{"gene":"PF3D7_0502000","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2025,"finding":"PF3D7_0502000 (VPS11/PfVps11) is a member of the Vps-C core complex in P. falciparum; immunoprecipitation and mass spectrometry of PfVps16 confirmed that VPS11 co-purifies with all canonical Vps-C complex members (Vps16, Vps18, Vps33) as well as the Vps3 CORVET component, establishing VPS11's membership in this tethering complex.","method":"Immunoprecipitation followed by mass spectrometry (PfVps16 as bait)","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal-style Co-IP with MS, single lab, single study; VPS11 detected as interactor but bait was Vps16, not VPS11 itself","pmids":["40626728"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"VPS11 (PF3D7_0502000) protein forms a 4-HNE (4-hydroxynonenal) adduct in P. falciparum parasites treated with the pro-oxidant endoperoxide plakortin, with specific binding sites identified by mass spectrometry, indicating the protein is susceptible to oxidative modification under antimalarial drug-induced oxidative stress.","method":"Mass spectrometry identification of 4-HNE protein conjugates","journal":"Free radical biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single MS identification of a post-translational adduct, no functional validation of the modification on VPS11 activity","pmids":["26459031"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"VPS11 (PF3D7_0502000) is identified bioinformatically as part of the conserved VpsC core of the HOPS and CORVET complexes in P. falciparum and other apicomplexan genomes, indicating excellent conservation of this subunit relative to other MTC components that are lost in Apicomplexa.","method":"Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — computational/bioinformatic prediction only, no direct experimental validation of VPS11 function or interactions","pmids":["24086721"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0502000 (VPS11) is a conserved subunit of the Vps-C core tethering complex in P. falciparum, co-purifying with PfVps16, PfVps18, PfVps33, and the CORVET component Vps3, implicating it in endolysosomal vesicle tethering and potentially in the biogenesis of apical complex organelles, though no direct functional experiments on VPS11 itself have been reported."},"narrative":{"mechanistic_narrative":"PF3D7_0502000 (VPS11) is a conserved subunit of the Vps-C core tethering machinery in Plasmodium falciparum [PMID:40626728, PMID:24086721]. Co-immunoprecipitation of PfVps16 followed by mass spectrometry established that VPS11 co-purifies with the canonical Vps-C members Vps16, Vps18, and Vps33, together with the CORVET-specific component Vps3, placing VPS11 within this membrane-tethering complex [PMID:40626728]. Comparative genomic analysis across apicomplexan genomes shows VPS11 is one of the well-conserved Vps-C core subunits shared by the HOPS and CORVET complexes, in contrast to other multisubunit tethering components lost in Apicomplexa [PMID:24086721]. VPS11 is also susceptible to oxidative post-translational modification, forming 4-HNE adducts at defined sites under plakortin-induced oxidative stress [PMID:26459031]. Beyond its assignment to the Vps-C complex by interaction and sequence conservation, no direct functional experiments on VPS11 itself — such as knockdown, knockout, or activity assays — have been reported in the available corpus.","teleology":[{"year":2013,"claim":"Before experimental interrogation, it was unknown whether the Vps-C tethering machinery is conserved in Apicomplexa; bioinformatic analysis established that VPS11 is a retained core subunit, marking it as a candidate component of Plasmodium endolysosomal trafficking.","evidence":"Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes","pmids":["24086721"],"confidence":"Low","gaps":["Computational prediction only, with no experimental validation of VPS11 expression, interactions, or function","Does not establish which complex (HOPS vs CORVET) VPS11 participates in physiologically","No subcellular localization for VPS11"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"It was unknown whether VPS11 is a target of antimalarial-induced oxidative stress; identification of site-specific 4-HNE adducts showed the protein is chemically modified under pro-oxidant drug treatment.","evidence":"Mass spectrometry identification of 4-HNE protein conjugates in plakortin-treated parasites","pmids":["26459031"],"confidence":"Low","gaps":["No functional consequence of the modification on VPS11 activity or complex assembly demonstrated","Does not establish whether oxidative modification of VPS11 contributes to the drug's mechanism of action","Single MS identification without independent confirmation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The predicted membership of VPS11 in the Vps-C core needed experimental confirmation; Co-IP/MS with PfVps16 as bait showed VPS11 co-purifies with all canonical Vps-C members and the CORVET component Vps3, confirming its incorporation into the tethering complex.","evidence":"Immunoprecipitation of PfVps16 followed by mass spectrometry","pmids":["40626728"],"confidence":"Medium","gaps":["Bait was Vps16, not VPS11 itself, so no VPS11-directed reciprocal validation was performed","Single lab, single study","Does not distinguish VPS11's specific contribution to HOPS versus CORVET function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"No direct functional experiment on VPS11 itself has been performed; its cellular role, essentiality, tethering activity, and contribution to specific trafficking pathways in P. falciparum remain uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No VPS11 knockout, knockdown, or conditional-depletion phenotype reported","No VPS11-directed localization or structural data","Role of VPS11 in endolysosomal or apical-organelle biogenesis untested experimentally"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Vps-C core complex (with PfVps16, PfVps18, PfVps33) [#0]","CORVET complex (co-purifies with Vps3 component) [#0]","HOPS/CORVET VpsC core (conserved subunit) [#2]"],"partners":["PFVPS16 [#0]","PFVPS18 [#0]","PFVPS33 [#0]","VPS3 (CORVET) [#0]"],"other_free_text":["Forms site-specific 4-HNE (4-hydroxynonenal) adducts under plakortin-induced oxidative stress [#1]","One of the well-conserved Vps-C core subunits retained across apicomplexan genomes [#2]","No direct functional (knockout/knockdown/activity) experiment on VPS11 itself reported in the 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":"26459031","id":"PMC_26459031","title":"Oxidative stress-mediated antimalarial activity of plakortin, a natural endoperoxide from the tropical sponge Plakortis simplex.","date":"2015","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26459031","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["vacuolar protein sorting-associated protein 11"],"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":["VPS11"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4891,"output_tokens":933,"usd":0.014334,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5596,"output_tokens":1969,"usd":0.038602,"stage2_stop_reason":"end_turn"},"total_usd":0.052936,"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\": 2025,\n      \"finding\": \"PF3D7_0502000 (VPS11/PfVps11) is a member of the Vps-C core complex in P. falciparum; immunoprecipitation and mass spectrometry of PfVps16 confirmed that VPS11 co-purifies with all canonical Vps-C complex members (Vps16, Vps18, Vps33) as well as the Vps3 CORVET component, establishing VPS11's membership in this tethering complex.\",\n      \"method\": \"Immunoprecipitation followed by mass spectrometry (PfVps16 as bait)\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal-style Co-IP with MS, single lab, single study; VPS11 detected as interactor but bait was Vps16, not VPS11 itself\",\n      \"pmids\": [\"40626728\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"VPS11 (PF3D7_0502000) protein forms a 4-HNE (4-hydroxynonenal) adduct in P. falciparum parasites treated with the pro-oxidant endoperoxide plakortin, with specific binding sites identified by mass spectrometry, indicating the protein is susceptible to oxidative modification under antimalarial drug-induced oxidative stress.\",\n      \"method\": \"Mass spectrometry identification of 4-HNE protein conjugates\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single MS identification of a post-translational adduct, no functional validation of the modification on VPS11 activity\",\n      \"pmids\": [\"26459031\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"VPS11 (PF3D7_0502000) is identified bioinformatically as part of the conserved VpsC core of the HOPS and CORVET complexes in P. falciparum and other apicomplexan genomes, indicating excellent conservation of this subunit relative to other MTC components that are lost in Apicomplexa.\",\n      \"method\": \"Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — computational/bioinformatic prediction only, no direct experimental validation of VPS11 function or interactions\",\n      \"pmids\": [\"24086721\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0502000 (VPS11) is a conserved subunit of the Vps-C core tethering complex in P. falciparum, co-purifying with PfVps16, PfVps18, PfVps33, and the CORVET component Vps3, implicating it in endolysosomal vesicle tethering and potentially in the biogenesis of apical complex organelles, though no direct functional experiments on VPS11 itself have been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0502000 (VPS11) is a conserved subunit of the Vps-C core tethering machinery in Plasmodium falciparum [#0, #2]. Co-immunoprecipitation of PfVps16 followed by mass spectrometry established that VPS11 co-purifies with the canonical Vps-C members Vps16, Vps18, and Vps33, together with the CORVET-specific component Vps3, placing VPS11 within this membrane-tethering complex [#0]. Comparative genomic analysis across apicomplexan genomes shows VPS11 is one of the well-conserved Vps-C core subunits shared by the HOPS and CORVET complexes, in contrast to other multisubunit tethering components lost in Apicomplexa [#2]. VPS11 is also susceptible to oxidative post-translational modification, forming 4-HNE adducts at defined sites under plakortin-induced oxidative stress [#1]. Beyond its assignment to the Vps-C complex by interaction and sequence conservation, no direct functional experiments on VPS11 itself — such as knockdown, knockout, or activity assays — have been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Before experimental interrogation, it was unknown whether the Vps-C tethering machinery is conserved in Apicomplexa; bioinformatic analysis established that VPS11 is a retained core subunit, marking it as a candidate component of Plasmodium endolysosomal trafficking.\",\n      \"evidence\": \"Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes\",\n      \"pmids\": [\"24086721\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, with no experimental validation of VPS11 expression, interactions, or function\",\n        \"Does not establish which complex (HOPS vs CORVET) VPS11 participates in physiologically\",\n        \"No subcellular localization for VPS11\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unknown whether VPS11 is a target of antimalarial-induced oxidative stress; identification of site-specific 4-HNE adducts showed the protein is chemically modified under pro-oxidant drug treatment.\",\n      \"evidence\": \"Mass spectrometry identification of 4-HNE protein conjugates in plakortin-treated parasites\",\n      \"pmids\": [\"26459031\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional consequence of the modification on VPS11 activity or complex assembly demonstrated\",\n        \"Does not establish whether oxidative modification of VPS11 contributes to the drug's mechanism of action\",\n        \"Single MS identification without independent confirmation\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The predicted membership of VPS11 in the Vps-C core needed experimental confirmation; Co-IP/MS with PfVps16 as bait showed VPS11 co-purifies with all canonical Vps-C members and the CORVET component Vps3, confirming its incorporation into the tethering complex.\",\n      \"evidence\": \"Immunoprecipitation of PfVps16 followed by mass spectrometry\",\n      \"pmids\": [\"40626728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Bait was Vps16, not VPS11 itself, so no VPS11-directed reciprocal validation was performed\",\n        \"Single lab, single study\",\n        \"Does not distinguish VPS11's specific contribution to HOPS versus CORVET function\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No direct functional experiment on VPS11 itself has been performed; its cellular role, essentiality, tethering activity, and contribution to specific trafficking pathways in P. falciparum remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No VPS11 knockout, knockdown, or conditional-depletion phenotype reported\",\n        \"No VPS11-directed localization or structural data\",\n        \"Role of VPS11 in endolysosomal or apical-organelle biogenesis untested experimentally\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\n      \"Vps-C core complex (with PfVps16, PfVps18, PfVps33) [#0]\",\n      \"CORVET complex (co-purifies with Vps3 component) [#0]\",\n      \"HOPS/CORVET VpsC core (conserved subunit) [#2]\"\n    ],\n    \"partners\": [\n      \"PfVps16 [#0]\",\n      \"PfVps18 [#0]\",\n      \"PfVps33 [#0]\",\n      \"Vps3 (CORVET) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Forms site-specific 4-HNE (4-hydroxynonenal) adducts under plakortin-induced oxidative stress [#1]\",\n      \"One of the well-conserved Vps-C core subunits retained across apicomplexan genomes [#2]\",\n      \"No direct functional (knockout/knockdown/activity) experiment on VPS11 itself reported in the corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0502000","name":null,"product":"vacuolar protein sorting-associated protein 11, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1101800","name":null,"product":"vacuolar protein sorting-associated protein 11, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1031900","name":null,"product":"vacuolar protein sorting-associated protein 11, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"VPS11","evaluation":null}