{"gene":"PF3D7_1229300","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2017,"finding":"PIC1 (PF3D7_1229300) was identified as a component of the gametocyte inner membrane complex (IMC) by immunoprecipitation and mass spectrometry using PhIL1 as bait, revealing PIC1 as part of the PhIL1-interacting protein network in P. falciparum gametocytes.","method":"Immunoprecipitation and mass spectrometry (PhIL1 as bait)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/MS experiment identifying PIC1 as a PhIL1-interacting candidate; PIC1 itself not functionally characterized beyond complex membership in this paper","pmids":["28985225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PIC1 (PF3D7_1229300) was identified by BioID proximity-labeling proteomics using PhIL1 as bait in asexual blood-stage P. falciparum parasites, placing PIC1 as an IMC-proximal candidate protein; endogenous GFP-tagging was used to validate a subset of candidates (though PIC1 is listed as a candidate without explicit statement that it was among the nine validated by GFP-tagging in this abstract).","method":"BioID proximity-dependent biotinylation and mass spectrometry","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single BioID/MS experiment; PIC1 identified as candidate but individual functional validation of PIC1 is not explicitly confirmed in the abstract","pmids":["33830607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PIC1 (PF3D7_1229300), referred to in the paper as PfPhIP (PhIL1 Interacting Protein), was shown by co-immunoprecipitation to associate with PhIL1 in the P. falciparum merozoite IMC; conditional knockdown of PIC1 resulted in significant defects in merozoite segmentation and abrogation of merozoite reorientation/gliding following initial RBC attachment, ultimately blocking host erythrocyte invasion, while initial RBC attachment was unaffected.","method":"Co-immunoprecipitation; conditional knockdown (experimental genetics) with invasion, reorientation, and segmentation phenotypic readouts","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP establishing complex membership combined with conditional knockdown showing specific, defined cellular phenotypes (reorientation, segmentation, invasion defects) in a single focused study","pmids":["34324609"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIC1 (PF3D7_1229300) is a component of the PhIL1-associated protein complex within the P. falciparum merozoite inner membrane complex; it physically interacts with PhIL1 (demonstrated by Co-IP), and its loss via conditional knockdown causes defects in merozoite segmentation and abrogates the reorientation/gliding step that follows initial RBC attachment, thereby blocking erythrocyte invasion without affecting the initial attachment event itself."},"narrative":{"mechanistic_narrative":"PIC1 (PF3D7_1229300) is a component of the PhIL1-associated protein complex within the inner membrane complex (IMC) of P. falciparum, identified through its physical association with PhIL1 [PMID:28985225, PMID:34324609]. It was first recovered as a PhIL1-interacting protein in gametocytes by immunoprecipitation and mass spectrometry [PMID:28985225], and its association with PhIL1 was subsequently confirmed by reciprocal co-immunoprecipitation in the merozoite IMC [PMID:34324609]. Functionally, conditional knockdown of PIC1 causes defects in merozoite segmentation and abrogates the reorientation/gliding step that follows initial erythrocyte attachment, thereby blocking host cell invasion while leaving the initial attachment event intact [PMID:34324609]. Beyond its role as a PhIL1-complex component required for merozoite morphogenesis and invasion, no further molecular mechanism, catalytic activity, or structural detail for PIC1 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Before this work it was unknown which proteins constitute the PhIL1 network; identifying PIC1 as a PhIL1 co-purifying protein established it as a member of the gametocyte IMC-associated complex.","evidence":"Immunoprecipitation and mass spectrometry using PhIL1 as bait in P. falciparum gametocytes","pmids":["28985225"],"confidence":"Medium","gaps":["Single Co-IP/MS experiment without reciprocal validation for PIC1","No functional role for PIC1 defined beyond complex membership","Direct versus indirect interaction with PhIL1 not distinguished"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Extending the PhIL1 interactome to asexual blood stages, proximity labeling placed PIC1 as an IMC-proximal candidate, indicating the association is not restricted to gametocytes.","evidence":"BioID proximity-dependent biotinylation and mass spectrometry with PhIL1 as bait in asexual blood-stage parasites","pmids":["33830607"],"confidence":"Low","gaps":["PIC1 identified as candidate but not explicitly confirmed among the GFP-validated subset","Proximity does not establish direct interaction","No functional consequence of PIC1 loss tested in this study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"It was unknown whether PIC1 has a functional role; reciprocal Co-IP plus conditional knockdown established PIC1 as a PhIL1-complex member required for merozoite segmentation and for the post-attachment reorientation step of invasion.","evidence":"Co-immunoprecipitation and conditional knockdown with invasion, reorientation, and segmentation readouts in P. falciparum merozoites","pmids":["34324609"],"confidence":"High","gaps":["Molecular mechanism linking PIC1 loss to segmentation and gliding defects unresolved","No structural model or biochemical activity for PIC1","Whether the invasion defect is a direct role or a secondary consequence of segmentation failure is not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular function of PIC1 within the PhIL1/IMC complex and how it mechanistically enables merozoite reorientation and gliding remain undefined.","evidence":"","pmids":[],"confidence":"High","gaps":["No catalytic or biochemical activity assigned to PIC1","Direct binding partners beyond PhIL1 not mapped","Structural basis of complex assembly unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PhIL1-associated inner membrane complex (IMC) protein network"],"partners":["PHIL1"],"other_free_text":["Conditional knockdown of PIC1 causes merozoite segmentation defects and abrogates post-attachment reorientation/gliding, blocking erythrocyte invasion without affecting initial attachment [#2].","Identified as a PhIL1-interacting/IMC-proximal candidate in both gametocytes [#0] and asexual blood-stage parasites [#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":980,"usd":0.015581,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5752,"output_tokens":1793,"usd":0.036792,"stage2_stop_reason":"end_turn"},"total_usd":0.052373,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"PIC1 (PF3D7_1229300) was identified as a component of the gametocyte inner membrane complex (IMC) by immunoprecipitation and mass spectrometry using PhIL1 as bait, revealing PIC1 as part of the PhIL1-interacting protein network in P. falciparum gametocytes.\",\n      \"method\": \"Immunoprecipitation and mass spectrometry (PhIL1 as bait)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/MS experiment identifying PIC1 as a PhIL1-interacting candidate; PIC1 itself not functionally characterized beyond complex membership in this paper\",\n      \"pmids\": [\"28985225\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PIC1 (PF3D7_1229300) was identified by BioID proximity-labeling proteomics using PhIL1 as bait in asexual blood-stage P. falciparum parasites, placing PIC1 as an IMC-proximal candidate protein; endogenous GFP-tagging was used to validate a subset of candidates (though PIC1 is listed as a candidate without explicit statement that it was among the nine validated by GFP-tagging in this abstract).\",\n      \"method\": \"BioID proximity-dependent biotinylation and mass spectrometry\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single BioID/MS experiment; PIC1 identified as candidate but individual functional validation of PIC1 is not explicitly confirmed in the abstract\",\n      \"pmids\": [\"33830607\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PIC1 (PF3D7_1229300), referred to in the paper as PfPhIP (PhIL1 Interacting Protein), was shown by co-immunoprecipitation to associate with PhIL1 in the P. falciparum merozoite IMC; conditional knockdown of PIC1 resulted in significant defects in merozoite segmentation and abrogation of merozoite reorientation/gliding following initial RBC attachment, ultimately blocking host erythrocyte invasion, while initial RBC attachment was unaffected.\",\n      \"method\": \"Co-immunoprecipitation; conditional knockdown (experimental genetics) with invasion, reorientation, and segmentation phenotypic readouts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP establishing complex membership combined with conditional knockdown showing specific, defined cellular phenotypes (reorientation, segmentation, invasion defects) in a single focused study\",\n      \"pmids\": [\"34324609\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PIC1 (PF3D7_1229300) is a component of the PhIL1-associated protein complex within the P. falciparum merozoite inner membrane complex; it physically interacts with PhIL1 (demonstrated by Co-IP), and its loss via conditional knockdown causes defects in merozoite segmentation and abrogates the reorientation/gliding step that follows initial RBC attachment, thereby blocking erythrocyte invasion without affecting the initial attachment event itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIC1 (PF3D7_1229300) is a component of the PhIL1-associated protein complex within the inner membrane complex (IMC) of P. falciparum, identified through its physical association with PhIL1 [#0, #2]. It was first recovered as a PhIL1-interacting protein in gametocytes by immunoprecipitation and mass spectrometry [#0], and its association with PhIL1 was subsequently confirmed by reciprocal co-immunoprecipitation in the merozoite IMC [#2]. Functionally, conditional knockdown of PIC1 causes defects in merozoite segmentation and abrogates the reorientation/gliding step that follows initial erythrocyte attachment, thereby blocking host cell invasion while leaving the initial attachment event intact [#2]. Beyond its role as a PhIL1-complex component required for merozoite morphogenesis and invasion, no further molecular mechanism, catalytic activity, or structural detail for PIC1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Before this work it was unknown which proteins constitute the PhIL1 network; identifying PIC1 as a PhIL1 co-purifying protein established it as a member of the gametocyte IMC-associated complex.\",\n      \"evidence\": \"Immunoprecipitation and mass spectrometry using PhIL1 as bait in P. falciparum gametocytes\",\n      \"pmids\": [\"28985225\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP/MS experiment without reciprocal validation for PIC1\",\n        \"No functional role for PIC1 defined beyond complex membership\",\n        \"Direct versus indirect interaction with PhIL1 not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extending the PhIL1 interactome to asexual blood stages, proximity labeling placed PIC1 as an IMC-proximal candidate, indicating the association is not restricted to gametocytes.\",\n      \"evidence\": \"BioID proximity-dependent biotinylation and mass spectrometry with PhIL1 as bait in asexual blood-stage parasites\",\n      \"pmids\": [\"33830607\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"PIC1 identified as candidate but not explicitly confirmed among the GFP-validated subset\",\n        \"Proximity does not establish direct interaction\",\n        \"No functional consequence of PIC1 loss tested in this study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown whether PIC1 has a functional role; reciprocal Co-IP plus conditional knockdown established PIC1 as a PhIL1-complex member required for merozoite segmentation and for the post-attachment reorientation step of invasion.\",\n      \"evidence\": \"Co-immunoprecipitation and conditional knockdown with invasion, reorientation, and segmentation readouts in P. falciparum merozoites\",\n      \"pmids\": [\"34324609\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism linking PIC1 loss to segmentation and gliding defects unresolved\",\n        \"No structural model or biochemical activity for PIC1\",\n        \"Whether the invasion defect is a direct role or a secondary consequence of segmentation failure is not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of PIC1 within the PhIL1/IMC complex and how it mechanistically enables merozoite reorientation and gliding remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No catalytic or biochemical activity assigned to PIC1\",\n        \"Direct binding partners beyond PhIL1 not mapped\",\n        \"Structural basis of complex assembly unknown\"\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\": [2]}\n    ],\n    \"complexes\": [\"PhIL1-associated inner membrane complex (IMC) protein network\"],\n    \"partners\": [\"PhIL1\"],\n    \"other_free_text\": [\n      \"Conditional knockdown of PIC1 causes merozoite segmentation defects and abrogates post-attachment reorientation/gliding, blocking erythrocyte invasion without affecting initial attachment [#2].\",\n      \"Identified as a PhIL1-interacting/IMC-proximal candidate in both gametocytes [#0] and asexual blood-stage parasites [#1].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1229300","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_1229300","name":null,"product":"PhIL1-interacting candidate PIC1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1443900","name":null,"product":"PhIL1-interacting candidate PIC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1448600","name":null,"product":"PhIL1-interacting candidate PIC1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIC1","evaluation":null}