{"gene":"PF3D7_1406700","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2014,"finding":"VPS29, as a component of the retromer complex in P. falciparum, co-localizes with Rab7 to a small number of punctate endosomal structures that are distinct from the Golgi apparatus (retromer does not redistribute to the ER upon brefeldin A treatment), lie in close proximity to the Golgi, are inherited by daughter merozoites, and develop adjacent to nascent rhoptries, suggesting a role for the retromer/endosome in rhoptry biogenesis and retrograde transport of PfSortilin from the endosome to the Golgi apparatus.","method":"Fluorescence co-localization microscopy, brefeldin A treatment, subcellular fractionation/immunofluorescence","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence (BFA treatment, co-localization with Rab7 and proximity to rhoptries), single lab but multiple orthogonal approaches","pmids":["24587025"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Recombinant P. falciparum VPS29 (PfVPS29) was expressed as a tag-free protein, found to be monomeric in solution by dynamic light scattering, chemical cross-linking, and size exclusion chromatography, and localizes to the cytoplasm of intraerythrocytic parasites; expression is detected from early trophozoite through schizont stages with maximum levels in the trophozoite stage.","method":"Recombinant protein expression and purification, MALDI-TOF mass spectrometry, circular dichroism spectroscopy, dynamic light scattering, chemical cross-linking, size exclusion chromatography, western blot, confocal immunofluorescence microscopy","journal":"Protein expression and purification","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal biophysical methods confirming monomeric state and direct localization experiment, single lab","pmids":["26690372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"VPS29 assembles into the retromer complex in P. falciparum asexual blood stages, as demonstrated by Surface Plasmon Resonance immunosensing that captured multiple retromer subunits from native parasite cell lysate using antibodies against individual components including VPS29.","method":"Surface Plasmon Resonance (SPR) immunosensing with subunit-specific antibodies on native parasite lysate","journal":"Biochimica et biophysica acta. Proteins and proteomics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — novel SPR-based co-complex detection from native lysate, single lab, single method","pmids":["29654975"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum VPS29 is a monomeric cytoplasmic subunit of the retromer complex that assembles with other retromer components in asexual blood stages and localizes to discrete endosomal puncta adjacent to the Golgi apparatus and nascent rhoptries, consistent with a role in retrograde endosome-to-Golgi protein sorting (including recycling of PfSortilin) and potentially in rhoptry biogenesis."},"narrative":{"mechanistic_narrative":"PF3D7_1406700 (VPS29) is a subunit of the retromer complex in Plasmodium falciparum asexual blood stages, where it is implicated in retrograde endosome-to-Golgi protein sorting and, potentially, rhoptry biogenesis [PMID:24587025, PMID:29654975]. As a retromer component, VPS29 co-localizes with Rab7 at a small number of punctate endosomal structures that lie close to but are distinct from the Golgi (the retromer does not redistribute to the ER upon brefeldin A treatment), are inherited by daughter merozoites, and develop adjacent to nascent rhoptries, linking the endosome/retromer to retrograde transport of PfSortilin from the endosome to the Golgi [PMID:24587025]. Native-lysate immunocapture confirms that VPS29 physically assembles with other retromer subunits [PMID:29654975]. Recombinant PfVPS29 is monomeric in solution and cytoplasmic in intraerythrocytic parasites, with expression from early trophozoite through schizont stages and peaking at the trophozoite stage [PMID:26690372]. Beyond its membership in the retromer complex and this localization/expression profile, no further gene-specific mechanistic detail for VPS29 (e.g. direct binding interfaces, catalytic activity, or genetic loss-of-function phenotype) has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing where the P. falciparum retromer resides addressed whether VPS29-containing retromer marks a defined endosomal compartment and links it to specific trafficking and organelle-biogenesis roles.","evidence":"Fluorescence co-localization with Rab7, brefeldin A treatment, and subcellular fractionation/immunofluorescence in P. falciparum","pmids":["24587025"],"confidence":"Medium","gaps":["Does not demonstrate VPS29-specific (versus whole-complex) contribution to PfSortilin recycling","Rhoptry-biogenesis role is inferred from proximity, not from functional perturbation of VPS29","No genetic knockdown/knockout of VPS29 to test necessity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Biophysical characterization of recombinant PfVPS29 answered its oligomeric state and cellular distribution, defining it as a monomeric cytoplasmic protein with a stage-dependent expression peak.","evidence":"Recombinant expression/purification with DLS, chemical cross-linking, size-exclusion chromatography, CD, and confocal immunofluorescence across blood stages","pmids":["26690372"],"confidence":"Medium","gaps":["Monomeric state shown for the isolated recombinant protein, not within the assembled complex in vivo","No structural model or defined binding surfaces for retromer partners","Cytoplasmic signal not resolved against the endosomal puncta seen in the retromer context"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Direct detection of retromer subunits captured via VPS29-specific antibodies from native lysate confirmed that VPS29 physically participates in the assembled retromer complex in vivo, not merely by co-localization.","evidence":"Surface Plasmon Resonance immunosensing with subunit-specific antibodies on native P. falciparum lysate","pmids":["29654975"],"confidence":"Medium","gaps":["Single method, single lab; no reciprocal or reconstituted validation of the VPS29 interface","Does not define stoichiometry or which subunits VPS29 contacts directly","Complex assembly not linked to a functional readout"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether VPS29 is individually required for retrograde PfSortilin sorting, rhoptry biogenesis, or parasite viability remains unresolved.","evidence":"No VPS29-specific loss-of-function or structural interaction study is present in the corpus","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown of VPS29","No direct demonstration of VPS29-dependent cargo sorting","No structure defining VPS29 contacts within the retromer"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["retromer complex"],"partners":["RAB7","PFSORTILIN"],"other_free_text":["VPS29 is a monomeric protein in solution (DLS, cross-linking, SEC) [#1]","Expressed from early trophozoite through schizont stages, peaking at the trophozoite stage [#1]","Retromer puncta develop adjacent to nascent rhoptries and are inherited by daughter merozoites, suggesting a possible role in rhoptry biogenesis [#0]","Retromer does not redistribute to the ER upon brefeldin A treatment [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24587025","id":"PMC_24587025","title":"Evidence for a Golgi-to-endosome protein sorting pathway in Plasmodium falciparum.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24587025","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26690372","id":"PMC_26690372","title":"Expression, purification and characterization of Plasmodium falciparum vacuolar protein sorting 29.","date":"2015","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/26690372","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS29","PfVPS29"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29654975","id":"PMC_29654975","title":"Detection of retromer assembly in Plasmodium falciparum by immunosensing coupled to Surface Plasmon Resonance.","date":"2018","source":"Biochimica et biophysica acta. Proteins and proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/29654975","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42515018","id":"PMC_42515018","title":"Antibody Responses to the Conserved Plasmodium falciparum Vacuolar Sorting Protein 29 in the Brazilian Amazon.","date":"2026","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/42515018","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS29","PfVPS29"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4935,"output_tokens":983,"usd":0.014775,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5744,"output_tokens":2034,"usd":0.039785,"stage2_stop_reason":"end_turn"},"total_usd":0.05456,"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\": 2014,\n      \"finding\": \"VPS29, as a component of the retromer complex in P. falciparum, co-localizes with Rab7 to a small number of punctate endosomal structures that are distinct from the Golgi apparatus (retromer does not redistribute to the ER upon brefeldin A treatment), lie in close proximity to the Golgi, are inherited by daughter merozoites, and develop adjacent to nascent rhoptries, suggesting a role for the retromer/endosome in rhoptry biogenesis and retrograde transport of PfSortilin from the endosome to the Golgi apparatus.\",\n      \"method\": \"Fluorescence co-localization microscopy, brefeldin A treatment, subcellular fractionation/immunofluorescence\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence (BFA treatment, co-localization with Rab7 and proximity to rhoptries), single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"24587025\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Recombinant P. falciparum VPS29 (PfVPS29) was expressed as a tag-free protein, found to be monomeric in solution by dynamic light scattering, chemical cross-linking, and size exclusion chromatography, and localizes to the cytoplasm of intraerythrocytic parasites; expression is detected from early trophozoite through schizont stages with maximum levels in the trophozoite stage.\",\n      \"method\": \"Recombinant protein expression and purification, MALDI-TOF mass spectrometry, circular dichroism spectroscopy, dynamic light scattering, chemical cross-linking, size exclusion chromatography, western blot, confocal immunofluorescence microscopy\",\n      \"journal\": \"Protein expression and purification\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal biophysical methods confirming monomeric state and direct localization experiment, single lab\",\n      \"pmids\": [\"26690372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"VPS29 assembles into the retromer complex in P. falciparum asexual blood stages, as demonstrated by Surface Plasmon Resonance immunosensing that captured multiple retromer subunits from native parasite cell lysate using antibodies against individual components including VPS29.\",\n      \"method\": \"Surface Plasmon Resonance (SPR) immunosensing with subunit-specific antibodies on native parasite lysate\",\n      \"journal\": \"Biochimica et biophysica acta. Proteins and proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — novel SPR-based co-complex detection from native lysate, single lab, single method\",\n      \"pmids\": [\"29654975\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum VPS29 is a monomeric cytoplasmic subunit of the retromer complex that assembles with other retromer components in asexual blood stages and localizes to discrete endosomal puncta adjacent to the Golgi apparatus and nascent rhoptries, consistent with a role in retrograde endosome-to-Golgi protein sorting (including recycling of PfSortilin) and potentially in rhoptry biogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1406700 (VPS29) is a subunit of the retromer complex in Plasmodium falciparum asexual blood stages, where it is implicated in retrograde endosome-to-Golgi protein sorting and, potentially, rhoptry biogenesis [#0, #2]. As a retromer component, VPS29 co-localizes with Rab7 at a small number of punctate endosomal structures that lie close to but are distinct from the Golgi (the retromer does not redistribute to the ER upon brefeldin A treatment), are inherited by daughter merozoites, and develop adjacent to nascent rhoptries, linking the endosome/retromer to retrograde transport of PfSortilin from the endosome to the Golgi [#0]. Native-lysate immunocapture confirms that VPS29 physically assembles with other retromer subunits [#2]. Recombinant PfVPS29 is monomeric in solution and cytoplasmic in intraerythrocytic parasites, with expression from early trophozoite through schizont stages and peaking at the trophozoite stage [#1]. Beyond its membership in the retromer complex and this localization/expression profile, no further gene-specific mechanistic detail for VPS29 (e.g. direct binding interfaces, catalytic activity, or genetic loss-of-function phenotype) has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing where the P. falciparum retromer resides addressed whether VPS29-containing retromer marks a defined endosomal compartment and links it to specific trafficking and organelle-biogenesis roles.\",\n      \"evidence\": \"Fluorescence co-localization with Rab7, brefeldin A treatment, and subcellular fractionation/immunofluorescence in P. falciparum\",\n      \"pmids\": [\"24587025\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not demonstrate VPS29-specific (versus whole-complex) contribution to PfSortilin recycling\",\n        \"Rhoptry-biogenesis role is inferred from proximity, not from functional perturbation of VPS29\",\n        \"No genetic knockdown/knockout of VPS29 to test necessity\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Biophysical characterization of recombinant PfVPS29 answered its oligomeric state and cellular distribution, defining it as a monomeric cytoplasmic protein with a stage-dependent expression peak.\",\n      \"evidence\": \"Recombinant expression/purification with DLS, chemical cross-linking, size-exclusion chromatography, CD, and confocal immunofluorescence across blood stages\",\n      \"pmids\": [\"26690372\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Monomeric state shown for the isolated recombinant protein, not within the assembled complex in vivo\",\n        \"No structural model or defined binding surfaces for retromer partners\",\n        \"Cytoplasmic signal not resolved against the endosomal puncta seen in the retromer context\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Direct detection of retromer subunits captured via VPS29-specific antibodies from native lysate confirmed that VPS29 physically participates in the assembled retromer complex in vivo, not merely by co-localization.\",\n      \"evidence\": \"Surface Plasmon Resonance immunosensing with subunit-specific antibodies on native P. falciparum lysate\",\n      \"pmids\": [\"29654975\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method, single lab; no reciprocal or reconstituted validation of the VPS29 interface\",\n        \"Does not define stoichiometry or which subunits VPS29 contacts directly\",\n        \"Complex assembly not linked to a functional readout\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether VPS29 is individually required for retrograde PfSortilin sorting, rhoptry biogenesis, or parasite viability remains unresolved.\",\n      \"evidence\": \"No VPS29-specific loss-of-function or structural interaction study is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout/knockdown of VPS29\",\n        \"No direct demonstration of VPS29-dependent cargo sorting\",\n        \"No structure defining VPS29 contacts within the retromer\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0010008\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042147\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"retromer complex\"],\n    \"partners\": [\"Rab7\", \"PfSortilin\"],\n    \"other_free_text\": [\n      \"VPS29 is a monomeric protein in solution (DLS, cross-linking, SEC) [#1]\",\n      \"Expressed from early trophozoite through schizont stages, peaking at the trophozoite stage [#1]\",\n      \"Retromer puncta develop adjacent to nascent rhoptries and are inherited by daughter merozoites, suggesting a possible role in rhoptry biogenesis [#0]\",\n      \"Retromer does not redistribute to the ER upon brefeldin A treatment [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1406700","name":null,"product":"vacuolar protein sorting-associated protein 29","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1035500","name":null,"product":"vacuolar protein sorting-associated protein 29, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1351400","name":null,"product":"vacuolar protein sorting-associated protein 29, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"VPS29","evaluation":null}