{"gene":"PF3D7_0903200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2013,"finding":"In P. falciparum, RAB7 (PfRAB7)-labeled vesicles showed increased colocalization with PfATG8-positive autophagosomes upon amino acid starvation, and the co-labeled structures became acidified, consistent with RAB7-mediated maturation of autophagosomes; immuno-electron microscopy detected RAB7 on double-membrane-bound vesicles and near/within the food vacuole, supporting a role for RAB7 in routing autophagosomes to the endosomal system and food vacuole.","method":"Fluorescence colocalization microscopy, acidification assay, immuno-electron microscopy","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immuno-EM with functional context (amino acid starvation), two orthogonal imaging methods in a single lab","pmids":["24025672"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"RAB7 (Rab7) co-localizes with the retromer complex to a small number of punctate endosomal structures in P. falciparum that are distinct from the Golgi apparatus (neither redistributes to the ER upon brefeldin A treatment) and lie in close proximity to the Golgi and nascent rhoptries, suggesting RAB7 marks an endosomal compartment involved in protein sorting and possibly rhoptry biogenesis.","method":"Confocal fluorescence microscopy, brefeldin A treatment, co-localization analysis","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization with organelle markers and pharmacological perturbation, single lab, multiple markers used","pmids":["24587025"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"RAB7 (PfRab7) physically interacts with the retromer subunit PfVPS26, as shown by co-immunoprecipitation; the RAB7–retromer complex assembles near the digestive vacuole (DV) and Golgi in trophozoites; chemical disruption of the DV with chloroquine or a heme polymerization inhibitor (compound 5f) caused retromer disassembly; RAB7 exhibits Mg2+-dependent GTPase activity, and a specific Rab7 GTPase inhibitor (CID 1067700) prevented retromer complex assembly and inhibited parasite growth, establishing that RAB7 GTPase activity is required for retromer assembly.","method":"Co-immunoprecipitation, confocal microscopy, GTPase activity assay, pharmacological inhibition (chloroquine, compound 5f, CID 1067700), parasite growth assay","journal":"Biochimica et biophysica acta. General subjects","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, in vitro GTPase assay, pharmacological perturbation of DV, and inhibitor-based functional validation, all in one study with multiple orthogonal methods","pmids":["32512169"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum RAB7 is a Mg2+-dependent GTPase that marks a late endosomal compartment near the Golgi and digestive vacuole; it physically interacts with the retromer subunit PfVPS26 and its GTPase activity is required for retromer complex assembly at that compartment, while also mediating maturation and acidification of PfATG8-positive autophagosomes during amino acid starvation, routing them to the food vacuole via the endosomal system."},"narrative":{"mechanistic_narrative":"PF3D7_0903200 (RAB7) is a Mg2+-dependent GTPase that marks a late endosomal compartment in Plasmodium falciparum and coordinates endosomal protein sorting and autophagosome maturation [PMID:24025672, PMID:24587025, PMID:32512169]. RAB7 localizes to a small number of punctate endosomal structures distinct from the Golgi—resistant to brefeldin A redistribution—positioned near the Golgi, nascent rhoptries, and the digestive vacuole [PMID:24587025]. At this compartment RAB7 physically interacts with the retromer subunit PfVPS26, and its GTPase activity is required for retromer complex assembly: the specific Rab7 GTPase inhibitor CID 1067700 prevents retromer assembly and inhibits parasite growth, while chemical disruption of the digestive vacuole causes retromer disassembly, linking retromer integrity to digestive vacuole function [PMID:32512169]. In parallel, upon amino acid starvation RAB7-labeled vesicles increasingly colocalize with PfATG8-positive autophagosomes, and the co-labeled double-membrane structures become acidified, indicating RAB7-mediated maturation of autophagosomes and their routing through the endosomal system to the food vacuole [PMID:24025672]. Beyond these roles in retromer assembly and autophagosome maturation, no further mechanistic detail for PF3D7_0903200 has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"To determine whether RAB7 participates in autophagy, its relationship to the autophagosome marker PfATG8 was tested, establishing RAB7 as a mediator of autophagosome maturation and delivery to the food vacuole.","evidence":"Fluorescence colocalization, acidification assay, and immuno-electron microscopy under amino acid starvation in P. falciparum","pmids":["24025672"],"confidence":"Medium","gaps":["Colocalization and acidification are correlative; RAB7 depletion was not used to show autophagosome maturation is RAB7-dependent","The molecular effectors linking RAB7 to ATG8-positive membranes are not identified","Whether the same RAB7 pool serves both autophagy and endosomal sorting is not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"To define the compartment RAB7 marks, its localization was compared against retromer and Golgi markers, showing RAB7 labels a distinct endosomal compartment near the Golgi and nascent rhoptries.","evidence":"Confocal co-localization with organelle markers and brefeldin A perturbation in P. falciparum","pmids":["24587025"],"confidence":"Medium","gaps":["A functional role in rhoptry biogenesis is inferred from proximity, not demonstrated","The identity of cargo sorted at this compartment is not established","Colocalization with retromer does not by itself demonstrate physical interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To test whether RAB7 functionally drives retromer assembly, its interaction with PfVPS26, its GTPase activity, and the effect of inhibiting that activity were examined, establishing RAB7 GTPase activity as required for retromer complex assembly and parasite growth.","evidence":"Co-immunoprecipitation, in vitro Mg2+-dependent GTPase assay, digestive-vacuole disruption (chloroquine, compound 5f), and Rab7 inhibitor CID 1067700 with growth assay in P. falciparum","pmids":["32512169"],"confidence":"High","gaps":["The GEF/GAP that regulate RAB7 nucleotide cycling are not identified","The full set of retromer and endosomal cargo dependent on RAB7 is not defined","How digestive vacuole integrity is mechanistically coupled to retromer assembly is not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How RAB7 nucleotide cycling is regulated, which effectors and cargo it engages, and whether its autophagy and retromer roles are mechanistically linked remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No RAB7 GEF or GAP identified in the corpus","No genetic loss-of-function (conditional knockout/knockdown) of RAB7 reported","No structural model of RAB7 or its complex with PfVPS26"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RAB7–retromer complex (with PfVPS26)"],"partners":["PFVPS26 (RETROMER SUBUNIT)","PFATG8 (COLOCALIZATION ON AUTOPHAGOSOMES)"],"other_free_text":["RAB7 GTPase activity is inhibited by CID 1067700, which blocks retromer assembly and parasite growth [#2]","Retromer assembly near the digestive vacuole is disrupted by chloroquine and heme polymerization inhibitor compound 5f [#2]","RAB7-positive compartment is brefeldin A-resistant and distinct from the Golgi [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24025672","id":"PMC_24025672","title":"Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation.","date":"2013","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/24025672","citation_count":79,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB7","PfRAB7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12657463","id":"PMC_12657463","title":"The Plasmodium falciparum family of Rab GTPases.","date":"2003","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/12657463","citation_count":74,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["RAB7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32512169","id":"PMC_32512169","title":"Rab7 of Plasmodium falciparum is involved in its retromer complex assembly near the digestive vacuole.","date":"2020","source":"Biochimica et biophysica acta. General subjects","url":"https://pubmed.ncbi.nlm.nih.gov/32512169","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB7","PfRAB7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36869438","id":"PMC_36869438","title":"Biological functions and structural biology of Plasmodium falciparum autophagy-related proteins: The under-explored options for novel antimalarial drug design.","date":"2023","source":"Chemical biology & drug design","url":"https://pubmed.ncbi.nlm.nih.gov/36869438","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5553,"output_tokens":1077,"usd":0.016407,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5848,"output_tokens":2361,"usd":0.044132,"stage2_stop_reason":"end_turn"},"total_usd":0.060539,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"In P. falciparum, RAB7 (PfRAB7)-labeled vesicles showed increased colocalization with PfATG8-positive autophagosomes upon amino acid starvation, and the co-labeled structures became acidified, consistent with RAB7-mediated maturation of autophagosomes; immuno-electron microscopy detected RAB7 on double-membrane-bound vesicles and near/within the food vacuole, supporting a role for RAB7 in routing autophagosomes to the endosomal system and food vacuole.\",\n      \"method\": \"Fluorescence colocalization microscopy, acidification assay, immuno-electron microscopy\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immuno-EM with functional context (amino acid starvation), two orthogonal imaging methods in a single lab\",\n      \"pmids\": [\"24025672\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RAB7 (Rab7) co-localizes with the retromer complex to a small number of punctate endosomal structures in P. falciparum that are distinct from the Golgi apparatus (neither redistributes to the ER upon brefeldin A treatment) and lie in close proximity to the Golgi and nascent rhoptries, suggesting RAB7 marks an endosomal compartment involved in protein sorting and possibly rhoptry biogenesis.\",\n      \"method\": \"Confocal fluorescence microscopy, brefeldin A treatment, co-localization analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization with organelle markers and pharmacological perturbation, single lab, multiple markers used\",\n      \"pmids\": [\"24587025\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RAB7 (PfRab7) physically interacts with the retromer subunit PfVPS26, as shown by co-immunoprecipitation; the RAB7–retromer complex assembles near the digestive vacuole (DV) and Golgi in trophozoites; chemical disruption of the DV with chloroquine or a heme polymerization inhibitor (compound 5f) caused retromer disassembly; RAB7 exhibits Mg2+-dependent GTPase activity, and a specific Rab7 GTPase inhibitor (CID 1067700) prevented retromer complex assembly and inhibited parasite growth, establishing that RAB7 GTPase activity is required for retromer assembly.\",\n      \"method\": \"Co-immunoprecipitation, confocal microscopy, GTPase activity assay, pharmacological inhibition (chloroquine, compound 5f, CID 1067700), parasite growth assay\",\n      \"journal\": \"Biochimica et biophysica acta. General subjects\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, in vitro GTPase assay, pharmacological perturbation of DV, and inhibitor-based functional validation, all in one study with multiple orthogonal methods\",\n      \"pmids\": [\"32512169\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum RAB7 is a Mg2+-dependent GTPase that marks a late endosomal compartment near the Golgi and digestive vacuole; it physically interacts with the retromer subunit PfVPS26 and its GTPase activity is required for retromer complex assembly at that compartment, while also mediating maturation and acidification of PfATG8-positive autophagosomes during amino acid starvation, routing them to the food vacuole via the endosomal system.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0903200 (RAB7) is a Mg2+-dependent GTPase that marks a late endosomal compartment in Plasmodium falciparum and coordinates endosomal protein sorting and autophagosome maturation [#0, #1, #2]. RAB7 localizes to a small number of punctate endosomal structures distinct from the Golgi—resistant to brefeldin A redistribution—positioned near the Golgi, nascent rhoptries, and the digestive vacuole [#1]. At this compartment RAB7 physically interacts with the retromer subunit PfVPS26, and its GTPase activity is required for retromer complex assembly: the specific Rab7 GTPase inhibitor CID 1067700 prevents retromer assembly and inhibits parasite growth, while chemical disruption of the digestive vacuole causes retromer disassembly, linking retromer integrity to digestive vacuole function [#2]. In parallel, upon amino acid starvation RAB7-labeled vesicles increasingly colocalize with PfATG8-positive autophagosomes, and the co-labeled double-membrane structures become acidified, indicating RAB7-mediated maturation of autophagosomes and their routing through the endosomal system to the food vacuole [#0]. Beyond these roles in retromer assembly and autophagosome maturation, no further mechanistic detail for PF3D7_0903200 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"To determine whether RAB7 participates in autophagy, its relationship to the autophagosome marker PfATG8 was tested, establishing RAB7 as a mediator of autophagosome maturation and delivery to the food vacuole.\",\n      \"evidence\": \"Fluorescence colocalization, acidification assay, and immuno-electron microscopy under amino acid starvation in P. falciparum\",\n      \"pmids\": [\"24025672\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Colocalization and acidification are correlative; RAB7 depletion was not used to show autophagosome maturation is RAB7-dependent\",\n        \"The molecular effectors linking RAB7 to ATG8-positive membranes are not identified\",\n        \"Whether the same RAB7 pool serves both autophagy and endosomal sorting is not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To define the compartment RAB7 marks, its localization was compared against retromer and Golgi markers, showing RAB7 labels a distinct endosomal compartment near the Golgi and nascent rhoptries.\",\n      \"evidence\": \"Confocal co-localization with organelle markers and brefeldin A perturbation in P. falciparum\",\n      \"pmids\": [\"24587025\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"A functional role in rhoptry biogenesis is inferred from proximity, not demonstrated\",\n        \"The identity of cargo sorted at this compartment is not established\",\n        \"Colocalization with retromer does not by itself demonstrate physical interaction\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To test whether RAB7 functionally drives retromer assembly, its interaction with PfVPS26, its GTPase activity, and the effect of inhibiting that activity were examined, establishing RAB7 GTPase activity as required for retromer complex assembly and parasite growth.\",\n      \"evidence\": \"Co-immunoprecipitation, in vitro Mg2+-dependent GTPase assay, digestive-vacuole disruption (chloroquine, compound 5f), and Rab7 inhibitor CID 1067700 with growth assay in P. falciparum\",\n      \"pmids\": [\"32512169\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The GEF/GAP that regulate RAB7 nucleotide cycling are not identified\",\n        \"The full set of retromer and endosomal cargo dependent on RAB7 is not defined\",\n        \"How digestive vacuole integrity is mechanistically coupled to retromer assembly is not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RAB7 nucleotide cycling is regulated, which effectors and cargo it engages, and whether its autophagy and retromer roles are mechanistically linked remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RAB7 GEF or GAP identified in the corpus\",\n        \"No genetic loss-of-function (conditional knockout/knockdown) of RAB7 reported\",\n        \"No structural model of RAB7 or its complex with PfVPS26\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0000287\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005525\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005770\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005776\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020020\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016197\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0016236\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006914\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"RAB7–retromer complex (with PfVPS26)\"\n    ],\n    \"partners\": [\n      \"PfVPS26 (retromer subunit)\",\n      \"PfATG8 (colocalization on autophagosomes)\"\n    ],\n    \"other_free_text\": [\n      \"RAB7 GTPase activity is inhibited by CID 1067700, which blocks retromer assembly and parasite growth [#2]\",\n      \"Retromer assembly near the digestive vacuole is disrupted by chloroquine and heme polymerization inhibitor compound 5f [#2]\",\n      \"RAB7-positive compartment is brefeldin A-resistant and distinct from the Golgi [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0903200","name":null,"product":"ras-related protein RAB7","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0418200","name":null,"product":"ras-related protein RAB7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0700900","name":null,"product":"ras-related protein RAB7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAB7","evaluation":null}