{"gene":"PF3D7_0530300","run_date":"2026-09-07T12:57:17+00:00","timeline":{"discoveries":[{"year":2021,"finding":"PIC6 (PF3D7_0530300) was identified as one of nine previously uncharacterized proteins enriched by PhIL1-BioID proximity labeling in asexual blood-stage P. falciparum, and validated as a new IMC protein by endogenous GFP-tagging, confirming its localization to the inner membrane complex.","method":"BioID proximity-dependent biotinylation using PhIL1 as bait, followed by mass spectrometry peptide identification and endogenous GFP-tagging for validation","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID proteomics plus GFP-tagging validation, single lab, two orthogonal methods","pmids":["33830607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PIC6 (PF3D7_0530300) was identified as a PhIL1-interacting candidate by immunoprecipitation and mass spectrometry of the gametocyte IMC, placing it as a component of the PhIL1-associated IMC complex in gametocytes.","method":"Immunoprecipitation followed by mass spectrometry","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment identifying PIC6 as a candidate interactor, no direct functional follow-up on PIC6 itself reported in the abstract","pmids":["28985225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIC6 (PF3D7_0530300) is a component of the inner membrane complex in Plasmodium falciparum, identified as a PhIL1-interacting candidate by co-immunoprecipitation/mass spectrometry in gametocytes and validated as an IMC-localized protein by BioID proximity proteomics and endogenous GFP-tagging in asexual blood stages; no further mechanistic or functional role has been established for PIC6 itself beyond its IMC membership."},"narrative":{"mechanistic_narrative":"PIC6 (PF3D7_0530300) is a component of the inner membrane complex (IMC) of Plasmodium falciparum, identified through its association with PhIL1 [PMID:33830607]. In asexual blood-stage parasites, PIC6 was recovered among previously uncharacterized proteins enriched by PhIL1-BioID proximity labeling, and endogenous GFP-tagging confirmed its localization to the IMC [PMID:33830607]. Beyond establishing PIC6 as a PhIL1-proximal IMC protein, no molecular activity, substrate, or functional role for PIC6 itself has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Before this work it was unknown which proteins associate with PhIL1 in the gametocyte IMC; co-immunoprecipitation placed PIC6 within the PhIL1-associated complex, marking it as a candidate IMC component.","evidence":"Immunoprecipitation followed by mass spectrometry of the gametocyte IMC in P. falciparum","pmids":["28985225"],"confidence":"Low","gaps":["Single Co-IP/MS identification without reciprocal validation or direct functional follow-up on PIC6","Does not establish whether the interaction is direct or bridged by other complex members","No localization confirmation of PIC6 itself in gametocytes"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether PIC6 is a bona fide IMC resident rather than a transient co-purifying protein was unresolved; proximity labeling plus endogenous tagging established PIC6 as a validated IMC protein in asexual blood stages.","evidence":"PhIL1-BioID proximity-dependent biotinylation with mass spectrometry, plus endogenous GFP-tagging for localization, in asexual blood-stage P. falciparum","pmids":["33830607"],"confidence":"Medium","gaps":["No functional characterization (knockout/knockdown) of PIC6 to define its role in the IMC","Molecular activity and direct binding partners of PIC6 remain undefined","No structural model or domain-level mechanism established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular function of PIC6 within the IMC, its essentiality, and whether it acts beyond passive complex membership remain unknown.","evidence":"No functional or mechanistic study of PIC6 itself is present in the corpus","pmids":[],"confidence":"Low","gaps":["No loss-of-function phenotype reported for PIC6","No defined biochemical activity or substrate","Role across life-cycle stages beyond IMC association undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PhIL1-associated IMC complex"],"partners":["PHIL1 (PROXIMITY/CO-IP ASSOCIATION)"],"other_free_text":["Identified as PhIL1-interacting candidate PIC6; established only as an IMC-localized, PhIL1-proximal protein with no intrinsic function characterized in the corpus."]}},"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":646,"usd":0.013076,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5231,"output_tokens":1321,"usd":0.02959,"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\": \"PIC6 (PF3D7_0530300) was identified as one of nine previously uncharacterized proteins enriched by PhIL1-BioID proximity labeling in asexual blood-stage P. falciparum, and validated as a new IMC protein by endogenous GFP-tagging, confirming its localization to the inner membrane complex.\",\n      \"method\": \"BioID proximity-dependent biotinylation using PhIL1 as bait, followed by mass spectrometry peptide identification and endogenous GFP-tagging for validation\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID proteomics plus GFP-tagging 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\": 2017,\n      \"finding\": \"PIC6 (PF3D7_0530300) was identified as a PhIL1-interacting candidate by immunoprecipitation and mass spectrometry of the gametocyte IMC, placing it as a component of the PhIL1-associated IMC complex in gametocytes.\",\n      \"method\": \"Immunoprecipitation followed by mass spectrometry\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment identifying PIC6 as a candidate interactor, no direct functional follow-up on PIC6 itself reported in the abstract\",\n      \"pmids\": [\"28985225\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PIC6 (PF3D7_0530300) is a component of the inner membrane complex in Plasmodium falciparum, identified as a PhIL1-interacting candidate by co-immunoprecipitation/mass spectrometry in gametocytes and validated as an IMC-localized protein by BioID proximity proteomics and endogenous GFP-tagging in asexual blood stages; no further mechanistic or functional role has been established for PIC6 itself beyond its IMC membership.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIC6 (PF3D7_0530300) is a component of the inner membrane complex (IMC) of Plasmodium falciparum, identified through its association with PhIL1 [#0]. In asexual blood-stage parasites, PIC6 was recovered among previously uncharacterized proteins enriched by PhIL1-BioID proximity labeling, and endogenous GFP-tagging confirmed its localization to the IMC [#0]. Beyond establishing PIC6 as a PhIL1-proximal IMC protein, no molecular activity, substrate, or functional role for PIC6 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Before this work it was unknown which proteins associate with PhIL1 in the gametocyte IMC; co-immunoprecipitation placed PIC6 within the PhIL1-associated complex, marking it as a candidate IMC component.\",\n      \"evidence\": \"Immunoprecipitation followed by mass spectrometry of the gametocyte IMC in P. falciparum\",\n      \"pmids\": [\"28985225\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS identification without reciprocal validation or direct functional follow-up on PIC6\",\n        \"Does not establish whether the interaction is direct or bridged by other complex members\",\n        \"No localization confirmation of PIC6 itself in gametocytes\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PIC6 is a bona fide IMC resident rather than a transient co-purifying protein was unresolved; proximity labeling plus endogenous tagging established PIC6 as a validated IMC protein in asexual blood stages.\",\n      \"evidence\": \"PhIL1-BioID proximity-dependent biotinylation with mass spectrometry, plus endogenous GFP-tagging for localization, in asexual blood-stage P. falciparum\",\n      \"pmids\": [\"33830607\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional characterization (knockout/knockdown) of PIC6 to define its role in the IMC\",\n        \"Molecular activity and direct binding partners of PIC6 remain undefined\",\n        \"No structural model or domain-level mechanism established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function of PIC6 within the IMC, its essentiality, and whether it acts beyond passive complex membership remain unknown.\",\n      \"evidence\": \"No functional or mechanistic study of PIC6 itself is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype reported for PIC6\",\n        \"No defined biochemical activity or substrate\",\n        \"Role across life-cycle stages beyond IMC association undetermined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"inner membrane complex\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"PhIL1-associated IMC complex\"],\n    \"partners\": [\"PhIL1 (proximity/co-IP association)\"],\n    \"other_free_text\": [\n      \"Identified as PhIL1-interacting candidate PIC6; established only as an IMC-localized, PhIL1-proximal protein with no intrinsic function characterized in the corpus.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0530300","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 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_0530300","name":null,"product":"PhIL1-interacting candidate PIC6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1244700","name":null,"product":"PhIL1-interacting candidate PIC6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1002400","name":null,"product":"PhIL1-interacting candidate PIC6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIC6","evaluation":null}