{"gene":"PF3D7_1310700","run_date":"2026-09-08T16:55:40+00:00","timeline":{"discoveries":[{"year":2021,"finding":"PIC5 (PF3D7_1310700) was identified as an uncharacterized candidate protein enriched by BioID proximity labeling using PhIL1 as bait in asexual blood-stage P. falciparum, and validated as an IMC protein by endogenous GFP-tagging, localizing to the inner membrane complex.","method":"BioID proximity-dependent biotinylation with PhIL1 as bait followed by mass spectrometry, validated by endogenous GFP-tagging and fluorescence microscopy","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID proteomics plus direct endogenous GFP-tagging for localization validation, single lab, two orthogonal methods","pmids":["33830607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PIC5 (PF3D7_1310700) was identified as a component of the PhIL1-associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of P. falciparum merozoites, via immunoprecipitation experiments using PhIL1 as bait.","method":"Co-immunoprecipitation and mass spectrometry","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/pulldown identifying PIC5 as a PhIL1-interacting candidate; no functional follow-up specific to PIC5 reported","pmids":["34324609"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PIC5 (PF3D7_1310700) was identified as a PhIL1-interacting candidate via immunoprecipitation and mass spectrometry of the PhIL1 complex in P. falciparum gametocytes, placing it as a component of the gametocyte IMC.","method":"Immunoprecipitation and mass spectrometry","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment identifying PIC5 as a PhIL1-interacting candidate; no functional characterization of PIC5 itself reported","pmids":["28985225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIC5 (PF3D7_1310700) localizes to the inner membrane complex of P. falciparum asexual blood-stage parasites and gametocytes, where it has been identified as a PhIL1-interacting candidate member of the PhIL1-associated IMC complex; beyond its complex membership and IMC localization, no independent functional role has been mechanistically established for PIC5 itself."},"narrative":{"mechanistic_narrative":"PIC5 (PF3D7_1310700) is an inner membrane complex (IMC) protein of Plasmodium falciparum identified as a PhIL1-interacting candidate across asexual blood-stage and sexual (gametocyte) parasites [PMID:33830607, PMID:28985225]. It was first recovered as an uncharacterized protein enriched by BioID proximity labeling using PhIL1 as bait in asexual blood stages, and endogenous GFP-tagging confirmed its localization to the IMC [PMID:33830607]. Immunoprecipitation of the PhIL1 complex placed PIC5 within the PhIL1-associated protein complex that co-exists with the glideosome motor complex in merozoites [PMID:34324609] and within the gametocyte IMC [PMID:28985225]. Beyond its membership in the PhIL1-associated IMC complex and its IMC localization, no independent molecular function, substrate, or phenotype has been characterized for PIC5 itself in the available corpus.","teleology":[{"year":2017,"claim":"The first question was whether PF3D7_1310700 associates with the IMC machinery in a specific developmental stage; identifying it in the gametocyte PhIL1 complex established it as a candidate component of the sexual-stage IMC.","evidence":"Immunoprecipitation and mass spectrometry of the PhIL1 complex in P. falciparum gametocytes","pmids":["28985225"],"confidence":"Low","gaps":["Single Co-IP/MS identifying PIC5 as a candidate; no reciprocal pulldown or direct-interaction validation","No functional characterization of PIC5 itself in gametocytes","Localization not independently confirmed by tagging in this study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether PF3D7_1310700 is a genuine IMC protein in asexual blood stages was unresolved; proximity labeling with PhIL1 plus endogenous tagging established both its physical proximity to PhIL1 and its IMC localization.","evidence":"BioID proximity-dependent biotinylation 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 demonstrate a direct binary interaction with PhIL1","No genetic knockdown/knockout to define a functional role","Molecular activity of PIC5 remains undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether PF3D7_1310700 belongs to the motility-associated IMC machinery of invasive stages was addressed by placing it in the PhIL1-associated complex that co-exists with the glideosome motor in merozoites.","evidence":"Co-immunoprecipitation and mass spectrometry using PhIL1 as bait in P. falciparum merozoites","pmids":["34324609"],"confidence":"Low","gaps":["Single Co-IP without PIC5-specific functional follow-up","Relationship of PIC5 to glideosome function not tested","Does not establish whether PIC5 is required for complex assembly or motility"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic molecular function of PIC5, and whether it is required for IMC integrity, gliding motility, invasion, or gametocyte development, remains unknown.","evidence":"No genetic disruption, biochemical activity assay, or structural study of PIC5 is present in the corpus","pmids":[],"confidence":"Low","gaps":["No loss-of-function phenotype for PIC5","No defined molecular activity or direct binding partner","No structural or domain-level characterization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PhIL1-associated IMC complex"],"partners":["PHIL1"],"other_free_text":["Identified as a PhIL1-interacting candidate (PIC) in asexual blood-stage merozoites and gametocytes; no independent function established beyond IMC complex membership [#0, #1, #2]","PhIL1-associated complex co-exists with the glideosome motor complex in the merozoite IMC [#1]"]}},"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":65,"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":33,"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":10,"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":5487,"output_tokens":872,"usd":0.014771,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5540,"output_tokens":1751,"usd":0.035737,"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\": \"PIC5 (PF3D7_1310700) was identified as an uncharacterized candidate protein enriched by BioID proximity labeling using PhIL1 as bait in asexual blood-stage P. falciparum, and validated as an IMC protein by endogenous GFP-tagging, localizing to the inner membrane complex.\",\n      \"method\": \"BioID proximity-dependent biotinylation with PhIL1 as bait followed by mass spectrometry, validated by endogenous GFP-tagging and fluorescence microscopy\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID proteomics plus direct endogenous GFP-tagging for localization validation, single lab, two orthogonal methods\",\n      \"pmids\": [\"33830607\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PIC5 (PF3D7_1310700) was identified as a component of the PhIL1-associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of P. falciparum merozoites, via immunoprecipitation experiments using PhIL1 as bait.\",\n      \"method\": \"Co-immunoprecipitation and mass spectrometry\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/pulldown identifying PIC5 as a PhIL1-interacting candidate; no functional follow-up specific to PIC5 reported\",\n      \"pmids\": [\"34324609\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PIC5 (PF3D7_1310700) was identified as a PhIL1-interacting candidate via immunoprecipitation and mass spectrometry of the PhIL1 complex in P. falciparum gametocytes, placing it as a component of the gametocyte IMC.\",\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 PIC5 as a PhIL1-interacting candidate; no functional characterization of PIC5 itself reported\",\n      \"pmids\": [\"28985225\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PIC5 (PF3D7_1310700) localizes to the inner membrane complex of P. falciparum asexual blood-stage parasites and gametocytes, where it has been identified as a PhIL1-interacting candidate member of the PhIL1-associated IMC complex; beyond its complex membership and IMC localization, no independent functional role has been mechanistically established for PIC5 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIC5 (PF3D7_1310700) is an inner membrane complex (IMC) protein of Plasmodium falciparum identified as a PhIL1-interacting candidate across asexual blood-stage and sexual (gametocyte) parasites [#0, #2]. It was first recovered as an uncharacterized protein enriched by BioID proximity labeling using PhIL1 as bait in asexual blood stages, and endogenous GFP-tagging confirmed its localization to the IMC [#0]. Immunoprecipitation of the PhIL1 complex placed PIC5 within the PhIL1-associated protein complex that co-exists with the glideosome motor complex in merozoites [#1] and within the gametocyte IMC [#2]. Beyond its membership in the PhIL1-associated IMC complex and its IMC localization, no independent molecular function, substrate, or phenotype has been characterized for PIC5 itself in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"The first question was whether PF3D7_1310700 associates with the IMC machinery in a specific developmental stage; identifying it in the gametocyte PhIL1 complex established it as a candidate component of the sexual-stage IMC.\",\n      \"evidence\": \"Immunoprecipitation and mass spectrometry of the PhIL1 complex in P. falciparum gametocytes\",\n      \"pmids\": [\"28985225\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS identifying PIC5 as a candidate; no reciprocal pulldown or direct-interaction validation\",\n        \"No functional characterization of PIC5 itself in gametocytes\",\n        \"Localization not independently confirmed by tagging in this study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PF3D7_1310700 is a genuine IMC protein in asexual blood stages was unresolved; proximity labeling with PhIL1 plus endogenous tagging established both its physical proximity to PhIL1 and its IMC localization.\",\n      \"evidence\": \"BioID proximity-dependent biotinylation 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 demonstrate a direct binary interaction with PhIL1\",\n        \"No genetic knockdown/knockout to define a functional role\",\n        \"Molecular activity of PIC5 remains undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PF3D7_1310700 belongs to the motility-associated IMC machinery of invasive stages was addressed by placing it in the PhIL1-associated complex that co-exists with the glideosome motor in merozoites.\",\n      \"evidence\": \"Co-immunoprecipitation and mass spectrometry using PhIL1 as bait in P. falciparum merozoites\",\n      \"pmids\": [\"34324609\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP without PIC5-specific functional follow-up\",\n        \"Relationship of PIC5 to glideosome function not tested\",\n        \"Does not establish whether PIC5 is required for complex assembly or motility\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic molecular function of PIC5, and whether it is required for IMC integrity, gliding motility, invasion, or gametocyte development, remains unknown.\",\n      \"evidence\": \"No genetic disruption, biochemical activity assay, or structural study of PIC5 is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype for PIC5\",\n        \"No defined molecular activity or direct binding partner\",\n        \"No structural or domain-level characterization\"\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    \"complexes\": [\"PhIL1-associated IMC complex\"],\n    \"partners\": [\"PhIL1\"],\n    \"other_free_text\": [\n      \"Identified as a PhIL1-interacting candidate (PIC) in asexual blood-stage merozoites and gametocytes; no independent function established beyond IMC complex membership [#0, #1, #2]\",\n      \"PhIL1-associated complex co-exists with the glideosome motor complex in the merozoite IMC [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1310700","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_1310700","name":null,"product":"PhIL1-interacting candidate PIC5","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1409200","name":null,"product":"PhIL1-interacting candidate PIC5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1411100","name":null,"product":"PhIL1-interacting candidate PIC5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIC5","evaluation":null}