{"gene":"PF3D7_0106800","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2014,"finding":"PbRab5C (the P. berghei ortholog of RAB5c) failed to complement loss of PbRab5B function in haploid asexual blood-stage P. berghei parasites, establishing that RAB5c has non-overlapping, distinct roles from RAB5b.","method":"Reverse genetics complementation assay in P. berghei (genetic epistasis/rescue experiment)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic complementation assay in P. berghei, single lab, single method; result is a negative (failure to complement) that is mechanistically informative","pmids":["24498355"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"PbRab5c (the P. berghei ortholog of RAB5c) did not complement the function of PbRab5b in a complementation analysis of Rab5 isotypes in P. berghei, further confirming that RAB5c and RAB5b have non-overlapping functions.","method":"Complementation analysis of Rab5 isotypes in P. berghei","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complementation assay replicated across two independent studies (PMIDs 24498355 and 27316546), both reporting the same negative result for RAB5c","pmids":["27316546"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"finding":"Rab5 proteins in P. falciparum (a group that includes RAB5c) dramatically mislocalize upon inhibition of the MEP isoprenoid biosynthesis pathway with fosmidomycin, consistent with loss of C-terminal prenylation required for membrane recruitment; this mislocalization correlates with defects in food vacuolar morphology and integrity.","method":"Fosmidomycin drug treatment followed by fluorescence microscopy of Rab5 localization; food vacuole morphology assessment","journal":"Eukaryotic cell","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization experiment implicates Rab5 family collectively; RAB5c is not individually distinguished from RAB5a/RAB5b in the experimental readout","pmids":["23223036"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"RAB5c (PF3D7_0106800) is one of three P. falciparum Rab5 GTPases and, based on complementation experiments in P. berghei, has a non-overlapping function distinct from RAB5b; it cannot substitute for RAB5b loss, suggesting unique trafficking roles, but its specific molecular mechanism, substrates, and localization have not been individually characterized."},"narrative":{"mechanistic_narrative":"RAB5c (PF3D7_0106800) is one of three Rab5-family GTPases in P. falciparum, and genetic evidence establishes that it carries out a distinct, non-overlapping trafficking function from its sibling RAB5b: the P. berghei ortholog of RAB5c fails to complement loss of RAB5b in asexual blood-stage parasites [PMID:24498355, PMID:27316546]. Beyond this functional distinction from RAB5b, the specific molecular activity, substrates, effectors, and individual localization of RAB5c have not been characterized in the available corpus. P. falciparum Rab5 proteins as a group mislocalize upon inhibition of the MEP isoprenoid pathway with fosmidomycin, consistent with a requirement for C-terminal prenylation for membrane recruitment and correlating with food-vacuole morphological defects, but this readout reflects the Rab5 family collectively and does not individually resolve RAB5c [PMID:23223036].","teleology":[{"year":2012,"claim":"The question of how P. falciparum Rab5 GTPases achieve their membrane localization was addressed by disrupting the isoprenoid supply, showing that Rab5 proteins depend on prenylation-linked membrane recruitment and are tied to food-vacuole integrity.","evidence":"Fosmidomycin inhibition of the MEP pathway with fluorescence microscopy of Rab5 localization and food-vacuole morphology in P. falciparum","pmids":["23223036"],"confidence":"Low","gaps":["The readout implicates the Rab5 family collectively and does not distinguish RAB5c from RAB5a or RAB5b","Prenylation of RAB5c was not directly demonstrated","No individual localization for RAB5c was established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Whether the three Rab5 isotypes are functionally redundant was tested by complementation, establishing that RAB5c cannot substitute for RAB5b and therefore performs a distinct trafficking role.","evidence":"Reverse-genetics complementation/epistasis assay using the P. berghei ortholog in haploid asexual blood-stage parasites","pmids":["24498355"],"confidence":"Medium","gaps":["A failure-to-complement is a negative result and does not define what RAB5c positively does","No substrates, effectors, or cargo identified","Result obtained in P. berghei ortholog, not directly in P. falciparum RAB5c"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"The non-redundancy of RAB5c with RAB5b was re-tested in an independent complementation analysis of all Rab5 isotypes, confirming the earlier negative complementation result.","evidence":"Complementation analysis of Rab5 isotypes using the P. berghei ortholog","pmids":["27316546"],"confidence":"Medium","gaps":["Still a negative complementation result; the specific RAB5c function remains undefined","No molecular mechanism, GEF/GAP, or effector identified","Findings rest on the P. berghei ortholog"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The specific molecular mechanism, subcellular localization, cargo, and effector partners of RAB5c remain undefined; the corpus establishes only that it is a Rab5-family GTPase with a role distinct from RAB5b.","evidence":"No direct experimental characterization of RAB5c alone in the available corpus","pmids":[],"confidence":"Low","gaps":["No individual localization of RAB5c determined","No GTPase activity, GEF/GAP, or effector interactions established","No cargo or vesicle-trafficking route assigned specifically to RAB5c"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["RAB5c is one of three P. falciparum Rab5-family GTPases; the timeline establishes only that its function is non-overlapping with RAB5b [#0, #1].","Prenylation-dependent membrane recruitment and food-vacuole integrity are attributes shown for the Rab5 family collectively, not resolved to RAB5c individually [#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":"23223036","id":"PMC_23223036","title":"Isoprenoid biosynthesis inhibition disrupts Rab5 localization and food vacuolar integrity in Plasmodium falciparum.","date":"2012","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/23223036","citation_count":56,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24498355","id":"PMC_24498355","title":"Plasmodium falciparum Rab5B is an N-terminally myristoylated Rab GTPase that is targeted to the parasite's plasma and food vacuole membranes.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24498355","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PbRAB5c"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27316546","id":"PMC_27316546","title":"Plasmodium Rab5b is secreted to the cytoplasmic face of the tubovesicular network in infected red blood cells together with N-acylated adenylate kinase 2.","date":"2016","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/27316546","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PbRAB5c"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5313,"output_tokens":1271,"usd":0.017502,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5545,"output_tokens":1808,"usd":0.036463,"stage2_stop_reason":"end_turn"},"total_usd":0.053965,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully identify which papers are about PF3D7_0106800 (RAB5c) versus its siblings RAB5a and RAB5b.\n\n- Paper [1]: Describes the whole P. falciparum Rab GTPase family including Pfrab5a and Pfrab5b, but mentions PfRab5C only implicitly as one of 11 family members. No specific mechanistic experiments on RAB5c.\n- Paper [2]: Studies \"Rab5 proteins\" (plural, mislocalization upon fosmidomycin) — includes RAB5c but does not distinguish individual Rab5 isotypes mechanistically. Mentions Rab5 proteins mislocalize.\n- Paper [3]: Focused on PfRab5B. Mentions that PbRab5A or PbRab5C FAILED to complement PbRab5B loss — this is a negative result for RAB5c's ability to substitute for RAB5b, which is mechanistically informative.\n- Paper [4]: Focused on PfRab5b. Also performs complementation analysis in P. berghei and confirms PbRab5a or PbRab5c did NOT complement PbRab5b — negative result for RAB5c.\n\nFrom papers [3] and [4]: The finding that PbRab5C cannot complement PbRab5B function is a negative result about RAB5c — it establishes non-overlapping roles.\n\nFrom paper [2]: Rab5 proteins (as a group including RAB5c) mislocalize upon fosmidomycin/MEP pathway inhibition. Since the paper lumps Rab5 isotypes together, I can note this with low specificity to RAB5c.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"PbRab5C (the P. berghei ortholog of RAB5c) failed to complement loss of PbRab5B function in haploid asexual blood-stage P. berghei parasites, establishing that RAB5c has non-overlapping, distinct roles from RAB5b.\",\n      \"method\": \"Reverse genetics complementation assay in P. berghei (genetic epistasis/rescue experiment)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic complementation assay in P. berghei, single lab, single method; result is a negative (failure to complement) that is mechanistically informative\",\n      \"pmids\": [\"24498355\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PbRab5c (the P. berghei ortholog of RAB5c) did not complement the function of PbRab5b in a complementation analysis of Rab5 isotypes in P. berghei, further confirming that RAB5c and RAB5b have non-overlapping functions.\",\n      \"method\": \"Complementation analysis of Rab5 isotypes in P. berghei\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complementation assay replicated across two independent studies (PMIDs 24498355 and 27316546), both reporting the same negative result for RAB5c\",\n      \"pmids\": [\"27316546\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Rab5 proteins in P. falciparum (a group that includes RAB5c) dramatically mislocalize upon inhibition of the MEP isoprenoid biosynthesis pathway with fosmidomycin, consistent with loss of C-terminal prenylation required for membrane recruitment; this mislocalization correlates with defects in food vacuolar morphology and integrity.\",\n      \"method\": \"Fosmidomycin drug treatment followed by fluorescence microscopy of Rab5 localization; food vacuole morphology assessment\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization experiment implicates Rab5 family collectively; RAB5c is not individually distinguished from RAB5a/RAB5b in the experimental readout\",\n      \"pmids\": [\"23223036\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"RAB5c (PF3D7_0106800) is one of three P. falciparum Rab5 GTPases and, based on complementation experiments in P. berghei, has a non-overlapping function distinct from RAB5b; it cannot substitute for RAB5b loss, suggesting unique trafficking roles, but its specific molecular mechanism, substrates, and localization have not been individually characterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RAB5c (PF3D7_0106800) is one of three Rab5-family GTPases in P. falciparum, and genetic evidence establishes that it carries out a distinct, non-overlapping trafficking function from its sibling RAB5b: the P. berghei ortholog of RAB5c fails to complement loss of RAB5b in asexual blood-stage parasites [#0, #1]. Beyond this functional distinction from RAB5b, the specific molecular activity, substrates, effectors, and individual localization of RAB5c have not been characterized in the available corpus. P. falciparum Rab5 proteins as a group mislocalize upon inhibition of the MEP isoprenoid pathway with fosmidomycin, consistent with a requirement for C-terminal prenylation for membrane recruitment and correlating with food-vacuole morphological defects, but this readout reflects the Rab5 family collectively and does not individually resolve RAB5c [#2].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"The question of how P. falciparum Rab5 GTPases achieve their membrane localization was addressed by disrupting the isoprenoid supply, showing that Rab5 proteins depend on prenylation-linked membrane recruitment and are tied to food-vacuole integrity.\",\n      \"evidence\": \"Fosmidomycin inhibition of the MEP pathway with fluorescence microscopy of Rab5 localization and food-vacuole morphology in P. falciparum\",\n      \"pmids\": [\"23223036\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"The readout implicates the Rab5 family collectively and does not distinguish RAB5c from RAB5a or RAB5b\",\n        \"Prenylation of RAB5c was not directly demonstrated\",\n        \"No individual localization for RAB5c was established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether the three Rab5 isotypes are functionally redundant was tested by complementation, establishing that RAB5c cannot substitute for RAB5b and therefore performs a distinct trafficking role.\",\n      \"evidence\": \"Reverse-genetics complementation/epistasis assay using the P. berghei ortholog in haploid asexual blood-stage parasites\",\n      \"pmids\": [\"24498355\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"A failure-to-complement is a negative result and does not define what RAB5c positively does\",\n        \"No substrates, effectors, or cargo identified\",\n        \"Result obtained in P. berghei ortholog, not directly in P. falciparum RAB5c\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The non-redundancy of RAB5c with RAB5b was re-tested in an independent complementation analysis of all Rab5 isotypes, confirming the earlier negative complementation result.\",\n      \"evidence\": \"Complementation analysis of Rab5 isotypes using the P. berghei ortholog\",\n      \"pmids\": [\"27316546\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Still a negative complementation result; the specific RAB5c function remains undefined\",\n        \"No molecular mechanism, GEF/GAP, or effector identified\",\n        \"Findings rest on the P. berghei ortholog\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular mechanism, subcellular localization, cargo, and effector partners of RAB5c remain undefined; the corpus establishes only that it is a Rab5-family GTPase with a role distinct from RAB5b.\",\n      \"evidence\": \"No direct experimental characterization of RAB5c alone in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No individual localization of RAB5c determined\",\n        \"No GTPase activity, GEF/GAP, or effector interactions established\",\n        \"No cargo or vesicle-trafficking route assigned specifically to RAB5c\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"RAB5c is one of three P. falciparum Rab5-family GTPases; the timeline establishes only that its function is non-overlapping with RAB5b [#0, #1].\",\n      \"Prenylation-dependent membrane recruitment and food-vacuole integrity are attributes shown for the Rab5 family collectively, not resolved to RAB5c individually [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0106800","name":null,"product":"ras-related protein Rab-5C","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0206500","name":null,"product":"ras-related protein Rab-5C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0206700","name":null,"product":"ras-related protein Rab-5C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAB5c","evaluation":null}