{"gene":"PF3D7_1431100","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2021,"finding":"PIP2 (PF3D7_1431100, referred to as PfPhIP in the source paper) 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 (IMC) of P. falciparum merozoites. Conditional downregulation of PIP2 caused significant defects in merozoite segmentation and completely abolished the ability of merozoites to reorient/glide following initial attachment to host RBCs, blocking invasion. Initial attachment to host RBCs was not affected. Parasites lacking PIP2 were unable to invade host erythrocytes.","method":"Experimental genetics (conditional knockdown/gene disruption), invasion assays, reorientation/gliding assays, immunofluorescence","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with defined cellular phenotypes (segmentation defect, reorientation failure, invasion block) measured by multiple orthogonal assays in a single lab study","pmids":["34324609"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PIP2 (PF3D7_1431100) physically interacts with PhIL1, as demonstrated by co-immunoprecipitation/pulldown within the PhIL1-associated complex in the merozoite IMC. Additional members of the complex in this context include PfGAPM2 and PfALV5.","method":"Co-immunoprecipitation, mass spectrometry, experimental genetics","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, Co-IP/MS identification of physical interaction with PhIL1, supported by genetic functional data in the same study","pmids":["34324609"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"A BioID proximity-labeling proteomics screen using PhIL1 as bait in asexual blood-stage P. falciparum identified PIP2 (PF3D7_1431100) among candidate proteins enriched in the PhIL1 proximal proteome, placing it in the IMC compartment.","method":"Proximity-dependent biotin identification (BioID), mass spectrometry","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single BioID screen identifying proximity, no direct functional validation of PF3D7_1431100 specifically in this paper","pmids":["33830607"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PIP2 (PF3D7_1431100) is a component of a PhIL1-associated protein complex residing in the inner membrane complex of P. falciparum merozoites; it physically interacts with PhIL1 and is required for merozoite segmentation, post-attachment reorientation/gliding, and invasion of host erythrocytes, but is dispensable for initial RBC attachment."},"narrative":{"mechanistic_narrative":"PIP2 (PF3D7_1431100) is a component of a PhIL1-associated protein complex that resides in the inner membrane complex (IMC) of Plasmodium falciparum merozoites and co-exists there with the glideosome motor complex [PMID:34324609]. It physically interacts with PhIL1, and within this complex is found alongside PfGAPM2 and PfALV5 [PMID:34324609]. Functionally, conditional downregulation of PIP2 disrupts merozoite segmentation and abolishes the post-attachment reorientation/gliding step, blocking erythrocyte invasion while leaving initial RBC attachment intact [PMID:34324609]. Beyond its membership in this PhIL1 complex and its role in merozoite segmentation and invasion, no further mechanistic detail — such as a defined biochemical activity or the structural basis of its interactions — has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"To place PF3D7_1431100 spatially, a proximity-labeling screen tested whether it associates with the IMC scaffold protein PhIL1, establishing its subcellular compartment.","evidence":"BioID proximity-dependent biotin identification with PhIL1 as bait, followed by mass spectrometry, in asexual blood-stage P. falciparum","pmids":["33830607"],"confidence":"Low","gaps":["Proximity labeling does not distinguish direct interaction from mere neighborhood within the IMC","No functional role for PF3D7_1431100 was tested in this screen"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To define whether PF3D7_1431100 is a bona fide member of a PhIL1 complex, its physical interaction with PhIL1 was tested, establishing it as a component of a distinct IMC complex containing PfGAPM2 and PfALV5.","evidence":"Co-immunoprecipitation/pulldown and mass spectrometry within the merozoite IMC of P. falciparum","pmids":["34324609"],"confidence":"Medium","gaps":["Whether the PhIL1 interaction is direct or bridged by other complex members is not resolved","Stoichiometry and structural architecture of the complex are unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"To determine the cellular function of PF3D7_1431100, its depletion was linked to specific stages of the invasion program, establishing it as required for merozoite segmentation and post-attachment reorientation/gliding but dispensable for initial attachment.","evidence":"Conditional knockdown/gene disruption with invasion, reorientation/gliding assays, and immunofluorescence in P. falciparum","pmids":["34324609"],"confidence":"Medium","gaps":["The molecular activity by which PF3D7_1431100 supports segmentation and gliding is undefined","Whether the segmentation and invasion defects are separable or a single upstream cause is not established","No structural or enzymatic characterization of the protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biochemical mechanism by which PF3D7_1431100 couples the PhIL1 complex to glideosome-driven reorientation and invasion remains unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined molecular/enzymatic activity for PF3D7_1431100","No structural model of PF3D7_1431100 or its interface with PhIL1","Functional role tested only in P. falciparum blood-stage merozoites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PhIL1-associated protein complex (IMC)"],"partners":["PHIL1","PFGAPM2","PFALV5"],"other_free_text":["Referred to as PfPhIP in the source paper but designated here as PIP2 (PF3D7_1431100).","Co-exists with the glideosome motor complex in the merozoite IMC.","Dispensable for initial RBC attachment but required for the subsequent reorientation/gliding and invasion steps."]}},"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":"21518218","id":"PMC_21518218","title":"Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation.","date":"2011","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21518218","citation_count":48,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17526861","id":"PMC_17526861","title":"Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human malaria parasite Plasmodium falciparum.","date":"2007","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/17526861","citation_count":46,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28137231","id":"PMC_28137231","title":"InsP3 Signaling in Apicomplexan Parasites.","date":"2017","source":"Current topics in medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28137231","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28400525","id":"PMC_28400525","title":"Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress.","date":"2017","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/28400525","citation_count":39,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"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":"12742582","id":"PMC_12742582","title":"Plasmodium falciparum histidine-rich protein II binds to actin, phosphatidylinositol 4,5-bisphosphate and erythrocyte ghosts in a pH-dependent manner and undergoes coil-to-helix transitions in anionic micelles.","date":"2003","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/12742582","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37489900","id":"PMC_37489900","title":"Global analysis of putative phospholipases in Plasmodium falciparum reveals an essential role of the phosphoinositide-specific phospholipase C in parasite maturation.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37489900","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"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":"30599160","id":"PMC_30599160","title":"Inner membrane complex 1l protein of Plasmodium falciparum links membrane lipids with cytoskeletal element 'actin' and its associated motor 'myosin'.","date":"2018","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/30599160","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"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},{"pmid":"38136946","id":"PMC_38136946","title":"Imidazolopiperazine (IPZ)-Induced Differential Transcriptomic Responses on Plasmodium falciparum Wild-Type and IPZ-Resistant Mutant Parasites.","date":"2023","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/38136946","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9759,"output_tokens":1286,"usd":0.024283,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5644,"output_tokens":1830,"usd":0.036985,"stage2_stop_reason":"end_turn"},"total_usd":0.061268,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify papers specifically about PF3D7_1431100 (PIP2, the PhIL1 Interacting Protein). Let me classify each paper:\n\n- Paper [1]: About PhIL1 and PIP1 (not PIP2/PF3D7_1431100), though it establishes the PhIL1 complex context. Uses immunoprecipitation revealing PhIL1 interacts with components - PIP2 is not named specifically here.\n- Paper [10]: This paper describes \"PfPhIP\" (PhIL1 Interacting Protein) = PF3D7_1431100. This is the key paper.\n- Paper [7]: About PhIL1 itself and its interactome; PIP2/PF3D7_1431100 may be among identified interactors.\n- Paper [6]: BioID from PhIL1 bait; may have identified PF3D7_1431100.\n- Papers [2],[3],[4],[5],[8],[9],[11],[12],[13]: About phospholipid PIP2 (the lipid molecule), PhIL1, IMC proteins, or other genes — not PF3D7_1431100 specifically.\n\nPaper [10] is the primary paper about PF3D7_1431100 (called \"PfPhIP\"). Papers [1], [7], [6] provide supporting context as PhIL1 interactome studies that identified this protein.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"PIP2 (PF3D7_1431100, referred to as PfPhIP in the source paper) 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 (IMC) of P. falciparum merozoites. Conditional downregulation of PIP2 caused significant defects in merozoite segmentation and completely abolished the ability of merozoites to reorient/glide following initial attachment to host RBCs, blocking invasion. Initial attachment to host RBCs was not affected. Parasites lacking PIP2 were unable to invade host erythrocytes.\",\n      \"method\": \"Experimental genetics (conditional knockdown/gene disruption), invasion assays, reorientation/gliding assays, immunofluorescence\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with defined cellular phenotypes (segmentation defect, reorientation failure, invasion block) measured by multiple orthogonal assays in a single lab study\",\n      \"pmids\": [\"34324609\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PIP2 (PF3D7_1431100) physically interacts with PhIL1, as demonstrated by co-immunoprecipitation/pulldown within the PhIL1-associated complex in the merozoite IMC. Additional members of the complex in this context include PfGAPM2 and PfALV5.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, experimental genetics\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, Co-IP/MS identification of physical interaction with PhIL1, supported by genetic functional data in the same study\",\n      \"pmids\": [\"34324609\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A BioID proximity-labeling proteomics screen using PhIL1 as bait in asexual blood-stage P. falciparum identified PIP2 (PF3D7_1431100) among candidate proteins enriched in the PhIL1 proximal proteome, placing it in the IMC compartment.\",\n      \"method\": \"Proximity-dependent biotin identification (BioID), mass spectrometry\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single BioID screen identifying proximity, no direct functional validation of PF3D7_1431100 specifically in this paper\",\n      \"pmids\": [\"33830607\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PIP2 (PF3D7_1431100) is a component of a PhIL1-associated protein complex residing in the inner membrane complex of P. falciparum merozoites; it physically interacts with PhIL1 and is required for merozoite segmentation, post-attachment reorientation/gliding, and invasion of host erythrocytes, but is dispensable for initial RBC attachment.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIP2 (PF3D7_1431100) is a component of a PhIL1-associated protein complex that resides in the inner membrane complex (IMC) of Plasmodium falciparum merozoites and co-exists there with the glideosome motor complex [#0]. It physically interacts with PhIL1, and within this complex is found alongside PfGAPM2 and PfALV5 [#1]. Functionally, conditional downregulation of PIP2 disrupts merozoite segmentation and abolishes the post-attachment reorientation/gliding step, blocking erythrocyte invasion while leaving initial RBC attachment intact [#0]. Beyond its membership in this PhIL1 complex and its role in merozoite segmentation and invasion, no further mechanistic detail — such as a defined biochemical activity or the structural basis of its interactions — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"To place PF3D7_1431100 spatially, a proximity-labeling screen tested whether it associates with the IMC scaffold protein PhIL1, establishing its subcellular compartment.\",\n      \"evidence\": \"BioID proximity-dependent biotin identification with PhIL1 as bait, followed by mass spectrometry, in asexual blood-stage P. falciparum\",\n      \"pmids\": [\"33830607\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Proximity labeling does not distinguish direct interaction from mere neighborhood within the IMC\",\n        \"No functional role for PF3D7_1431100 was tested in this screen\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To define whether PF3D7_1431100 is a bona fide member of a PhIL1 complex, its physical interaction with PhIL1 was tested, establishing it as a component of a distinct IMC complex containing PfGAPM2 and PfALV5.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown and mass spectrometry within the merozoite IMC of P. falciparum\",\n      \"pmids\": [\"34324609\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the PhIL1 interaction is direct or bridged by other complex members is not resolved\",\n        \"Stoichiometry and structural architecture of the complex are unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To determine the cellular function of PF3D7_1431100, its depletion was linked to specific stages of the invasion program, establishing it as required for merozoite segmentation and post-attachment reorientation/gliding but dispensable for initial attachment.\",\n      \"evidence\": \"Conditional knockdown/gene disruption with invasion, reorientation/gliding assays, and immunofluorescence in P. falciparum\",\n      \"pmids\": [\"34324609\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular activity by which PF3D7_1431100 supports segmentation and gliding is undefined\",\n        \"Whether the segmentation and invasion defects are separable or a single upstream cause is not established\",\n        \"No structural or enzymatic characterization of the protein\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which PF3D7_1431100 couples the PhIL1 complex to glideosome-driven reorientation and invasion remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined molecular/enzymatic activity for PF3D7_1431100\",\n        \"No structural model of PF3D7_1431100 or its interface with PhIL1\",\n        \"Functional role tested only in P. falciparum blood-stage merozoites\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"inner membrane complex\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"erythrocyte invasion by merozoite\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"merozoite segmentation\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"gliding motility / post-attachment reorientation\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"PhIL1-associated protein complex (IMC)\"\n    ],\n    \"partners\": [\n      \"PhIL1\",\n      \"PfGAPM2\",\n      \"PfALV5\"\n    ],\n    \"other_free_text\": [\n      \"Referred to as PfPhIP in the source paper but designated here as PIP2 (PF3D7_1431100).\",\n      \"Co-exists with the glideosome motor complex in the merozoite IMC.\",\n      \"Dispensable for initial RBC attachment but required for the subsequent reorientation/gliding and invasion steps.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1431100","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_1343700, PF3D7_0423500). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1431100","name":null,"product":"PhIL1 interacting protein PIP2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1013600","name":null,"product":"PhIL1 interacting protein PIP2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1327600","name":null,"product":"PhIL1 interacting protein PIP2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIP2","evaluation":null}