{"gene":"PF3D7_1106000","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2013,"finding":"PfRuvB2 (PF3D7_1106000) possesses ATPase activity and weak DNA helicase activity in vitro, as demonstrated with recombinant and endogenous protein preparations.","method":"In vitro ATPase and DNA helicase activity assays using recombinant and endogenous PfRuvB2","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro enzymatic assays on recombinant and endogenous protein, single lab, single study","pmids":["24161468"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PfRuvB2 (PF3D7_1106000) interacts with PfRuvB3 but not with PfRuvB1, as established by immunopurification of the PfRuvB3 complex followed by in vitro interaction studies.","method":"Immunopurification (co-immunopurification) of PfRuvB3 complex and in vitro interaction assay","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal complex purification plus direct in vitro interaction assay, single lab, single study","pmids":["24161468"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"The helicase activity of PfRuvB2 (PF3D7_1106000) is significantly upregulated by PfRuvB3 when added to the helicase reaction, and the PfRuvB2/PfRuvB3 complex preferentially translocates and unwinds DNA in the 5'-3' direction.","method":"In vitro DNA helicase activity assay with and without PfRuvB3; directional translocation assay","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct enzymatic reconstitution with defined components showing stimulation, single lab, single study","pmids":["24161468"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PfRuvB2 (PF3D7_1106000) is expressed in all asexual intraerythrocytic developmental stages and localizes predominantly to the nucleus during merozoite, ring, and trophozoite stages, but relocalizes partially to the cytoplasm during schizont stage, coinciding with the stage at which PfRuvB3 (an intraerythrocytic mitosis-specific protein) is present.","method":"In vivo immunofluorescence/localization studies across intraerythrocytic stages","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — direct localization experiment with stage-specific functional context, single lab, single study","pmids":["24161468"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1106000 (RUVB2) is a nuclear AAA+ ATPase with weak intrinsic DNA helicase activity that translocates 5'→3', physically interacts with PfRuvB3 (but not PfRuvB1) in a complex that significantly stimulates its helicase activity, and relocalizes partially from the nucleus to the cytoplasm during schizont stage, suggesting that PfRuvB3 modulates RUVB2 enzymatic activity specifically during intraerythrocytic mitosis."},"narrative":{"mechanistic_narrative":"PF3D7_1106000 (RUVB2) is a nuclear AAA+ ATPase of Plasmodium falciparum that couples ATP hydrolysis to weak intrinsic DNA helicase activity, positioning it as an enzymatic component of the parasite's intraerythrocytic developmental program [PMID:24161468]. Recombinant and endogenous RUVB2 hydrolyze ATP and unwind DNA in vitro, but the helicase activity is only weak on its own [PMID:24161468]. RUVB2 physically associates with PfRuvB3, and specifically not with PfRuvB1, and PfRuvB3 significantly stimulates RUVB2 helicase activity, with the RUVB2/PfRuvB3 complex preferentially translocating and unwinding DNA in the 5'→3' direction [PMID:24161468]. RUVB2 is expressed throughout asexual intraerythrocytic development and is predominantly nuclear in merozoite, ring, and trophozoite stages, but partially relocalizes to the cytoplasm during the schizont stage, coinciding with the appearance of the mitosis-specific partner PfRuvB3 [PMID:24161468]. Beyond this in vitro enzymatic and interaction characterization, no further mechanistic role, substrate, or in vivo function of RUVB2 has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing that RUVB2 is itself an enzyme addressed whether the protein carries catalytic activity or is merely a structural complex member, demonstrating it is an ATP-hydrolyzing DNA helicase.","evidence":"In vitro ATPase and DNA helicase assays on recombinant and endogenous RUVB2","pmids":["24161468"],"confidence":"Medium","gaps":["helicase activity is weak, leaving the physiological substrate unidentified","no structural model of the active site or nucleotide-binding fold","activity shown only in vitro, not linked to an in vivo DNA transaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Defining RUVB2's binding partner clarified which RuvB-family members it partners with, showing a selective interaction with PfRuvB3 and not PfRuvB1.","evidence":"Immunopurification of the PfRuvB3 complex plus in vitro interaction assay","pmids":["24161468"],"confidence":"Medium","gaps":["stoichiometry and higher-order architecture of the RUVB2/PfRuvB3 complex not resolved","interaction interface not mapped","whether additional proteins join this complex in vivo is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Reconstituting RUVB2 with PfRuvB3 answered whether the partner modulates catalysis, showing PfRuvB3 stimulates RUVB2 helicase activity and confers 5'→3' directional translocation.","evidence":"In vitro DNA helicase assay with/without PfRuvB3 and directional translocation assay","pmids":["24161468"],"confidence":"Medium","gaps":["the DNA substrate acted upon in the cell is not identified","mechanism by which PfRuvB3 stimulates activity not defined","biological process requiring this unwinding activity unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Mapping RUVB2 expression and localization across the asexual cycle addressed when and where the enzyme acts, showing predominantly nuclear localization that partially shifts to the cytoplasm at schizont stage in concert with PfRuvB3.","evidence":"In vivo immunofluorescence/localization across intraerythrocytic developmental stages","pmids":["24161468"],"confidence":"Medium","gaps":["functional consequence of the schizont-stage cytoplasmic relocalization unknown","no loss-of-function or essentiality data for RUVB2","trigger driving the nuclear-to-cytoplasmic shift not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo DNA transaction, cellular process, and essentiality of RUVB2 remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no genetic knockout/knockdown phenotype for RUVB2","physiological DNA substrate and pathway (e.g. replication, repair, chromatin remodeling) not established","structural basis of RUVB2/PfRuvB3 complex not determined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RUVB2/PfRuvB3 helicase complex [#1, #2]"],"partners":["PFRUVB3 (INTERACTS AND STIMULATES ACTIVITY) [#1, #2]","PFRUVB1 (DOES NOT INTERACT) [#1]"],"other_free_text":["RUVB2 helicase activity is weak on its own and significantly stimulated by PfRuvB3 [#0, #2]","RUVB2/PfRuvB3 complex translocates and unwinds DNA preferentially in the 5'→3' direction [#2]","Expressed throughout asexual intraerythrocytic development; partial nuclear-to-cytoplasmic relocalization at schizont stage coincides with PfRuvB3 presence [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23060959","id":"PMC_23060959","title":"Plasmodium falciparum RuvB proteins: Emerging importance and expectations beyond cell cycle progression.","date":"2012","source":"Communicative & integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/23060959","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23219504","id":"PMC_23219504","title":"Plasmodium falciparum RuvB1 is an active DNA helicase and translocates in the 5'-3' direction.","date":"2012","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/23219504","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RUVB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24161468","id":"PMC_24161468","title":"Plasmodium falciparum RuvB2 translocates in 5'-3' direction, relocalizes during schizont stage and its enzymatic activities are up regulated by RuvB3 of the same complex.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/24161468","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RUVB2","PfRUVB2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4205,"output_tokens":1107,"usd":0.01461,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5865,"output_tokens":2311,"usd":0.04355,"stage2_stop_reason":"end_turn"},"total_usd":0.05816,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"PfRuvB2 (PF3D7_1106000) possesses ATPase activity and weak DNA helicase activity in vitro, as demonstrated with recombinant and endogenous protein preparations.\",\n      \"method\": \"In vitro ATPase and DNA helicase activity assays using recombinant and endogenous PfRuvB2\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro enzymatic assays on recombinant and endogenous protein, single lab, single study\",\n      \"pmids\": [\"24161468\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PfRuvB2 (PF3D7_1106000) interacts with PfRuvB3 but not with PfRuvB1, as established by immunopurification of the PfRuvB3 complex followed by in vitro interaction studies.\",\n      \"method\": \"Immunopurification (co-immunopurification) of PfRuvB3 complex and in vitro interaction assay\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal complex purification plus direct in vitro interaction assay, single lab, single study\",\n      \"pmids\": [\"24161468\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The helicase activity of PfRuvB2 (PF3D7_1106000) is significantly upregulated by PfRuvB3 when added to the helicase reaction, and the PfRuvB2/PfRuvB3 complex preferentially translocates and unwinds DNA in the 5'-3' direction.\",\n      \"method\": \"In vitro DNA helicase activity assay with and without PfRuvB3; directional translocation assay\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct enzymatic reconstitution with defined components showing stimulation, single lab, single study\",\n      \"pmids\": [\"24161468\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PfRuvB2 (PF3D7_1106000) is expressed in all asexual intraerythrocytic developmental stages and localizes predominantly to the nucleus during merozoite, ring, and trophozoite stages, but relocalizes partially to the cytoplasm during schizont stage, coinciding with the stage at which PfRuvB3 (an intraerythrocytic mitosis-specific protein) is present.\",\n      \"method\": \"In vivo immunofluorescence/localization studies across intraerythrocytic stages\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — direct localization experiment with stage-specific functional context, single lab, single study\",\n      \"pmids\": [\"24161468\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1106000 (RUVB2) is a nuclear AAA+ ATPase with weak intrinsic DNA helicase activity that translocates 5'→3', physically interacts with PfRuvB3 (but not PfRuvB1) in a complex that significantly stimulates its helicase activity, and relocalizes partially from the nucleus to the cytoplasm during schizont stage, suggesting that PfRuvB3 modulates RUVB2 enzymatic activity specifically during intraerythrocytic mitosis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1106000 (RUVB2) is a nuclear AAA+ ATPase of Plasmodium falciparum that couples ATP hydrolysis to weak intrinsic DNA helicase activity, positioning it as an enzymatic component of the parasite's intraerythrocytic developmental program [#0]. Recombinant and endogenous RUVB2 hydrolyze ATP and unwind DNA in vitro, but the helicase activity is only weak on its own [#0]. RUVB2 physically associates with PfRuvB3, and specifically not with PfRuvB1, and PfRuvB3 significantly stimulates RUVB2 helicase activity, with the RUVB2/PfRuvB3 complex preferentially translocating and unwinding DNA in the 5'\\u21923' direction [#1, #2]. RUVB2 is expressed throughout asexual intraerythrocytic development and is predominantly nuclear in merozoite, ring, and trophozoite stages, but partially relocalizes to the cytoplasm during the schizont stage, coinciding with the appearance of the mitosis-specific partner PfRuvB3 [#3]. Beyond this in vitro enzymatic and interaction characterization, no further mechanistic role, substrate, or in vivo function of RUVB2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing that RUVB2 is itself an enzyme addressed whether the protein carries catalytic activity or is merely a structural complex member, demonstrating it is an ATP-hydrolyzing DNA helicase.\",\n      \"evidence\": \"In vitro ATPase and DNA helicase assays on recombinant and endogenous RUVB2\",\n      \"pmids\": [\"24161468\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"helicase activity is weak, leaving the physiological substrate unidentified\",\n        \"no structural model of the active site or nucleotide-binding fold\",\n        \"activity shown only in vitro, not linked to an in vivo DNA transaction\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defining RUVB2's binding partner clarified which RuvB-family members it partners with, showing a selective interaction with PfRuvB3 and not PfRuvB1.\",\n      \"evidence\": \"Immunopurification of the PfRuvB3 complex plus in vitro interaction assay\",\n      \"pmids\": [\"24161468\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"stoichiometry and higher-order architecture of the RUVB2/PfRuvB3 complex not resolved\",\n        \"interaction interface not mapped\",\n        \"whether additional proteins join this complex in vivo is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Reconstituting RUVB2 with PfRuvB3 answered whether the partner modulates catalysis, showing PfRuvB3 stimulates RUVB2 helicase activity and confers 5'\\u21923' directional translocation.\",\n      \"evidence\": \"In vitro DNA helicase assay with/without PfRuvB3 and directional translocation assay\",\n      \"pmids\": [\"24161468\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"the DNA substrate acted upon in the cell is not identified\",\n        \"mechanism by which PfRuvB3 stimulates activity not defined\",\n        \"biological process requiring this unwinding activity unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Mapping RUVB2 expression and localization across the asexual cycle addressed when and where the enzyme acts, showing predominantly nuclear localization that partially shifts to the cytoplasm at schizont stage in concert with PfRuvB3.\",\n      \"evidence\": \"In vivo immunofluorescence/localization across intraerythrocytic developmental stages\",\n      \"pmids\": [\"24161468\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"functional consequence of the schizont-stage cytoplasmic relocalization unknown\",\n        \"no loss-of-function or essentiality data for RUVB2\",\n        \"trigger driving the nuclear-to-cytoplasmic shift not identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo DNA transaction, cellular process, and essentiality of RUVB2 remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no genetic knockout/knockdown phenotype for RUVB2\",\n        \"physiological DNA substrate and pathway (e.g. replication, repair, chromatin remodeling) not established\",\n        \"structural basis of RUVB2/PfRuvB3 complex not determined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0004386\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0043139\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"RUVB2/PfRuvB3 helicase complex [#1, #2]\"],\n    \"partners\": [\"PfRuvB3 (interacts and stimulates activity) [#1, #2]\", \"PfRuvB1 (does not interact) [#1]\"],\n    \"other_free_text\": [\n      \"RUVB2 helicase activity is weak on its own and significantly stimulated by PfRuvB3 [#0, #2]\",\n      \"RUVB2/PfRuvB3 complex translocates and unwinds DNA preferentially in the 5'\\u21923' direction [#2]\",\n      \"Expressed throughout asexual intraerythrocytic development; partial nuclear-to-cytoplasmic relocalization at schizont stage coincides with PfRuvB3 presence [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1106000","name":null,"product":"RuvB-like helicase 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0940900","name":null,"product":"RuvB-like helicase 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0903600","name":null,"product":"RuvB-like helicase 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RUVB2","evaluation":null}