{"gene":"PF3D7_1423800","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2013,"finding":"VPS3 (PF3D7_1423800) was identified as a subunit of the CORVET complex with an ancient pan-eukaryotic origin; bioinformatic analysis across twelve apicomplexan genomes demonstrated that VPS3 is conserved in Plasmodium falciparum as part of the CORVET/HOPS VpsC-associated machinery, and that those subunits identified appear to be expressed with similar patterns to fully conserved MTC proteins, suggesting function as minimal complexes or with analogous partners.","method":"Comparative genomic/bioinformatic analysis across twelve apicomplexan genomes and outgroup taxa","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic prediction only, no direct biochemical or genetic experiment performed on VPS3 protein itself","pmids":["24086721"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"VPS3 (PF3D7_1423800), the CORVET-specific component, was identified as an interactor of PfVps16 (the P. falciparum ortholog of Vps16) by immunoprecipitation followed by mass spectrometry, placing VPS3 within the P. falciparum Vps-C tethering complex.","method":"Immunoprecipitation and mass spectrometry (co-IP/MS)","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, co-IP/MS is a single method but mass spectrometry provides confident identification; no reciprocal pull-down or functional mutagenesis reported in the abstract","pmids":["40626728"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"VPS3 (PF3D7_1423800) is a conserved CORVET-specific component in P. falciparum that physically associates with the Vps-C core complex (including PfVps16) as demonstrated by co-immunoprecipitation and mass spectrometry, implicating it in the parasite's endosomal vesicle tethering machinery, though its precise functional role beyond complex membership has not been experimentally established."},"narrative":{"mechanistic_narrative":"VPS3 (PF3D7_1423800) is a CORVET-specific component of the Vps-C endosomal tethering machinery in Plasmodium falciparum [PMID:40626728]. It was first recognized through comparative genomics as an ancient, pan-eukaryotically conserved CORVET/HOPS-associated subunit retained across apicomplexan genomes, expressed in patterns consistent with functioning as part of a minimal multisubunit tethering complex [PMID:24086721]. Direct biochemical evidence places VPS3 within the parasite's Vps-C complex: immunoprecipitation and mass spectrometry identified it as an interactor of PfVps16, the P. falciparum ortholog of the Vps16 core subunit [PMID:40626728]. Beyond its physical membership in this complex, the specific molecular function, substrates, and cellular role of VPS3 itself have not been experimentally characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing whether the CORVET tethering machinery is conserved in apicomplexans was the first question; comparative genomics showed VPS3 is retained as an ancient, conserved Vps-C-associated subunit in P. falciparum, framing it as candidate endosomal machinery.","evidence":"Comparative genomic/bioinformatic analysis across twelve apicomplexan genomes and outgroup taxa","pmids":["24086721"],"confidence":"Low","gaps":["Bioinformatic prediction only; no biochemical or genetic experiment performed on the VPS3 protein","Complex membership inferred from conservation, not demonstrated in the parasite","No localization or interaction data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether VPS3 physically resides in the parasite Vps-C complex, rather than merely being predicted to, was addressed by pulling it down alongside a core subunit, providing the first direct biochemical placement within the tethering machinery.","evidence":"Immunoprecipitation and mass spectrometry identifying VPS3 as a PfVps16 interactor","pmids":["40626728"],"confidence":"Medium","gaps":["Single method (co-IP/MS) without reciprocal pull-down validation","No functional mutagenesis, knockdown, or knockout to test VPS3's role","Whether VPS3 defines a CORVET versus HOPS assignment functionally is not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular function of VPS3 beyond complex membership remains unknown, including its contribution to vesicle tethering, essentiality, and cellular localization in the parasite.","evidence":"No direct functional experiment on VPS3 present in the corpus","pmids":[],"confidence":"Low","gaps":["No genetic loss-of-function phenotype for VPS3","No subcellular localization data for VPS3","No defined role in a specific endosomal trafficking pathway"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CORVET complex","Vps-C core tethering complex"],"partners":["PFVPS16"],"other_free_text":["Identified as a CORVET-specific subunit conserved across apicomplexans [#0].","Physically associates with the Vps-C tethering complex via interaction with PfVps16, shown by co-IP/MS [#1].","No functional role for VPS3 beyond complex membership has been experimentally established in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24086721","id":"PMC_24086721","title":"Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24086721","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40626728","id":"PMC_40626728","title":"The Plasmodium falciparum homolog of Vps16 interacts with the core members of the Vps-C tethering complex.","date":"2025","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/40626728","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4248,"output_tokens":675,"usd":0.011435,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5284,"output_tokens":1463,"usd":0.031497,"stage2_stop_reason":"end_turn"},"total_usd":0.042932,"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\": 2013,\n      \"finding\": \"VPS3 (PF3D7_1423800) was identified as a subunit of the CORVET complex with an ancient pan-eukaryotic origin; bioinformatic analysis across twelve apicomplexan genomes demonstrated that VPS3 is conserved in Plasmodium falciparum as part of the CORVET/HOPS VpsC-associated machinery, and that those subunits identified appear to be expressed with similar patterns to fully conserved MTC proteins, suggesting function as minimal complexes or with analogous partners.\",\n      \"method\": \"Comparative genomic/bioinformatic analysis across twelve apicomplexan genomes and outgroup taxa\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic prediction only, no direct biochemical or genetic experiment performed on VPS3 protein itself\",\n      \"pmids\": [\"24086721\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VPS3 (PF3D7_1423800), the CORVET-specific component, was identified as an interactor of PfVps16 (the P. falciparum ortholog of Vps16) by immunoprecipitation followed by mass spectrometry, placing VPS3 within the P. falciparum Vps-C tethering complex.\",\n      \"method\": \"Immunoprecipitation and mass spectrometry (co-IP/MS)\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, co-IP/MS is a single method but mass spectrometry provides confident identification; no reciprocal pull-down or functional mutagenesis reported in the abstract\",\n      \"pmids\": [\"40626728\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"VPS3 (PF3D7_1423800) is a conserved CORVET-specific component in P. falciparum that physically associates with the Vps-C core complex (including PfVps16) as demonstrated by co-immunoprecipitation and mass spectrometry, implicating it in the parasite's endosomal vesicle tethering machinery, though its precise functional role beyond complex membership has not been experimentally established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"VPS3 (PF3D7_1423800) is a CORVET-specific component of the Vps-C endosomal tethering machinery in Plasmodium falciparum [#1]. It was first recognized through comparative genomics as an ancient, pan-eukaryotically conserved CORVET/HOPS-associated subunit retained across apicomplexan genomes, expressed in patterns consistent with functioning as part of a minimal multisubunit tethering complex [#0]. Direct biochemical evidence places VPS3 within the parasite's Vps-C complex: immunoprecipitation and mass spectrometry identified it as an interactor of PfVps16, the P. falciparum ortholog of the Vps16 core subunit [#1]. Beyond its physical membership in this complex, the specific molecular function, substrates, and cellular role of VPS3 itself have not been experimentally characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing whether the CORVET tethering machinery is conserved in apicomplexans was the first question; comparative genomics showed VPS3 is retained as an ancient, conserved Vps-C-associated subunit in P. falciparum, framing it as candidate endosomal machinery.\",\n      \"evidence\": \"Comparative genomic/bioinformatic analysis across twelve apicomplexan genomes and outgroup taxa\",\n      \"pmids\": [\"24086721\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Bioinformatic prediction only; no biochemical or genetic experiment performed on the VPS3 protein\",\n        \"Complex membership inferred from conservation, not demonstrated in the parasite\",\n        \"No localization or interaction data\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether VPS3 physically resides in the parasite Vps-C complex, rather than merely being predicted to, was addressed by pulling it down alongside a core subunit, providing the first direct biochemical placement within the tethering machinery.\",\n      \"evidence\": \"Immunoprecipitation and mass spectrometry identifying VPS3 as a PfVps16 interactor\",\n      \"pmids\": [\"40626728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method (co-IP/MS) without reciprocal pull-down validation\",\n        \"No functional mutagenesis, knockdown, or knockout to test VPS3's role\",\n        \"Whether VPS3 defines a CORVET versus HOPS assignment functionally is not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function of VPS3 beyond complex membership remains unknown, including its contribution to vesicle tethering, essentiality, and cellular localization in the parasite.\",\n      \"evidence\": \"No direct functional experiment on VPS3 present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic loss-of-function phenotype for VPS3\",\n        \"No subcellular localization data for VPS3\",\n        \"No defined role in a specific endosomal trafficking pathway\"\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:0006886\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"CORVET complex\",\n      \"Vps-C core tethering complex\"\n    ],\n    \"partners\": [\n      \"PfVps16\"\n    ],\n    \"other_free_text\": [\n      \"Identified as a CORVET-specific subunit conserved across apicomplexans [#0].\",\n      \"Physically associates with the Vps-C tethering complex via interaction with PfVps16, shown by co-IP/MS [#1].\",\n      \"No functional role for VPS3 beyond complex membership has been experimentally established in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1423800","name":null,"product":"vacuolar protein sorting-associated protein 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1019600","name":null,"product":"vacuolar protein sorting-associated protein 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1334200","name":null,"product":"vacuolar protein sorting-associated protein 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"VPS3","evaluation":null}