{"gene":"PF3D7_0308300","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2021,"finding":"PIC4 (PF3D7_0308300) was identified as a candidate IMC protein by BioID proximity-labelling using PhIL1 as bait in P. falciparum asexual blood-stage parasites, and was subsequently validated by endogenous GFP-tagging, confirming its localization to the inner membrane complex.","method":"BioID proximity-dependent biotinylation proteomics with PhIL1 as bait, followed by endogenous GFP-tagging for localization validation","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (BioID proteomics and endogenous GFP tagging) in a single lab; no functional perturbation of PIC4 itself reported","pmids":["33830607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PIC4 (PF3D7_0308300) was identified as a PhIL1-interacting candidate by immunoprecipitation and mass spectrometry of the gametocyte IMC in P. falciparum, placing it as a component of the PhIL1-associated IMC complex.","method":"Immunoprecipitation followed by mass spectrometry","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment identifying PIC4 as an interactor; no independent validation of PIC4 specifically reported in this paper","pmids":["28985225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIC4 (PF3D7_0308300) is a component of the PhIL1-associated inner membrane complex in P. falciparum, identified by PhIL1 immunoprecipitation/mass spectrometry and BioID proximity proteomics with subsequent endogenous GFP-tagging confirming its IMC localization; no direct functional experiments on PIC4 itself have been reported."},"narrative":{"mechanistic_narrative":"PIC4 (PF3D7_0308300) is a component of the PhIL1-associated inner membrane complex (IMC) of Plasmodium falciparum [PMID:33830607]. It was first identified as a PhIL1-interacting candidate through immunoprecipitation/mass spectrometry of the gametocyte IMC [PMID:28985225], and its association with the PhIL1-defined compartment was corroborated in asexual blood-stage parasites by BioID proximity proteomics using PhIL1 as bait, with endogenous GFP-tagging confirming IMC localization [PMID:33830607]. Beyond this membership in the PhIL1-associated IMC and its subcellular localization, no direct functional characterization of PIC4 itself has been reported in the available corpus.","teleology":[{"year":2017,"claim":"To define the protein composition of the PhIL1-associated IMC, an interactome was needed; this placed PIC4 among the candidate members of that complex.","evidence":"Immunoprecipitation followed by mass spectrometry of the gametocyte IMC in P. falciparum","pmids":["28985225"],"confidence":"Low","gaps":["Single Co-IP/MS experiment with no independent validation of PIC4 specifically","Does not distinguish direct binding to PhIL1 from indirect complex membership","No functional role for PIC4 tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To confirm that the candidate was a genuine IMC constituent rather than a co-purification artifact, orthogonal proximity labelling and direct localization were required; this established PIC4 as an IMC-localized PhIL1-proximal protein in asexual stages.","evidence":"BioID proximity-dependent biotinylation proteomics with PhIL1 as bait plus endogenous GFP-tagging for localization in P. falciparum asexual blood-stage parasites","pmids":["33830607"],"confidence":"Medium","gaps":["No functional perturbation of PIC4 (knockout, knockdown, or conditional depletion) reported","Molecular activity and binding partners of PIC4 itself undefined","Both proteomic identifications originate from a related experimental lineage centered on PhIL1"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular function of PIC4, its specific role within the IMC, and the consequences of its loss for parasite biology remain unestablished in the available corpus.","evidence":"No direct functional experiments on PIC4 reported","pmids":[],"confidence":"Low","gaps":["No loss-of-function phenotype for PIC4 determined","No structural or biochemical activity assigned to PIC4","Whether PIC4 binds PhIL1 directly or via other complex members is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PhIL1-associated inner membrane complex"],"partners":["PHIL1 (BAIT/ASSOCIATED COMPLEX MEMBER)"],"other_free_text":["PIC4 (PF3D7_0308300) is defined in the corpus only by its membership in the PhIL1-associated IMC; no direct functional data on PIC4 itself have been reported.","Identified in P. falciparum in both gametocyte (Co-IP/MS) and asexual blood-stage (BioID + GFP-tagging) contexts."]}},"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":630,"usd":0.012956,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5203,"output_tokens":1404,"usd":0.030558,"stage2_stop_reason":"end_turn"},"total_usd":0.043514,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"PIC4 (PF3D7_0308300) was identified as a candidate IMC protein by BioID proximity-labelling using PhIL1 as bait in P. falciparum asexual blood-stage parasites, and was subsequently validated by endogenous GFP-tagging, confirming its localization to the inner membrane complex.\",\n      \"method\": \"BioID proximity-dependent biotinylation proteomics with PhIL1 as bait, followed by endogenous GFP-tagging for localization validation\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (BioID proteomics and endogenous GFP tagging) in a single lab; no functional perturbation of PIC4 itself reported\",\n      \"pmids\": [\"33830607\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PIC4 (PF3D7_0308300) was identified as a PhIL1-interacting candidate by immunoprecipitation and mass spectrometry of the gametocyte IMC in P. falciparum, placing it as a component of the PhIL1-associated IMC complex.\",\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 PIC4 as an interactor; no independent validation of PIC4 specifically reported in this paper\",\n      \"pmids\": [\"28985225\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PIC4 (PF3D7_0308300) is a component of the PhIL1-associated inner membrane complex in P. falciparum, identified by PhIL1 immunoprecipitation/mass spectrometry and BioID proximity proteomics with subsequent endogenous GFP-tagging confirming its IMC localization; no direct functional experiments on PIC4 itself have been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIC4 (PF3D7_0308300) is a component of the PhIL1-associated inner membrane complex (IMC) of Plasmodium falciparum [#0]. It was first identified as a PhIL1-interacting candidate through immunoprecipitation/mass spectrometry of the gametocyte IMC [#1], and its association with the PhIL1-defined compartment was corroborated in asexual blood-stage parasites by BioID proximity proteomics using PhIL1 as bait, with endogenous GFP-tagging confirming IMC localization [#0]. Beyond this membership in the PhIL1-associated IMC and its subcellular localization, no direct functional characterization of PIC4 itself has been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"To define the protein composition of the PhIL1-associated IMC, an interactome was needed; this placed PIC4 among the candidate members of that complex.\",\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 experiment with no independent validation of PIC4 specifically\",\n        \"Does not distinguish direct binding to PhIL1 from indirect complex membership\",\n        \"No functional role for PIC4 tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To confirm that the candidate was a genuine IMC constituent rather than a co-purification artifact, orthogonal proximity labelling and direct localization were required; this established PIC4 as an IMC-localized PhIL1-proximal protein in asexual stages.\",\n      \"evidence\": \"BioID proximity-dependent biotinylation proteomics with PhIL1 as bait plus endogenous GFP-tagging for localization in P. falciparum asexual blood-stage parasites\",\n      \"pmids\": [\"33830607\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional perturbation of PIC4 (knockout, knockdown, or conditional depletion) reported\",\n        \"Molecular activity and binding partners of PIC4 itself undefined\",\n        \"Both proteomic identifications originate from a related experimental lineage centered on PhIL1\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of PIC4, its specific role within the IMC, and the consequences of its loss for parasite biology remain unestablished in the available corpus.\",\n      \"evidence\": \"No direct functional experiments on PIC4 reported\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype for PIC4 determined\",\n        \"No structural or biochemical activity assigned to PIC4\",\n        \"Whether PIC4 binds PhIL1 directly or via other complex members is unknown\"\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 inner membrane complex\"],\n    \"partners\": [\"PhIL1 (bait/associated complex member)\"],\n    \"other_free_text\": [\n      \"PIC4 (PF3D7_0308300) is defined in the corpus only by its membership in the PhIL1-associated IMC; no direct functional data on PIC4 itself have been reported.\",\n      \"Identified in P. falciparum in both gametocyte (Co-IP/MS) and asexual blood-stage (BioID + GFP-tagging) contexts.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0308300","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_0308300","name":null,"product":"PhIL1-interacting candidate PIC4","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIC4","evaluation":null}