{"gene":"PF3D7_0316500","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2024,"finding":"Conditional disruption of PfNuf2 in P. falciparum is associated with aberrant mitotic spindle organisation, disruption of the centromere marker CENH3, and impaired karyokinesis, as visualised by ultrastructure-expansion microscopy (U-ExM). Unexpectedly, PfNuf2 disruption also leads to disengagement of the centriolar plaque (centrosome equivalent) from the nuclear envelope, severing the connection between the nucleus and the apical complex and resulting in formation of merozoites lacking nuclei.","method":"Conditional genetic disruption (loss-of-function) combined with ultrastructure-expansion microscopy (U-ExM) with fluorescent markers for spindle, centromere (CENH3), and centriolar plaque","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with multiple orthogonal imaging readouts (U-ExM, centromere marker, spindle organisation, centriolar plaque positioning) in a single rigorous study","pmids":["38987258"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"NUF2 (PBANKA_0414300) in P. berghei localises to nuclear periphery puncta during asexual blood-stage divisions, is undetectable in G1/ring stages, first appears at onset of DNA replication in trophozoites, accumulates as punctate foci during chromosome segregation, and becomes undetectable in fully budded schizonts. During mosquito stages NUF2 also localises dynamically to kinetochore structures. Immunoprecipitation of NUF2-3xHA followed by mass spectrometry identified interacting partners consistent with NDC80 complex membership.","method":"Live-cell fluorescence microscopy of endogenously tagged NUF2-mScarlet-I; U-ExM co-localisation with spindle and pole markers; immunoprecipitation (IP) of NUF2-3xHA followed by mass spectrometry","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — reciprocal IP-MS and direct live imaging across life-cycle stages in single study, single lab","pmids":["36006241"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"finding":"NUF2 in P. berghei is a subunit of the outer kinetochore NDC80 complex, forming a heterodimer with NDC80; it localises to kinetochores during nuclear division across multiple life-cycle stages including highly unusual arrangements during sexual stages, as shown by NDC80-GFP live-cell imaging. The NDC80–NUF2 dimer mediates microtubule plus-end binding through calponin homology domains.","method":"Live-cell imaging of GFP-tagged NDC80 complex components in P. berghei; deep homology searches identifying NUF2 and SPC24 as NDC80 complex subunits; spatiotemporal tracking across life-cycle stages","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — live imaging and bioinformatic identification, single lab, no in vitro reconstitution of Plasmodium-specific complex","pmids":["32501284"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"In P. berghei male gametogenesis, NUF2 marks kinetochores and co-localises with ARK1 at spindle-pole MTOCs before activation and along spindle microtubules and kinetochores during mitosis, as shown by U-ExM. ARK1, identified by reciprocal immunoprecipitation of crosslinked PbARK2–PbEB1 complexes followed by protein mass spectrometry, associates with NUF2-marked kinetochore structures, placing NUF2 in the kinetochore compartment that interacts with Aurora-related kinase complexes during chromosome segregation.","method":"U-ExM co-localisation with ARK1-mBFP2-2xTy and NUF2/AKiT5 markers; reciprocal crosslink immunoprecipitation followed by mass spectrometry (identifying NUF2 as an ARK2-associated kinetochore protein)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — U-ExM imaging and crosslink IP-MS results mentioned for PbARK2/NUF2 interaction, but NUF2-specific functional data are limited in this paper; single study","pmids":["42323312"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PfNuf2/PbNuf2 (PF3D7_0316500) is an outer kinetochore NDC80 complex subunit that localises to nuclear-peripheral kinetochore puncta during DNA replication and chromosome segregation across multiple Plasmodium life-cycle stages; conditional disruption of PfNuf2 in P. falciparum impairs mitotic spindle organisation, disrupts centromere integrity (CENH3), causes failed karyokinesis, and—unexpectedly—disengages the centriolar plaque from the nuclear envelope, thereby uncoupling the nucleus from the apical complex and producing anucleate merozoites, revealing an unanticipated role for the kinetochore/spindle complex in positioning the nascent apical complex during merozoite formation."},"narrative":{"mechanistic_narrative":"NUF2 (PF3D7_0316500) is an outer kinetochore protein that functions as a subunit of the NDC80 complex, coordinating chromosome segregation during the unusual nuclear divisions of Plasmodium across multiple life-cycle stages [PMID:38987258, PMID:32501284]. In P. berghei, NUF2 forms a heterodimer with NDC80, and this NDC80–NUF2 dimer mediates microtubule plus-end binding through calponin homology domains [PMID:32501284]; NUF2-3xHA immunoprecipitation followed by mass spectrometry recovered partners consistent with NDC80 complex membership [PMID:36006241]. NUF2 localises to nuclear-peripheral kinetochore puncta in a cell-cycle-dependent manner—absent in G1/ring stages, first appearing at the onset of DNA replication, accumulating as punctate foci during chromosome segregation, and becoming undetectable in fully budded schizonts—and it marks kinetochore structures dynamically during mosquito stages [PMID:36006241]. In P. falciparum, conditional disruption of NUF2 causes aberrant mitotic spindle organisation, disruption of the centromere marker CENH3, and impaired karyokinesis; unexpectedly, it also disengages the centriolar plaque from the nuclear envelope, uncoupling the nucleus from the apical complex and producing anucleate merozoites, revealing a role for the kinetochore/spindle machinery in positioning the nascent apical complex [PMID:38987258]. NUF2 further co-localises with Aurora-related kinase ARK1 at spindle-pole MTOCs and along spindle microtubules and kinetochores during male gametogenesis, and was recovered as an ARK2-associated kinetochore protein by crosslink immunoprecipitation, placing it in a kinetochore compartment that interacts with Aurora-related kinase complexes during chromosome segregation [PMID:42323312].","teleology":[{"year":2020,"claim":"Establishing NUF2 as a component of the Plasmodium outer kinetochore addressed whether this apicomplexan parasite possesses a canonical NDC80-based microtubule-attachment module, defining the molecular identity of the protein.","evidence":"Live-cell imaging of GFP-tagged NDC80 complex components and deep homology searches in P. berghei, with spatiotemporal tracking across life-cycle stages","pmids":["32501284"],"confidence":"Medium","gaps":["No in vitro reconstitution of the Plasmodium-specific NDC80–NUF2 dimer","Direct microtubule-binding activity of NUF2 itself not biochemically isolated from the dimer","Single lab, homology-based subunit assignment"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"Defining the cell-cycle-dependent localisation of NUF2 and its interaction partners clarified when and where the protein acts during the atypical closed mitoses of Plasmodium and confirmed its NDC80 complex membership by proteomics.","evidence":"Live-cell fluorescence of endogenously tagged NUF2-mScarlet-I, U-ExM co-localisation with spindle/pole markers, and reciprocal IP-MS of NUF2-3xHA in P. berghei","pmids":["36006241"],"confidence":"Medium","gaps":["Functional consequence of NUF2 loss not tested in this study","Interaction partner list not resolved to direct versus indirect contacts","Single-lab dataset"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"Conditional loss-of-function established what NUF2 is required for in vivo and revealed an unanticipated role beyond chromosome segregation in coupling the nucleus to the developing apical complex.","evidence":"Conditional genetic disruption combined with U-ExM using spindle, CENH3 centromere, and centriolar plaque markers in P. falciparum","pmids":["38987258"],"confidence":"High","gaps":["Molecular mechanism by which NUF2/kinetochore loss disengages the centriolar plaque from the nuclear envelope is unresolved","Whether the anucleate-merozoite phenotype is a direct NUF2 function or an indirect consequence of segregation failure not distinguished","No structural basis for the observed defects"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Placing NUF2 in a kinetochore compartment that associates with Aurora-related kinases during male gametogenesis began to connect kinetochore attachment to regulatory kinase signalling in sexual-stage division.","evidence":"U-ExM co-localisation of NUF2 with ARK1 and reciprocal crosslink IP-MS recovering NUF2 as an ARK2-associated kinetochore protein in P. berghei","pmids":["42323312"],"confidence":"Medium","gaps":["NUF2-specific functional data are limited in this study","Whether NUF2 is a direct binding partner or substrate of ARK1/ARK2 is not established","Single study"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How NUF2 mechanistically links kinetochore/spindle integrity to centriolar plaque anchoring at the nuclear envelope, and whether this coupling is regulated by Aurora-related kinases, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or reconstitution data for the Plasmodium NDC80–NUF2 dimer","Mechanistic connection between kinetochore function and apical-complex positioning uncharacterized","Regulatory inputs from Aurora-related kinases onto NUF2 not defined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["NDC80 outer kinetochore complex (NUF2–NDC80 heterodimer)"],"partners":["NDC80 (DIRECT HETERODIMER PARTNER)","SPC24 (NDC80 COMPLEX SUBUNIT)","CENH3 (CENTROMERE MARKER; INTEGRITY AFFECTED BY NUF2 LOSS)","ARK1 (AURORA-RELATED KINASE; CO-LOCALISES AT KINETOCHORES/MTOCS)","ARK2 (AURORA-RELATED KINASE; NUF2 RECOVERED AS ARK2-ASSOCIATED PROTEIN)"],"other_free_text":["Cell-cycle-dependent localisation in P. berghei: absent in G1/ring, appears at onset of DNA replication, accumulates during chromosome segregation, undetectable in fully budded schizonts","Conditional disruption in P. falciparum disengages the centriolar plaque from the nuclear envelope and produces anucleate merozoites, indicating a role in coupling the nucleus to the apical complex","Functions across multiple Plasmodium life-cycle stages including asexual blood stages, mosquito stages, and male gametogenesis"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"38987258","id":"PMC_38987258","title":"Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38987258","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42323312","id":"","title":"A modular chromosomal passenger complex rewires chromosome segregation in Plasmodium berghei.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42323312","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40488521","id":"","title":"A dynamic barrier: remodeling of the nuclear envelope during closed mitosis in malaria parasites.","date":"2025","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/40488521","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42399518","id":"","title":"Essential nucleus-apical pole linkage maintains division fidelity during Plasmodium progeny formation.","date":"2026","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/42399518","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39235260","id":"","title":"The three Plasmodium falciparum Aurora-related kinases display distinct temporal and spatial associations with mitotic structures in asexual blood stage parasites and gametocytes.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/39235260","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36006241","id":"","title":"Composition and organization of kinetochores show plasticity in apicomplexan chromosome segregation.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/36006241","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32501284","id":"","title":"Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/32501284","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35800888","id":"","title":"Kinetochore Architecture Employs Diverse Linker Strategies Across Evolution.","date":"2022","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/35800888","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32582569","id":"","title":"Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes.","date":"2020","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32582569","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33912479","id":"","title":"The Modular Circuitry of Apicomplexan Cell Division Plasticity.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33912479","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NUF2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14390,"output_tokens":1581,"usd":0.033443,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6577,"output_tokens":2958,"usd":0.053417,"stage2_stop_reason":"end_turn"},"total_usd":0.08686,"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\": 2024,\n      \"finding\": \"Conditional disruption of PfNuf2 in P. falciparum is associated with aberrant mitotic spindle organisation, disruption of the centromere marker CENH3, and impaired karyokinesis, as visualised by ultrastructure-expansion microscopy (U-ExM). Unexpectedly, PfNuf2 disruption also leads to disengagement of the centriolar plaque (centrosome equivalent) from the nuclear envelope, severing the connection between the nucleus and the apical complex and resulting in formation of merozoites lacking nuclei.\",\n      \"method\": \"Conditional genetic disruption (loss-of-function) combined with ultrastructure-expansion microscopy (U-ExM) with fluorescent markers for spindle, centromere (CENH3), and centriolar plaque\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with multiple orthogonal imaging readouts (U-ExM, centromere marker, spindle organisation, centriolar plaque positioning) in a single rigorous study\",\n      \"pmids\": [\"38987258\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NUF2 (PBANKA_0414300) in P. berghei localises to nuclear periphery puncta during asexual blood-stage divisions, is undetectable in G1/ring stages, first appears at onset of DNA replication in trophozoites, accumulates as punctate foci during chromosome segregation, and becomes undetectable in fully budded schizonts. During mosquito stages NUF2 also localises dynamically to kinetochore structures. Immunoprecipitation of NUF2-3xHA followed by mass spectrometry identified interacting partners consistent with NDC80 complex membership.\",\n      \"method\": \"Live-cell fluorescence microscopy of endogenously tagged NUF2-mScarlet-I; U-ExM co-localisation with spindle and pole markers; immunoprecipitation (IP) of NUF2-3xHA followed by mass spectrometry\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — reciprocal IP-MS and direct live imaging across life-cycle stages in single study, single lab\",\n      \"pmids\": [\"36006241\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NUF2 in P. berghei is a subunit of the outer kinetochore NDC80 complex, forming a heterodimer with NDC80; it localises to kinetochores during nuclear division across multiple life-cycle stages including highly unusual arrangements during sexual stages, as shown by NDC80-GFP live-cell imaging. The NDC80–NUF2 dimer mediates microtubule plus-end binding through calponin homology domains.\",\n      \"method\": \"Live-cell imaging of GFP-tagged NDC80 complex components in P. berghei; deep homology searches identifying NUF2 and SPC24 as NDC80 complex subunits; spatiotemporal tracking across life-cycle stages\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — live imaging and bioinformatic identification, single lab, no in vitro reconstitution of Plasmodium-specific complex\",\n      \"pmids\": [\"32501284\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In P. berghei male gametogenesis, NUF2 marks kinetochores and co-localises with ARK1 at spindle-pole MTOCs before activation and along spindle microtubules and kinetochores during mitosis, as shown by U-ExM. ARK1, identified by reciprocal immunoprecipitation of crosslinked PbARK2–PbEB1 complexes followed by protein mass spectrometry, associates with NUF2-marked kinetochore structures, placing NUF2 in the kinetochore compartment that interacts with Aurora-related kinase complexes during chromosome segregation.\",\n      \"method\": \"U-ExM co-localisation with ARK1-mBFP2-2xTy and NUF2/AKiT5 markers; reciprocal crosslink immunoprecipitation followed by mass spectrometry (identifying NUF2 as an ARK2-associated kinetochore protein)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — U-ExM imaging and crosslink IP-MS results mentioned for PbARK2/NUF2 interaction, but NUF2-specific functional data are limited in this paper; single study\",\n      \"pmids\": [\"42323312\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfNuf2/PbNuf2 (PF3D7_0316500) is an outer kinetochore NDC80 complex subunit that localises to nuclear-peripheral kinetochore puncta during DNA replication and chromosome segregation across multiple Plasmodium life-cycle stages; conditional disruption of PfNuf2 in P. falciparum impairs mitotic spindle organisation, disrupts centromere integrity (CENH3), causes failed karyokinesis, and—unexpectedly—disengages the centriolar plaque from the nuclear envelope, thereby uncoupling the nucleus from the apical complex and producing anucleate merozoites, revealing an unanticipated role for the kinetochore/spindle complex in positioning the nascent apical complex during merozoite formation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUF2 (PF3D7_0316500) is an outer kinetochore protein that functions as a subunit of the NDC80 complex, coordinating chromosome segregation during the unusual nuclear divisions of Plasmodium across multiple life-cycle stages [#0, #2]. In P. berghei, NUF2 forms a heterodimer with NDC80, and this NDC80\\u2013NUF2 dimer mediates microtubule plus-end binding through calponin homology domains [#2]; NUF2-3xHA immunoprecipitation followed by mass spectrometry recovered partners consistent with NDC80 complex membership [#1]. NUF2 localises to nuclear-peripheral kinetochore puncta in a cell-cycle-dependent manner\\u2014absent in G1/ring stages, first appearing at the onset of DNA replication, accumulating as punctate foci during chromosome segregation, and becoming undetectable in fully budded schizonts\\u2014and it marks kinetochore structures dynamically during mosquito stages [#1]. In P. falciparum, conditional disruption of NUF2 causes aberrant mitotic spindle organisation, disruption of the centromere marker CENH3, and impaired karyokinesis; unexpectedly, it also disengages the centriolar plaque from the nuclear envelope, uncoupling the nucleus from the apical complex and producing anucleate merozoites, revealing a role for the kinetochore/spindle machinery in positioning the nascent apical complex [#0]. NUF2 further co-localises with Aurora-related kinase ARK1 at spindle-pole MTOCs and along spindle microtubules and kinetochores during male gametogenesis, and was recovered as an ARK2-associated kinetochore protein by crosslink immunoprecipitation, placing it in a kinetochore compartment that interacts with Aurora-related kinase complexes during chromosome segregation [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing NUF2 as a component of the Plasmodium outer kinetochore addressed whether this apicomplexan parasite possesses a canonical NDC80-based microtubule-attachment module, defining the molecular identity of the protein.\",\n      \"evidence\": \"Live-cell imaging of GFP-tagged NDC80 complex components and deep homology searches in P. berghei, with spatiotemporal tracking across life-cycle stages\",\n      \"pmids\": [\"32501284\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution of the Plasmodium-specific NDC80\\u2013NUF2 dimer\",\n        \"Direct microtubule-binding activity of NUF2 itself not biochemically isolated from the dimer\",\n        \"Single lab, homology-based subunit assignment\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defining the cell-cycle-dependent localisation of NUF2 and its interaction partners clarified when and where the protein acts during the atypical closed mitoses of Plasmodium and confirmed its NDC80 complex membership by proteomics.\",\n      \"evidence\": \"Live-cell fluorescence of endogenously tagged NUF2-mScarlet-I, U-ExM co-localisation with spindle/pole markers, and reciprocal IP-MS of NUF2-3xHA in P. berghei\",\n      \"pmids\": [\"36006241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of NUF2 loss not tested in this study\",\n        \"Interaction partner list not resolved to direct versus indirect contacts\",\n        \"Single-lab dataset\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Conditional loss-of-function established what NUF2 is required for in vivo and revealed an unanticipated role beyond chromosome segregation in coupling the nucleus to the developing apical complex.\",\n      \"evidence\": \"Conditional genetic disruption combined with U-ExM using spindle, CENH3 centromere, and centriolar plaque markers in P. falciparum\",\n      \"pmids\": [\"38987258\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism by which NUF2/kinetochore loss disengages the centriolar plaque from the nuclear envelope is unresolved\",\n        \"Whether the anucleate-merozoite phenotype is a direct NUF2 function or an indirect consequence of segregation failure not distinguished\",\n        \"No structural basis for the observed defects\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Placing NUF2 in a kinetochore compartment that associates with Aurora-related kinases during male gametogenesis began to connect kinetochore attachment to regulatory kinase signalling in sexual-stage division.\",\n      \"evidence\": \"U-ExM co-localisation of NUF2 with ARK1 and reciprocal crosslink IP-MS recovering NUF2 as an ARK2-associated kinetochore protein in P. berghei\",\n      \"pmids\": [\"42323312\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"NUF2-specific functional data are limited in this study\",\n        \"Whether NUF2 is a direct binding partner or substrate of ARK1/ARK2 is not established\",\n        \"Single study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NUF2 mechanistically links kinetochore/spindle integrity to centriolar plaque anchoring at the nuclear envelope, and whether this coupling is regulated by Aurora-related kinases, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or reconstitution data for the Plasmodium NDC80\\u2013NUF2 dimer\",\n        \"Mechanistic connection between kinetochore function and apical-complex positioning uncharacterized\",\n        \"Regulatory inputs from Aurora-related kinases onto NUF2 not defined\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000776\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0005816\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0034399\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0007080\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0051301\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"NDC80 outer kinetochore complex (NUF2\\u2013NDC80 heterodimer)\"\n    ],\n    \"partners\": [\n      \"NDC80 (direct heterodimer partner)\",\n      \"SPC24 (NDC80 complex subunit)\",\n      \"CENH3 (centromere marker; integrity affected by NUF2 loss)\",\n      \"ARK1 (Aurora-related kinase; co-localises at kinetochores/MTOCs)\",\n      \"ARK2 (Aurora-related kinase; NUF2 recovered as ARK2-associated protein)\"\n    ],\n    \"other_free_text\": [\n      \"Cell-cycle-dependent localisation in P. berghei: absent in G1/ring, appears at onset of DNA replication, accumulates during chromosome segregation, undetectable in fully budded schizonts\",\n      \"Conditional disruption in P. falciparum disengages the centriolar plaque from the nuclear envelope and produces anucleate merozoites, indicating a role in coupling the nucleus to the apical complex\",\n      \"Functions across multiple Plasmodium life-cycle stages including asexual blood stages, mosquito stages, and male gametogenesis\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0316500","name":null,"product":"kinetochore protein NUF2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0414300","name":null,"product":"kinetochore protein NUF2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0825300","name":null,"product":"kinetochore protein NUF2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NUF2","evaluation":null}