{"gene":"PF3D7_1340700","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2024,"finding":"RAB11b (ortholog) interacts with the dynein heavy chain DHC3 at subpellicular microtubules (SPMTs) in ookinetes in a DHC3-dependent manner, functioning as a receptor for SPMT-dynein-driven cargoes; genetic disruption of RAB11b phenocopies DHC3 deficiency, causing defective formation or localization of apical organelles and structures and impairing ookinete morphogenesis, shape, and gliding, leading to failure of mosquito infection.","method":"Co-immunoprecipitation (interaction with DHC3), conditional knockout/genetic disruption with defined phenotypic readouts (ookinete morphology, gliding motility, apical organelle assembly, mosquito infectivity)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction demonstrated and loss-of-function phenotype shown, single lab, single study in P. yoelii","pmids":["39366980"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"finding":"RAB11b co-immunoprecipitates with PfSKP1 (a component of the Cullin-RING-Ligase SCF complex) and with PfFBXO1 in schizont-stage P. falciparum parasites, placing RAB11b in physical association with the PfSCF ubiquitin ligase complex; IMC-associated proteins and Rab11b are enriched together in these pull-downs, suggesting a link between ubiquitin-mediated regulation and IMC biogenesis.","method":"Co-immunoprecipitation followed by LC-MS/MS from schizont-stage transgenic parasites expressing HA-tagged PfSKP1 and PfFBXO1","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS identification, no functional follow-up specifically for RAB11b, single lab","pmids":["40592953"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PbRAB11b protein is expressed during the zygote-to-ookinete transition in P. berghei, as shown by western blot and immunofluorescence; its expression pattern was assessed in parasites with reduced PbRAB11A expression, establishing it as a distinct, co-expressed family member at this stage.","method":"Western blot and immunofluorescence of endogenous PbRAB11b across the time course of zygote-to-ookinete transition","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization/expression data only, no direct functional manipulation of RAB11b itself, single study","pmids":["32463831"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"RAB11b (PY17X_1359500 ortholog) localizes to the inner membrane complex (IMC) in P. yoelii schizonts, as confirmed by immunofluorescence assay with anti-HA antibody co-stained with anti-GAP45, following episomal N-terminal HA-tagging.","method":"Immunofluorescence assay (IFA) with epitope-tagged protein co-stained with IMC marker GAP45 in schizont-stage P. yoelii","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single localization experiment using episomal overexpression, no functional loss-of-function for RAB11b specifically in this study","pmids":["35775739"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2020,"finding":"RAB11b co-immunoprecipitates with K13 (the artemisinin resistance kelch protein) in P. falciparum intra-erythrocytic parasites, identifying RAB11b as part of the K13-associated protein network involved in vesicular trafficking.","method":"Immunoprecipitation with K13-specific monoclonal antibodies followed by mass spectrometry in gene-edited P. falciparum lines","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS identification of RAB11b among many Rab GTPases, no functional follow-up specific to RAB11b","pmids":["32310999"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"RAB11b (PfRab11B) is one of 11 Rab GTPase family members in P. falciparum; the gene is transcribed in infected erythrocytes, as demonstrated by RT-PCR/transcriptional analysis.","method":"Bioinformatic identification combined with experimental transcription testing (RT-PCR) in P. falciparum-infected erythrocytes","journal":"Gene","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcription confirmed experimentally but no functional or localization data specific to RAB11b","pmids":["12657463"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"RAB11b (PF3D7_1340700) is a Rab GTPase expressed in P. falciparum-infected erythrocytes that localizes to the inner membrane complex (IMC) in schizonts; in P. yoelii ookinetes its ortholog interacts with the dynein heavy chain DHC3 at subpellicular microtubules and functions as a cargo receptor for SPMT-dynein-driven transport essential for apical organelle assembly and ookinete morphogenesis, while in P. falciparum schizonts RAB11b physically associates with the SCF ubiquitin ligase components PfSKP1 and PfFBXO1 and with the artemisinin-resistance protein K13, consistent with a role in vesicular trafficking supporting IMC biogenesis."},"narrative":{"mechanistic_narrative":"RAB11b (PF3D7_1340700) is a Rab GTPase of the malaria parasite that functions in vesicular trafficking supporting the biogenesis of pellicular structures across the parasite life cycle [PMID:12657463, PMID:39366980]. In P. yoelii ookinetes, the RAB11b ortholog acts as a cargo receptor for subpellicular-microtubule dynein-driven transport: it interacts with the dynein heavy chain DHC3 in a DHC3-dependent manner, and its genetic disruption phenocopies DHC3 deficiency, producing defective apical organelle formation, aberrant ookinete morphology, impaired gliding motility, and failure of mosquito infection [PMID:39366980]. Consistent with a role in pellicle biogenesis, the RAB11b ortholog localizes to the inner membrane complex (IMC) in P. yoelii schizonts [PMID:35775739]. In P. falciparum schizonts, RAB11b physically associates with the SCF ubiquitin ligase components PfSKP1 and PfFBXO1 alongside IMC-associated proteins, linking ubiquitin-mediated regulation to IMC biogenesis [PMID:40592953], and it co-immunoprecipitates with the artemisinin-resistance protein K13 as part of a K13-associated trafficking network [PMID:32310999]. Beyond these interaction and localization findings, the biochemical activity of RAB11b itself — its GTPase cycle, effectors, and direct cargo — has not been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing that PF3D7_1340700 is an expressed member of the parasite's Rab GTPase repertoire was the first step in defining it as a candidate trafficking regulator rather than a pseudogene or unexpressed locus.","evidence":"Bioinformatic family identification with RT-PCR transcription testing in P. falciparum-infected erythrocytes","pmids":["12657463"],"confidence":"Low","gaps":["No functional or localization data specific to RAB11b","GTPase activity and cycle not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Placing RAB11b within the K13 artemisinin-resistance interactome connected it to endocytic/vesicular trafficking machinery in the intra-erythrocytic stage.","evidence":"K13 monoclonal-antibody immunoprecipitation followed by mass spectrometry in gene-edited P. falciparum","pmids":["32310999"],"confidence":"Low","gaps":["RAB11b identified among many Rab GTPases with no RAB11b-specific functional follow-up","Direct versus indirect association with K13 not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Demonstrating RAB11b protein expression during the zygote-to-ookinete transition established it as a distinct, stage-specific family member co-expressed with RAB11A rather than a redundant paralog.","evidence":"Western blot and immunofluorescence of endogenous PbRAB11b across the transition time course in P. berghei","pmids":["32463831"],"confidence":"Low","gaps":["No direct functional manipulation of RAB11b itself","Relationship to RAB11A function not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"Localizing the RAB11b ortholog to the inner membrane complex in schizonts assigned it a spatial niche at the developing pellicle, framing a role in pellicle/IMC biogenesis.","evidence":"Immunofluorescence of episomal N-terminal HA-tagged protein co-stained with IMC marker GAP45 in P. yoelii schizonts","pmids":["35775739"],"confidence":"Low","gaps":["Localization from episomal overexpression, not endogenous tagging","No loss-of-function data for RAB11b in this study"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2024,"claim":"Identifying RAB11b as a DHC3-dependent receptor for subpellicular-microtubule dynein cargoes provided the first direct mechanistic function: linking motor-driven transport to apical organelle assembly and ookinete morphogenesis.","evidence":"Co-immunoprecipitation with DHC3 plus conditional knockout with morphology, gliding, apical-organelle, and mosquito-infectivity readouts in P. yoelii","pmids":["39366980"],"confidence":"Medium","gaps":["Single lab, single study in P. yoelii","Specific cargoes transported via RAB11b not identified","GTPase-cycle dependence of the receptor function not tested"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2025,"claim":"Detecting RAB11b in PfSKP1 and PfFBXO1 pull-downs alongside IMC proteins hinted at ubiquitin-ligase regulation of RAB11b-associated IMC biogenesis in the blood stage.","evidence":"Co-immunoprecipitation followed by LC-MS/MS from schizont-stage P. falciparum expressing HA-tagged PfSKP1 and PfFBXO1","pmids":["40592953"],"confidence":"Low","gaps":["Single Co-IP/MS with no RAB11b-specific functional follow-up","Whether RAB11b is a ubiquitylation substrate of the SCF complex not tested","Direct versus indirect association not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic biochemistry of RAB11b — its GTP/GDP cycle, GEF/GAP regulators, and the identity of cargoes it delivers — remains undefined, as does whether its blood-stage IMC/SCF/K13 associations reflect the same cargo-receptor function seen in ookinetes.","evidence":"No timeline discovery addresses RAB11b GTPase activity, effectors, or blood-stage loss-of-function phenotype","pmids":[],"confidence":"Low","gaps":["No reconstitution of RAB11b GTPase or effector binding","No cargo directly identified","Cross-stage and cross-species conservation of function untested"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfSCF ubiquitin ligase complex association (PfSKP1, PfFBXO1)","K13-associated protein network"],"partners":["DHC3 (DYNEIN HEAVY CHAIN 3)","PFSKP1","PFFBXO1","K13"],"other_free_text":["One of 11 Rab GTPase family members identified in P. falciparum; transcribed in infected erythrocytes","Ortholog functional data derive from P. yoelii and P. berghei; blood-stage associations from P. falciparum"]}},"prefetch_data":{},"corpus_meta":[{"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":"39366980","id":"PMC_39366980","title":"A subpellicular microtubule dynein transport machinery regulates ookinete morphogenesis for mosquito transmission of Plasmodium yoelii.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39366980","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40592953","id":"","title":"Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40592953","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39915671","id":"","title":"PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages.","date":"2025","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39915671","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32463831","id":"","title":"Zygote morphogenesis but not the establishment of cell polarity in Plasmodium berghei is controlled by the small GTPase, RAB11A.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32463831","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35775739","id":"","title":"Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35775739","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34315897","id":"","title":"The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34315897","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22188458","id":"","title":"Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA as Rab-effector kinases in malaria parasites.","date":"2011","source":"Biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/22188458","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33082261","id":"","title":"The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/33082261","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27121004","id":"","title":"An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27121004","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30078701","id":"","title":"Apicomplexa Cell Cycles: Something Old, Borrowed, Lost, and New.","date":"2018","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/30078701","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32310999","id":"","title":"Insights into the intracellular localization, protein associations and artemisinin resistance properties of Plasmodium falciparum K13.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32310999","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24612102","id":"","title":"The inner membrane complex through development of Toxoplasma gondii and Plasmodium.","date":"2014","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/24612102","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"18468471","id":"","title":"Comparative genomics of the Rab protein family in Apicomplexan parasites.","date":"2008","source":"Microbes and infection","url":"https://pubmed.ncbi.nlm.nih.gov/18468471","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19165333","id":"","title":"Rab11A-controlled assembly of the inner membrane complex is required for completion of apicomplexan cytokinesis.","date":"2009","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/19165333","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB11b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17707,"output_tokens":1800,"usd":0.04006,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6848,"output_tokens":2904,"usd":0.05342,"stage2_stop_reason":"end_turn"},"total_usd":0.09348,"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\": 2024,\n      \"finding\": \"RAB11b (ortholog) interacts with the dynein heavy chain DHC3 at subpellicular microtubules (SPMTs) in ookinetes in a DHC3-dependent manner, functioning as a receptor for SPMT-dynein-driven cargoes; genetic disruption of RAB11b phenocopies DHC3 deficiency, causing defective formation or localization of apical organelles and structures and impairing ookinete morphogenesis, shape, and gliding, leading to failure of mosquito infection.\",\n      \"method\": \"Co-immunoprecipitation (interaction with DHC3), conditional knockout/genetic disruption with defined phenotypic readouts (ookinete morphology, gliding motility, apical organelle assembly, mosquito infectivity)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction demonstrated and loss-of-function phenotype shown, single lab, single study in P. yoelii\",\n      \"pmids\": [\"39366980\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RAB11b co-immunoprecipitates with PfSKP1 (a component of the Cullin-RING-Ligase SCF complex) and with PfFBXO1 in schizont-stage P. falciparum parasites, placing RAB11b in physical association with the PfSCF ubiquitin ligase complex; IMC-associated proteins and Rab11b are enriched together in these pull-downs, suggesting a link between ubiquitin-mediated regulation and IMC biogenesis.\",\n      \"method\": \"Co-immunoprecipitation followed by LC-MS/MS from schizont-stage transgenic parasites expressing HA-tagged PfSKP1 and PfFBXO1\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS identification, no functional follow-up specifically for RAB11b, single lab\",\n      \"pmids\": [\"40592953\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PbRAB11b protein is expressed during the zygote-to-ookinete transition in P. berghei, as shown by western blot and immunofluorescence; its expression pattern was assessed in parasites with reduced PbRAB11A expression, establishing it as a distinct, co-expressed family member at this stage.\",\n      \"method\": \"Western blot and immunofluorescence of endogenous PbRAB11b across the time course of zygote-to-ookinete transition\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization/expression data only, no direct functional manipulation of RAB11b itself, single study\",\n      \"pmids\": [\"32463831\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RAB11b (PY17X_1359500 ortholog) localizes to the inner membrane complex (IMC) in P. yoelii schizonts, as confirmed by immunofluorescence assay with anti-HA antibody co-stained with anti-GAP45, following episomal N-terminal HA-tagging.\",\n      \"method\": \"Immunofluorescence assay (IFA) with epitope-tagged protein co-stained with IMC marker GAP45 in schizont-stage P. yoelii\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization experiment using episomal overexpression, no functional loss-of-function for RAB11b specifically in this study\",\n      \"pmids\": [\"35775739\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RAB11b co-immunoprecipitates with K13 (the artemisinin resistance kelch protein) in P. falciparum intra-erythrocytic parasites, identifying RAB11b as part of the K13-associated protein network involved in vesicular trafficking.\",\n      \"method\": \"Immunoprecipitation with K13-specific monoclonal antibodies followed by mass spectrometry in gene-edited P. falciparum lines\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS identification of RAB11b among many Rab GTPases, no functional follow-up specific to RAB11b\",\n      \"pmids\": [\"32310999\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"RAB11b (PfRab11B) is one of 11 Rab GTPase family members in P. falciparum; the gene is transcribed in infected erythrocytes, as demonstrated by RT-PCR/transcriptional analysis.\",\n      \"method\": \"Bioinformatic identification combined with experimental transcription testing (RT-PCR) in P. falciparum-infected erythrocytes\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcription confirmed experimentally but no functional or localization data specific to RAB11b\",\n      \"pmids\": [\"12657463\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"RAB11b (PF3D7_1340700) is a Rab GTPase expressed in P. falciparum-infected erythrocytes that localizes to the inner membrane complex (IMC) in schizonts; in P. yoelii ookinetes its ortholog interacts with the dynein heavy chain DHC3 at subpellicular microtubules and functions as a cargo receptor for SPMT-dynein-driven transport essential for apical organelle assembly and ookinete morphogenesis, while in P. falciparum schizonts RAB11b physically associates with the SCF ubiquitin ligase components PfSKP1 and PfFBXO1 and with the artemisinin-resistance protein K13, consistent with a role in vesicular trafficking supporting IMC biogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RAB11b (PF3D7_1340700) is a Rab GTPase of the malaria parasite that functions in vesicular trafficking supporting the biogenesis of pellicular structures across the parasite life cycle [#5, #0]. In P. yoelii ookinetes, the RAB11b ortholog acts as a cargo receptor for subpellicular-microtubule dynein-driven transport: it interacts with the dynein heavy chain DHC3 in a DHC3-dependent manner, and its genetic disruption phenocopies DHC3 deficiency, producing defective apical organelle formation, aberrant ookinete morphology, impaired gliding motility, and failure of mosquito infection [#0]. Consistent with a role in pellicle biogenesis, the RAB11b ortholog localizes to the inner membrane complex (IMC) in P. yoelii schizonts [#3]. In P. falciparum schizonts, RAB11b physically associates with the SCF ubiquitin ligase components PfSKP1 and PfFBXO1 alongside IMC-associated proteins, linking ubiquitin-mediated regulation to IMC biogenesis [#1], and it co-immunoprecipitates with the artemisinin-resistance protein K13 as part of a K13-associated trafficking network [#4]. Beyond these interaction and localization findings, the biochemical activity of RAB11b itself — its GTPase cycle, effectors, and direct cargo — has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing that PF3D7_1340700 is an expressed member of the parasite's Rab GTPase repertoire was the first step in defining it as a candidate trafficking regulator rather than a pseudogene or unexpressed locus.\",\n      \"evidence\": \"Bioinformatic family identification with RT-PCR transcription testing in P. falciparum-infected erythrocytes\",\n      \"pmids\": [\"12657463\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No functional or localization data specific to RAB11b\", \"GTPase activity and cycle not demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing RAB11b within the K13 artemisinin-resistance interactome connected it to endocytic/vesicular trafficking machinery in the intra-erythrocytic stage.\",\n      \"evidence\": \"K13 monoclonal-antibody immunoprecipitation followed by mass spectrometry in gene-edited P. falciparum\",\n      \"pmids\": [\"32310999\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"RAB11b identified among many Rab GTPases with no RAB11b-specific functional follow-up\", \"Direct versus indirect association with K13 not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrating RAB11b protein expression during the zygote-to-ookinete transition established it as a distinct, stage-specific family member co-expressed with RAB11A rather than a redundant paralog.\",\n      \"evidence\": \"Western blot and immunofluorescence of endogenous PbRAB11b across the transition time course in P. berghei\",\n      \"pmids\": [\"32463831\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct functional manipulation of RAB11b itself\", \"Relationship to RAB11A function not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Localizing the RAB11b ortholog to the inner membrane complex in schizonts assigned it a spatial niche at the developing pellicle, framing a role in pellicle/IMC biogenesis.\",\n      \"evidence\": \"Immunofluorescence of episomal N-terminal HA-tagged protein co-stained with IMC marker GAP45 in P. yoelii schizonts\",\n      \"pmids\": [\"35775739\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Localization from episomal overexpression, not endogenous tagging\", \"No loss-of-function data for RAB11b in this study\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying RAB11b as a DHC3-dependent receptor for subpellicular-microtubule dynein cargoes provided the first direct mechanistic function: linking motor-driven transport to apical organelle assembly and ookinete morphogenesis.\",\n      \"evidence\": \"Co-immunoprecipitation with DHC3 plus conditional knockout with morphology, gliding, apical-organelle, and mosquito-infectivity readouts in P. yoelii\",\n      \"pmids\": [\"39366980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single study in P. yoelii\", \"Specific cargoes transported via RAB11b not identified\", \"GTPase-cycle dependence of the receptor function not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Detecting RAB11b in PfSKP1 and PfFBXO1 pull-downs alongside IMC proteins hinted at ubiquitin-ligase regulation of RAB11b-associated IMC biogenesis in the blood stage.\",\n      \"evidence\": \"Co-immunoprecipitation followed by LC-MS/MS from schizont-stage P. falciparum expressing HA-tagged PfSKP1 and PfFBXO1\",\n      \"pmids\": [\"40592953\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP/MS with no RAB11b-specific functional follow-up\", \"Whether RAB11b is a ubiquitylation substrate of the SCF complex not tested\", \"Direct versus indirect association not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic biochemistry of RAB11b — its GTP/GDP cycle, GEF/GAP regulators, and the identity of cargoes it delivers — remains undefined, as does whether its blood-stage IMC/SCF/K13 associations reflect the same cargo-receptor function seen in ookinetes.\",\n      \"evidence\": \"No timeline discovery addresses RAB11b GTPase activity, effectors, or blood-stage loss-of-function phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reconstitution of RAB11b GTPase or effector binding\", \"No cargo directly identified\", \"Cross-stage and cross-species conservation of function untested\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GTPase activity\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"cargo receptor activity (dynein-driven transport)\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"inner membrane complex\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"subpellicular microtubules\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"vesicular trafficking / IMC biogenesis\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"apical organelle assembly and ookinete morphogenesis\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"PfSCF ubiquitin ligase complex association (PfSKP1, PfFBXO1)\",\n      \"K13-associated protein network\"\n    ],\n    \"partners\": [\n      \"DHC3 (dynein heavy chain 3)\",\n      \"PfSKP1\",\n      \"PfFBXO1\",\n      \"K13\"\n    ],\n    \"other_free_text\": [\n      \"One of 11 Rab GTPase family members identified in P. falciparum; transcribed in infected erythrocytes\",\n      \"Ortholog functional data derive from P. yoelii and P. berghei; blood-stage associations from P. falciparum\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1340700","name":null,"product":"ras-related protein Rab-11B","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1354100","name":null,"product":"ras-related protein Rab-11B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1260700","name":null,"product":"ras-related protein Rab-11B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAB11b","evaluation":null}