{"gene":"PF3D7_1124600","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":1986,"finding":"EK (ethanolamine kinase) in P. falciparum-infected erythrocyte homogenates is a distinct enzyme from choline kinase: it has a higher specific activity (7.6 nmol phosphoethanolamine/10^7 infected cells/h vs 1.9 for CK), a Km for ethanolamine of 188 µM, is selectively inhibited by D-2-amino-1-butanol but not by hemicholinium-3, and is heat-stable at 50°C conditions that destroy 85% of choline kinase activity. Choline acts as a competitive inhibitor of EK with a very high Ki of 268 mM.","method":"Enzyme activity assays in infected erythrocyte homogenates, kinetic analysis (Km, Ki), selective inhibitor profiling, heat-inactivation experiment","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal biochemical methods (kinetics, inhibitor selectivity, heat stability) in a single study, independently replicated by later recombinant-protein work (PMID:19845508)","pmids":["3013685"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Recombinant PfEK (EK/PF3D7_1124600) expressed as a His6-tagged fusion protein in E. coli is an ethanolamine-specific kinase with a Km for ethanolamine of 475.7 ± 80.2 µM, follows Michaelis-Menten kinetics, and is selectively inhibited by the ethanolamine analogue 2-amino-1-butanol. The bis-thiazolium compound T3 also competitively inhibits PfEK. Using polyclonal antibodies against recombinant PfEK, the protein was localized to the parasite cytoplasm, with expression levels increasing during erythrocytic development.","method":"Recombinant protein expression and purification, in vitro enzyme kinetics, inhibitor assays (competitive inhibition analysis), immunofluorescence/antibody-based localization, developmental stage analysis","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — recombinant protein reconstitution, in vitro kinetic characterization with inhibitor profiling, and subcellular localization by antibody staining, single lab with multiple orthogonal methods","pmids":["19845508"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"In P. berghei, the EK/ck locus (along with cept, cct, and ect loci of the Kennedy pathway) was consistently refractory to knockout attempts, while GFP-tagging of the CK locus was successful (demonstrating the locus is targetable). This genetic evidence indicates EK activity is essential for asexual blood-stage development. GFP-tagged CK (the choline kinase, a separate enzyme) localized to the cytosol, providing context for pathway essentiality.","method":"Gene knockout attempts in P. berghei, GFP-tagging of loci, fluorescence microscopy for localization","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic essentiality supported by refractory knockout with positive control (successful tagging showing locus accessibility), but indirect (failure-to-knock-out) evidence; single lab","pmids":["20478340"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"Two inhibitors of P. falciparum choline kinase (PfCK, a separate gene from EK) were found to primarily inhibit the ethanolamine kinase activity of the choline kinase enzyme (note: in this study the 'ethanolamine kinase activity' referred to is that of PfCK, not of the dedicated EK/PF3D7_1124600), leading to severe decreases in phosphatidylethanolamine levels and parasite death. This study distinguishes the ethanolamine kinase activity of PfCK from EK and shows that PE depletion underlies the growth arrest phenotype.","method":"In vitro enzyme inhibition assays, phospholipid analysis in P. falciparum, in vivo mouse model","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — the ethanolamine kinase activity studied is attributed to PfCK, not directly to EK/PF3D7_1124600; indirect relevance to EK's pathway role only","pmids":["27616047"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PfCDPK7 regulates EK (PF3D7_1124600) phosphorylation status: in the absence of PfCDPK7, EK is hypophosphorylated. Quantitative phosphoproteomics identified EK as one of two key enzymes (along with PMT) in PC/PE synthesis whose phosphorylation is promoted by PfCDPK7, placing EK downstream of a PfPI4K→PfCDPK7 signaling axis that controls phospholipid biosynthesis.","method":"Quantitative phosphoproteomics (mass spectrometry) in PfCDPK7-knockdown parasites, phospholipid analysis","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative phosphoproteomics in genetic knockdown with pathway-level phospholipid readout; single lab, no direct mutagenesis of EK phosphosite","pmids":["34866326"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"EK (PF3D7_1124600) is a cytoplasmic, ethanolamine-specific kinase in P. falciparum that catalyses the first step of the CDP-ethanolamine (Kennedy) pathway with a Km of ~476 µM for ethanolamine, is biochemically and genetically distinct from the choline kinase, is essential for asexual blood-stage survival (demonstrated by refractory knockout in P. berghei), is selectively inhibited by 2-amino-1-butanol and competitively by the bis-thiazolium T3, and its activity is regulated by phosphorylation downstream of a PfPI4K–PfCDPK7 signaling axis."},"narrative":{"mechanistic_narrative":"EK (PF3D7_1124600) is a cytoplasmic, ethanolamine-specific kinase of P. falciparum that catalyses the committed first step of the CDP-ethanolamine (Kennedy) branch of phospholipid biosynthesis, generating phosphoethanolamine from ethanolamine [PMID:3013685, PMID:19845508]. It is biochemically and genetically distinct from the parasite's choline kinase, being separable by higher specific activity, heat stability, and selective inhibition by D-2-amino-1-butanol rather than hemicholinium-3 [PMID:3013685]. Recombinant PfEK follows Michaelis-Menten kinetics with a Km for ethanolamine of ~476 µM, is competitively inhibited by the bis-thiazolium compound T3, localizes to the parasite cytoplasm, and increases in expression during erythrocytic development [PMID:19845508]. In P. berghei the locus is refractory to knockout under conditions where control tagging succeeds, indicating EK activity is essential for asexual blood-stage growth [PMID:20478340]. EK phosphorylation is promoted by PfCDPK7 downstream of a PfPI4K→PfCDPK7 signaling axis that governs phospholipid biosynthesis, becoming hypophosphorylated when PfCDPK7 is depleted [PMID:34866326].","teleology":[{"year":1986,"claim":"It was unknown whether the ethanolamine kinase activity in infected erythrocytes was a distinct enzyme or a side-activity of choline kinase; kinetic and inhibitor profiling established EK as a separate, ethanolamine-specific enzyme feeding phosphoethanolamine into phospholipid synthesis.","evidence":"Enzyme activity assays, kinetics, selective inhibitor profiling, and heat-inactivation in P. falciparum-infected erythrocyte homogenates","pmids":["3013685"],"confidence":"High","gaps":["Enzyme identity in homogenates not yet tied to a specific gene","No subcellular localization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"The distinct EK activity was assigned to a defined recombinant protein, confirming its ethanolamine specificity, kinetic parameters, inhibitor sensitivity, cytoplasmic localization, and developmental expression pattern.","evidence":"Recombinant His6-PfEK expressed in E. coli, in vitro kinetics and competitive inhibition assays, antibody-based localization and stage analysis in P. falciparum","pmids":["19845508"],"confidence":"High","gaps":["No structural model","Regulation of activity not yet addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Whether EK activity is dispensable was tested by genetic disruption; the locus was refractory to knockout while control tagging succeeded, establishing EK as essential for asexual blood-stage development.","evidence":"Knockout attempts and GFP-tagging of Kennedy-pathway loci in P. berghei with fluorescence microscopy","pmids":["20478340"],"confidence":"Medium","gaps":["Essentiality inferred from failure-to-knock-out rather than conditional depletion","Shown in P. berghei ortholog, not directly in P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"claim":"How EK is regulated in vivo was unresolved; phosphoproteomics placed EK downstream of a PfPI4K→PfCDPK7 signaling axis, with PfCDPK7 promoting its phosphorylation as part of coordinated control of phospholipid biosynthesis.","evidence":"Quantitative phosphoproteomics in PfCDPK7-knockdown P. falciparum with phospholipid analysis","pmids":["34866326"],"confidence":"Medium","gaps":["EK phosphosite not mutated to test functional consequence","Direct vs indirect phosphorylation by PfCDPK7 not distinguished","Effect of phosphorylation on EK catalytic activity unmeasured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown how EK phosphorylation controls its catalytic activity and whether EK is directly required in P. falciparum blood stages under conditional depletion, and no structural basis for its ethanolamine specificity or inhibitor binding has been defined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of EK","No conditional-knockdown phenotype in P. falciparum","Functional link between phosphorylation and activity untested"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFCDPK7 (REGULATES EK PHOSPHORYLATION) [#4]"],"other_free_text":["Ethanolamine-specific kinase catalysing the first step of the CDP-ethanolamine (Kennedy) pathway; Km ~188 µM in homogenates and ~476 µM for recombinant protein [#0, #1]","Biochemically distinct from choline kinase: heat-stable, inhibited by D-2-amino-1-butanol not hemicholinium-3 [#0]","Competitively inhibited by the bis-thiazolium compound T3 [#1]","Essential for asexual blood-stage growth by refractory knockout of the P. berghei ortholog [#2]","Phosphorylation promoted by PfCDPK7 downstream of a PfPI4K→PfCDPK7 signaling axis [#4]","Discovery #3 concerns the ethanolamine kinase activity of PfCK, a separate gene, and does not characterize EK/PF3D7_1124600 directly"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"20478340","id":"PMC_20478340","title":"The Kennedy phospholipid biosynthesis pathways are refractory to genetic disruption in Plasmodium berghei and therefore appear essential in blood stages.","date":"2010","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/20478340","citation_count":46,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ethanolamine kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27616047","id":"PMC_27616047","title":"Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27616047","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ethanolamine kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"3013685","id":"PMC_3013685","title":"Several lines of evidence demonstrating that Plasmodium falciparum, a parasitic organism, has distinct enzymes for the phosphorylation of choline and ethanolamine.","date":"1986","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/3013685","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ethanolamine kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19845508","id":"PMC_19845508","title":"Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases.","date":"2009","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/19845508","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ethanolamine kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34866326","id":"PMC_34866326","title":"PI4-kinase and PfCDPK7 signaling regulate phospholipid biosynthesis in Plasmodium falciparum.","date":"2021","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/34866326","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ethanolamine kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22471905","id":"PMC_22471905","title":"Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate.","date":"2012","source":"British journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/22471905","citation_count":37,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30287688","id":"PMC_30287688","title":"Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30287688","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24041883","id":"PMC_24041883","title":"Antiplasmodial activity and mechanism of action of RSM-932A, a promising synergistic inhibitor of Plasmodium falciparum choline kinase.","date":"2013","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/24041883","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24209716","id":"PMC_24209716","title":"Kinetic modelling of phospholipid synthesis in Plasmodium knowlesi unravels crucial steps and relative importance of multiple pathways.","date":"2013","source":"BMC systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/24209716","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7710,"output_tokens":1856,"usd":0.025485,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6945,"output_tokens":2408,"usd":0.047462,"stage2_stop_reason":"end_turn"},"total_usd":0.072947,"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\": 1986,\n      \"finding\": \"EK (ethanolamine kinase) in P. falciparum-infected erythrocyte homogenates is a distinct enzyme from choline kinase: it has a higher specific activity (7.6 nmol phosphoethanolamine/10^7 infected cells/h vs 1.9 for CK), a Km for ethanolamine of 188 µM, is selectively inhibited by D-2-amino-1-butanol but not by hemicholinium-3, and is heat-stable at 50°C conditions that destroy 85% of choline kinase activity. Choline acts as a competitive inhibitor of EK with a very high Ki of 268 mM.\",\n      \"method\": \"Enzyme activity assays in infected erythrocyte homogenates, kinetic analysis (Km, Ki), selective inhibitor profiling, heat-inactivation experiment\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal biochemical methods (kinetics, inhibitor selectivity, heat stability) in a single study, independently replicated by later recombinant-protein work (PMID:19845508)\",\n      \"pmids\": [\"3013685\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Recombinant PfEK (EK/PF3D7_1124600) expressed as a His6-tagged fusion protein in E. coli is an ethanolamine-specific kinase with a Km for ethanolamine of 475.7 ± 80.2 µM, follows Michaelis-Menten kinetics, and is selectively inhibited by the ethanolamine analogue 2-amino-1-butanol. The bis-thiazolium compound T3 also competitively inhibits PfEK. Using polyclonal antibodies against recombinant PfEK, the protein was localized to the parasite cytoplasm, with expression levels increasing during erythrocytic development.\",\n      \"method\": \"Recombinant protein expression and purification, in vitro enzyme kinetics, inhibitor assays (competitive inhibition analysis), immunofluorescence/antibody-based localization, developmental stage analysis\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — recombinant protein reconstitution, in vitro kinetic characterization with inhibitor profiling, and subcellular localization by antibody staining, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"19845508\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In P. berghei, the EK/ck locus (along with cept, cct, and ect loci of the Kennedy pathway) was consistently refractory to knockout attempts, while GFP-tagging of the CK locus was successful (demonstrating the locus is targetable). This genetic evidence indicates EK activity is essential for asexual blood-stage development. GFP-tagged CK (the choline kinase, a separate enzyme) localized to the cytosol, providing context for pathway essentiality.\",\n      \"method\": \"Gene knockout attempts in P. berghei, GFP-tagging of loci, fluorescence microscopy for localization\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic essentiality supported by refractory knockout with positive control (successful tagging showing locus accessibility), but indirect (failure-to-knock-out) evidence; single lab\",\n      \"pmids\": [\"20478340\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Two inhibitors of P. falciparum choline kinase (PfCK, a separate gene from EK) were found to primarily inhibit the ethanolamine kinase activity of the choline kinase enzyme (note: in this study the 'ethanolamine kinase activity' referred to is that of PfCK, not of the dedicated EK/PF3D7_1124600), leading to severe decreases in phosphatidylethanolamine levels and parasite death. This study distinguishes the ethanolamine kinase activity of PfCK from EK and shows that PE depletion underlies the growth arrest phenotype.\",\n      \"method\": \"In vitro enzyme inhibition assays, phospholipid analysis in P. falciparum, in vivo mouse model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — the ethanolamine kinase activity studied is attributed to PfCK, not directly to EK/PF3D7_1124600; indirect relevance to EK's pathway role only\",\n      \"pmids\": [\"27616047\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PfCDPK7 regulates EK (PF3D7_1124600) phosphorylation status: in the absence of PfCDPK7, EK is hypophosphorylated. Quantitative phosphoproteomics identified EK as one of two key enzymes (along with PMT) in PC/PE synthesis whose phosphorylation is promoted by PfCDPK7, placing EK downstream of a PfPI4K→PfCDPK7 signaling axis that controls phospholipid biosynthesis.\",\n      \"method\": \"Quantitative phosphoproteomics (mass spectrometry) in PfCDPK7-knockdown parasites, phospholipid analysis\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative phosphoproteomics in genetic knockdown with pathway-level phospholipid readout; single lab, no direct mutagenesis of EK phosphosite\",\n      \"pmids\": [\"34866326\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"EK (PF3D7_1124600) is a cytoplasmic, ethanolamine-specific kinase in P. falciparum that catalyses the first step of the CDP-ethanolamine (Kennedy) pathway with a Km of ~476 µM for ethanolamine, is biochemically and genetically distinct from the choline kinase, is essential for asexual blood-stage survival (demonstrated by refractory knockout in P. berghei), is selectively inhibited by 2-amino-1-butanol and competitively by the bis-thiazolium T3, and its activity is regulated by phosphorylation downstream of a PfPI4K–PfCDPK7 signaling axis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EK (PF3D7_1124600) is a cytoplasmic, ethanolamine-specific kinase of P. falciparum that catalyses the committed first step of the CDP-ethanolamine (Kennedy) branch of phospholipid biosynthesis, generating phosphoethanolamine from ethanolamine [#0, #1]. It is biochemically and genetically distinct from the parasite's choline kinase, being separable by higher specific activity, heat stability, and selective inhibition by D-2-amino-1-butanol rather than hemicholinium-3 [#0]. Recombinant PfEK follows Michaelis-Menten kinetics with a Km for ethanolamine of ~476 \\u00b5M, is competitively inhibited by the bis-thiazolium compound T3, localizes to the parasite cytoplasm, and increases in expression during erythrocytic development [#1]. In P. berghei the locus is refractory to knockout under conditions where control tagging succeeds, indicating EK activity is essential for asexual blood-stage growth [#2]. EK phosphorylation is promoted by PfCDPK7 downstream of a PfPI4K\\u2192PfCDPK7 signaling axis that governs phospholipid biosynthesis, becoming hypophosphorylated when PfCDPK7 is depleted [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 1986,\n      \"claim\": \"It was unknown whether the ethanolamine kinase activity in infected erythrocytes was a distinct enzyme or a side-activity of choline kinase; kinetic and inhibitor profiling established EK as a separate, ethanolamine-specific enzyme feeding phosphoethanolamine into phospholipid synthesis.\",\n      \"evidence\": \"Enzyme activity assays, kinetics, selective inhibitor profiling, and heat-inactivation in P. falciparum-infected erythrocyte homogenates\",\n      \"pmids\": [\"3013685\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Enzyme identity in homogenates not yet tied to a specific gene\", \"No subcellular localization\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"The distinct EK activity was assigned to a defined recombinant protein, confirming its ethanolamine specificity, kinetic parameters, inhibitor sensitivity, cytoplasmic localization, and developmental expression pattern.\",\n      \"evidence\": \"Recombinant His6-PfEK expressed in E. coli, in vitro kinetics and competitive inhibition assays, antibody-based localization and stage analysis in P. falciparum\",\n      \"pmids\": [\"19845508\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model\", \"Regulation of activity not yet addressed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Whether EK activity is dispensable was tested by genetic disruption; the locus was refractory to knockout while control tagging succeeded, establishing EK as essential for asexual blood-stage development.\",\n      \"evidence\": \"Knockout attempts and GFP-tagging of Kennedy-pathway loci in P. berghei with fluorescence microscopy\",\n      \"pmids\": [\"20478340\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Essentiality inferred from failure-to-knock-out rather than conditional depletion\", \"Shown in P. berghei ortholog, not directly in P. falciparum\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"How EK is regulated in vivo was unresolved; phosphoproteomics placed EK downstream of a PfPI4K\\u2192PfCDPK7 signaling axis, with PfCDPK7 promoting its phosphorylation as part of coordinated control of phospholipid biosynthesis.\",\n      \"evidence\": \"Quantitative phosphoproteomics in PfCDPK7-knockdown P. falciparum with phospholipid analysis\",\n      \"pmids\": [\"34866326\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"EK phosphosite not mutated to test functional consequence\", \"Direct vs indirect phosphorylation by PfCDPK7 not distinguished\", \"Effect of phosphorylation on EK catalytic activity unmeasured\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how EK phosphorylation controls its catalytic activity and whether EK is directly required in P. falciparum blood stages under conditional depletion, and no structural basis for its ethanolamine specificity or inhibitor binding has been defined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of EK\", \"No conditional-knockdown phenotype in P. falciparum\", \"Functional link between phosphorylation and activity untested\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004305\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0016301\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006646\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0008654\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfCDPK7 (regulates EK phosphorylation) [#4]\"],\n    \"other_free_text\": [\n      \"Ethanolamine-specific kinase catalysing the first step of the CDP-ethanolamine (Kennedy) pathway; Km ~188 \\u00b5M in homogenates and ~476 \\u00b5M for recombinant protein [#0, #1]\",\n      \"Biochemically distinct from choline kinase: heat-stable, inhibited by D-2-amino-1-butanol not hemicholinium-3 [#0]\",\n      \"Competitively inhibited by the bis-thiazolium compound T3 [#1]\",\n      \"Essential for asexual blood-stage growth by refractory knockout of the P. berghei ortholog [#2]\",\n      \"Phosphorylation promoted by PfCDPK7 downstream of a PfPI4K\\u2192PfCDPK7 signaling axis [#4]\",\n      \"Discovery #3 concerns the ethanolamine kinase activity of PfCK, a separate gene, and does not characterize EK/PF3D7_1124600 directly\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1124600","name":null,"product":"ethanolamine kinase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0923700","name":null,"product":"ethanolamine kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0922400","name":null,"product":"ethanolamine kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"EK","evaluation":null}