{"gene":"PF3D7_1231100","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2003,"finding":"RAB2 (PF3D7_1231100) is transcribed in P. falciparum-infected erythrocytes and was predicted, based on phylogenetic comparison to yeast, to have a role in vacuole size regulation. Ten members of the P. falciparum Rab family, including RAB2, were shown to be transcribed in infected erythrocytes by experimental testing.","method":"Bioinformatic analyses, experimental transcription testing, phylogenetic comparison","journal":"Gene","confidence":"Low","confidence_rationale":"Tier 4 / Weak — transcription confirmed experimentally but functional role in vacuole size is purely phylogenetic inference, no direct functional assay of RAB2 protein itself","pmids":["12657463"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"P. falciparum GAPDH (pfGAPDH) is recruited to HeLa cell microsomal membranes in a Rab2-dependent manner, as demonstrated by a quantitative binding assay. The N-terminal domain of pfGAPDH (residues 1–192) mediates this recruitment and competitively inhibits Rab2-stimulated membrane association. This experiment used mammalian Rab2, not the parasite's own RAB2, to demonstrate evolutionary conservation of Rab2-dependent membrane recruitment.","method":"Quantitative microsomal membrane binding assay using HeLa cell microsomes and mammalian Rab2; competitive inhibition with recombinant pfGAPDH fragments","journal":"Biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro binding assay with domain mapping, but uses mammalian Rab2 (not P. falciparum RAB2 protein itself); single lab, two orthogonal approaches (binding assay + fragment competition)","pmids":["12974391"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"RAB2 protein levels are upregulated in P. falciparum parasites under proteasomal stress (cellular homeostasis disruption), as detected by quantitative global proteomics, suggesting increased vesicular trafficking as a stress response. This is a correlative proteomics observation rather than a direct functional experiment on RAB2.","method":"Quantitative global proteomic analysis of proteasome-inhibitor-treated P. falciparum parasites","journal":"Cell death & disease","confidence":"Low","confidence_rationale":"Tier 4 / Weak — single proteomics observation, no direct functional manipulation of RAB2, correlation only","pmids":["26136076"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"RAB2 (PF3D7_1231100) was identified as a putative interactor of PfCK1 (casein kinase 1) by co-immunoprecipitation/mass spectrometry from P. falciparum parasites expressing tagged PfCK1, corroborating a possible role for RAB2 in vesicular trafficking pathways regulated by PfCK1.","method":"Co-immunoprecipitation followed by mass spectrometry (IP/MS) from parasites expressing GFP- or His-tagged PfCK1","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment, no reciprocal pulldown, no functional follow-up on RAB2 specifically","pmids":["26629826"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"In silico interaction network analysis of P. falciparum COPII complexes suggests that RAB2, along with ERD2 and Rab1, may act as a regulatory protein for COPII complexes involved in ER-to-Golgi vesicular trafficking. This is a computational prediction without direct experimental validation.","method":"In silico protein interaction network analysis (computational)","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — purely computational/in silico prediction, no experimental validation of RAB2-COPII interaction","pmids":["30704415"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Expression of a dominant-negative host cell Rab2a (equivalent of Rab2) in HeLa cells resulted in only a slight developmental delay in P. berghei liver stage parasites during the first 24 h, but parasites recovered at later time points with no significant impact on overall parasite fitness. Therefore dominant-negative Rab2 (host cell) did not significantly impair P. berghei liver stage development.","method":"Bioluminescence imaging of P. berghei liver stage parasites in HeLa cells expressing dominant-negative host Rab2a","journal":"Journal of cell science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — this experiment tests HOST CELL Rab2a, not the parasite's own RAB2 (PF3D7_1231100); single experiment, negative/minor result","pmids":["34013963"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"P. falciparum RAB2 (PF3D7_1231100) is a transcribed Rab GTPase implicated in ER-to-Golgi vesicular trafficking; mammalian Rab2 (not directly the parasite protein) has been shown to recruit P. falciparum GAPDH to membranes via its N-terminal domain in a heterologous assay, RAB2 has been identified as a putative PfCK1 interactor by co-immunoprecipitation, and in silico analyses suggest it may regulate COPII complexes, but no direct in vivo functional experiment has been performed on the parasite's own RAB2 protein."},"narrative":{"mechanistic_narrative":"PF3D7_1231100 (RAB2) is a Rab-family GTPase of Plasmodium falciparum implicated in vesicular trafficking; it is transcribed across the intraerythrocytic stages, where it was originally assigned by phylogenetic comparison a role in vacuole size regulation, though only transcription was experimentally confirmed [PMID:12657463]. Direct functional characterization of the parasite's own RAB2 protein is absent from the available corpus: the mechanistic evidence linking Rab2 to membrane trafficking derives from mammalian Rab2, which recruits P. falciparum GAPDH to microsomal membranes via the GAPDH N-terminal domain (residues 1–192) in a heterologous binding assay establishing conservation of the recruitment mechanism rather than an activity of PF3D7_1231100 itself [PMID:12974391]. Within the parasite, RAB2 protein is upregulated under proteasomal stress [PMID:26136076] and was recovered as a putative co-immunoprecipitating partner of the casein kinase PfCK1 [PMID:26629826], and in silico network analysis places it alongside ERD2 and Rab1 as a candidate regulator of COPII-dependent ER-to-Golgi trafficking [PMID:30704415]. Beyond these correlative, heterologous, and computational observations, no direct in vivo functional experiment on PF3D7_1231100 has been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing whether RAB2 is expressed at all in the blood stage was the first prerequisite for any functional hypothesis; transcription testing confirmed it is expressed and, by analogy to yeast, tentatively assigned a trafficking/vacuole role.","evidence":"Experimental transcription testing plus phylogenetic comparison across the P. falciparum Rab family in infected erythrocytes","pmids":["12657463"],"confidence":"Low","gaps":["Vacuole-size role is pure phylogenetic inference with no functional assay","No protein-level detection or localization of RAB2","No GTPase activity demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"claim":"To test whether Rab2-dependent membrane recruitment is conserved for a Plasmodium substrate, GAPDH recruitment was reconstituted heterologously, showing pfGAPDH binds microsomal membranes in a Rab2-dependent manner through its N-terminal domain.","evidence":"Quantitative HeLa microsomal membrane binding assay with mammalian Rab2 and competitive inhibition by recombinant pfGAPDH fragments (residues 1–192)","pmids":["12974391"],"confidence":"Medium","gaps":["Used mammalian Rab2, not PF3D7_1231100, so the activity is not demonstrated for the parasite protein","No evidence this interaction occurs in the parasite","Functional consequence of GAPDH recruitment unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether RAB2 responds to cellular stress was probed by global proteomics, revealing upregulation of RAB2 protein under proteasome inhibition and hinting at increased trafficking as a homeostatic response.","evidence":"Quantitative global proteomics of proteasome-inhibitor-treated P. falciparum parasites","pmids":["26136076"],"confidence":"Low","gaps":["Correlative abundance change only, no functional manipulation","Mechanism linking proteasomal stress to RAB2 levels unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To place RAB2 in a signaling context, PfCK1 interactome profiling recovered RAB2 as a putative partner, connecting it to kinase-regulated trafficking pathways.","evidence":"Co-immunoprecipitation/mass spectrometry from parasites expressing tagged PfCK1","pmids":["26629826"],"confidence":"Low","gaps":["Single Co-IP/MS without reciprocal pulldown","No validation that RAB2 is a direct PfCK1 substrate or binder","No functional follow-up on RAB2"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"A computational attempt to assign RAB2 to a defined trafficking step predicted it, with ERD2 and Rab1, as a COPII regulatory protein in ER-to-Golgi transport.","evidence":"In silico protein interaction network analysis of P. falciparum COPII complexes","pmids":["30704415"],"confidence":"Low","gaps":["Purely computational, no experimental validation of RAB2–COPII association","No demonstration of RAB2 localization to ER-Golgi membranes"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Testing whether the host-cell Rab2 trafficking machinery is required by intracellular parasites, dominant-negative host Rab2a caused only a transient early liver-stage delay in P. berghei, indicating host Rab2 is largely dispensable and leaving the parasite's own RAB2 untested.","evidence":"Bioluminescence imaging of P. berghei liver-stage parasites in HeLa cells expressing dominant-negative host Rab2a","pmids":["34013963"],"confidence":"Low","gaps":["Tests host-cell Rab2a, not parasite PF3D7_1231100","Different species (P. berghei) and life-cycle stage than the blood-stage RAB2 findings","Minor/negative phenotype limits interpretation"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"No direct in vivo functional experiment has been performed on the parasite's own RAB2 protein; its GTPase activity, membrane localization, effectors, and role in COPII/ER-to-Golgi trafficking within the parasite remain uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No knockout, knockdown, or conditional depletion of PF3D7_1231100","No demonstrated GTPase activity or GEF/GAP/effector for the parasite protein","No direct subcellular localization of RAB2 in P. falciparum"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFCK1 (CASEIN KINASE 1) — PUTATIVE CO-IP INTERACTOR [#3]"],"other_free_text":["Transcribed in P. falciparum-infected erythrocytes; vacuole-size role inferred only phylogenetically [#0]","Mammalian Rab2 (not PF3D7_1231100) recruits P. falciparum GAPDH to microsomal membranes via the GAPDH N-terminal domain, demonstrating conservation of the recruitment mechanism [#1]","RAB2 protein upregulated under proteasomal stress in P. falciparum [#2]","Predicted COPII regulator alongside ERD2 and Rab1 by in silico network analysis [#4]","Dominant-negative HOST-cell Rab2a caused only transient early P. berghei liver-stage delay; this tests host Rab2, not the parasite RAB2 [#5]"]}},"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":"12974391","id":"PMC_12974391","title":"The N'-terminal domain of glyceraldehyde-3-phosphate dehydrogenase of the apicomplexan Plasmodium falciparum mediates GTPase Rab2-dependent recruitment to membranes.","date":"2003","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12974391","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34013963","id":"","title":"Hijacking of the host cell Golgi by Plasmodium berghei liver stage parasites.","date":"2021","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/34013963","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31537845","id":"","title":"The interactome of 2-Cys peroxiredoxins in Plasmodium falciparum.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31537845","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25580350","id":"","title":"Exploiting unique structural and functional properties of malarial glycolytic enzymes for antimalarial drug development.","date":"2014","source":"Malaria research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/25580350","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24146604","id":"","title":"Prediction of the P. falciparum target space relevant to malaria drug discovery.","date":"2013","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/24146604","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26136076","id":"","title":"Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite.","date":"2015","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/26136076","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26629826","id":"","title":"Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26629826","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30704415","id":"","title":"A genome-wide analysis of coatomer protein (COP) subunits of apicomplexan parasites and their evolutionary relationships.","date":"2019","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/30704415","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["RAB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11542,"output_tokens":1749,"usd":0.03043,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6841,"output_tokens":3040,"usd":0.055102,"stage2_stop_reason":"end_turn"},"total_usd":0.085532,"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\": 2003,\n      \"finding\": \"RAB2 (PF3D7_1231100) is transcribed in P. falciparum-infected erythrocytes and was predicted, based on phylogenetic comparison to yeast, to have a role in vacuole size regulation. Ten members of the P. falciparum Rab family, including RAB2, were shown to be transcribed in infected erythrocytes by experimental testing.\",\n      \"method\": \"Bioinformatic analyses, experimental transcription testing, phylogenetic comparison\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — transcription confirmed experimentally but functional role in vacuole size is purely phylogenetic inference, no direct functional assay of RAB2 protein itself\",\n      \"pmids\": [\"12657463\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"P. falciparum GAPDH (pfGAPDH) is recruited to HeLa cell microsomal membranes in a Rab2-dependent manner, as demonstrated by a quantitative binding assay. The N-terminal domain of pfGAPDH (residues 1–192) mediates this recruitment and competitively inhibits Rab2-stimulated membrane association. This experiment used mammalian Rab2, not the parasite's own RAB2, to demonstrate evolutionary conservation of Rab2-dependent membrane recruitment.\",\n      \"method\": \"Quantitative microsomal membrane binding assay using HeLa cell microsomes and mammalian Rab2; competitive inhibition with recombinant pfGAPDH fragments\",\n      \"journal\": \"Biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro binding assay with domain mapping, but uses mammalian Rab2 (not P. falciparum RAB2 protein itself); single lab, two orthogonal approaches (binding assay + fragment competition)\",\n      \"pmids\": [\"12974391\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"RAB2 protein levels are upregulated in P. falciparum parasites under proteasomal stress (cellular homeostasis disruption), as detected by quantitative global proteomics, suggesting increased vesicular trafficking as a stress response. This is a correlative proteomics observation rather than a direct functional experiment on RAB2.\",\n      \"method\": \"Quantitative global proteomic analysis of proteasome-inhibitor-treated P. falciparum parasites\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — single proteomics observation, no direct functional manipulation of RAB2, correlation only\",\n      \"pmids\": [\"26136076\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"RAB2 (PF3D7_1231100) was identified as a putative interactor of PfCK1 (casein kinase 1) by co-immunoprecipitation/mass spectrometry from P. falciparum parasites expressing tagged PfCK1, corroborating a possible role for RAB2 in vesicular trafficking pathways regulated by PfCK1.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry (IP/MS) from parasites expressing GFP- or His-tagged PfCK1\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment, no reciprocal pulldown, no functional follow-up on RAB2 specifically\",\n      \"pmids\": [\"26629826\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In silico interaction network analysis of P. falciparum COPII complexes suggests that RAB2, along with ERD2 and Rab1, may act as a regulatory protein for COPII complexes involved in ER-to-Golgi vesicular trafficking. This is a computational prediction without direct experimental validation.\",\n      \"method\": \"In silico protein interaction network analysis (computational)\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — purely computational/in silico prediction, no experimental validation of RAB2-COPII interaction\",\n      \"pmids\": [\"30704415\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Expression of a dominant-negative host cell Rab2a (equivalent of Rab2) in HeLa cells resulted in only a slight developmental delay in P. berghei liver stage parasites during the first 24 h, but parasites recovered at later time points with no significant impact on overall parasite fitness. Therefore dominant-negative Rab2 (host cell) did not significantly impair P. berghei liver stage development.\",\n      \"method\": \"Bioluminescence imaging of P. berghei liver stage parasites in HeLa cells expressing dominant-negative host Rab2a\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — this experiment tests HOST CELL Rab2a, not the parasite's own RAB2 (PF3D7_1231100); single experiment, negative/minor result\",\n      \"pmids\": [\"34013963\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum RAB2 (PF3D7_1231100) is a transcribed Rab GTPase implicated in ER-to-Golgi vesicular trafficking; mammalian Rab2 (not directly the parasite protein) has been shown to recruit P. falciparum GAPDH to membranes via its N-terminal domain in a heterologous assay, RAB2 has been identified as a putative PfCK1 interactor by co-immunoprecipitation, and in silico analyses suggest it may regulate COPII complexes, but no direct in vivo functional experiment has been performed on the parasite's own RAB2 protein.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1231100 (RAB2) is a Rab-family GTPase of Plasmodium falciparum implicated in vesicular trafficking; it is transcribed across the intraerythrocytic stages, where it was originally assigned by phylogenetic comparison a role in vacuole size regulation, though only transcription was experimentally confirmed [#0]. Direct functional characterization of the parasite's own RAB2 protein is absent from the available corpus: the mechanistic evidence linking Rab2 to membrane trafficking derives from mammalian Rab2, which recruits P. falciparum GAPDH to microsomal membranes via the GAPDH N-terminal domain (residues 1\\u2013192) in a heterologous binding assay establishing conservation of the recruitment mechanism rather than an activity of PF3D7_1231100 itself [#1]. Within the parasite, RAB2 protein is upregulated under proteasomal stress [#2] and was recovered as a putative co-immunoprecipitating partner of the casein kinase PfCK1 [#3], and in silico network analysis places it alongside ERD2 and Rab1 as a candidate regulator of COPII-dependent ER-to-Golgi trafficking [#4]. Beyond these correlative, heterologous, and computational observations, no direct in vivo functional experiment on PF3D7_1231100 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing whether RAB2 is expressed at all in the blood stage was the first prerequisite for any functional hypothesis; transcription testing confirmed it is expressed and, by analogy to yeast, tentatively assigned a trafficking/vacuole role.\",\n      \"evidence\": \"Experimental transcription testing plus phylogenetic comparison across the P. falciparum Rab family in infected erythrocytes\",\n      \"pmids\": [\"12657463\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Vacuole-size role is pure phylogenetic inference with no functional assay\",\n        \"No protein-level detection or localization of RAB2\",\n        \"No GTPase activity demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"To test whether Rab2-dependent membrane recruitment is conserved for a Plasmodium substrate, GAPDH recruitment was reconstituted heterologously, showing pfGAPDH binds microsomal membranes in a Rab2-dependent manner through its N-terminal domain.\",\n      \"evidence\": \"Quantitative HeLa microsomal membrane binding assay with mammalian Rab2 and competitive inhibition by recombinant pfGAPDH fragments (residues 1\\u2013192)\",\n      \"pmids\": [\"12974391\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Used mammalian Rab2, not PF3D7_1231100, so the activity is not demonstrated for the parasite protein\",\n        \"No evidence this interaction occurs in the parasite\",\n        \"Functional consequence of GAPDH recruitment unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether RAB2 responds to cellular stress was probed by global proteomics, revealing upregulation of RAB2 protein under proteasome inhibition and hinting at increased trafficking as a homeostatic response.\",\n      \"evidence\": \"Quantitative global proteomics of proteasome-inhibitor-treated P. falciparum parasites\",\n      \"pmids\": [\"26136076\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Correlative abundance change only, no functional manipulation\",\n        \"Mechanism linking proteasomal stress to RAB2 levels unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To place RAB2 in a signaling context, PfCK1 interactome profiling recovered RAB2 as a putative partner, connecting it to kinase-regulated trafficking pathways.\",\n      \"evidence\": \"Co-immunoprecipitation/mass spectrometry from parasites expressing tagged PfCK1\",\n      \"pmids\": [\"26629826\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS without reciprocal pulldown\",\n        \"No validation that RAB2 is a direct PfCK1 substrate or binder\",\n        \"No functional follow-up on RAB2\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"A computational attempt to assign RAB2 to a defined trafficking step predicted it, with ERD2 and Rab1, as a COPII regulatory protein in ER-to-Golgi transport.\",\n      \"evidence\": \"In silico protein interaction network analysis of P. falciparum COPII complexes\",\n      \"pmids\": [\"30704415\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational, no experimental validation of RAB2\\u2013COPII association\",\n        \"No demonstration of RAB2 localization to ER-Golgi membranes\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Testing whether the host-cell Rab2 trafficking machinery is required by intracellular parasites, dominant-negative host Rab2a caused only a transient early liver-stage delay in P. berghei, indicating host Rab2 is largely dispensable and leaving the parasite's own RAB2 untested.\",\n      \"evidence\": \"Bioluminescence imaging of P. berghei liver-stage parasites in HeLa cells expressing dominant-negative host Rab2a\",\n      \"pmids\": [\"34013963\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Tests host-cell Rab2a, not parasite PF3D7_1231100\",\n        \"Different species (P. berghei) and life-cycle stage than the blood-stage RAB2 findings\",\n        \"Minor/negative phenotype limits interpretation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No direct in vivo functional experiment has been performed on the parasite's own RAB2 protein; its GTPase activity, membrane localization, effectors, and role in COPII/ER-to-Golgi trafficking within the parasite remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockout, knockdown, or conditional depletion of PF3D7_1231100\",\n        \"No demonstrated GTPase activity or GEF/GAP/effector for the parasite protein\",\n        \"No direct subcellular localization of RAB2 in P. falciparum\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GTPase activity\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"ER-to-Golgi vesicular transport\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"vesicle-mediated transport\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"COPII vesicle regulation\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfCK1 (casein kinase 1) — putative co-IP interactor [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Transcribed in P. falciparum-infected erythrocytes; vacuole-size role inferred only phylogenetically [#0]\",\n      \"Mammalian Rab2 (not PF3D7_1231100) recruits P. falciparum GAPDH to microsomal membranes via the GAPDH N-terminal domain, demonstrating conservation of the recruitment mechanism [#1]\",\n      \"RAB2 protein upregulated under proteasomal stress in P. falciparum [#2]\",\n      \"Predicted COPII regulator alongside ERD2 and Rab1 by in silico network analysis [#4]\",\n      \"Dominant-negative HOST-cell Rab2a caused only transient early P. berghei liver-stage delay; this tests host Rab2, not the parasite RAB2 [#5]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1231100","name":null,"product":"ras-related protein Rab-2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1445800","name":null,"product":"ras-related protein Rab-2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1450500","name":null,"product":"ras-related protein Rab-2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAB2","evaluation":null}