{"gene":"PF3D7_0415000","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2021,"finding":"PfGet3 (PF3D7_0415000) associates with a subset of predicted tail-anchored (TA) proteins in P. falciparum, as revealed by proximity labelling studies, and in vitro association studies validated direct interactions between PfGet3 and the P. falciparum homologs of Get4 and Get2, establishing PfGet3 as a component of a conserved GET pathway complex mediating post-translational membrane insertion of TA proteins.","method":"Proximity labelling (BioID), in vitro association/pulldown assays, bioinformatic prediction of TA proteins","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — proximity labelling plus in vitro association assays from a single lab; two orthogonal methods but no mutagenesis or structural validation","pmids":["34780541"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfGet3 (PF3D7_0415000) functions as the P. falciparum homolog of the GET3 ATPase, physically associating with the Get4 and Get2 homologs to form a conserved Guided Entry of Tail-Anchored (GET) pathway complex that mediates post-translational targeting of a subset of tail-anchored membrane proteins to cellular membranes in the parasite."},"narrative":{"mechanistic_narrative":"PF3D7_0415000 (GET3) is the Plasmodium falciparum homolog of the GET3 ATPase and functions as a component of a conserved Guided Entry of Tail-Anchored (GET) pathway complex that mediates post-translational membrane insertion of tail-anchored (TA) proteins in the parasite [PMID:34780541]. Proximity labelling identified an association between GET3 and a subset of predicted TA proteins, and in vitro association assays validated direct interactions with the P. falciparum homologs of Get4 and Get2, placing GET3 within a multi-subunit targeting complex [PMID:34780541]. Beyond this membership in the GET complex and its association with candidate TA-protein clients [PMID:34780541], no further mechanistic detail — including catalytic activity, structure, or the specific membranes targeted — has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"It was unknown whether P. falciparum possesses a functional GET pathway; this work established GET3 as the parasite's GET3 homolog operating within a conserved complex for tail-anchored protein targeting.","evidence":"Proximity labelling (BioID) identifying associated TA proteins plus in vitro association/pulldown assays confirming binding to the Get4 and Get2 homologs, in P. falciparum","pmids":["34780541"],"confidence":"Medium","gaps":["No mutagenesis or structural validation of the interactions","ATPase activity of GET3 not demonstrated biochemically","The specific TA-protein clients and target membranes not functionally confirmed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether GET3's ATPase activity, its structural mechanism of TA-protein capture and release, and the essentiality of the pathway for parasite viability remain uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No enzymatic characterization of the ATPase cycle","No structural model of GET3 or its complex","No loss-of-function phenotype in the parasite"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GET pathway targeting complex (with Get4 and Get2 homologs)"],"partners":["P. FALCIPARUM GET4 HOMOLOG","P. FALCIPARUM GET2 HOMOLOG","PREDICTED TAIL-ANCHORED (TA) PROTEINS"],"other_free_text":["Interactions with Get4 and Get2 homologs validated in vitro; association with TA proteins detected by proximity labelling [#0].","Catalytic ATPase activity, structure, and functional essentiality of PF3D7_0415000 remain uncharacterized in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"34780541","id":"PMC_34780541","title":"A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34780541","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GET3","PfGET3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35444689","id":"","title":"In-Silico Functional Annotation of Plasmodium falciparum Hypothetical Proteins to Identify Novel Drug Targets.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35444689","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GET3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4667,"output_tokens":414,"usd":0.010105,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4900,"output_tokens":1168,"usd":0.02685,"stage2_stop_reason":"end_turn"},"total_usd":0.036955,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"PfGet3 (PF3D7_0415000) associates with a subset of predicted tail-anchored (TA) proteins in P. falciparum, as revealed by proximity labelling studies, and in vitro association studies validated direct interactions between PfGet3 and the P. falciparum homologs of Get4 and Get2, establishing PfGet3 as a component of a conserved GET pathway complex mediating post-translational membrane insertion of TA proteins.\",\n      \"method\": \"Proximity labelling (BioID), in vitro association/pulldown assays, bioinformatic prediction of TA proteins\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — proximity labelling plus in vitro association assays from a single lab; two orthogonal methods but no mutagenesis or structural validation\",\n      \"pmids\": [\"34780541\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfGet3 (PF3D7_0415000) functions as the P. falciparum homolog of the GET3 ATPase, physically associating with the Get4 and Get2 homologs to form a conserved Guided Entry of Tail-Anchored (GET) pathway complex that mediates post-translational targeting of a subset of tail-anchored membrane proteins to cellular membranes in the parasite.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0415000 (GET3) is the Plasmodium falciparum homolog of the GET3 ATPase and functions as a component of a conserved Guided Entry of Tail-Anchored (GET) pathway complex that mediates post-translational membrane insertion of tail-anchored (TA) proteins in the parasite [#0]. Proximity labelling identified an association between GET3 and a subset of predicted TA proteins, and in vitro association assays validated direct interactions with the P. falciparum homologs of Get4 and Get2, placing GET3 within a multi-subunit targeting complex [#0]. Beyond this membership in the GET complex and its association with candidate TA-protein clients [#0], no further mechanistic detail — including catalytic activity, structure, or the specific membranes targeted — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown whether P. falciparum possesses a functional GET pathway; this work established GET3 as the parasite's GET3 homolog operating within a conserved complex for tail-anchored protein targeting.\",\n      \"evidence\": \"Proximity labelling (BioID) identifying associated TA proteins plus in vitro association/pulldown assays confirming binding to the Get4 and Get2 homologs, in P. falciparum\",\n      \"pmids\": [\"34780541\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mutagenesis or structural validation of the interactions\",\n        \"ATPase activity of GET3 not demonstrated biochemically\",\n        \"The specific TA-protein clients and target membranes not functionally confirmed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether GET3's ATPase activity, its structural mechanism of TA-protein capture and release, and the essentiality of the pathway for parasite viability remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No enzymatic characterization of the ATPase cycle\",\n        \"No structural model of GET3 or its complex\",\n        \"No loss-of-function phenotype in the parasite\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0043495\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071816\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"GET pathway targeting complex (with Get4 and Get2 homologs)\"],\n    \"partners\": [\"P. falciparum Get4 homolog\", \"P. falciparum Get2 homolog\", \"predicted tail-anchored (TA) proteins\"],\n    \"other_free_text\": [\n      \"Interactions with Get4 and Get2 homologs validated in vitro; association with TA proteins detected by proximity labelling [#0].\",\n      \"Catalytic ATPase activity, structure, and functional essentiality of PF3D7_0415000 remain uncharacterized in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0415000","name":null,"product":"ATPase GET3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0717000","name":null,"product":"arsenical pump-driving ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0506600","name":null,"product":"ATPase GET3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GET3","evaluation":null}