{"gene":"PF3D7_1010600","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2016,"finding":"eIF2beta (PfeIF2β) directly interacts with Plasmodium falciparum Protein Phosphatase 1 (PfPP1c) via two binding motifs: (29)FGEKKK(34) and (103)KVAW(106); mutation of both motifs together (but not individually) abolishes the interaction with PfPP1c.","method":"Interaction studies using wild-type and single/double mutated versions of PfeIF2β; Xenopus oocyte GVBD assay as functional readout of PP1 regulation","journal":"Frontiers in microbiology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — direct binding confirmed by mutagenesis of both motifs with functional validation in Xenopus oocytes, single lab but multiple orthogonal methods","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"eIF2beta (PfeIF2β) binds PfeIF2γ and PfeIF5, confirming its canonical role as a subunit of the translation initiation complex.","method":"Protein interaction assays (binding studies with partners of the translation complex)","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab pulldown/interaction assay confirming canonical complex membership, two interacting partners tested","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"eIF2beta (PfeIF2β) expressed in Xenopus oocytes induces Germinal Vesicle Break Down (GVBD), indicating it can regulate PP1 activity; combined mutation of both PP1-binding motifs abolishes this induction.","method":"Xenopus oocyte microinjection/expression with GVBD as readout; site-directed mutagenesis of PP1-binding motifs","journal":"Frontiers in microbiology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — functional reconstitution in Xenopus oocyte system with mutagenesis validation, single lab","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"eIF2beta (PfeIF2β) localizes to both cytoplasm and nuclear extracts of P. falciparum intraerythrocytic stages, consistent with potential nuclear as well as cytoplasmic functions.","method":"Subcellular fractionation of P. falciparum","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single fractionation method, no functional consequence directly linked to nuclear localization","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Attempted knockout of eIF2beta in P. falciparum failed to yield viable parasites, indicating the gene is essential for the intraerythrocytic cycle.","method":"Genetic manipulation / attempted knockout with no viable parasites detected","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic manipulation attempted in P. falciparum, single lab, single method; essentiality inferred from absence of viable knockouts","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"The P. falciparum eIF2beta sequence contains a deletion of 111 amino acids compared to its human counterpart, yet retains two PP1-binding motifs ((29)FGEKKK(34) and (103)KVAW(106)).","method":"Sequence analysis / bioinformatics","journal":"Frontiers in microbiology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational sequence analysis only, no direct experimental validation of structural consequence","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum eIF2beta (PF3D7_1010600) is an essential intraerythrocytic-stage protein that functions both as a canonical subunit of the eIF2 translation initiation complex (binding eIF2γ and eIF5) and as a direct regulator of Protein Phosphatase 1 (PfPP1c) through two critical binding motifs (FGEKKK and KVAW); it localizes to both cytoplasm and nucleus, and its PP1-regulatory activity is functionally validated by induction of GVBD in Xenopus oocytes in a motif-dependent manner."},"narrative":{"mechanistic_narrative":"P. falciparum eIF2beta (PF3D7_1010600) is a bifunctional intraerythrocytic-stage protein that serves both as a canonical translation initiation factor subunit and as a direct regulator of Protein Phosphatase 1 [PMID:27303372]. In its translation role it binds PfeIF2γ and PfeIF5, confirming its incorporation into the eIF2 initiation complex [PMID:27303372]. Independently, eIF2beta binds PfPP1c through two motifs, (29)FGEKKK(34) and (103)KVAW(106); only combined mutation of both motifs abolishes the interaction, indicating the two motifs function redundantly for phosphatase binding [PMID:27303372]. This regulatory activity is functionally significant: expression of eIF2beta in Xenopus oocytes induces germinal vesicle breakdown in a manner requiring both PP1-binding motifs, demonstrating that eIF2beta modulates PP1 activity [PMID:27303372]. The protein distributes to both cytoplasm and nucleus of intraerythrocytic parasites [PMID:27303372], and attempted knockout yielded no viable parasites, establishing it as essential for the asexual blood-stage cycle [PMID:27303372]. All available mechanistic knowledge of PF3D7_1010600 derives from a single study; no further partners, structural detail, or in vivo phosphatase substrates have been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Establishing whether PF3D7_1010600 retains its canonical translation-initiation role addressed whether it is a bona fide eIF2 subunit in Plasmodium.","evidence":"protein interaction/binding assays with translation complex partners in P. falciparum","pmids":["27303372"],"confidence":"Medium","gaps":["Binding to eIF2γ and eIF5 shown but stoichiometry and assembled complex not reconstituted","No demonstration of translation initiation activity in vivo","eIF2α subunit interaction not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Identifying that eIF2beta directly binds PfPP1c through two defined motifs revealed a moonlighting phosphatase-regulatory function beyond translation.","evidence":"interaction studies with wild-type and single/double motif mutants of PfeIF2β in P. falciparum","pmids":["27303372"],"confidence":"High","gaps":["Whether the two motifs bind independently or cooperatively at the structural level is unresolved","The physiological consequence of PP1 regulation in the parasite is not defined","No native complex isolated from parasites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Demonstrating motif-dependent GVBD induction in Xenopus oocytes provided a functional readout confirming eIF2beta regulates PP1 activity rather than merely binding it.","evidence":"Xenopus oocyte microinjection/expression with GVBD readout and site-directed mutagenesis of PP1-binding motifs","pmids":["27303372"],"confidence":"High","gaps":["Heterologous oocyte system may not reflect parasite PP1 regulation","Direction of regulation (activation vs inhibition) not quantified biochemically","No parasite-based validation of the regulatory effect"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Subcellular fractionation and essentiality testing addressed where eIF2beta acts and whether it is required for parasite survival.","evidence":"subcellular fractionation and attempted gene knockout in P. falciparum","pmids":["27303372"],"confidence":"Medium","gaps":["Nuclear localization not linked to a specific function","Essentiality inferred from failed knockout rather than conditional depletion","Single fractionation method without orthogonal imaging"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How eIF2beta balances its translation-initiation and PP1-regulatory roles, and what PP1-dependent processes it controls in the parasite, remains unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No conditional depletion to dissect essential function","No identification of PP1 substrates or pathways regulated via eIF2beta","No structural model of the eIF2beta–PP1c interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["eIF2 translation initiation complex (binds PfeIF2γ and PfeIF5)"],"partners":["PFPP1C (PROTEIN PHOSPHATASE 1)","PFEIF2Γ","PFEIF5"],"other_free_text":["Binds PfPP1c via two redundant motifs (29)FGEKKK(34) and (103)KVAW(106); combined mutation abolishes interaction [#0]","Essential for the P. falciparum intraerythrocytic cycle; knockout not viable [#4]","P. falciparum sequence carries a 111-amino-acid deletion relative to the human counterpart yet retains both PP1-binding motifs [#5]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27303372","id":"PMC_27303372","title":"Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1.","date":"2016","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27303372","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["eIF2beta","PfeIF2beta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36582189","id":"","title":"Combining IP3 affinity chromatography and bioinformatics reveals a novel protein-IP3 binding site on Plasmodium falciparum MDR1 transporter.","date":"2022","source":"Current research in microbial sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36582189","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["eIF2beta"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4670,"output_tokens":1468,"usd":0.018015,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6488,"output_tokens":2260,"usd":0.04447,"stage2_stop_reason":"end_turn"},"total_usd":0.062485,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"eIF2beta (PfeIF2β) directly interacts with Plasmodium falciparum Protein Phosphatase 1 (PfPP1c) via two binding motifs: (29)FGEKKK(34) and (103)KVAW(106); mutation of both motifs together (but not individually) abolishes the interaction with PfPP1c.\",\n      \"method\": \"Interaction studies using wild-type and single/double mutated versions of PfeIF2β; Xenopus oocyte GVBD assay as functional readout of PP1 regulation\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct binding confirmed by mutagenesis of both motifs with functional validation in Xenopus oocytes, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"eIF2beta (PfeIF2β) binds PfeIF2γ and PfeIF5, confirming its canonical role as a subunit of the translation initiation complex.\",\n      \"method\": \"Protein interaction assays (binding studies with partners of the translation complex)\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab pulldown/interaction assay confirming canonical complex membership, two interacting partners tested\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"eIF2beta (PfeIF2β) expressed in Xenopus oocytes induces Germinal Vesicle Break Down (GVBD), indicating it can regulate PP1 activity; combined mutation of both PP1-binding motifs abolishes this induction.\",\n      \"method\": \"Xenopus oocyte microinjection/expression with GVBD as readout; site-directed mutagenesis of PP1-binding motifs\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — functional reconstitution in Xenopus oocyte system with mutagenesis validation, single lab\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"eIF2beta (PfeIF2β) localizes to both cytoplasm and nuclear extracts of P. falciparum intraerythrocytic stages, consistent with potential nuclear as well as cytoplasmic functions.\",\n      \"method\": \"Subcellular fractionation of P. falciparum\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single fractionation method, no functional consequence directly linked to nuclear localization\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Attempted knockout of eIF2beta in P. falciparum failed to yield viable parasites, indicating the gene is essential for the intraerythrocytic cycle.\",\n      \"method\": \"Genetic manipulation / attempted knockout with no viable parasites detected\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic manipulation attempted in P. falciparum, single lab, single method; essentiality inferred from absence of viable knockouts\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The P. falciparum eIF2beta sequence contains a deletion of 111 amino acids compared to its human counterpart, yet retains two PP1-binding motifs ((29)FGEKKK(34) and (103)KVAW(106)).\",\n      \"method\": \"Sequence analysis / bioinformatics\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational sequence analysis only, no direct experimental validation of structural consequence\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum eIF2beta (PF3D7_1010600) is an essential intraerythrocytic-stage protein that functions both as a canonical subunit of the eIF2 translation initiation complex (binding eIF2γ and eIF5) and as a direct regulator of Protein Phosphatase 1 (PfPP1c) through two critical binding motifs (FGEKKK and KVAW); it localizes to both cytoplasm and nucleus, and its PP1-regulatory activity is functionally validated by induction of GVBD in Xenopus oocytes in a motif-dependent manner.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"P. falciparum eIF2beta (PF3D7_1010600) is a bifunctional intraerythrocytic-stage protein that serves both as a canonical translation initiation factor subunit and as a direct regulator of Protein Phosphatase 1 [#0, #1]. In its translation role it binds PfeIF2\\u03b3 and PfeIF5, confirming its incorporation into the eIF2 initiation complex [#1]. Independently, eIF2beta binds PfPP1c through two motifs, (29)FGEKKK(34) and (103)KVAW(106); only combined mutation of both motifs abolishes the interaction, indicating the two motifs function redundantly for phosphatase binding [#0]. This regulatory activity is functionally significant: expression of eIF2beta in Xenopus oocytes induces germinal vesicle breakdown in a manner requiring both PP1-binding motifs, demonstrating that eIF2beta modulates PP1 activity [#2]. The protein distributes to both cytoplasm and nucleus of intraerythrocytic parasites [#3], and attempted knockout yielded no viable parasites, establishing it as essential for the asexual blood-stage cycle [#4]. All available mechanistic knowledge of PF3D7_1010600 derives from a single study; no further partners, structural detail, or in vivo phosphatase substrates have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing whether PF3D7_1010600 retains its canonical translation-initiation role addressed whether it is a bona fide eIF2 subunit in Plasmodium.\",\n      \"evidence\": \"protein interaction/binding assays with translation complex partners in P. falciparum\",\n      \"pmids\": [\"27303372\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding to eIF2\\u03b3 and eIF5 shown but stoichiometry and assembled complex not reconstituted\", \"No demonstration of translation initiation activity in vivo\", \"eIF2\\u03b1 subunit interaction not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identifying that eIF2beta directly binds PfPP1c through two defined motifs revealed a moonlighting phosphatase-regulatory function beyond translation.\",\n      \"evidence\": \"interaction studies with wild-type and single/double motif mutants of PfeIF2\\u03b2 in P. falciparum\",\n      \"pmids\": [\"27303372\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the two motifs bind independently or cooperatively at the structural level is unresolved\", \"The physiological consequence of PP1 regulation in the parasite is not defined\", \"No native complex isolated from parasites\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrating motif-dependent GVBD induction in Xenopus oocytes provided a functional readout confirming eIF2beta regulates PP1 activity rather than merely binding it.\",\n      \"evidence\": \"Xenopus oocyte microinjection/expression with GVBD readout and site-directed mutagenesis of PP1-binding motifs\",\n      \"pmids\": [\"27303372\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Heterologous oocyte system may not reflect parasite PP1 regulation\", \"Direction of regulation (activation vs inhibition) not quantified biochemically\", \"No parasite-based validation of the regulatory effect\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Subcellular fractionation and essentiality testing addressed where eIF2beta acts and whether it is required for parasite survival.\",\n      \"evidence\": \"subcellular fractionation and attempted gene knockout in P. falciparum\",\n      \"pmids\": [\"27303372\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Nuclear localization not linked to a specific function\", \"Essentiality inferred from failed knockout rather than conditional depletion\", \"Single fractionation method without orthogonal imaging\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How eIF2beta balances its translation-initiation and PP1-regulatory roles, and what PP1-dependent processes it controls in the parasite, remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No conditional depletion to dissect essential function\", \"No identification of PP1 substrates or pathways regulated via eIF2beta\", \"No structural model of the eIF2beta\\u2013PP1c interaction\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003743\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0008157\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006413\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"eIF2 translation initiation complex (binds PfeIF2\\u03b3 and PfeIF5)\"\n    ],\n    \"partners\": [\n      \"PfPP1c (Protein Phosphatase 1)\",\n      \"PfeIF2\\u03b3\",\n      \"PfeIF5\"\n    ],\n    \"other_free_text\": [\n      \"Binds PfPP1c via two redundant motifs (29)FGEKKK(34) and (103)KVAW(106); combined mutation abolishes interaction [#0]\",\n      \"Essential for the P. falciparum intraerythrocytic cycle; knockout not viable [#4]\",\n      \"P. falciparum sequence carries a 111-amino-acid deletion relative to the human counterpart yet retains both PP1-binding motifs [#5]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1010600","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1010600","name":null,"product":"eukaryotic translation initiation factor 2 subunit beta","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1209000","name":null,"product":"eukaryotic translation initiation factor 2 subunit beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0810400","name":null,"product":"eukaryotic translation initiation factor 2 subunit beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"eIF2beta","evaluation":null}