NEK1 is a NIMA-related serine/threonine protein kinase with an N-terminal catalytic domain and an extended regulatory region. It forms a stable cellular complex with CFAP410 (C21ORF2) and acts in primary-cilium assembly and genome maintenance. NEK1 kinase activity limits centriole microtubule elongation through a pathway operating alongside CP110-CEP97, and is required for normal ciliogenesis, while nuclear and cytoplasmic pools support DNA-damage checkpoint signaling and homologous-recombination repair. NEK1 helps maintain the ATR-ATRIP signaling complex and also phosphorylates VDAC1 in a mitochondrial-associated pathway that limits injury-induced cell death. In human motor-neuron models, NEK1 loss also perturbs microtubule homeostasis and nuclear import. Biallelic loss of function causes skeletal ciliopathies, and other NEK1 variants confer susceptibility to amyotrophic lateral sclerosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000242 pericentriolar material | IDA PMID:21211617 NEK1 mutations cause short-rib polydactyly syndrome type maj... | ACCEPT | Summary: NEK1 associates with the centrosomal/pericentriolar region in ciliated human cells. Reason: Retain the curated IDA localization from PMID:21211617; the retrieved article supports a basal-body-associated function, and the UniProt record explicitly attributes pericentriolar-material localization to this paper. The ciliary phenotype and independent basal-body colocalization in PMID:26167768 corroborate the location. PMID:42265085 further identifies a kinase-dependent centriole-length control function; NEK1 occupancy at the basal body changes during ciliogenesis, so the localization is not constitutive. Supporting Evidence: PMID:26167768 C21orf2 co-localises with NEK1 and SPATA7 at the basal body in hTERT-RPE1 cells PMID:42265085 Nek1 is removed from the basal body during ciliogenesis in a Cep78-dependent manner |
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: NEK1 is a catalytically active protein kinase. Reason: Protein kinase activity is directly supported by biochemical phosphorylation assays. The broad term is valid alongside the more specific serine/threonine kinase annotations. The PAINT inference represents inheritance from a curated ancestral node; target NEK1 experimental evidence among its sources is legitimate, not circular. Supporting Evidence: PMID:19158487 Whereas Nek1 immune complexes could specifically phosphorylate wild type GST-VDAC1, they could not phosphorylate the GST-VDAC1-S193A mutant |
| GO:0004672 protein kinase activity | IDA PMID:15604234 NIMA-related protein kinase 1 is involved early in the ioniz... | ACCEPT | Summary: NEK1 is a catalytically active protein kinase. Reason: Protein kinase activity is directly supported by biochemical phosphorylation assays. The broad term is valid alongside the more specific serine/threonine kinase annotations. The original IDA evidence is consistent with the characterized catalytic domain and protein-substrate phosphorylation. Supporting Evidence: PMID:15604234 Nek1 kinase activity is increased within 4 minutes PMID:19158487 Whereas Nek1 immune complexes could specifically phosphorylate wild type GST-VDAC1, they could not phosphorylate the GST-VDAC1-S193A mutant |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: NEK1 is a catalytically active protein kinase. Reason: Protein kinase activity is directly supported by biochemical phosphorylation assays. The broad term is valid alongside the more specific serine/threonine kinase annotations. The original IEA evidence is consistent with the characterized catalytic domain and protein-substrate phosphorylation. Supporting Evidence: PMID:19158487 Whereas Nek1 immune complexes could specifically phosphorylate wild type GST-VDAC1, they could not phosphorylate the GST-VDAC1-S193A mutant |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: NEK1 is a serine/threonine protein kinase with directly demonstrated serine-substrate phosphorylation. Reason: The EC mapping agrees with the NEK kinase domain and experimentally demonstrated protein phosphorylation. The serine-specific annotation separately captures the best-characterized substrate chemistry. Supporting Evidence: PMID:20230784 Nek1 phosphorylates VDAC1 on Ser193 to prevent excessive cell death after injury. file:human/NEK1/NEK1-deep-research-falcon.md NEK1βs primary molecular function is ATP-dependent phosphorylation of protein serine/threonine residues. |
| GO:0005515 protein binding | IPI PMID:14690447 Identification of proteins that interact with the central co... | MODIFY | Summary: The curated interaction is with YWHAH (14-3-3 eta), allowing a more informative binding term. Reason: The preserved GOA IPI assertion identifies its interaction partner as UniProtKB:Q04917, which the fetched NEK1 UniProt interaction record identifies as YWHAH (14-3-3 eta). The refinement rests on that original curated partner identity: replace generic protein binding with 14-3-3 protein binding. It does not assert YWHAH phosphorylation, independently re-establish the interaction experiment, or rely on a potential-substrate screen from another paper. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:14690447 Identification of proteins that interact with the central co... | REMOVE | Summary: GOA records an interaction with FEZ1, but generic protein binding is not an informative molecular function. Reason: Remove the uninformative generic binding annotation under the curation policy, without rejecting the reported interaction. The original interaction evidence and partner are retained in this record. They do not establish substrate phosphorylation, transport, or another specific activity, so no replacement function is inferred. |
| GO:0005515 protein binding | IPI PMID:14690447 Identification of proteins that interact with the central co... | REMOVE | Summary: GOA records an interaction with FEZ2, but generic protein binding is not an informative molecular function. Reason: Remove the uninformative generic binding annotation under the curation policy, without rejecting the reported interaction. The original interaction evidence and partner are retained in this record. They do not establish substrate phosphorylation, transport, or another specific activity, so no replacement function is inferred. |
| GO:0005515 protein binding | IPI PMID:24510904 Unbiased screen for interactors of leucine-rich repeat kinas... | REMOVE | Summary: The interaction-array study supplies the curated NEK1-LRRK2 binding assertion, but generic protein binding does not describe a specific NEK1 function. Reason: Full text was retrieved after retry. Retain the original interaction assertion as provenance, but remove its uninformative generic molecular-function term under the curation policy. This does not reject the NEK1-LRRK2 interaction, and no LRRK2 phosphorylation or Parkinson-disease pathway role is inferred from binding alone. |
| GO:0005515 protein binding | IPI PMID:24947832 Differential protein-protein interactions of LRRK1 and LRRK2... | REMOVE | Summary: GOA records an interaction with LRRK2, but generic protein binding is not an informative molecular function. Reason: Remove the uninformative generic binding annotation under the curation policy, without rejecting the reported interaction. The original interaction evidence and partner are retained in this record. They do not establish substrate phosphorylation, transport, or another specific activity, so no replacement function is inferred. |
| GO:0005515 protein binding | IPI PMID:26167768 An siRNA-based functional genomics screen for theΒ identifica... | REMOVE | Summary: GOA records an interaction with CFAP410/C21ORF2, but generic protein binding is not an informative molecular function. Reason: Remove the uninformative generic binding annotation under the curation policy, without rejecting the reported interaction. The association with CFAP410 is mechanistically relevant to ciliogenesis and DNA repair, but association alone does not establish an adapter or other specific molecular activity for NEK1; those processes and its kinase activity are represented separately. Supporting Evidence: PMID:26167768 revealed that C21orf2, NEK1, and a retinal ciliopathy protein, SPATA724, are part of the same protein complex. |
| GO:0005515 protein binding | IPI PMID:26290490 The NEK1 interactor, C21ORF2, is required for efficient DNA ... | REMOVE | Summary: GOA records an interaction with CFAP410/C21ORF2, but generic protein binding is not an informative molecular function. Reason: Remove the uninformative generic binding annotation under the curation policy, without rejecting the reported interaction. The association with CFAP410 is mechanistically relevant to ciliogenesis and DNA repair, but association alone does not establish an adapter or other specific molecular activity for NEK1; those processes and its kinase activity are represented separately. Supporting Evidence: PMID:26290490 The interaction between C21ORF2 and NEK1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: The curated interaction is with YWHAH (14-3-3 eta), allowing a more informative binding term. Reason: The preserved GOA IPI assertion identifies its interaction partner as UniProtKB:Q04917, which the fetched NEK1 UniProt interaction record identifies as YWHAH (14-3-3 eta). The refinement rests on that original curated partner identity: replace generic protein binding with 14-3-3 protein binding. It does not assert YWHAH phosphorylation, independently re-establish the interaction experiment, or rely on a potential-substrate screen from another paper. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The curated interaction is with YWHAH (14-3-3 eta), allowing a more informative binding term. Reason: The preserved GOA IPI assertion identifies its interaction partner as UniProtKB:Q04917, which the fetched NEK1 UniProt interaction record identifies as YWHAH (14-3-3 eta). The refinement rests on that original curated partner identity: replace generic protein binding with 14-3-3 protein binding. It does not assert YWHAH phosphorylation, independently re-establish the interaction experiment, or rely on a potential-substrate screen from another paper. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records an interaction with ALS2, but generic protein binding is not an informative molecular function. Reason: Remove the uninformative generic binding annotation under the curation policy, without rejecting the reported interaction. The original interaction evidence and partner are retained in this record. They do not establish substrate phosphorylation, transport, or another specific activity, so no replacement function is inferred. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: The curated interaction is with YWHAH (14-3-3 eta), allowing a more informative binding term. Reason: The preserved GOA IPI assertion identifies its interaction partner as UniProtKB:Q04917, which the fetched NEK1 UniProt interaction record identifies as YWHAH (14-3-3 eta). The refinement rests on that original curated partner identity: replace generic protein binding with 14-3-3 protein binding. It does not assert YWHAH phosphorylation, independently re-establish the interaction experiment, or rely on a potential-substrate screen from another paper. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: The curated interaction is with YWHAH (14-3-3 eta), allowing a more informative binding term. Reason: The preserved GOA IPI assertion identifies its interaction partner as UniProtKB:Q04917, which the fetched NEK1 UniProt interaction record identifies as YWHAH (14-3-3 eta). The refinement rests on that original curated partner identity: replace generic protein binding with 14-3-3 protein binding. It does not assert YWHAH phosphorylation, independently re-establish the interaction experiment, or rely on a potential-substrate screen from another paper. Proposed replacements: 14-3-3 protein binding |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: NEK1 binds ATP as the phosphate donor for protein phosphorylation. Reason: The ATP-binding protein kinase domain supports the InterPro mapping, and ATP-dependent substrate phosphorylation is measured directly; this is a valid biochemical capability even though the kinase term is more informative. Supporting Evidence: PMID:19158487 Kinase assays were carried out using immune complexes with either 5 ΞΌg of Ξ²-casein or 3 ΞΌg of GST-VDAC1 in the presence of 3 ΞΌCi of Ξ³-32P-ATP |
| GO:0005634 nucleus | IDA PMID:15604234 NIMA-related protein kinase 1 is involved early in the ioniz... | ACCEPT | Summary: NEK1 occupies both cytoplasmic and nuclear pools and redistributes to nuclear DNA-damage foci. Reason: The IDA localization is consistent with direct microscopy and DNA-damage recruitment. This localization supports its compartment-dependent kinase functions without implying exclusive residence. Supporting Evidence: PMID:15604234 a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: NEK1 occupies both cytoplasmic and nuclear pools and redistributes to nuclear DNA-damage foci. Reason: The IEA localization is consistent with direct microscopy and DNA-damage recruitment. This localization supports its compartment-dependent kinase functions without implying exclusive residence. Supporting Evidence: PMID:15604234 a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence supports NEK1 localization to the nucleoplasm. Reason: The current HPA NEK1 subcellular page (ENSG00000137601, accessed 2026-09-12) lists nucleoplasm as the main location and cytosol and centriolar satellites as additional supported locations. Retain the original curated IDA localization; this does not by itself demonstrate catalytic activity in every stained compartment. |
| GO:0005737 cytoplasm | EXP PMID:18843199 Never-in-mitosis related kinase 1 functions in DNA damage re... | ACCEPT | Summary: NEK1 occupies both cytoplasmic and nuclear pools and redistributes to nuclear DNA-damage foci. Reason: The EXP localization is consistent with direct microscopy and DNA-damage recruitment. This localization supports its compartment-dependent kinase functions without implying exclusive residence. Supporting Evidence: PMID:15604234 a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. PMID:18843199 In Nek1(-/-) murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. |
| GO:0005737 cytoplasm | IDA PMID:15604234 NIMA-related protein kinase 1 is involved early in the ioniz... | ACCEPT | Summary: NEK1 occupies both cytoplasmic and nuclear pools and redistributes to nuclear DNA-damage foci. Reason: The IDA localization is consistent with direct microscopy and DNA-damage recruitment. This localization supports its compartment-dependent kinase functions without implying exclusive residence. Supporting Evidence: PMID:15604234 a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: NEK1 occupies both cytoplasmic and nuclear pools and redistributes to nuclear DNA-damage foci. Reason: The IEA localization is consistent with direct microscopy and DNA-damage recruitment. This localization supports its compartment-dependent kinase functions without implying exclusive residence. Supporting Evidence: PMID:15604234 a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: NEK1 is a centrosome-associated kinase relevant to primary-cilium formation. Reason: Retain the original centrosomal localization. The centrosome proteomics study PMID:21399614 supports the curated IDA record; later human-cell basal-body microscopy independently corroborates centrosome association. PMID:42265085 further identifies a kinase-dependent centriole-length control function; NEK1 occupancy at the basal body changes during ciliogenesis, so the localization is not constitutive. Supporting Evidence: PMID:26167768 C21orf2 co-localises with NEK1 and SPATA7 at the basal body in hTERT-RPE1 cells PMID:42265085 Nek1 is removed from the basal body during ciliogenesis in a Cep78-dependent manner |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: NEK1 is a centrosome-associated kinase relevant to primary-cilium formation. Reason: Retain the original centrosomal localization. The integrated localization inference agrees with human-cell microscopy and the experimentally required role in ciliogenesis. PMID:42265085 further identifies a kinase-dependent centriole-length control function; NEK1 occupancy at the basal body changes during ciliogenesis, so the localization is not constitutive. Supporting Evidence: PMID:26167768 C21orf2 co-localises with NEK1 and SPATA7 at the basal body in hTERT-RPE1 cells PMID:42265085 Nek1 is removed from the basal body during ciliogenesis in a Cep78-dependent manner |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence supports NEK1 localization to the cytosol. Reason: The current HPA NEK1 subcellular page (ENSG00000137601, accessed 2026-09-12) lists nucleoplasm as the main location and cytosol and centriolar satellites as additional supported locations. Retain the original curated IDA localization; this does not by itself demonstrate catalytic activity in every stained compartment. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9861642 | ACCEPT | Summary: NEK1 acts in the cytosol, including phosphorylation of cytosolic ME1 in the curated Reactome reaction. Reason: The Reactome reaction explicitly assigns NEK1-catalyzed phosphorylation of cytosolic malic enzyme 1; independent HPA imaging also supports cytosolic localization. Its primary experimental source is PMID:31735643, which describes the reversible control of ME1 Ser336 phosphorylation by NEK1 and PGAM5. Supporting Evidence: Reactome:R-HSA-9861642 Serine/threonine-protein kinase NEK1 (aka NimA-related protein kinase 1) phosphorylates cytosolic malic enzyme 1 (ME1) at Ser-336, inhibiting its catalytic activity |
| GO:0006468 protein phosphorylation | IDA PMID:19158487 Nek1 regulates cell death and mitochondrial membrane permeab... | ACCEPT | Summary: NEK1 catalyzes phosphorylation of protein substrates, including VDAC1. Reason: The original paper combines substrate interaction, kinase assays and Ser193 mutagenesis, directly supporting protein phosphorylation. Supporting Evidence: PMID:19158487 Whereas Nek1 immune complexes could specifically phosphorylate wild type GST-VDAC1, they could not phosphorylate the GST-VDAC1-S193A mutant |
| GO:0016301 kinase activity | IMP PMID:19158487 Nek1 regulates cell death and mitochondrial membrane permeab... | MODIFY | Summary: The measured activity is phosphorylation of serine residues in a protein substrate. Reason: The original VDAC1 study provides substantially more specificity than generic kinase activity: NEK1 phosphorylates VDAC1 Ser193, supported by the Ser193Ala substrate mutant. Proposed replacements: protein serine kinase activity Supporting Evidence: PMID:19158487 Whereas Nek1 immune complexes could specifically phosphorylate wild type GST-VDAC1, they could not phosphorylate the GST-VDAC1-S193A mutant |
| GO:0034451 centriolar satellite | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence supports NEK1 localization to the centriolar satellite. Reason: The current HPA NEK1 subcellular page (ENSG00000137601, accessed 2026-09-12) lists nucleoplasm as the main location and cytosol and centriolar satellites as additional supported locations. Retain the original curated IDA localization; this does not by itself demonstrate catalytic activity in every stained compartment. |
| GO:0060271 cilium assembly | IMP PMID:21211617 NEK1 mutations cause short-rib polydactyly syndrome type maj... | MODIFY | Summary: NEK1 is required for normal primary-cilium assembly. Reason: Patient-cell defects in the original study and knockout/rescue experiments in PMID:37188479 establish a core ciliogenesis role. Kinase-inactive NEK1 fails to support normal ciliogenesis; the relevant ciliary substrates remain unresolved. PMID:42265085 further identifies a kinase-dependent centriole-length control function; NEK1 occupancy at the basal body changes during ciliogenesis, so the localization is not constitutive. Refine the broad assembly term to non-motile cilium assembly because the cited patient-cell and RPE1 knockout/rescue experiments concern primary cilia, matching the specificity used for CFAP410. Proposed replacements: non-motile cilium assembly Supporting Evidence: PMID:21211617 We found that absence of functional full-length NEK1 severely reduces cilia number and alters ciliar morphology PMID:37188479 We also found that the kinase activity of NEK1 is essential for ciliogenesis PMID:42265085 Nek1 is removed from the basal body during ciliogenesis in a Cep78-dependent manner |
| GO:0071889 14-3-3 protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: NEK1 associates with 14-3-3 proteins. Reason: The orthology-based annotation is consistent with human NEK1 interaction records for YWHAH and the original two-hybrid literature. Retain as a regulatory interaction rather than a defining core molecular activity; the human equivalent of the mouse phosphorylation-site mechanism is not inferred here. Supporting Evidence: PMID:19158487 identified proteins involved in the DNA damage response (ZBRK1, MRE11, 53BP1) and in apoptosis signaling (14-3-3) as potential substrates for Nek1. |
| GO:0071889 14-3-3 protein binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: NEK1 associates with 14-3-3 proteins. Reason: The orthology-based annotation is consistent with human NEK1 interaction records for YWHAH and the original two-hybrid literature. Retain as a regulatory interaction rather than a defining core molecular activity; the human equivalent of the mouse phosphorylation-site mechanism is not inferred here. Supporting Evidence: PMID:19158487 identified proteins involved in the DNA damage response (ZBRK1, MRE11, 53BP1) and in apoptosis signaling (14-3-3) as potential substrates for Nek1. |
| GO:0106310 protein serine kinase activity | EXP PMID:20230784 Phosphorylation by Nek1 regulates opening and closing of vol... | ACCEPT | Summary: NEK1 catalyzes phosphorylation of serine residues in protein substrates. Reason: Phosphorylation of VDAC1 at Ser193 is supported by biochemical assays and site-directed substrate mutation in the cited experimental work. The Rhea reaction mapping is consistent with this directly demonstrated chemistry. Supporting Evidence: PMID:20230784 Nek1 phosphorylates VDAC1 on Ser193 to prevent excessive cell death after injury. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: NEK1 catalyzes phosphorylation of serine residues in protein substrates. Reason: Phosphorylation of VDAC1 at Ser193 is supported by biochemical assays and site-directed substrate mutation in the cited experimental work. The Rhea reaction mapping is consistent with this directly demonstrated chemistry. Supporting Evidence: PMID:20230784 Nek1 phosphorylates VDAC1 on Ser193 to prevent excessive cell death after injury. |
| GO:2000001 regulation of DNA damage checkpoint | IEA GO_REF:0000107 | ACCEPT | Summary: NEK1 regulates DNA-damage checkpoint signaling, including efficient ATR pathway activation. Reason: The orthology transfer is corroborated by human-cell perturbation and rescue experiments. NEK1 kinase activity and ATR-ATRIP association promote checkpoint signaling. This does not imply direct NEK1 phosphorylation of ATR Thr1989, which the 2013 study explicitly excluded. Supporting Evidence: PMID:18843199 In Nek1(-/-) murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. PMID:23345434 The ability of Nek1 to promote ATR activation relies on the kinase activity of Nek1 and its interaction with ATR-ATRIP. file:human/NEK1/NEK1-deep-research-openscientist.md T1989 is an **ATR autophosphorylation** site |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:26290490 The NEK1 interactor, C21ORF2, is required for efficient DNA ... | NEW | Summary: NEK1 promotes homologous-recombination repair of DNA double-strand breaks. Reason: Human U2OS reporter assays show defective HR after NEK1 knockdown; later genetic studies corroborate a requirement for NEK1 and CFAP410. The role is retained without assuming a disputed RAD54 Ser572 phosphorylation mechanism. Supporting Evidence: PMID:26290490 Knockdown of both C21ORF2 and NEK1 resulted in defective HR repair |
| GO:0005739 mitochondrion | IDA PMID:19158487 Nek1 regulates cell death and mitochondrial membrane permeab... | NEW | Summary: A fraction of cellular NEK1 associates with mitochondria. Reason: Fractionation and microscopy support a mitochondrial-associated pool relevant to VDAC1 phosphorylation. The evidence does not resolve an exclusive mitochondrial membrane subcompartment. Supporting Evidence: PMID:19158487 a consistent and significant portion fractionates with and localizes at mitochondria |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:19158487 Nek1 regulates cell death and mitochondrial membrane permeab... | NEW | Summary: NEK1 kinase activity limits injury-induced mitochondrial apoptosis. Reason: VDAC1 substrate mutants and NEK1 perturbation link kinase activity to mitochondrial permeability and caspase activation. This is an experimentally supported survival role under genotoxic stress; it does not establish VDAC1 as an obligatory structural component of the permeability-transition pore. Figure 2F documents caspase activation after kinase-dead K33A expression with GFP and wild-type controls; the unshown cytochrome-c relocalization observation is not used as the supporting result. Supporting Evidence: PMID:19158487 activated caspase-9 and caspase-3 (Fig. 2F). Overexpression of GFP alone or wild type Nek1 tagged with GFP had no such effects. |
| GO:1903723 negative regulation of centriole elongation | IMP PMID:42265085 Nek1 defines a branch of centriolar microtubule length contr... | NEW | Summary: NEK1 kinase activity restricts centriolar microtubule elongation. Reason: Human-cell NEK1 knockout and acute degradation produce hyperelongated centriolar microtubules. Wild-type rescue restores control, whereas kinase-dead NEK1 fails to restore it fully. The kinase-dead phenotype is milder than the knockout phenotype, so a noncatalytic contribution remains possible. The phenotype occurs with CP110-Cep97 still present and is enhanced by CP110 co-depletion, supporting a parallel length-control mechanism rather than assigning NEK1 as a CP110-Cep97 subunit. Supporting Evidence: PMID:42265085 Loss of Nek1 induces pronounced centriolar microtubule hyperelongation without displacement of the CP110-Cep97 complex, indicating that Nek1 restricts centriole extension through a distinct mechanism. PMID:42265085 we cannot exclude that the kinase-independent function of Nek1 is also involved. |
| GO:0005814 centriole | IDA PMID:42265085 Nek1 defines a branch of centriolar microtubule length contr... | NEW | Summary: NEK1 localizes to distal centriole ends in cycling human cells. Reason: Localization mapping resolves the centrosomal pool to the distal ends of mother and daughter centrioles. This is dynamic: the basal-body pool is removed during ciliogenesis in a CEP78-dependent manner, so localization should not be interpreted as constitutive residence at the ciliated mother centriole. Supporting Evidence: PMID:42265085 Nek1 localizes alongside CP110 and Cep97 at the distal end of the centriole PMID:42265085 Nek1 is removed from the basal body during ciliogenesis in a Cep78-dependent manner |
| GO:0005930 axoneme | IDA PMID:42265085 Nek1 defines a branch of centriolar microtubule length contr... | NEW | Summary: NEK1 is detected along the ciliary axoneme in serum-starved human RPE1 cells. Reason: Ultrastructure expansion microscopy of endogenous NEK1 in RPE1 cells after 48 hours of serum starvation detects an axonemal pool. In this same setting the basal-body signal is depleted. These observations support condition-dependent localization rather than constitutive basal-body residence, but do not demonstrate physical movement of individual NEK1 molecules from the mother centriole into the axoneme. Supporting Evidence: PMID:42265085 Nek1 localized along the ciliary axoneme (Fig.Β 7c, arrows). |
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Download this section (compressed HTML)Q: Which endogenous NEK1 substrates drive primary-cilium assembly, and does CFAP410 regulate substrate access, localization, stability, or catalytic output?
Q: Which phosphorylation events mediate NEK1-dependent homologous recombination, given disagreement over RAD54 Ser572 as a NEK1 substrate?
Q: How do ALS-associated and skeletal-ciliopathy variants differentially affect NEK1 kinase activity, CFAP410 association, ciliogenesis, and DNA repair?
Q: Do endogenous phosphorylation of alpha-tubulin or importin-beta1 and the relevant phosphosites mediate NEK1-dependent microtubule homeostasis and nuclear import in human motor neurons?
Q: Does basal-body NEK1 disappear by degradation or redistribution into the ciliary axoneme during ciliogenesis, and what does CEP78 regulate in this transition?
Experiment: Compare endogenous phosphoproteomes of NEK1-null human ciliated cells rescued at matched expression with wild-type, kinase-inactive, and CFAP410-binding-defective NEK1, followed by direct substrate assays and ciliary rescue tests.
Hypothesis: NEK1-dependent ciliary functions require a subset of endogenous phosphorylation events sensitive to both kinase activity and CFAP410 association.
Type: Comparative phosphoproteomics and substrate validation
Experiment: Measure endogenous RAD54 Ser572 phosphorylation by targeted mass spectrometry after irradiation in synchronized NEK1-null and rescued cells, alongside HR reporter activity and RAD51-focus clearance.
Hypothesis: NEK1 regulates RAD54 Ser572 phosphorylation in defined human cell-cycle and damage contexts.
Type: Targeted phosphoproteomics and functional repair assays
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