{"gene":"PF3D7_1228300","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2001,"finding":"Recombinant NEK1 (Pfnek-1) expressed in bacteria is capable of autophosphorylation and phosphorylation of exogenous protein substrates, with substrate specificity similar to other NIMA/Nek family kinases. Mutational analysis showed that only one of the serine residues in the SMAHS motif (substituting the canonical FXXT motif) is essential for kinase activity in vitro.","method":"Bacterially expressed recombinant protein, in vitro kinase assay, active-site mutagenesis","journal":"European journal of biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase reconstitution plus mutagenesis of the active-site motif, single lab but two orthogonal methods","pmids":["11322879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2001,"finding":"Recombinant NEK1 (Pfnek-1) specifically phosphorylates Pfmap-2 (an atypical P. falciparum MAPK homologue) in vitro, and co-incubation of NEK1 and Pfmap-2 results in a synergistic increase in exogenous substrate labelling, suggesting NEK1 can modulate MAPK pathway output.","method":"In vitro kinase assay with recombinant proteins","journal":"European journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro phosphorylation assay with a defined substrate, single lab, single method","pmids":["11322879"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Reverse genetics demonstrated that NEK1 (Pfnek-1) is required for completion of the asexual erythrocytic cycle in P. falciparum, establishing a non-redundant essential role distinct from the other Pfnek family members. Immunofluorescence further showed NEK1 expression is detectable in male (but not female) gametocytes.","method":"Reverse genetics (gene disruption/knockdown), immunofluorescence","journal":"Microbiology (Reading, England)","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean reverse-genetics loss-of-function with defined cell-cycle phenotype plus localization by immunofluorescence, single lab two orthogonal methods","pmids":["21757488"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"A genetic selection for P. falciparum parasites resistant to the Aurora kinase inhibitor Hesperadin identified mutations in NEK1 (PF3D7_1228300) as the resistance mechanism, and loss of NEK1 catalytic activity conferred protection against the drug. This demonstrates a functional epistatic interaction between PfArk1 (Aurora-related kinase) and NEK1 in controlling parasite proliferation.","method":"Drug-resistance selection, whole-genome sequencing, genetic epistasis analysis","journal":"Communications biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis established by resistance selection and sequencing with functional validation of loss-of-catalytic-activity, single lab, two orthogonal methods","pmids":["33219324"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"In P. berghei, NEK1 localises to the microtubule organising centre (MTOC) during male gametogenesis and is an essential regulator of spindle formation, kinetochore attachment, and chromosome segregation during the rapid closed endomitosis of male gamete formation. Conditional knockdown of NEK1 disrupted MTOC organisation and caused failure of chromosome segregation.","method":"Live cell imaging, ultrastructure expansion microscopy (U-ExM), electron microscopy, conditional gene knockdown, proteomics","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (live imaging, U-ExM, EM, conditional KD, proteomics) in a single rigorous study establishing spatiotemporal localization and functional role","pmids":["39255311"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"P. falciparum/berghei NEK1 (PF3D7_1228300) is an active NIMA-related protein kinase that autophosphorylates, phosphorylates the MAPK homologue Pfmap-2 in vitro, and is essential for asexual erythrocytic replication; it functions epistatically with the Aurora-related kinase PfArk1, and in male gametogenesis it localises to and is required for microtubule organising centre (MTOC) organisation, spindle formation, and kinetochore-mediated chromosome segregation."},"narrative":{"mechanistic_narrative":"PF3D7_1228300 (NEK1) is a NIMA-related protein kinase that governs cell-cycle progression and mitotic apparatus organization in Plasmodium [PMID:11322879, PMID:39255311]. It is catalytically active as a recombinant protein, autophosphorylating and phosphorylating exogenous substrates with a specificity typical of NIMA/Nek-family kinases; activity depends on a single essential serine within a variant SMAHS motif that substitutes for the canonical FXXT [PMID:11322879]. Among defined substrates, NEK1 phosphorylates the atypical P. falciparum MAPK homologue Pfmap-2 in vitro, and co-incubation of the two kinases synergistically increases substrate labelling, placing NEK1 upstream of or coordinate with MAPK-pathway output [PMID:11322879]. In P. falciparum, NEK1 is non-redundantly required to complete the asexual erythrocytic cycle and is expressed in male but not female gametocytes [PMID:21757488]. Its function is epistatically linked to the Aurora-related kinase PfArk1: mutations abolishing NEK1 catalytic activity confer resistance to the Aurora inhibitor Hesperadin, connecting NEK1 to PfArk1-dependent control of proliferation [PMID:33219324]. During P. berghei male gametogenesis NEK1 localizes to the microtubule organising centre and is essential for spindle formation, kinetochore attachment, and chromosome segregation through the rapid closed endomitosis of gamete formation [PMID:39255311].","teleology":[{"year":2001,"claim":"Establishing whether PF3D7_1228300 encodes a functional kinase and defining its catalytic requirements answered the basic question of biochemical activity and revealed an atypical active-site motif.","evidence":"Bacterially expressed recombinant protein tested by in vitro autophosphorylation and substrate kinase assays with active-site mutagenesis","pmids":["11322879"],"confidence":"High","gaps":["In vitro activity does not define physiological substrates or regulation in the parasite","The relevance of the variant SMAHS motif to cellular signalling was not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2001,"claim":"Identifying Pfmap-2 as an in vitro substrate began to place NEK1 within a signalling relationship to the MAPK pathway.","evidence":"In vitro kinase assay with recombinant NEK1 and Pfmap-2 showing specific phosphorylation and synergistic substrate labelling","pmids":["11322879"],"confidence":"Medium","gaps":["Phosphorylation shown only in vitro, not demonstrated in vivo","Functional consequence of Pfmap-2 phosphorylation for MAPK signalling not established","No reciprocal or cellular validation of the interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Reverse genetics resolved whether NEK1 is dispensable relative to sibling Nek kinases, establishing a non-redundant essential role in asexual replication and a sex-specific expression pattern.","evidence":"Gene disruption/knockdown and immunofluorescence in P. falciparum","pmids":["21757488"],"confidence":"High","gaps":["The molecular process NEK1 controls in the asexual cycle was not defined","Basis of male-restricted gametocyte expression not explained"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"A drug-resistance selection connected NEK1 catalytic activity to the Aurora-related kinase PfArk1, defining a functional epistatic link controlling proliferation.","evidence":"Hesperadin resistance selection, whole-genome sequencing, and genetic epistasis analysis in P. falciparum","pmids":["33219324"],"confidence":"High","gaps":["Direct biochemical interaction or phospho-relationship between NEK1 and PfArk1 not demonstrated","Mechanism by which loss of NEK1 activity confers drug protection unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"High-resolution imaging and conditional knockdown assigned NEK1 a spatiotemporal role at the MTOC in male gametogenesis, linking it to spindle and kinetochore-mediated chromosome segregation.","evidence":"Live imaging, U-ExM, electron microscopy, conditional knockdown, and proteomics in P. berghei","pmids":["39255311"],"confidence":"High","gaps":["Substrates NEK1 phosphorylates at the MTOC not identified","Whether the asexual essential role reflects the same MTOC/spindle function is untested","Relationship of MTOC role to PfArk1 epistasis not integrated"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The in vivo substrates and regulatory logic that couple NEK1 catalytic activity to PfArk1, MTOC organisation, and asexual-cycle progression remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No physiological substrate identified beyond in vitro Pfmap-2","Mechanistic basis of NEK1–PfArk1 epistasis unknown","Whether asexual and gametogenesis roles share a common molecular mechanism unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFMAP-2 (ATYPICAL P. FALCIPARUM MAPK HOMOLOGUE, IN VITRO SUBSTRATE) [#1]","PFARK1 (AURORA-RELATED KINASE, FUNCTIONAL EPISTATIC PARTNER) [#3]"],"other_free_text":["Active kinase with an atypical SMAHS active-site motif substituting the canonical FXXT; a single serine is essential for activity [#0].","Non-redundant essential role in the P. falciparum asexual erythrocytic cycle, distinct from other Pfnek family members [#2].","Male-restricted gametocyte expression in P. falciparum [#2]; essential for MTOC organisation, spindle formation, and chromosome segregation during P. berghei male gametogenesis [#4].","Loss of NEK1 catalytic activity confers resistance to the Aurora inhibitor Hesperadin [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11322879","id":"PMC_11322879","title":"Pfnek-1, a NIMA-related kinase from the human malaria parasite Plasmodium falciparum Biochemical properties and possible involvement in MAPK regulation.","date":"2001","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11322879","citation_count":94,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NIMA","PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18512987","id":"PMC_18512987","title":"Alisiaquinones and alisiaquinol, dual inhibitors of Plasmodium falciparum enzyme targets from a New Caledonian deep water sponge.","date":"2008","source":"Journal of natural products","url":"https://pubmed.ncbi.nlm.nih.gov/18512987","citation_count":50,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16513357","id":"PMC_16513357","title":"Antimalarial potential of xestoquinone, a protein kinase inhibitor isolated from a Vanuatu marine sponge Xestospongia sp.","date":"2006","source":"Bioorganic & medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16513357","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23462523","id":"PMC_23462523","title":"Nima- and Aurora-related kinases of malaria parasites.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/23462523","citation_count":43,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NIMA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21757488","id":"PMC_21757488","title":"Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle.","date":"2011","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/21757488","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NIMA","PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30409996","id":"PMC_30409996","title":"Inducing controlled cell cycle arrest and re-entry during asexual proliferation of Plasmodium falciparum malaria parasites.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30409996","citation_count":34,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NIMA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20098604","id":"PMC_20098604","title":"Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a Vanuatu marine sponge Pseudoceratina sp.","date":"2009","source":"Marine drugs","url":"https://pubmed.ncbi.nlm.nih.gov/20098604","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33219324","id":"PMC_33219324","title":"Human Aurora kinase inhibitor Hesperadin reveals epistatic interaction between Plasmodium falciparum PfArk1 and PfNek1 kinases.","date":"2020","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/33219324","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39255311","id":"PMC_39255311","title":"Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation.","date":"2024","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/39255311","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NEK1","NIMA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37208735","id":"PMC_37208735","title":"Isoliensinine from Cissampelos pariera rhizomes exhibits potential gametocytocidal and anti-malarial activities against Plasmodium falciparum clinical isolates.","date":"2023","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/37208735","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33612795","id":"PMC_33612795","title":"Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development.","date":"2020","source":"Tropical biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/33612795","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NEK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8081,"output_tokens":1453,"usd":0.023019,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6423,"output_tokens":2755,"usd":0.050495,"stage2_stop_reason":"end_turn"},"total_usd":0.073514,"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\": 2001,\n      \"finding\": \"Recombinant NEK1 (Pfnek-1) expressed in bacteria is capable of autophosphorylation and phosphorylation of exogenous protein substrates, with substrate specificity similar to other NIMA/Nek family kinases. Mutational analysis showed that only one of the serine residues in the SMAHS motif (substituting the canonical FXXT motif) is essential for kinase activity in vitro.\",\n      \"method\": \"Bacterially expressed recombinant protein, in vitro kinase assay, active-site mutagenesis\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase reconstitution plus mutagenesis of the active-site motif, single lab but two orthogonal methods\",\n      \"pmids\": [\"11322879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Recombinant NEK1 (Pfnek-1) specifically phosphorylates Pfmap-2 (an atypical P. falciparum MAPK homologue) in vitro, and co-incubation of NEK1 and Pfmap-2 results in a synergistic increase in exogenous substrate labelling, suggesting NEK1 can modulate MAPK pathway output.\",\n      \"method\": \"In vitro kinase assay with recombinant proteins\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro phosphorylation assay with a defined substrate, single lab, single method\",\n      \"pmids\": [\"11322879\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Reverse genetics demonstrated that NEK1 (Pfnek-1) is required for completion of the asexual erythrocytic cycle in P. falciparum, establishing a non-redundant essential role distinct from the other Pfnek family members. Immunofluorescence further showed NEK1 expression is detectable in male (but not female) gametocytes.\",\n      \"method\": \"Reverse genetics (gene disruption/knockdown), immunofluorescence\",\n      \"journal\": \"Microbiology (Reading, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean reverse-genetics loss-of-function with defined cell-cycle phenotype plus localization by immunofluorescence, single lab two orthogonal methods\",\n      \"pmids\": [\"21757488\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"A genetic selection for P. falciparum parasites resistant to the Aurora kinase inhibitor Hesperadin identified mutations in NEK1 (PF3D7_1228300) as the resistance mechanism, and loss of NEK1 catalytic activity conferred protection against the drug. This demonstrates a functional epistatic interaction between PfArk1 (Aurora-related kinase) and NEK1 in controlling parasite proliferation.\",\n      \"method\": \"Drug-resistance selection, whole-genome sequencing, genetic epistasis analysis\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis established by resistance selection and sequencing with functional validation of loss-of-catalytic-activity, single lab, two orthogonal methods\",\n      \"pmids\": [\"33219324\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In P. berghei, NEK1 localises to the microtubule organising centre (MTOC) during male gametogenesis and is an essential regulator of spindle formation, kinetochore attachment, and chromosome segregation during the rapid closed endomitosis of male gamete formation. Conditional knockdown of NEK1 disrupted MTOC organisation and caused failure of chromosome segregation.\",\n      \"method\": \"Live cell imaging, ultrastructure expansion microscopy (U-ExM), electron microscopy, conditional gene knockdown, proteomics\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (live imaging, U-ExM, EM, conditional KD, proteomics) in a single rigorous study establishing spatiotemporal localization and functional role\",\n      \"pmids\": [\"39255311\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum/berghei NEK1 (PF3D7_1228300) is an active NIMA-related protein kinase that autophosphorylates, phosphorylates the MAPK homologue Pfmap-2 in vitro, and is essential for asexual erythrocytic replication; it functions epistatically with the Aurora-related kinase PfArk1, and in male gametogenesis it localises to and is required for microtubule organising centre (MTOC) organisation, spindle formation, and kinetochore-mediated chromosome segregation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1228300 (NEK1) is a NIMA-related protein kinase that governs cell-cycle progression and mitotic apparatus organization in Plasmodium [#0, #4]. It is catalytically active as a recombinant protein, autophosphorylating and phosphorylating exogenous substrates with a specificity typical of NIMA/Nek-family kinases; activity depends on a single essential serine within a variant SMAHS motif that substitutes for the canonical FXXT [#0]. Among defined substrates, NEK1 phosphorylates the atypical P. falciparum MAPK homologue Pfmap-2 in vitro, and co-incubation of the two kinases synergistically increases substrate labelling, placing NEK1 upstream of or coordinate with MAPK-pathway output [#1]. In P. falciparum, NEK1 is non-redundantly required to complete the asexual erythrocytic cycle and is expressed in male but not female gametocytes [#2]. Its function is epistatically linked to the Aurora-related kinase PfArk1: mutations abolishing NEK1 catalytic activity confer resistance to the Aurora inhibitor Hesperadin, connecting NEK1 to PfArk1-dependent control of proliferation [#3]. During P. berghei male gametogenesis NEK1 localizes to the microtubule organising centre and is essential for spindle formation, kinetochore attachment, and chromosome segregation through the rapid closed endomitosis of gamete formation [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing whether PF3D7_1228300 encodes a functional kinase and defining its catalytic requirements answered the basic question of biochemical activity and revealed an atypical active-site motif.\",\n      \"evidence\": \"Bacterially expressed recombinant protein tested by in vitro autophosphorylation and substrate kinase assays with active-site mutagenesis\",\n      \"pmids\": [\"11322879\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vitro activity does not define physiological substrates or regulation in the parasite\", \"The relevance of the variant SMAHS motif to cellular signalling was not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identifying Pfmap-2 as an in vitro substrate began to place NEK1 within a signalling relationship to the MAPK pathway.\",\n      \"evidence\": \"In vitro kinase assay with recombinant NEK1 and Pfmap-2 showing specific phosphorylation and synergistic substrate labelling\",\n      \"pmids\": [\"11322879\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphorylation shown only in vitro, not demonstrated in vivo\", \"Functional consequence of Pfmap-2 phosphorylation for MAPK signalling not established\", \"No reciprocal or cellular validation of the interaction\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Reverse genetics resolved whether NEK1 is dispensable relative to sibling Nek kinases, establishing a non-redundant essential role in asexual replication and a sex-specific expression pattern.\",\n      \"evidence\": \"Gene disruption/knockdown and immunofluorescence in P. falciparum\",\n      \"pmids\": [\"21757488\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The molecular process NEK1 controls in the asexual cycle was not defined\", \"Basis of male-restricted gametocyte expression not explained\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"A drug-resistance selection connected NEK1 catalytic activity to the Aurora-related kinase PfArk1, defining a functional epistatic link controlling proliferation.\",\n      \"evidence\": \"Hesperadin resistance selection, whole-genome sequencing, and genetic epistasis analysis in P. falciparum\",\n      \"pmids\": [\"33219324\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical interaction or phospho-relationship between NEK1 and PfArk1 not demonstrated\", \"Mechanism by which loss of NEK1 activity confers drug protection unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"High-resolution imaging and conditional knockdown assigned NEK1 a spatiotemporal role at the MTOC in male gametogenesis, linking it to spindle and kinetochore-mediated chromosome segregation.\",\n      \"evidence\": \"Live imaging, U-ExM, electron microscopy, conditional knockdown, and proteomics in P. berghei\",\n      \"pmids\": [\"39255311\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Substrates NEK1 phosphorylates at the MTOC not identified\", \"Whether the asexual essential role reflects the same MTOC/spindle function is untested\", \"Relationship of MTOC role to PfArk1 epistasis not integrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo substrates and regulatory logic that couple NEK1 catalytic activity to PfArk1, MTOC organisation, and asexual-cycle progression remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No physiological substrate identified beyond in vitro Pfmap-2\", \"Mechanistic basis of NEK1\\u2013PfArk1 epistasis unknown\", \"Whether asexual and gametogenesis roles share a common molecular mechanism unresolved\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004672\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0046777\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0004674\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0007067\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0051301\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0007143\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Pfmap-2 (atypical P. falciparum MAPK homologue, in vitro substrate) [#1]\",\n      \"PfArk1 (Aurora-related kinase, functional epistatic partner) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Active kinase with an atypical SMAHS active-site motif substituting the canonical FXXT; a single serine is essential for activity [#0].\",\n      \"Non-redundant essential role in the P. falciparum asexual erythrocytic cycle, distinct from other Pfnek family members [#2].\",\n      \"Male-restricted gametocyte expression in P. falciparum [#2]; essential for MTOC organisation, spindle formation, and chromosome segregation during P. berghei male gametogenesis [#4].\",\n      \"Loss of NEK1 catalytic activity confers resistance to the Aurora inhibitor Hesperadin [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1228300","name":null,"product":"NIMA related kinase 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1443000","name":null,"product":"NIMA related kinase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1447700","name":null,"product":"NIMA related kinase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NEK1","evaluation":null}