{"gene":"PF3D7_1420600","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2018,"finding":"Mutations in PF3D7_1420600 (PfPanK1/Pfpank1) confer resistance to pantothenate analogues pantothenol and CJ-15,801, and significantly alter PfPanK activity; two mutations confer a fitness cost, establishing that Pfpank1 encodes a functional pantothenate kinase essential for normal parasite growth.","method":"Resistance selection under drug pressure followed by whole-genome sequencing to identify mutations in Pfpank1, with functional assessment of PanK activity and parasite fitness in resistant lines","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple resistant lines independently acquired mutations in PF3D7_1420600, functional PanK activity measured, fitness costs documented; multiple orthogonal methods in a single rigorous study","pmids":["29614109"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PF3D7_1420600 (PfPanK1) forms a heteromeric complex with PfPanK2 and the multifunctional protein Pf14-3-3I; this heteromeric complex constitutes a single, functional pantothenate kinase, representing the first example of a heteromeric PanK complex in nature (all previously characterised PanKs form homodimers).","method":"Co-immunoprecipitation and biochemical characterisation of the PfPanK1/PfPanK2/Pf14-3-3I complex; demonstration of PanK enzymatic activity of the complex","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP identifying complex partners, enzymatic activity confirmed, orthogonal validation in T. gondii system, single lab with multiple methods","pmids":["34324601"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Recombinant PF3D7_1420600 (PfPanK1) was purified and biochemically characterised; it catalyses phosphorylation of pantothenate and also accepts pantetheine as a primary substrate, indicating CoA biosynthesis in P. falciparum blood stages can bypass pantothenate.","method":"Recombinant protein production, purification, and in vitro enzymatic activity assay with pantothenate and pantetheine as substrates; inhibitor screening assay identifying four natural-product inhibitors","journal":"Frontiers in cellular and infection microbiology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro biochemical characterisation of recombinant PfPanK1 with substrate specificity determination; single lab but rigorous enzymatic assay","pmids":["33768012"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Genetic knockout of PanK1 in P. yoelii shows normal asexual blood stage and sexual stage differentiation, but severe deficiency in ookinete, oocyst, and sporozoite formation inside the mosquito vector, establishing an essential role for PanK1 in mosquito-stage transmission.","method":"Genetic knockout (gene deletion) in P. yoelii followed by stage-specific phenotypic analysis and quantitative transcriptional analysis of CoA biosynthesis genes in wild-type versus knockout parasites","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with defined stage-specific phenotypic readout and quantitative transcriptional analysis; single lab, multiple life cycle stages assessed","pmids":["27644319"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2023,"finding":"In amodiaquine-resistant P. berghei ANKA parasites, PF3D7_1420600 (PANK1) acquires a nonsynonymous mutation (Asn394His) and shows differential mRNA expression (downregulated at trophozoite stage, upregulated at schizont stage), suggesting PANK1 is under amodiaquine drug pressure; however the causal role of these mutations in resistance was not experimentally confirmed.","method":"PCR and sequencing of PANK1 in drug-resistant lines; qPCR measurement of PANK1 mRNA at trophozoite and schizont stages; in silico identification of ligand-binding motifs","journal":"Open research Africa","confidence":"Low","confidence_rationale":"Tier 4 / Weak — mutation identified by sequencing with no reverse-genetics functional validation; authors explicitly state causal role requires further investigation","pmids":["38915420"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]}],"current_model":"PF3D7_1420600 (PfPanK1) is a functional pantothenate kinase that forms a novel heteromeric complex with PfPanK2 and Pf14-3-3I in P. falciparum; the recombinant enzyme phosphorylates both pantothenate and pantetheine in vitro, resistance-conferring mutations in Pfpank1 alter its activity and establish its essentiality for blood-stage growth, and its ortholog in P. yoelii is specifically required for mosquito-stage transmission (ookinete, oocyst, and sporozoite formation) but not for asexual or sexual blood-stage development."},"narrative":{"mechanistic_narrative":"PF3D7_1420600 (PfPanK1) is a functional pantothenate kinase that catalyzes the first committed step of coenzyme A biosynthesis in Plasmodium and is essential for blood-stage parasite growth [PMID:29614109]. Rather than acting as a conventional homodimer, PfPanK1 assembles into a heteromeric complex with PfPanK2 and the multifunctional protein Pf14-3-3I, and this tripartite assembly constitutes a single functional pantothenate kinase — the first example of a heteromeric PanK complex described in nature [PMID:34324601]. Recombinant PfPanK1 phosphorylates pantothenate and additionally accepts pantetheine as a primary substrate, indicating that blood-stage CoA biosynthesis can bypass pantothenate [PMID:33768012]. Its essentiality and druggability are underscored by resistance-conferring mutations selected under pantothenate-analogue pressure (pantothenol and CJ-15,801), which alter PfPanK activity and impose fitness costs [PMID:29614109], and by natural-product inhibitors identified against the recombinant enzyme [PMID:33768012]. Across the life cycle, the requirement is stage-specific: in P. yoelii, PanK1 knockout leaves asexual and sexual blood-stage development intact but severely impairs ookinete, oocyst, and sporozoite formation, establishing an essential role in mosquito-stage transmission [PMID:27644319].","teleology":[{"year":2016,"claim":"Whether PanK1 is required uniformly across the parasite life cycle was unknown; genetic ablation resolved that its essential contribution is stage-specific rather than global.","evidence":"Gene-deletion knockout in P. yoelii with stage-resolved phenotyping and transcriptional analysis of CoA biosynthesis genes","pmids":["27644319"],"confidence":"High","gaps":["Does not identify the molecular basis of the mosquito-stage requirement","Does not address whether the P. falciparum ortholog shows the same stage dependence","Enzymatic activity of PyPanK1 not directly measured"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2018,"claim":"Whether Pfpank1 encodes a functional, growth-essential pantothenate kinase in blood-stage P. falciparum was established by drug-resistance genetics linking the gene to PanK activity and fitness.","evidence":"Resistance selection against pantothenate analogues followed by whole-genome sequencing, PanK activity measurement, and fitness assessment in resistant lines","pmids":["29614109"],"confidence":"High","gaps":["Does not resolve how each mutation alters catalysis at the structural level","Direct in vitro enzymology of the mutant proteins not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"The catalytic substrate range of the enzyme was defined, showing PfPanK1 accepts pantetheine in addition to pantothenate and thereby permitting a pantothenate-bypass route to CoA.","evidence":"Recombinant PfPanK1 purification and in vitro kinase assays with pantothenate and pantetheine, plus inhibitor screening","pmids":["33768012"],"confidence":"High","gaps":["Kinetic parameters distinguishing the two substrates in the physiological complex not established","Inhibitor mechanism of action not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"The quaternary organization of the active enzyme was unknown; co-IP and activity reconstitution revealed a novel heteromeric PanK complex rather than the canonical homodimer.","evidence":"Reciprocal co-immunoprecipitation identifying PfPanK1/PfPanK2/Pf14-3-3I, with enzymatic activity confirmed for the complex","pmids":["34324601"],"confidence":"High","gaps":["Stoichiometry and architecture of the complex not structurally defined","Individual catalytic contribution of PfPanK1 versus PfPanK2 within the complex unresolved","Regulatory role of Pf14-3-3I not mechanistically dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"A possible link between PANK1 and amodiaquine response was raised by sequence and expression changes under drug pressure, but a causal role was not demonstrated.","evidence":"Sequencing and stage-specific qPCR of PANK1 in amodiaquine-resistant P. berghei ANKA, with in silico ligand-binding motif analysis","pmids":["38915420"],"confidence":"Low","gaps":["No reverse-genetics validation of the Asn394His mutation in resistance","Causal role explicitly unconfirmed by the authors","Functional consequence of the differential expression not tested"],"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":null,"claim":"How the heteromeric PfPanK1/PfPanK2/Pf14-3-3I complex is structurally organized and regulated, and what molecular process drives the mosquito-stage-specific requirement, remain open.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of the heteromeric complex","Mechanistic basis of stage-specific essentiality unresolved","Role of Pf14-3-3I in modulating PanK activity uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfPanK1/PfPanK2/Pf14-3-3I heteromeric pantothenate kinase complex [#1]"],"partners":["PFPANK2 [#1]","PF14-3-3I [#1]"],"other_free_text":["Recombinant PfPanK1 phosphorylates both pantothenate and pantetheine, enabling a pantothenate-bypass route to CoA in blood stages [#2].","Resistance-conferring mutations selected under pantothenate-analogue pressure alter PanK activity and carry fitness costs, indicating essentiality for blood-stage growth [#0].","In P. yoelii, PanK1 is dispensable for asexual and sexual blood stages but essential for ookinete, oocyst, and sporozoite formation (mosquito-stage transmission) [#3].","In amodiaquine-resistant P. berghei ANKA, a PANK1 Asn394His mutation and stage-dependent mRNA changes were observed, but the causal role in resistance was not confirmed [#4] (Low confidence)."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29614109","id":"PMC_29614109","title":"Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues.","date":"2018","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/29614109","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPANK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27644319","id":"PMC_27644319","title":"Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27644319","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PANK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34324601","id":"PMC_34324601","title":"A novel heteromeric pantothenate kinase complex in apicomplexan parasites.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34324601","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PANK1","PfPANK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33768012","id":"PMC_33768012","title":"Characterization of Plasmodium falciparum Pantothenate Kinase and Identification of Its Inhibitors From Natural Products.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33768012","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPANK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38915420","id":"PMC_38915420","title":"Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in Plasmodium berghei ANKA.","date":"2023","source":"Open research Africa","url":"https://pubmed.ncbi.nlm.nih.gov/38915420","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PANK1","pantothenate kinase 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5389,"output_tokens":1589,"usd":0.020001,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6611,"output_tokens":2611,"usd":0.049165,"stage2_stop_reason":"end_turn"},"total_usd":0.069166,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Mutations in PF3D7_1420600 (PfPanK1/Pfpank1) confer resistance to pantothenate analogues pantothenol and CJ-15,801, and significantly alter PfPanK activity; two mutations confer a fitness cost, establishing that Pfpank1 encodes a functional pantothenate kinase essential for normal parasite growth.\",\n      \"method\": \"Resistance selection under drug pressure followed by whole-genome sequencing to identify mutations in Pfpank1, with functional assessment of PanK activity and parasite fitness in resistant lines\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple resistant lines independently acquired mutations in PF3D7_1420600, functional PanK activity measured, fitness costs documented; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"29614109\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PF3D7_1420600 (PfPanK1) forms a heteromeric complex with PfPanK2 and the multifunctional protein Pf14-3-3I; this heteromeric complex constitutes a single, functional pantothenate kinase, representing the first example of a heteromeric PanK complex in nature (all previously characterised PanKs form homodimers).\",\n      \"method\": \"Co-immunoprecipitation and biochemical characterisation of the PfPanK1/PfPanK2/Pf14-3-3I complex; demonstration of PanK enzymatic activity of the complex\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP identifying complex partners, enzymatic activity confirmed, orthogonal validation in T. gondii system, single lab with multiple methods\",\n      \"pmids\": [\"34324601\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Recombinant PF3D7_1420600 (PfPanK1) was purified and biochemically characterised; it catalyses phosphorylation of pantothenate and also accepts pantetheine as a primary substrate, indicating CoA biosynthesis in P. falciparum blood stages can bypass pantothenate.\",\n      \"method\": \"Recombinant protein production, purification, and in vitro enzymatic activity assay with pantothenate and pantetheine as substrates; inhibitor screening assay identifying four natural-product inhibitors\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro biochemical characterisation of recombinant PfPanK1 with substrate specificity determination; single lab but rigorous enzymatic assay\",\n      \"pmids\": [\"33768012\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Genetic knockout of PanK1 in P. yoelii shows normal asexual blood stage and sexual stage differentiation, but severe deficiency in ookinete, oocyst, and sporozoite formation inside the mosquito vector, establishing an essential role for PanK1 in mosquito-stage transmission.\",\n      \"method\": \"Genetic knockout (gene deletion) in P. yoelii followed by stage-specific phenotypic analysis and quantitative transcriptional analysis of CoA biosynthesis genes in wild-type versus knockout parasites\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with defined stage-specific phenotypic readout and quantitative transcriptional analysis; single lab, multiple life cycle stages assessed\",\n      \"pmids\": [\"27644319\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In amodiaquine-resistant P. berghei ANKA parasites, PF3D7_1420600 (PANK1) acquires a nonsynonymous mutation (Asn394His) and shows differential mRNA expression (downregulated at trophozoite stage, upregulated at schizont stage), suggesting PANK1 is under amodiaquine drug pressure; however the causal role of these mutations in resistance was not experimentally confirmed.\",\n      \"method\": \"PCR and sequencing of PANK1 in drug-resistant lines; qPCR measurement of PANK1 mRNA at trophozoite and schizont stages; in silico identification of ligand-binding motifs\",\n      \"journal\": \"Open research Africa\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — mutation identified by sequencing with no reverse-genetics functional validation; authors explicitly state causal role requires further investigation\",\n      \"pmids\": [\"38915420\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1420600 (PfPanK1) is a functional pantothenate kinase that forms a novel heteromeric complex with PfPanK2 and Pf14-3-3I in P. falciparum; the recombinant enzyme phosphorylates both pantothenate and pantetheine in vitro, resistance-conferring mutations in Pfpank1 alter its activity and establish its essentiality for blood-stage growth, and its ortholog in P. yoelii is specifically required for mosquito-stage transmission (ookinete, oocyst, and sporozoite formation) but not for asexual or sexual blood-stage development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1420600 (PfPanK1) is a functional pantothenate kinase that catalyzes the first committed step of coenzyme A biosynthesis in Plasmodium and is essential for blood-stage parasite growth [#0]. Rather than acting as a conventional homodimer, PfPanK1 assembles into a heteromeric complex with PfPanK2 and the multifunctional protein Pf14-3-3I, and this tripartite assembly constitutes a single functional pantothenate kinase — the first example of a heteromeric PanK complex described in nature [#1]. Recombinant PfPanK1 phosphorylates pantothenate and additionally accepts pantetheine as a primary substrate, indicating that blood-stage CoA biosynthesis can bypass pantothenate [#2]. Its essentiality and druggability are underscored by resistance-conferring mutations selected under pantothenate-analogue pressure (pantothenol and CJ-15,801), which alter PfPanK activity and impose fitness costs [#0], and by natural-product inhibitors identified against the recombinant enzyme [#2]. Across the life cycle, the requirement is stage-specific: in P. yoelii, PanK1 knockout leaves asexual and sexual blood-stage development intact but severely impairs ookinete, oocyst, and sporozoite formation, establishing an essential role in mosquito-stage transmission [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether PanK1 is required uniformly across the parasite life cycle was unknown; genetic ablation resolved that its essential contribution is stage-specific rather than global.\",\n      \"evidence\": \"Gene-deletion knockout in P. yoelii with stage-resolved phenotyping and transcriptional analysis of CoA biosynthesis genes\",\n      \"pmids\": [\"27644319\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not identify the molecular basis of the mosquito-stage requirement\", \"Does not address whether the P. falciparum ortholog shows the same stage dependence\", \"Enzymatic activity of PyPanK1 not directly measured\"],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether Pfpank1 encodes a functional, growth-essential pantothenate kinase in blood-stage P. falciparum was established by drug-resistance genetics linking the gene to PanK activity and fitness.\",\n      \"evidence\": \"Resistance selection against pantothenate analogues followed by whole-genome sequencing, PanK activity measurement, and fitness assessment in resistant lines\",\n      \"pmids\": [\"29614109\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not resolve how each mutation alters catalysis at the structural level\", \"Direct in vitro enzymology of the mutant proteins not shown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The catalytic substrate range of the enzyme was defined, showing PfPanK1 accepts pantetheine in addition to pantothenate and thereby permitting a pantothenate-bypass route to CoA.\",\n      \"evidence\": \"Recombinant PfPanK1 purification and in vitro kinase assays with pantothenate and pantetheine, plus inhibitor screening\",\n      \"pmids\": [\"33768012\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinetic parameters distinguishing the two substrates in the physiological complex not established\", \"Inhibitor mechanism of action not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The quaternary organization of the active enzyme was unknown; co-IP and activity reconstitution revealed a novel heteromeric PanK complex rather than the canonical homodimer.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation identifying PfPanK1/PfPanK2/Pf14-3-3I, with enzymatic activity confirmed for the complex\",\n      \"pmids\": [\"34324601\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and architecture of the complex not structurally defined\", \"Individual catalytic contribution of PfPanK1 versus PfPanK2 within the complex unresolved\", \"Regulatory role of Pf14-3-3I not mechanistically dissected\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"A possible link between PANK1 and amodiaquine response was raised by sequence and expression changes under drug pressure, but a causal role was not demonstrated.\",\n      \"evidence\": \"Sequencing and stage-specific qPCR of PANK1 in amodiaquine-resistant P. berghei ANKA, with in silico ligand-binding motif analysis\",\n      \"pmids\": [\"38915420\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reverse-genetics validation of the Asn394His mutation in resistance\", \"Causal role explicitly unconfirmed by the authors\", \"Functional consequence of the differential expression not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the heteromeric PfPanK1/PfPanK2/Pf14-3-3I complex is structurally organized and regulated, and what molecular process drives the mosquito-stage-specific requirement, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of the heteromeric complex\", \"Mechanistic basis of stage-specific essentiality unresolved\", \"Role of Pf14-3-3I in modulating PanK activity uncharacterized\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004594\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0015937\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\"PfPanK1/PfPanK2/Pf14-3-3I heteromeric pantothenate kinase complex [#1]\"],\n    \"partners\": [\"PfPanK2 [#1]\", \"Pf14-3-3I [#1]\"],\n    \"other_free_text\": [\n      \"Recombinant PfPanK1 phosphorylates both pantothenate and pantetheine, enabling a pantothenate-bypass route to CoA in blood stages [#2].\",\n      \"Resistance-conferring mutations selected under pantothenate-analogue pressure alter PanK activity and carry fitness costs, indicating essentiality for blood-stage growth [#0].\",\n      \"In P. yoelii, PanK1 is dispensable for asexual and sexual blood stages but essential for ookinete, oocyst, and sporozoite formation (mosquito-stage transmission) [#3].\",\n      \"In amodiaquine-resistant P. berghei ANKA, a PANK1 Asn394His mutation and stage-dependent mRNA changes were observed, but the causal role in resistance was not confirmed [#4] (Low confidence).\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1420600","name":null,"product":"pantothenate kinase 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1022600","name":null,"product":"pantothenate kinase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1337400","name":null,"product":"pantothenate kinase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PANK1","evaluation":null}