{"gene":"PF3D7_0419700","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2006,"finding":"Pf34 (PF3D7_0419700) was experimentally confirmed to carry a glycosylphosphatidylinositol (GPI) anchor, identified by proteomic analysis of proteins labeled with radioactive glucosamine in P. falciparum schizont/merozoite stages.","method":"Radioactive glucosamine metabolic labeling followed by proteomic identification (mass spectrometry)","journal":"Molecular & cellular proteomics : MCP","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct biochemical labeling with radioactive glucosamine confirmed GPI modification; replicated by subsequent studies","pmids":["16603573"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Pf34 (PF3D7_0419700) localizes to the merozoite apex, specifically to the rhoptry neck, as determined by indirect immunofluorescence assay. It is expressed in mature asexual blood stages and is carried into the newly invaded ring stage, consistent with a role in parasitophorous vacuole formation.","method":"Indirect immunofluorescence assay (IFA) and Western blot on stage-specific parasite lysates","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by IFA with functional inference from transfer into ring stage; single lab, two complementary methods","pmids":["17521656"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Pf34 (PF3D7_0419700) is associated with parasite-derived detergent-resistant microdomains (DRMs), indicating it resides in lipid raft-like membrane structures at the merozoite surface.","method":"Detergent-resistant microdomain (DRM) fractionation followed by Western blot","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical fractionation directly demonstrated DRM association; single lab but consistent with GPI-anchor data from independent proteomics study","pmids":["17521656"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Peptides from the central region of Pf34 (PF3D7_0419700) bind with high affinity to protease-sensitive receptors on red blood cell surfaces and inhibit P. falciparum merozoite invasion of RBCs in vitro, suggesting Pf34 acts as an adhesin during invasion.","method":"Receptor-ligand binding assays with synthetic peptides and in vitro invasion inhibition assays","journal":"Peptides","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct receptor-ligand binding assay plus functional invasion inhibition; single lab, two orthogonal methods","pmids":["20654670"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"Pf34 (PF3D7_0419700) interacts with human fibroblast growth factor receptor 4 (FGFR4) in a plate-based protein-protein interaction screen; this interaction was biochemically characterized for affinity and blocked by a monoclonal antibody. Pf34 also interacts with the rhoptry neck protein PfRON6. Antibodies to Pf34 had a modest inhibitory effect on sporozoite invasion into primary human hepatocytes. Pf34 was refractory to attempted genetic deletion.","method":"Plate-based recombinant protein interaction screen, affinity characterization (KD measurement), monoclonal antibody blockade, sporozoite invasion inhibition assay in primary human hepatocytes","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical interaction screen with affinity measurement and functional antibody blockade; single study with multiple orthogonal methods","pmids":["38755636"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"Pf34 (PF3D7_0419700) is a GPI-anchored, rhoptry neck protein expressed in mature P. falciparum asexual blood stages that localizes to the merozoite apex within detergent-resistant microdomains, is transferred into newly invaded rings, binds protease-sensitive receptors on red blood cells (with peptides from its central region inhibiting merozoite invasion in vitro), interacts with the host hepatocyte receptor FGFR4 and with the parasite rhoptry neck protein PfRON6, and may function as an adhesin during both merozoite and sporozoite invasion."},"narrative":{"mechanistic_narrative":"Pf34 (PF3D7_0419700) is a GPI-anchored apical antigen of mature Plasmodium falciparum asexual blood stages that functions as a candidate adhesin during host-cell invasion [PMID:16603573, PMID:20654670]. It localizes to the merozoite apex at the rhoptry neck, resides within detergent-resistant (lipid raft-like) microdomains, and is carried forward into newly invaded ring-stage parasites [PMID:17521656]. Peptides from its central region bind protease-sensitive receptors on the red blood cell surface and inhibit merozoite invasion in vitro, indicating a role in the adhesive events of RBC entry [PMID:20654670]. Pf34 physically interacts with the parasite rhoptry neck protein PfRON6 and with the human hepatocyte receptor FGFR4, and antibodies against Pf34 modestly inhibit sporozoite invasion of primary hepatocytes; the gene is refractory to genetic deletion [PMID:38755636]. Beyond these findings, the precise molecular role of Pf34 within the invasion machinery has not been further characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing that Pf34 is post-translationally modified answered whether it is membrane-associated, showing it carries a GPI anchor consistent with a surface-exposed role.","evidence":"Radioactive glucosamine metabolic labeling and mass-spectrometry identification in schizont/merozoite stages","pmids":["16603573"],"confidence":"High","gaps":["Does not localize the protein within the merozoite","Does not define a function for the GPI-anchored protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Localization and biochemical fractionation addressed where Pf34 acts, placing it at the rhoptry neck within lipid raft-like microdomains and showing it is transferred into the nascent ring, implicating it in invasion/parasitophorous vacuole formation.","evidence":"Indirect immunofluorescence, stage-specific Western blot, and detergent-resistant microdomain fractionation","pmids":["17521656"],"confidence":"Medium","gaps":["Functional role inferred from transfer into rings, not tested directly","Single lab; no genetic manipulation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Receptor-binding and invasion assays tested whether Pf34 engages the host cell, showing central-region peptides bind protease-sensitive RBC receptors and inhibit merozoite invasion, framing Pf34 as an invasion adhesin.","evidence":"Synthetic peptide receptor-ligand binding assays and in vitro RBC invasion inhibition","pmids":["20654670"],"confidence":"Medium","gaps":["RBC receptor identity not defined","Peptide binding may not reflect native full-length protein behavior"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Interaction screening extended Pf34's adhesin role across life-cycle stages, identifying binding to host FGFR4 and to parasite PfRON6, antibody-inhibitable sporozoite invasion of hepatocytes, and essentiality inferred from failed deletion.","evidence":"Plate-based recombinant protein interaction screen with affinity measurement, monoclonal antibody blockade, sporozoite invasion assay in primary human hepatocytes, and attempted gene knockout","pmids":["38755636"],"confidence":"Medium","gaps":["FGFR4 interaction shown with recombinant proteins, not in vivo","Sporozoite invasion inhibition was modest","Refractoriness to deletion not confirmed by conditional approaches"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The native molecular function of Pf34 within the rhoptry/invasion apparatus and the identity of its RBC receptor remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No conditional knockdown to establish essentiality or invasion phenotype","RBC receptor bound by central-region peptides not molecularly identified","Structural basis of PfRON6 and FGFR4 interactions unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFRON6","FGFR4 (HUMAN, HOST)"],"other_free_text":["GPI-anchored, confirmed by radioactive glucosamine labeling [#0]","Central-region peptides bind protease-sensitive RBC receptors and inhibit merozoite invasion [#3]","Carried into newly invaded ring stage [#1]","Refractory to genetic deletion [#4]","Antibodies modestly inhibit sporozoite invasion of primary human hepatocytes [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16603573","id":"PMC_16603573","title":"Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum.","date":"2006","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/16603573","citation_count":216,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf34"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17521656","id":"PMC_17521656","title":"Plasmodium falciparum Pf34, a novel GPI-anchored rhoptry protein found in detergent-resistant microdomains.","date":"2007","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/17521656","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf34"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19837093","id":"PMC_19837093","title":"Characterization and antigenicity of the promising vaccine candidate Plasmodium vivax 34kDa rhoptry antigen (Pv34).","date":"2009","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/19837093","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf34"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20654670","id":"PMC_20654670","title":"Conserved high activity binding peptides from the Plasmodium falciparum Pf34 rhoptry protein inhibit merozoites in vitro invasion of red blood cells.","date":"2010","source":"Peptides","url":"https://pubmed.ncbi.nlm.nih.gov/20654670","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf34"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38755636","id":"PMC_38755636","title":"A screen for Plasmodium falciparum sporozoite surface protein binding to human hepatocyte surface receptors identifies novel host-pathogen interactions.","date":"2024","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/38755636","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf34"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34425378","id":"PMC_34425378","title":"Genetic diversity and expression profile of Plasmodium falciparum Pf34 gene supports its immunogenicity.","date":"2021","source":"Current research in translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34425378","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pf34"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6235,"output_tokens":1403,"usd":0.019875,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6366,"output_tokens":2131,"usd":0.042553,"stage2_stop_reason":"end_turn"},"total_usd":0.062428,"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\": 2006,\n      \"finding\": \"Pf34 (PF3D7_0419700) was experimentally confirmed to carry a glycosylphosphatidylinositol (GPI) anchor, identified by proteomic analysis of proteins labeled with radioactive glucosamine in P. falciparum schizont/merozoite stages.\",\n      \"method\": \"Radioactive glucosamine metabolic labeling followed by proteomic identification (mass spectrometry)\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct biochemical labeling with radioactive glucosamine confirmed GPI modification; replicated by subsequent studies\",\n      \"pmids\": [\"16603573\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Pf34 (PF3D7_0419700) localizes to the merozoite apex, specifically to the rhoptry neck, as determined by indirect immunofluorescence assay. It is expressed in mature asexual blood stages and is carried into the newly invaded ring stage, consistent with a role in parasitophorous vacuole formation.\",\n      \"method\": \"Indirect immunofluorescence assay (IFA) and Western blot on stage-specific parasite lysates\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by IFA with functional inference from transfer into ring stage; single lab, two complementary methods\",\n      \"pmids\": [\"17521656\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Pf34 (PF3D7_0419700) is associated with parasite-derived detergent-resistant microdomains (DRMs), indicating it resides in lipid raft-like membrane structures at the merozoite surface.\",\n      \"method\": \"Detergent-resistant microdomain (DRM) fractionation followed by Western blot\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical fractionation directly demonstrated DRM association; single lab but consistent with GPI-anchor data from independent proteomics study\",\n      \"pmids\": [\"17521656\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Peptides from the central region of Pf34 (PF3D7_0419700) bind with high affinity to protease-sensitive receptors on red blood cell surfaces and inhibit P. falciparum merozoite invasion of RBCs in vitro, suggesting Pf34 acts as an adhesin during invasion.\",\n      \"method\": \"Receptor-ligand binding assays with synthetic peptides and in vitro invasion inhibition assays\",\n      \"journal\": \"Peptides\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct receptor-ligand binding assay plus functional invasion inhibition; single lab, two orthogonal methods\",\n      \"pmids\": [\"20654670\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Pf34 (PF3D7_0419700) interacts with human fibroblast growth factor receptor 4 (FGFR4) in a plate-based protein-protein interaction screen; this interaction was biochemically characterized for affinity and blocked by a monoclonal antibody. Pf34 also interacts with the rhoptry neck protein PfRON6. Antibodies to Pf34 had a modest inhibitory effect on sporozoite invasion into primary human hepatocytes. Pf34 was refractory to attempted genetic deletion.\",\n      \"method\": \"Plate-based recombinant protein interaction screen, affinity characterization (KD measurement), monoclonal antibody blockade, sporozoite invasion inhibition assay in primary human hepatocytes\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical interaction screen with affinity measurement and functional antibody blockade; single study with multiple orthogonal methods\",\n      \"pmids\": [\"38755636\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"Pf34 (PF3D7_0419700) is a GPI-anchored, rhoptry neck protein expressed in mature P. falciparum asexual blood stages that localizes to the merozoite apex within detergent-resistant microdomains, is transferred into newly invaded rings, binds protease-sensitive receptors on red blood cells (with peptides from its central region inhibiting merozoite invasion in vitro), interacts with the host hepatocyte receptor FGFR4 and with the parasite rhoptry neck protein PfRON6, and may function as an adhesin during both merozoite and sporozoite invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Pf34 (PF3D7_0419700) is a GPI-anchored apical antigen of mature Plasmodium falciparum asexual blood stages that functions as a candidate adhesin during host-cell invasion [#0, #3]. It localizes to the merozoite apex at the rhoptry neck, resides within detergent-resistant (lipid raft-like) microdomains, and is carried forward into newly invaded ring-stage parasites [#1, #2]. Peptides from its central region bind protease-sensitive receptors on the red blood cell surface and inhibit merozoite invasion in vitro, indicating a role in the adhesive events of RBC entry [#3]. Pf34 physically interacts with the parasite rhoptry neck protein PfRON6 and with the human hepatocyte receptor FGFR4, and antibodies against Pf34 modestly inhibit sporozoite invasion of primary hepatocytes; the gene is refractory to genetic deletion [#4]. Beyond these findings, the precise molecular role of Pf34 within the invasion machinery has not been further characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that Pf34 is post-translationally modified answered whether it is membrane-associated, showing it carries a GPI anchor consistent with a surface-exposed role.\",\n      \"evidence\": \"Radioactive glucosamine metabolic labeling and mass-spectrometry identification in schizont/merozoite stages\",\n      \"pmids\": [\"16603573\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not localize the protein within the merozoite\", \"Does not define a function for the GPI-anchored protein\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Localization and biochemical fractionation addressed where Pf34 acts, placing it at the rhoptry neck within lipid raft-like microdomains and showing it is transferred into the nascent ring, implicating it in invasion/parasitophorous vacuole formation.\",\n      \"evidence\": \"Indirect immunofluorescence, stage-specific Western blot, and detergent-resistant microdomain fractionation\",\n      \"pmids\": [\"17521656\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional role inferred from transfer into rings, not tested directly\", \"Single lab; no genetic manipulation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Receptor-binding and invasion assays tested whether Pf34 engages the host cell, showing central-region peptides bind protease-sensitive RBC receptors and inhibit merozoite invasion, framing Pf34 as an invasion adhesin.\",\n      \"evidence\": \"Synthetic peptide receptor-ligand binding assays and in vitro RBC invasion inhibition\",\n      \"pmids\": [\"20654670\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"RBC receptor identity not defined\", \"Peptide binding may not reflect native full-length protein behavior\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Interaction screening extended Pf34's adhesin role across life-cycle stages, identifying binding to host FGFR4 and to parasite PfRON6, antibody-inhibitable sporozoite invasion of hepatocytes, and essentiality inferred from failed deletion.\",\n      \"evidence\": \"Plate-based recombinant protein interaction screen with affinity measurement, monoclonal antibody blockade, sporozoite invasion assay in primary human hepatocytes, and attempted gene knockout\",\n      \"pmids\": [\"38755636\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"FGFR4 interaction shown with recombinant proteins, not in vivo\", \"Sporozoite invasion inhibition was modest\", \"Refractoriness to deletion not confirmed by conditional approaches\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The native molecular function of Pf34 within the rhoptry/invasion apparatus and the identity of its RBC receptor remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No conditional knockdown to establish essentiality or invasion phenotype\", \"RBC receptor bound by central-region peptides not molecularly identified\", \"Structural basis of PfRON6 and FGFR4 interactions unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005102\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0046790\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0045121\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0046658\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfRON6\", \"FGFR4 (human, host)\"],\n    \"other_free_text\": [\n      \"GPI-anchored, confirmed by radioactive glucosamine labeling [#0]\",\n      \"Central-region peptides bind protease-sensitive RBC receptors and inhibit merozoite invasion [#3]\",\n      \"Carried into newly invaded ring stage [#1]\",\n      \"Refractory to genetic deletion [#4]\",\n      \"Antibodies modestly inhibit sporozoite invasion of primary human hepatocytes [#4]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0419700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 4 cited papers name other catalogue genes (PF3D7_0206800, PF3D7_0930300, PF3D7_0707300). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0419700","name":null,"product":"apical merozoite protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0721800","name":null,"product":"apical merozoite protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0512400","name":null,"product":"apical merozoite protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"Pf34","evaluation":null}