{"gene":"PF3D7_0913200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2001,"finding":"PF3D7_0913200 (EF-1beta) is phosphorylated by protein kinase C (PKC), and this phosphorylation results in a ~400% increase in its nucleotide exchange activity, catalytically regenerating GTP-bound EF-1alpha for each translation elongation cycle.","method":"In vitro kinase assay with PKC; nucleotide exchange activity assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro biochemical assay establishing phosphorylation and functional consequence, single lab, single paper","pmids":["11251817"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2001,"finding":"PKC-phosphorylated EF-1beta (PF3D7_0913200) is selectively dephosphorylated by P. falciparum protein phosphatase 2C (PfPP2C), which downregulates nucleotide exchange activity back to basal levels, establishing PfPP2C as a writer/eraser regulating EF-1beta activity.","method":"Far-Western analysis to identify PfPP2C substrates; in vitro dephosphorylation assay with recombinant and native PfPP2C; nucleotide exchange activity assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro reconstitution of dephosphorylation and functional readout, single lab, single paper","pmids":["11251817"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"EF-1beta (PF3D7_0913200) forms a native multi-subunit translation elongation factor complex in P. falciparum that contains at least two copies of EF-1beta, the G-protein EF-1alpha, and two newly identified subunits EF-1gamma and EF-1delta; the complex was purified under native conditions by tandem affinity purification (TAP) of a PTP-tagged EF-1beta followed by mass spectrometry.","method":"Tandem affinity purification (TAP) of PTP-tagged EF-1beta expressed in transgenic parasites, followed by mass spectrometric identification of co-purifying proteins","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — native complex purification by TAP-MS in transgenic parasites, single lab, single paper","pmids":["17307963"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"EF-1beta (PF3D7_0913200) functions as a nucleotide exchange factor in P. falciparum translation elongation, regenerating GTP-bound EF-1alpha; its activity is upregulated ~4-fold by PKC-mediated phosphorylation and restored to basal levels by dephosphorylation via PfPP2C, and it assembles as at least two copies within a native elongation factor complex containing EF-1alpha, EF-1gamma, and EF-1delta."},"narrative":{"mechanistic_narrative":"EF-1beta (PF3D7_0913200) is a nucleotide exchange factor of the Plasmodium falciparum translation elongation machinery, regenerating GTP-bound EF-1alpha for successive elongation cycles [PMID:11251817]. Its exchange activity is dynamically regulated by reversible phosphorylation: protein kinase C phosphorylates EF-1beta and raises its nucleotide exchange activity roughly four-fold [PMID:11251817], while P. falciparum protein phosphatase 2C (PfPP2C) selectively dephosphorylates it and returns activity to basal levels, defining a writer/eraser pair that tunes EF-1beta output [PMID:11251817]. In native parasites EF-1beta assembles into a multi-subunit elongation factor complex containing at least two copies of itself together with EF-1alpha, EF-1gamma, and EF-1delta [PMID:17307963]. Beyond this biochemical and complex-membership picture, no structural model, in vivo essentiality data, or higher-resolution mechanism of EF-1beta has been characterized in the available corpus.","teleology":[{"year":2001,"claim":"Establishing that EF-1beta acts as a phosphorylation-controlled nucleotide exchange factor answered how P. falciparum couples a signaling kinase to the rate of GTP regeneration on EF-1alpha during elongation.","evidence":"In vitro PKC kinase assay coupled to a nucleotide exchange activity assay in P. falciparum","pmids":["11251817"],"confidence":"Medium","gaps":["Phosphosite(s) on EF-1beta not mapped","Functional consequence shown in vitro only, not in intact parasites","Identity of the physiological PKC-type kinase in vivo not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2001,"claim":"Identifying PfPP2C as the phosphatase that reverses PKC phosphorylation defined the eraser side of a reversible switch controlling EF-1beta exchange activity.","evidence":"Far-Western substrate identification plus in vitro dephosphorylation with recombinant and native PfPP2C and a nucleotide exchange readout in P. falciparum","pmids":["11251817"],"confidence":"Medium","gaps":["In vivo relevance of the phosphorylation/dephosphorylation cycle not demonstrated","Whether PfPP2C acts on EF-1beta within the native complex is unknown","Stoichiometry and kinetics of the switch not quantified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Native purification defined the composition of the EF-1beta-containing elongation factor complex, showing EF-1beta is a multi-copy subunit assembled with EF-1alpha, EF-1gamma, and EF-1delta.","evidence":"Tandem affinity purification of PTP-tagged EF-1beta from transgenic parasites followed by mass spectrometry in P. falciparum","pmids":["17307963"],"confidence":"Medium","gaps":["No structural model or subunit arrangement determined","How phosphorylation state affects complex assembly or activity not tested","Direct binary interactions among subunits not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether EF-1beta is essential in blood-stage parasites and how its phosphorylation cycle is integrated into translational control in vivo remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic knockout/knockdown phenotype in the corpus","No in vivo demonstration of the PKC/PfPP2C regulatory cycle","No structural characterization of EF-1beta or its complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Eukaryotic elongation factor 1 complex (EF-1beta, EF-1alpha, EF-1gamma, EF-1delta)"],"partners":["EF-1ALPHA","EF-1GAMMA","EF-1DELTA","PROTEIN KINASE C (PKC)","P. FALCIPARUM PROTEIN PHOSPHATASE 2C (PFPP2C)"],"other_free_text":["Nucleotide exchange activity increased ~4-fold by PKC phosphorylation and restored to basal levels by PfPP2C dephosphorylation [#0, #1]","Present in at least two copies within the native elongation factor complex [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11251817","id":"PMC_11251817","title":"Plasmodium protein phosphatase 2C dephosphorylates translation elongation factor 1beta and inhibits its PKC-mediated nucleotide exchange activity in vitro.","date":"2001","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11251817","citation_count":55,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EF-1beta","elongation factor 1-beta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17307963","id":"PMC_17307963","title":"Purification of components of the translation elongation factor complex of Plasmodium falciparum by tandem affinity purification.","date":"2007","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/17307963","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3850,"output_tokens":941,"usd":0.012833,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5642,"output_tokens":1887,"usd":0.037692,"stage2_stop_reason":"end_turn"},"total_usd":0.050525,"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\": 2001,\n      \"finding\": \"PF3D7_0913200 (EF-1beta) is phosphorylated by protein kinase C (PKC), and this phosphorylation results in a ~400% increase in its nucleotide exchange activity, catalytically regenerating GTP-bound EF-1alpha for each translation elongation cycle.\",\n      \"method\": \"In vitro kinase assay with PKC; nucleotide exchange activity assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro biochemical assay establishing phosphorylation and functional consequence, single lab, single paper\",\n      \"pmids\": [\"11251817\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"PKC-phosphorylated EF-1beta (PF3D7_0913200) is selectively dephosphorylated by P. falciparum protein phosphatase 2C (PfPP2C), which downregulates nucleotide exchange activity back to basal levels, establishing PfPP2C as a writer/eraser regulating EF-1beta activity.\",\n      \"method\": \"Far-Western analysis to identify PfPP2C substrates; in vitro dephosphorylation assay with recombinant and native PfPP2C; nucleotide exchange activity assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro reconstitution of dephosphorylation and functional readout, single lab, single paper\",\n      \"pmids\": [\"11251817\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"EF-1beta (PF3D7_0913200) forms a native multi-subunit translation elongation factor complex in P. falciparum that contains at least two copies of EF-1beta, the G-protein EF-1alpha, and two newly identified subunits EF-1gamma and EF-1delta; the complex was purified under native conditions by tandem affinity purification (TAP) of a PTP-tagged EF-1beta followed by mass spectrometry.\",\n      \"method\": \"Tandem affinity purification (TAP) of PTP-tagged EF-1beta expressed in transgenic parasites, followed by mass spectrometric identification of co-purifying proteins\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — native complex purification by TAP-MS in transgenic parasites, single lab, single paper\",\n      \"pmids\": [\"17307963\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"EF-1beta (PF3D7_0913200) functions as a nucleotide exchange factor in P. falciparum translation elongation, regenerating GTP-bound EF-1alpha; its activity is upregulated ~4-fold by PKC-mediated phosphorylation and restored to basal levels by dephosphorylation via PfPP2C, and it assembles as at least two copies within a native elongation factor complex containing EF-1alpha, EF-1gamma, and EF-1delta.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EF-1beta (PF3D7_0913200) is a nucleotide exchange factor of the Plasmodium falciparum translation elongation machinery, regenerating GTP-bound EF-1alpha for successive elongation cycles [#0]. Its exchange activity is dynamically regulated by reversible phosphorylation: protein kinase C phosphorylates EF-1beta and raises its nucleotide exchange activity roughly four-fold [#0], while P. falciparum protein phosphatase 2C (PfPP2C) selectively dephosphorylates it and returns activity to basal levels, defining a writer/eraser pair that tunes EF-1beta output [#1]. In native parasites EF-1beta assembles into a multi-subunit elongation factor complex containing at least two copies of itself together with EF-1alpha, EF-1gamma, and EF-1delta [#2]. Beyond this biochemical and complex-membership picture, no structural model, in vivo essentiality data, or higher-resolution mechanism of EF-1beta has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing that EF-1beta acts as a phosphorylation-controlled nucleotide exchange factor answered how P. falciparum couples a signaling kinase to the rate of GTP regeneration on EF-1alpha during elongation.\",\n      \"evidence\": \"In vitro PKC kinase assay coupled to a nucleotide exchange activity assay in P. falciparum\",\n      \"pmids\": [\"11251817\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phosphosite(s) on EF-1beta not mapped\",\n        \"Functional consequence shown in vitro only, not in intact parasites\",\n        \"Identity of the physiological PKC-type kinase in vivo not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identifying PfPP2C as the phosphatase that reverses PKC phosphorylation defined the eraser side of a reversible switch controlling EF-1beta exchange activity.\",\n      \"evidence\": \"Far-Western substrate identification plus in vitro dephosphorylation with recombinant and native PfPP2C and a nucleotide exchange readout in P. falciparum\",\n      \"pmids\": [\"11251817\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"In vivo relevance of the phosphorylation/dephosphorylation cycle not demonstrated\",\n        \"Whether PfPP2C acts on EF-1beta within the native complex is unknown\",\n        \"Stoichiometry and kinetics of the switch not quantified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Native purification defined the composition of the EF-1beta-containing elongation factor complex, showing EF-1beta is a multi-copy subunit assembled with EF-1alpha, EF-1gamma, and EF-1delta.\",\n      \"evidence\": \"Tandem affinity purification of PTP-tagged EF-1beta from transgenic parasites followed by mass spectrometry in P. falciparum\",\n      \"pmids\": [\"17307963\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model or subunit arrangement determined\",\n        \"How phosphorylation state affects complex assembly or activity not tested\",\n        \"Direct binary interactions among subunits not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether EF-1beta is essential in blood-stage parasites and how its phosphorylation cycle is integrated into translational control in vivo remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic knockout/knockdown phenotype in the corpus\",\n        \"No in vivo demonstration of the PKC/PfPP2C regulatory cycle\",\n        \"No structural characterization of EF-1beta or its complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003746\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005085\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006414\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\"Eukaryotic elongation factor 1 complex (EF-1beta, EF-1alpha, EF-1gamma, EF-1delta)\"],\n    \"partners\": [\"EF-1alpha\", \"EF-1gamma\", \"EF-1delta\", \"protein kinase C (PKC)\", \"P. falciparum protein phosphatase 2C (PfPP2C)\"],\n    \"other_free_text\": [\n      \"Nucleotide exchange activity increased ~4-fold by PKC phosphorylation and restored to basal levels by PfPP2C dephosphorylation [#0, #1]\",\n      \"Present in at least two copies within the native elongation factor complex [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0913200","name":null,"product":"elongation factor 1-beta","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0814200","name":null,"product":"elongation factor 1-beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0711100","name":null,"product":"elongation factor 1-beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"EF-1beta","evaluation":null}