{"gene":"PF3D7_0512600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2021,"finding":"RAB1b (PF3D7_0512600) was isolated as a binding partner of PfRab5b by co-immunoprecipitation and mass spectrometry in P. falciparum, and both proteins co-localize adjacent to the ER in early erythrocytic stages. Super-resolution immunofluorescence showed RAB1b and PfArf1 localize to different ER subdomains. Expression of an inactive mutant of RAB1b decreased export of the PEXEL-positive protein Rifin, whereas RAB1b mutants did not affect transport of N-myristoylated adenylate kinase 2 (PfAK2) to the parasitophorous vacuole membrane.","method":"Co-immunoprecipitation with mass spectrometry, super-resolution immunofluorescence, and expression of active/inactive GTPase mutants with trafficking readouts","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP/MS identification plus functional mutant analysis and super-resolution localization, single lab","pmids":["33604307"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"RAB1b (PF3D7_0512600) was co-immunoprecipitated with K13 (the artemisinin-resistance protein) using K13-specific monoclonal antibodies in P. falciparum, placing RAB1b among a set of Rab GTPases physically associated with K13 in vesicular trafficking compartments.","method":"Co-immunoprecipitation with K13-specific monoclonal antibodies followed by mass spectrometry","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS identification, no functional follow-up specific to RAB1b, single lab","pmids":["32310999"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"RAB1b (PF3D7_0512600) is transcribed in P. falciparum infected erythrocytes, as demonstrated by experimental testing of transcription predictions; the gene is one of 11 members of the P. falciparum Rab GTPase family.","method":"Experimental verification of transcription (RT-based) combined with bioinformatic and phylogenetic analyses","journal":"Gene","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcription confirmation only, no protein-level functional experiment specific to RAB1b, single study","pmids":["12657463"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum RAB1b (PF3D7_0512600) is a Rab GTPase that localizes to a subdomain of the ER in early erythrocytic stages, physically associates with PfRab5b and K13, and is required (based on inactive-mutant expression) for efficient export of PEXEL-positive proteins such as Rifin, but does not appear to regulate transport of the PEXEL-negative protein PfAK2 to the parasitophorous vacuole."},"narrative":{"mechanistic_narrative":"PF3D7_0512600 (RAB1b) is a member of the P. falciparum Rab GTPase family that functions in early-secretory/ER-associated vesicular trafficking during the erythrocytic stage [PMID:33604307, PMID:12657463]. RAB1b was identified as a binding partner of PfRab5b, with which it co-localizes at a subdomain adjacent to the ER; super-resolution imaging places RAB1b in an ER subdomain distinct from that occupied by PfArf1 [PMID:33604307]. Functionally, expression of a GTPase-inactive RAB1b mutant reduces export of the PEXEL-positive protein Rifin but does not perturb delivery of the N-myristoylated, PEXEL-negative protein PfAK2 to the parasitophorous vacuole membrane, indicating a selective role in PEXEL-dependent protein export [PMID:33604307]. RAB1b is also physically associated with the artemisinin-resistance protein K13 in vesicular trafficking compartments [PMID:32310999]. Beyond these associations and the mutant-based export phenotype, the biochemical activity, effectors, and regulatory cycle of RAB1b itself have not been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing that PF3D7_0512600 is an expressed member of the parasite Rab GTPase family confirmed it as a bona fide candidate trafficking regulator rather than a pseudogene.","evidence":"Experimental verification of transcription in infected erythrocytes with phylogenetic assignment to the 11-member P. falciparum Rab family","pmids":["12657463"],"confidence":"Low","gaps":["Transcription confirmation only; no protein-level or functional data specific to RAB1b","No evidence of GTPase activity or subcellular localization at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Physical association of RAB1b with the artemisinin-resistance protein K13 placed it within K13-linked vesicular trafficking compartments, hinting at a role in the pathways relevant to drug resistance.","evidence":"Co-immunoprecipitation with K13-specific monoclonal antibodies followed by mass spectrometry in P. falciparum","pmids":["32310999"],"confidence":"Low","gaps":["Single Co-IP/MS identification with no RAB1b-specific functional follow-up","Direct versus indirect nature of the K13 association not resolved","Functional consequence of the K13–RAB1b association for resistance untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Reciprocal interaction with PfRab5b, ER-subdomain localization, and mutant-based trafficking assays defined a selective function for RAB1b in PEXEL-dependent protein export.","evidence":"Co-IP/MS identification of PfRab5b binding, super-resolution immunofluorescence, and expression of active/inactive GTPase mutants with Rifin versus PfAK2 trafficking readouts","pmids":["33604307"],"confidence":"Medium","gaps":["Inactive-mutant overexpression is indirect; no direct loss-of-function (knockout/knockdown) of RAB1b","Effectors, GEF/GAP regulators, and intrinsic GTPase activity of RAB1b not defined","Mechanism distinguishing PEXEL-positive from PEXEL-negative cargo not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How RAB1b's GTPase cycle is regulated and which effectors mediate its role in PEXEL-dependent export remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No GEF, GAP, or effector identified for RAB1b","No direct-depletion phenotype or structural model","Functional significance of the K13 association untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFRAB5B","K13","PFARF1 (DISTINCT ER SUBDOMAIN, NOT A BINDING PARTNER)"],"other_free_text":["Inactive-mutant expression reduces export of the PEXEL-positive protein Rifin but not transport of the PEXEL-negative protein PfAK2 to the parasitophorous vacuole membrane [#0]","Member of the 11-member P. falciparum Rab GTPase family, transcribed in infected erythrocytes [#2]"]}},"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":"33604307","id":"PMC_33604307","title":"Rab5b-Associated Arf1 GTPase Regulates Export of N-Myristoylated Adenylate Kinase 2 From the Endoplasmic Reticulum in Plasmodium falciparum.","date":"2021","source":"Frontiers in cellular and infection 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Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/34440567","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB1b"],"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":["RAB1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30609697","id":"","title":"Druggable Targets in Cyclic Nucleotide Signaling Pathways in Apicomplexan Parasites and Kinetoplastids against Disabling Protozoan Diseases in Humans.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30609697","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB1b"],"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":["RAB1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22911692","id":"","title":"Bacteria and protozoa differentially modulate the expression of Rab proteins.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22911692","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22873208","id":"","title":"Untangling the evolution of Rab G proteins: implications of a comprehensive genomic analysis.","date":"2012","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/22873208","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAB1b"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14074,"output_tokens":956,"usd":0.028281,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5674,"output_tokens":1883,"usd":0.037722,"stage2_stop_reason":"end_turn"},"total_usd":0.066003,"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\": 2021,\n      \"finding\": \"RAB1b (PF3D7_0512600) was isolated as a binding partner of PfRab5b by co-immunoprecipitation and mass spectrometry in P. falciparum, and both proteins co-localize adjacent to the ER in early erythrocytic stages. Super-resolution immunofluorescence showed RAB1b and PfArf1 localize to different ER subdomains. Expression of an inactive mutant of RAB1b decreased export of the PEXEL-positive protein Rifin, whereas RAB1b mutants did not affect transport of N-myristoylated adenylate kinase 2 (PfAK2) to the parasitophorous vacuole membrane.\",\n      \"method\": \"Co-immunoprecipitation with mass spectrometry, super-resolution immunofluorescence, and expression of active/inactive GTPase mutants with trafficking readouts\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP/MS identification plus functional mutant analysis and super-resolution localization, single lab\",\n      \"pmids\": [\"33604307\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RAB1b (PF3D7_0512600) was co-immunoprecipitated with K13 (the artemisinin-resistance protein) using K13-specific monoclonal antibodies in P. falciparum, placing RAB1b among a set of Rab GTPases physically associated with K13 in vesicular trafficking compartments.\",\n      \"method\": \"Co-immunoprecipitation with K13-specific monoclonal antibodies followed by mass spectrometry\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS identification, no functional follow-up specific to RAB1b, single lab\",\n      \"pmids\": [\"32310999\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"RAB1b (PF3D7_0512600) is transcribed in P. falciparum infected erythrocytes, as demonstrated by experimental testing of transcription predictions; the gene is one of 11 members of the P. falciparum Rab GTPase family.\",\n      \"method\": \"Experimental verification of transcription (RT-based) combined with bioinformatic and phylogenetic analyses\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcription confirmation only, no protein-level functional experiment specific to RAB1b, single study\",\n      \"pmids\": [\"12657463\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum RAB1b (PF3D7_0512600) is a Rab GTPase that localizes to a subdomain of the ER in early erythrocytic stages, physically associates with PfRab5b and K13, and is required (based on inactive-mutant expression) for efficient export of PEXEL-positive proteins such as Rifin, but does not appear to regulate transport of the PEXEL-negative protein PfAK2 to the parasitophorous vacuole.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0512600 (RAB1b) is a member of the P. falciparum Rab GTPase family that functions in early-secretory/ER-associated vesicular trafficking during the erythrocytic stage [#0, #2]. RAB1b was identified as a binding partner of PfRab5b, with which it co-localizes at a subdomain adjacent to the ER; super-resolution imaging places RAB1b in an ER subdomain distinct from that occupied by PfArf1 [#0]. Functionally, expression of a GTPase-inactive RAB1b mutant reduces export of the PEXEL-positive protein Rifin but does not perturb delivery of the N-myristoylated, PEXEL-negative protein PfAK2 to the parasitophorous vacuole membrane, indicating a selective role in PEXEL-dependent protein export [#0]. RAB1b is also physically associated with the artemisinin-resistance protein K13 in vesicular trafficking compartments [#1]. Beyond these associations and the mutant-based export phenotype, the biochemical activity, effectors, and regulatory cycle of RAB1b itself have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing that PF3D7_0512600 is an expressed member of the parasite Rab GTPase family confirmed it as a bona fide candidate trafficking regulator rather than a pseudogene.\",\n      \"evidence\": \"Experimental verification of transcription in infected erythrocytes with phylogenetic assignment to the 11-member P. falciparum Rab family\",\n      \"pmids\": [\"12657463\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcription confirmation only; no protein-level or functional data specific to RAB1b\",\n        \"No evidence of GTPase activity or subcellular localization at this stage\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Physical association of RAB1b with the artemisinin-resistance protein K13 placed it within K13-linked vesicular trafficking compartments, hinting at a role in the pathways relevant to drug resistance.\",\n      \"evidence\": \"Co-immunoprecipitation with K13-specific monoclonal antibodies followed by mass spectrometry in P. falciparum\",\n      \"pmids\": [\"32310999\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS identification with no RAB1b-specific functional follow-up\",\n        \"Direct versus indirect nature of the K13 association not resolved\",\n        \"Functional consequence of the K13–RAB1b association for resistance untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Reciprocal interaction with PfRab5b, ER-subdomain localization, and mutant-based trafficking assays defined a selective function for RAB1b in PEXEL-dependent protein export.\",\n      \"evidence\": \"Co-IP/MS identification of PfRab5b binding, super-resolution immunofluorescence, and expression of active/inactive GTPase mutants with Rifin versus PfAK2 trafficking readouts\",\n      \"pmids\": [\"33604307\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Inactive-mutant overexpression is indirect; no direct loss-of-function (knockout/knockdown) of RAB1b\",\n        \"Effectors, GEF/GAP regulators, and intrinsic GTPase activity of RAB1b not defined\",\n        \"Mechanism distinguishing PEXEL-positive from PEXEL-negative cargo not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RAB1b's GTPase cycle is regulated and which effectors mediate its role in PEXEL-dependent export remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No GEF, GAP, or effector identified for RAB1b\",\n        \"No direct-depletion phenotype or structural model\",\n        \"Functional significance of the K13 association untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005789\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfRab5b\", \"K13\", \"PfArf1 (distinct ER subdomain, not a binding partner)\"],\n    \"other_free_text\": [\n      \"Inactive-mutant expression reduces export of the PEXEL-positive protein Rifin but not transport of the PEXEL-negative protein PfAK2 to the parasitophorous vacuole membrane [#0]\",\n      \"Member of the 11-member P. falciparum Rab GTPase family, transcribed in infected erythrocytes [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0512600","name":null,"product":"ras-related protein Rab-1B","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1112300","name":null,"product":"ras-related protein Rab-1B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1020500","name":null,"product":"ras-related protein Rab-1B, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAB1b","evaluation":null}