{"gene":"PF3D7_1438600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2021,"finding":"PF3D7_1438600 (GET4), the P. falciparum homolog of Get4, was shown by in vitro association studies to interact with PfGet3 (the P. falciparum homolog of Get3), placing GET4 as a component of the conserved Guided Entry of Tail-Anchored (GET) pathway in P. falciparum.","method":"In vitro association assay (pull-down/binding experiment) and proximity labelling (BioID-type) to identify GET pathway constituents","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, in vitro association confirmed interaction, supported by proximity labelling, but no mutagenesis or structural validation","pmids":["34780541"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1438600 (GET4) is a component of the conserved Guided Entry of Tail-Anchored (GET) protein trafficking pathway in P. falciparum, where it physically associates with PfGet3 and is implicated in the post-translational membrane insertion of tail-anchored proteins."},"narrative":{"mechanistic_narrative":"PF3D7_1438600 (GET4) is the P. falciparum homolog of Get4 and a component of the conserved Guided Entry of Tail-Anchored (GET) protein trafficking pathway, implicated in the post-translational membrane insertion of tail-anchored proteins in this parasite [PMID:34780541]. Its assignment to this pathway rests on in vitro association studies showing that GET4 physically interacts with PfGet3, the parasite homolog of the GET pathway ATPase [PMID:34780541]. Beyond this demonstrated association with PfGet3, no further mechanistic detail about GET4 itself—its structure, substrate range, or role in tail-anchored protein insertion—has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"It was unknown whether P. falciparum encodes a functional GET pathway; identifying GET4 and its binding partner established that the parasite possesses a conserved tail-anchored protein insertion machinery.","evidence":"In vitro association/pull-down assay plus proximity labelling identifying GET pathway constituents in P. falciparum","pmids":["34780541"],"confidence":"Medium","gaps":["Interaction shown by in vitro association without mutagenesis mapping the GET4–PfGet3 interface","No structural validation of GET4 or the GET4–PfGet3 complex","Functional role of GET4 in tail-anchored protein insertion not directly demonstrated in the parasite"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether GET4 is essential for tail-anchored protein targeting, which substrates it handles, and how it functions within the assembled GET complex in P. falciparum remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No loss-of-function or genetic essentiality data for GET4 in P. falciparum","No identified tail-anchored substrates trafficked via GET4","Stoichiometry and architecture of the parasite GET complex uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GET pathway (Guided Entry of Tail-Anchored proteins)"],"partners":["PFGET3 (PF3D7 HOMOLOG OF GET3)"],"other_free_text":["GET4 is a P. falciparum homolog of Get4 assigned to the GET pathway by in vitro association with PfGet3 [#0]; the corpus establishes its GET pathway membership and PfGet3 interaction but no independent function for GET4 itself."]}},"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":["GET4"],"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":["GET4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4672,"output_tokens":366,"usd":0.009753,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4839,"output_tokens":1075,"usd":0.025535,"stage2_stop_reason":"end_turn"},"total_usd":0.035288,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"PF3D7_1438600 (GET4), the P. falciparum homolog of Get4, was shown by in vitro association studies to interact with PfGet3 (the P. falciparum homolog of Get3), placing GET4 as a component of the conserved Guided Entry of Tail-Anchored (GET) pathway in P. falciparum.\",\n      \"method\": \"In vitro association assay (pull-down/binding experiment) and proximity labelling (BioID-type) to identify GET pathway constituents\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, in vitro association confirmed interaction, supported by proximity labelling, 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\": \"PF3D7_1438600 (GET4) is a component of the conserved Guided Entry of Tail-Anchored (GET) protein trafficking pathway in P. falciparum, where it physically associates with PfGet3 and is implicated in the post-translational membrane insertion of tail-anchored proteins.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1438600 (GET4) is the P. falciparum homolog of Get4 and a component of the conserved Guided Entry of Tail-Anchored (GET) protein trafficking pathway, implicated in the post-translational membrane insertion of tail-anchored proteins in this parasite [#0]. Its assignment to this pathway rests on in vitro association studies showing that GET4 physically interacts with PfGet3, the parasite homolog of the GET pathway ATPase [#0]. Beyond this demonstrated association with PfGet3, no further mechanistic detail about GET4 itself—its structure, substrate range, or role in tail-anchored protein insertion—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown whether P. falciparum encodes a functional GET pathway; identifying GET4 and its binding partner established that the parasite possesses a conserved tail-anchored protein insertion machinery.\",\n      \"evidence\": \"In vitro association/pull-down assay plus proximity labelling identifying GET pathway constituents in P. falciparum\",\n      \"pmids\": [\"34780541\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction shown by in vitro association without mutagenesis mapping the GET4–PfGet3 interface\",\n        \"No structural validation of GET4 or the GET4–PfGet3 complex\",\n        \"Functional role of GET4 in tail-anchored protein insertion not directly demonstrated in the parasite\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether GET4 is essential for tail-anchored protein targeting, which substrates it handles, and how it functions within the assembled GET complex in P. falciparum remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No loss-of-function or genetic essentiality data for GET4 in P. falciparum\",\n        \"No identified tail-anchored substrates trafficked via GET4\",\n        \"Stoichiometry and architecture of the parasite GET complex uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071816\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"GET pathway (Guided Entry of Tail-Anchored proteins)\"],\n    \"partners\": [\"PfGet3 (PF3D7 homolog of Get3)\"],\n    \"other_free_text\": [\n      \"GET4 is a P. falciparum homolog of Get4 assigned to the GET pathway by in vitro association with PfGet3 [#0]; the corpus establishes its GET pathway membership and PfGet3 interaction but no independent function for GET4 itself.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1438600","name":null,"product":"Golgi to ER traffic protein 4","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1302500","name":null,"product":"conserved protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1243800","name":null,"product":"Golgi to ER traffic protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GET4","evaluation":null}