, and segmentation assays, and immunoprecipitation to define complex membership, in P. falciparum merozoites\",\n      \"pmids\": [\"34324609\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular activity of PIC3 that drives reorientation is unknown\",\n        \"How PIC3 mechanistically couples the PhIL1 complex to the glideosome motor is undefined\",\n        \"Whether the segmentation and reorientation defects are separable functions is not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of PIC3, its direct binding partners within the PhIL1 complex, and the mechanism by which it enables merozoite reorientation remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No enzymatic or structural function assigned to PIC3\",\n        \"No direct (versus proximity/co-purifying) interaction partner mapped\",\n        \"Molecular link between PIC3, the PhIL1 complex, and the glideosome motor not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"PhIL1-associated inner membrane complex\"],\n    \"partners\": [\"PhIL1 (association / proximity)\"],\n    \"other_free_text\": [\n      \"PIC3 (PF3D7_0415800) is a member of the PhIL1-interacting candidate protein set; the corpus establishes it as a component of the PhIL1-associated IMC complex that co-exists with the glideosome, not an independently characterized enzyme.\",\n      \"Genetic depletion impairs merozoite segmentation and abolishes post-attachment reorientation/gliding, blocking erythrocyte invasion while leaving initial attachment intact.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0415800","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 3 cited papers name other catalogue genes (PF3D7_0109000, PF3D7_1355600, PF3D7_1343700). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0415800","name":null,"product":"PhIL1-interacting candidate PIC3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0507400","name":null,"product":"PhIL1-interacting candidate PIC3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}