NDE1 (nuclear distribution protein nudE homolog 1) is a coiled-coil dynein regulator of the NudE family, paralogous to NDEL1. Its N-terminal coiled coil dimerizes (and can form mixed complexes with NDEL1) and binds LIS1, while the C-terminal region binds the cytoplasmic dynein intermediate and light chains; NDE1 thereby recruits LIS1 to autoinhibited dynein and promotes LIS1-mediated assembly of active dynein-dynactin-cargo adaptor complexes, dissociating when dynactin binds the intermediate chain; at high levels it inhibits motility. NDE1 is concentrated at the centrosome/mother centriole throughout the cell cycle, on the mitotic spindle and spindle poles, and at kinetochores, where it is recruited by CENP-F and is needed for kinetochore dynein, chromosome alignment and spindle orientation. In late G2, CENP-F bound to the nucleoporin NUP133 recruits NDE1/NDEL1 and thus dynein and LIS1 to the nuclear envelope, keeping centrosomes tethered to the nucleus and, in radial glial progenitors of the developing neocortex, driving apical interkinetic nuclear migration; NDE1, regulated by CDK1 phosphorylation, is specifically required for this step and for subsequent mitotic entry. NDE1 also restrains primary cilium length at the mother centriole, acts as a RAB9 effector linking late endosomes to dynein for retrograde transport to the trans-Golgi network, and contributes to neuronal migration. Biallelic loss-of-function mutations cause microlissencephaly (lissencephaly 4) and microhydranencephaly, reflecting failed neural progenitor proliferation and neurogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for establishment of mitotic spindle orientation. Reason: NudE-family proteins regulate cortical/kinetochore dynein, and loss of Nde1 in mice causes defective mitotic orientation in cortical progenitors; depletion in human cells causes spindle rotation. Accept. Supporting Evidence: PMID:15473967 however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. PMID:19468067 Importantly, we also found that depletion of hSpindly or ZW10 induced frequent spindle rotation, similar to what had previously been observed upon depletion of the dynein regulator Nde1 (Feng and Walsh, 2004) |
| GO:0000132 establishment of mitotic spindle orientation | IMP PMID:19468067 Mitotic control of kinetochore-associated dynein and spindle... | ACCEPT | Summary: IMP: Nde1-depleted HeLa cells show spindle rotation, attributed to impaired dynein function. Reason: Directly shown in the full text (Nde1 siRNA control arm of the Spindly study). Supporting Evidence: PMID:19468067 Importantly, we also found that depletion of hSpindly or ZW10 induced frequent spindle rotation, similar to what had previously been observed upon depletion of the dynein regulator Nde1 (Feng and Walsh, 2004) PMID:19468067 Considering that depletion of hSpindly, ZW10, or Nde1 all affect the subcellular localization of dynein, we conclude that the observed spindle rotation most likely reflects the impairment of dynein/dynactin function rather than chromosome misalignment, mitotic delay, or cell adhesion conditions. |
| GO:0000776 kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for kinetochore localization of NudE-family proteins. Reason: NDE1 localizes to prometaphase kinetochores via CENP-F, before dynein. Supporting Evidence: PMID:17682047 We find that NudE and NudEL each localize to mitotic kinetochores before dynein, dynactin, ZW10, and LIS1 PMID:17600710 We show that Ndel1, Nde1, and Lis1 localize to kinetochores in a Cenp-F-dependent manner. |
| GO:0000776 kinetochore | IDA PMID:17600710 Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtub... | ACCEPT | Summary: IDA: Nde1 localizes to kinetochores in a Cenp-F-dependent manner. Reason: Directly supported; kinetochore is a core site of NDE1 dynein regulation. Supporting Evidence: PMID:17600710 We show that Ndel1, Nde1, and Lis1 localize to kinetochores in a Cenp-F-dependent manner. PMID:17600710 In addition, Nde1, but not Ndel1, is required for kinetochore localization of Dynein. |
| GO:0001764 neuron migration | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara IEA from mouse Nde1 for neuron migration. Reason: Nde1-null mice show retarded neuronal migration, and NDE1 knockdown in rat brain impairs postmitotic neuronal migration comparably to NDEL1 knockdown; as a LIS1-dynein regulator NDE1 contributes to neuronal nucleokinesis. Supporting Evidence: PMID:15473967 BrdU birthdating revealed retarded and modestly disorganized neuronal migration PMID:27553190 NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. |
| GO:0005515 protein binding | IPI PMID:16547491 p78/MCRS1 forms a complex with centrosomal protein Nde1 and ... | REMOVE | Summary: IPI with MCRS1 (p78) from yeast two-hybrid and co-IP. Reason: Generic protein binding is uninformative; the functional consequence of the NDE1-MCRS1 association at the centrosome is not established. Supporting Evidence: PMID:16547491 Here, we demonstrate that both Nde1 and Su48 can associate with p78/MCRS1, a protein implicated in cancer development. |
| GO:0005515 protein binding | IPI PMID:16682949 Centrosomal proteins Nde1 and Su48 form a complex regulated ... | REMOVE | Summary: IPI with ZNF365 (Su48) at the centrosome. Reason: Generic protein binding is uninformative; no specific MF can be derived. Supporting Evidence: PMID:16682949 Here, we demonstrate that Su48 can associate with Nde1. |
| GO:0005515 protein binding | IPI PMID:17600710 Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtub... | REMOVE | Summary: IPI with CENPF; CENP-F recruits Nde1 to kinetochores. Reason: Generic protein binding is uninformative. The informative relationship is that CENP-F acts as the adaptor that docks NDE1 at kinetochores and nuclear pores; on the NDE1 side this is captured by its kinetochore/nuclear-envelope location and its dynein-regulator activity, not by a binding term. Supporting Evidence: PMID:17600710 We show that Ndel1, Nde1, and Lis1 localize to kinetochores in a Cenp-F-dependent manner. |
| GO:0005515 protein binding | IPI PMID:22843697 The mitosis and neurodevelopment proteins NDE1 and NDEL1 for... | MODIFY | Summary: IPI with NDEL1; purified NDE1 and NDEL1 form mixed complexes. Reason: The paper shows a direct NDE1-NDEL1 interaction in mixed complexes (the paralogs co-assemble via their coiled coils); protein heterodimerization activity is more informative than protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:22843697 analysis of mixed NDE1-NDEL1 complexes demonstrates that NDE1 and NDEL1 can interact directly. |
| GO:0005515 protein binding | IPI PMID:25332407 Identification of Rare, Single-Nucleotide Mutations in NDE1 ... | REMOVE | Summary: IPI with YWHAE (14-3-3 epsilon) in a study of NDE1 schizophrenia-associated variants. Reason: Generic protein binding is uninformative; the functional role of the NDE1-14-3-3 interaction is not defined. Supporting Evidence: PMID:25332407 Furthermore, functional assays showed that S214F affected axonal outgrowth and the interaction between NDE1 and YWHAE (14-3-3 epsilon; a neurodevelopmental regulator). |
| GO:0005515 protein binding | IPI PMID:29961565 Endogenous Cell Type-Specific Disrupted in Schizophrenia 1 I... | REMOVE | Summary: IPI with DISC1 from endogenous DISC1 interactomes in iPSC-derived neural cells. Reason: Generic protein binding from an affinity-purification interactome is uninformative. Supporting Evidence: PMID:29961565 We further differentiated these cells and used affinity purification to determine protein-protein interactions involving DISC1 in iPSC-derived neural progenitor cells and astrocytes. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | REMOVE | Summary: IPI with DISC1 from the HENA aggregated network dataset. Reason: Generic protein binding from an aggregated data set is uninformative. Supporting Evidence: PMID:22843697 The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI with NDEL1 from a proteome-scale AP-MS network (BioPlex). Reason: Generic protein binding from a high-throughput screen; the NDE1-NDEL1 interaction is captured by the heterodimerization MODIFY on the PMID:22843697 row. Supporting Evidence: PMID:22843697 The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI with DISC1 from a proteome-scale AP-MS network. Reason: Generic protein binding from a high-throughput screen is uninformative. Supporting Evidence: PMID:22843697 The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: IPI with YWHAE from the OpenCell endogenous tagging interactome. Reason: Generic protein binding from a high-throughput screen is uninformative. Supporting Evidence: PMID:22843697 The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: IPI with NDEL1 from a multimodal cell map dataset. Reason: Generic protein binding from a high-throughput dataset; see the heterodimerization MODIFY for the direct NDE1-NDEL1 interaction. Supporting Evidence: PMID:22843697 The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: IPI with DISC1 from a multimodal cell map dataset. Reason: Generic protein binding from a high-throughput dataset is uninformative. Supporting Evidence: PMID:22843697 The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 |
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for centrosome. Reason: NDE1 is a well-established centrosomal protein; patient mutations abolish centrosomal localization. Supporting Evidence: PMID:21529752 NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. PMID:21529751 We show that the patient NDE1 proteins are unstable, cannot bind cytoplasmic dynein, and do not localize properly to the centrosome. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: IDA from a human centrosome proteomics/antibody localization screen. Reason: Consistent with extensive evidence for centrosomal NDE1. Supporting Evidence: PMID:21399614 From a background of non-specific proteins, we distinguished 126 known and 40 candidate centrosomal proteins, of which 22 were confirmed as novel components. PMID:21529752 NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. |
| GO:0005813 centrosome | IDA PMID:21529752 The essential role of centrosomal NDE1 in human cerebral cor... | ACCEPT | Summary: IDA: NDE1 at the centrosome of neuroepithelial cells; patient mutant protein fails to localize there. Reason: Directly supported. Supporting Evidence: PMID:21529752 NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for centrosome. Reason: Consistent with experimental data. Supporting Evidence: PMID:21529752 NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. |
| GO:0005815 microtubule organizing center | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara IEA for microtubule organizing center. Reason: Parent of centrosome; consistent. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005819 spindle | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for spindle. Reason: NDE1 accumulates on the mitotic spindle of apical neural precursors. Supporting Evidence: PMID:21529752 We show that NDE1 accumulates on the mitotic spindle of apical neural precursors in early neurogenesis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Mad1 binds kinetochore', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'MAD2 converted to an inhibitory state', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'MAD2 associates with the Mad1 kinetochore complex', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Release of activated MAD2 from kinetochores', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Phosphorylation of cohesin by PLK1 at centromeres', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'PP2A-B56 dephosphorylates centromeric cohesin', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'ESPL1 cleaves centromeric cohesin', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Separation of sister chromatids', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'CDK1 phosphorylates CDCA5 at centromeres', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Kinetochore assembly', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574840 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'AJUBA facilitates AURKA autophosphorylation', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2574845 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'AJUBA binds centrosome-associated AURKA', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000310 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'AURKA phosphorylates PLK1', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3000319 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'BORA binds PLK1 and AURKA', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Kinetochore capture of astral microtubules', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380272 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Plk1-mediated phosphorylation of Nlp', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380283 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Recruitment of additional gamma tubulin/gamma TuRC to the centrosome', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380294 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Loss of C-Nap-1 from centrosomes', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380303 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Dissociation of Phospho-Nlp from the centrosome', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380311 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Recruitment of Plk1 to centrosomes', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380316 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Association of NuMA with microtubules', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380455 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Recruitment of CDK11p58 to the centrosomes', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380508 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Translocation of NuMA to the centrosomes', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'RAB3IP stimulates nucleotide exchange on RAB8A', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626220 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'C2CD3 binds the mother centriole', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'C2CD3 and OFD1 recruit distal appendage proteins to the centriole', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'CP110 and CEP97 dissociate from the centriole', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'The distal appendage proteins recruit TTBK2', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Recruitment of transition zone proteins', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'MARK4 binds ODF2 in the centriole', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'CDC42:GTP recruits DIAPH2-2 to kinetochores', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'AURKB phosphorylates DIAPH2-2 at kinetochores', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'Kinetochore capture of astral microtubules regulated by CDC42/DIAPH2', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853405 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'TPX2 binds AURKA at centrosomes', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853419 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'TPX2 promotes AURKA autophosphorylation', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | KEEP AS NON CORE | Summary: Reactome TAS for cytosol from the reaction 'EML4 recruits NUDC to mitotic spindle', where NDE1 is a member of the kinetochore or centrosome complex represented in the cytosolic compartment. Reason: NDE1 is a soluble cytoplasmic protein that concentrates at centrosomes, kinetochores, the nuclear envelope and vesicles. Cytosol is correct but uninformative; the Reactome reactions list NDE1 only as a component of large centrosome/kinetochore sets. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location IEA for cytoskeleton. Reason: Correct but general; centrosome, spindle and kinetochore are more informative. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0005871 kinesin complex | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA placing NudE-family proteins in the kinesin complex. Reason: NDE1 is a regulator of cytoplasmic dynein, not a subunit of a kinesin complex. The node draws on rat Ndel1 data; even if Ndel1 associates with kinesin-1 in some contexts, this does not make NDE1 part of a kinesin complex, and no human NDE1 data support it. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000100519 SOURCE WEAK OR INFERRED Node seeded by rat Ndel1 (RGD:621235); a kinesin association of a dynein regulator does not justify part_of kinesin complex for the NudE family. Supporting Evidence: PMID:17682047 Surprisingly, NudE interacted not with the dynein motor domain but with both the intermediate chain IC2C and the light chain LC8. |
| GO:0007020 microtubule nucleation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for microtubule nucleation (mouse Nde1 source). Reason: Nde1 loss affects centrosome duplication and spindle assembly in mouse cells, and NDE1 associates with gamma-tubulin; a contribution to centrosomal microtubule nucleation is plausible but secondary to its dynein-regulatory role. Supporting Evidence: PMID:15473967 In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. file:human/NDE1/NDE1-uniprot.txt Interacts with CENPF, dynactin, tubulin gamma, PAFAH1B1, PCM1 and PCNT. |
| GO:0007059 chromosome segregation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for chromosome segregation. Reason: NudE/NudEL are required at kinetochores for chromosome alignment and correct segregation. Supporting Evidence: PMID:17600710 Accordingly, suppression of Nde1 inhibits metaphase chromosome alignment and activates the spindle checkpoint. PMID:17682047 Inhibition of NudE and NudEL caused metaphase arrest with misoriented chromosomes and defective microtubule attachment. |
| GO:0007100 mitotic centrosome separation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for mitotic centrosome separation (mouse Ndel1 source). Reason: NudE/NudEL are part of the NUP133-CENP-F chain that anchors dynein to the nuclear envelope and keeps separating centrosomes on the nucleus in prophase; plausible for NDE1 but secondary. Supporting Evidence: PMID:21383080 We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry PMID:21383080 Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for microtubule binding. Reason: The PAINT node is seeded by mouse Nde1/Ndel1 experimental data. NDE1 associates with microtubules and microtubule plus ends at kinetochores, but its principal molecular activities are binding dynein and LIS1; direct microtubule binding is a minor property. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Concentrates at the plus ends of microtubules coincident with kinetochores in metaphase and anaphase in a CENPF-dependent manner. |
| GO:0008017 microtubule binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Combined IEA for microtubule binding. Reason: As for the IBA row. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Concentrates at the plus ends of microtubules coincident with kinetochores in metaphase and anaphase in a CENPF-dependent manner. |
| GO:0008017 microtubule binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Nde1 for microtubule binding. Reason: As for the IBA row. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Concentrates at the plus ends of microtubules coincident with kinetochores in metaphase and anaphase in a CENPF-dependent manner. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: HDA: detected in an NK-cell membrane proteome. Reason: NDE1 is peripheral to membranes (e.g. Rab9-positive late endosome membranes); a proteomic detection is consistent but uninformative. Supporting Evidence: PMID:19946888 Mass spectrometric analysis identified 1843 proteins with high confidence scores. |
| GO:0016477 cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for cell migration. Reason: NudE-family proteins support neuronal migration through LIS1-dynein; neuron migration is the more specific and better-supported term. Supporting Evidence: PMID:27553190 NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara IEA (rat) for protein domain specific binding. Reason: An uninformative binding term transferred electronically; the specific interactions (dynein intermediate/light chain, LIS1, CENP-F, RAB9) are better represented by dynein complex binding and adaptor activity. Supporting Evidence: PMID:17682047 Surprisingly, NudE interacted not with the dynein motor domain but with both the intermediate chain IC2C and the light chain LC8. |
| GO:0021987 cerebral cortex development | IMP PMID:21529752 The essential role of centrosomal NDE1 in human cerebral cor... | KEEP AS NON CORE | Summary: IMP: homozygous NDE1 mutations cause extreme microcephaly with deficient cortical lamination. Reason: Well-supported organismal role (LIS4/microlissencephaly), but it is a developmental consequence of NDE1's cellular role in neural progenitor INM, mitotic entry and spindle function. Supporting Evidence: PMID:21529752 Thus, NDE1 deficiency causes both a severe failure of neurogenesis and a deficiency in cortical lamination. |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:34793709 Nde1 is a Rab9 effector for loading late endosomes to cytopl... | ACCEPT | Summary: EXP: NDE1 colocalizes with RAB9A on vesicle membranes. Reason: NDE1 is recruited to Rab9-positive late endosomes as a Rab9 effector that tethers them to dynein. Supporting Evidence: PMID:34793709 Therefore, Nde1 is a Rab9 effector that tethers Rab9-associated late endosomes to the dynein motor for their retrograde transport to the TGN. |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location IEA for cytoplasmic vesicle membrane. Reason: Consistent with the Rab9 effector study. Supporting Evidence: PMID:34793709 Therefore, Nde1 is a Rab9 effector that tethers Rab9-associated late endosomes to the dynein motor for their retrograde transport to the TGN. |
| GO:0031023 microtubule organizing center organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara IEA for microtubule organizing center organization. Reason: Nde1-null cells have centrosome duplication and spindle assembly defects; a secondary role. Supporting Evidence: PMID:15473967 In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. |
| GO:0031616 spindle pole centrosome | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara IEA for spindle pole centrosome. Reason: Consistent with centrosome and spindle-pole localization in mitosis. Supporting Evidence: PMID:21529752 NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. PMID:21529752 We show that NDE1 accumulates on the mitotic spindle of apical neural precursors in early neurogenesis. |
| GO:0031616 spindle pole centrosome | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Nde1 for spindle pole centrosome. Reason: As above. Supporting Evidence: PMID:21529752 NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. |
| GO:0032154 cleavage furrow | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location IEA for cleavage furrow. Reason: Reported localization during cytokinesis without an established function there. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Also localizes to the cleavage furrow during cytokinesis. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara IEA for identical protein binding. Reason: NDE1 self-association is a coiled-coil homodimer (and higher-order tetramer); protein homodimerization activity is the more informative term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:22843697 We determined that full-length NDE1 forms needle-like dimers and tetramers in solution |
| GO:0042802 identical protein binding | IPI PMID:22843697 The mitosis and neurodevelopment proteins NDE1 and NDEL1 for... | MODIFY | Summary: IPI: full-length NDE1 forms dimers and tetramers. Reason: Replace identical protein binding with protein homodimerization activity, which the biophysical data directly support. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:22843697 We determined that full-length NDE1 forms needle-like dimers and tetramers in solution file:human/NDE1/NDE1-uniprot.txt Homodimer (PubMed:34793709). |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara IEA from mouse for synapse. Reason: Transferred from mouse; no human data. NDE1 function is predominantly in progenitors and dividing cells; a synaptic pool is possible but uncharacterized. Supporting Evidence: file:human/NDE1/NDE1-uniprot.txt Localizes to the interphase and S phase centrosome. During mitosis, partially associated with the mitotic spindle. |
| GO:0047496 vesicle transport along microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for vesicle transport along microtubule. Reason: NDE1 acts as a Rab9 effector linking late endosomes to dynein for retrograde transport; NudE family regulation of dynein cargo transport is well established. Supporting Evidence: PMID:34793709 Therefore, Nde1 is a Rab9 effector that tethers Rab9-associated late endosomes to the dynein motor for their retrograde transport to the TGN. PMID:34793709 Rab9A mutants unable to bind to Nde1 also failed to associate with dynein, Lis1, and dynactin. |
| GO:0050000 chromosome localization | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for chromosome localization. Reason: NDE1 is required for kinetochore dynein and metaphase chromosome alignment; the IBA term is appropriately general for the family. Supporting Evidence: PMID:17600710 Accordingly, suppression of Nde1 inhibits metaphase chromosome alignment and activates the spindle checkpoint. |
| GO:0050000 chromosome localization | IMP PMID:17600710 Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtub... | MODIFY | Summary: IMP: Nde1 suppression inhibits metaphase chromosome alignment. Reason: The evidence specifically shows failed metaphase alignment; metaphase chromosome alignment is the precise child term. Proposed replacements: metaphase chromosome alignment Supporting Evidence: PMID:17600710 Accordingly, suppression of Nde1 inhibits metaphase chromosome alignment and activates the spindle checkpoint. PMID:17600710 In addition, Nde1, but not Ndel1, is required for kinetochore localization of Dynein. |
| GO:0051298 centrosome duplication | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara IEA for centrosome duplication. Reason: Supported by Nde1-null mouse cell data, but the human knockdown phenotype on centrosome number is modest; secondary role. Supporting Evidence: PMID:15473967 In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. PMID:16682949 Ablation of Nde1 by gene specific small interfering RNA causes mitotic delay and cell death, coupled with a modest decrease in the incidence of the cells that harbor excessive centrosomes. |
| GO:0051298 centrosome duplication | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Nde1 for centrosome duplication. Reason: As for the IEA row. Supporting Evidence: PMID:15473967 In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. |
| GO:0051642 centrosome localization | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for centrosome localization. Reason: NudE/NudEL, recruited by CENP-F to the NUP133 pore platform, anchor dynein at the nuclear envelope and keep centrosomes tethered to the nucleus in prophase; the NudE family also couples nucleus and centrosome in migrating neurons. Supporting Evidence: PMID:21383080 We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry PMID:21383080 Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. |
| GO:0070840 dynein complex binding | IDA PMID:17682047 NudE and NudEL are required for mitotic progression and are ... | NEW | Summary: NudE binds cytoplasmic dynein directly through the dynein intermediate chain and LC8 light chain; patient truncations that remove the C-terminal region abolish dynein binding. Reason: Binding to the dynein complex is the defining molecular property of NDE1 and is absent from GOA. Comparator: other dynein regulators/adaptors (LIS1/PAFAH1B1, BICD2, NUMA1) carry GO:0070840, so this is a coverage gap rather than a convention. Molecular function, so the process-participation test does not apply. Supporting Evidence: PMID:17682047 Surprisingly, NudE interacted not with the dynein motor domain but with both the intermediate chain IC2C and the light chain LC8. PMID:37940657 Before the initiation of motility, the association of dynactin with dynein triggers the dissociation of Nde1 from dynein by competing against Nde1 binding to the dynein intermediate chain. PMID:21529751 We show that the patient NDE1 proteins are unstable, cannot bind cytoplasmic dynein, and do not localize properly to the centrosome. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:34793709 Nde1 is a Rab9 effector for loading late endosomes to cytopl... | NEW | Summary: NDE1 bridges partners to dynein: as a Rab9 effector it tethers Rab9-positive late endosomes to dynein-dynactin-LIS1, and it stably recruits LIS1 to the dynein holoenzyme. Reason: Crystal structure plus mutational analysis show that RAB9A binding to NDE1 is required for RAB9A association with dynein, LIS1 and dynactin, i.e. NDE1 is the adaptor. Single-molecule work shows NudE recruits LIS1 onto dynein. Supporting Evidence: PMID:34793709 Therefore, Nde1 is a Rab9 effector that tethers Rab9-associated late endosomes to the dynein motor for their retrograde transport to the TGN. PMID:34793709 Rab9A mutants unable to bind to Nde1 also failed to associate with dynein, Lis1, and dynactin. PMID:20403325 We find that NudE stably recruits LIS1 to the dynein holoenzyme molecule, where LIS1 interacts with the motor domain during the prepowerstroke state of the dynein crossbridge cycle. PMID:37940657 We find that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of dynein-dynactin adaptor complexes. |
| GO:0022027 interkinetic nuclear migration | ISS PMID:27553190 Severe NDE1-mediated microcephaly results from neural progen... | NEW | Summary: NDE1 knockdown in embryonic rat radial glial progenitors completely blocks apical (G2) interkinetic nuclear migration; nuclei arrest near the ventricle, as with CENP-F or NUP133 knockdown. CDK1 phosphosites T215/T243 are required. Reason: Participation: NDE1 is part of the motor-regulatory machinery itself (binds dynein and recruits LIS1 to it at the nuclear envelope), not merely a requirement. Comparator: adaptors/regulators in the same role (Hook3, PCM1, TACC proteins) carry GO:0022027. Paralog asymmetry: NDEL1 knockdown does not block apical INM. Supporting Evidence: PMID:27553190 However, NDE1 inhibition alone causes a complete block of apical INM, contributing to a large reduction in mitotic index with no evidence for ectopic mitoses. PMID:27553190 Altogether, these results provide further evidence for the requirement of NDE1 during late-G2 dynein recruitment to the nuclear envelope, and reveal a new NDE1-specific role after completion of apical INM but before mitotic entry. PMID:27553190 RNAi against the NDE1 paralogue NDEL1 has no such effects. PMID:39167527 We find that Nde1 T215 and T243 phosphomutants block apical interkinetic nuclear migration (INM) and, consequently, mitosis in radial glial progenitor cells. file:human/NDE1/NDE1-deep-research-falcon.md Depletion impairs apical interkinetic nuclear migration, whereas NDEL1 depletion does not reproduce this progenitor phenotype. |
| GO:0005635 nuclear envelope | IDA PMID:21383080 A Nup133-dependent NPC-anchored network tethers centrosomes ... | NEW | Summary: In late G2/prophase NudE and NudEL accumulate at the nuclear envelope, recruited by NUP133-bound CENP-F, together with dynein and dynactin. Reason: Nuclear-envelope localization is the site of NDE1 action in apical interkinetic nuclear migration and centrosome-nucleus tethering and is not represented in GOA. Supporting Evidence: PMID:21383080 At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. PMID:21383080 Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. PMID:27553190 Altogether, these results provide further evidence for the requirement of NDE1 during late-G2 dynein recruitment to the nuclear envelope, and reveal a new NDE1-specific role after completion of apical INM but before mitotic entry. |
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Download this section (compressed HTML)Q: Should NDE1 and NDEL1 be modelled as one interchangeable NudE-family unit in nuclear migration, given that NDE1 but not NDEL1 knockdown blocks apical interkinetic nuclear migration in radial glia, whereas both act comparably in postmitotic neuronal migration?
Suggested experts: neural progenitor/dynein biologists, GO-CAM curators
Q: Is direct microtubule binding a genuine NDE1 activity or an indirect association via dynein/LIS1?
Suggested experts: dynein biochemists
Q: What is the role of the nuclear pool of NDE1 reported to interact with cohesin and safeguard heterochromatin replication in neural progenitors?
Suggested experts: genome-stability researchers
Experiment: Rescue NDE1 knockdown in radial glial progenitors with NDE1 mutants unable to bind CENP-F, LIS1, or dynein intermediate chain, and image apical INM.
Hypothesis: Apical INM requires NDE1 to bridge CENP-F-anchored nuclear pores to LIS1-dynein.
Type: in utero electroporation with live imaging
Experiment: Single-molecule assays comparing NDE1 and NDEL1 for LIS1 recruitment and dynein-dynactin-adaptor complex assembly.
Hypothesis: NDE1 and NDEL1 differ quantitatively in how they load LIS1 onto dynein, explaining NDE1-specific requirements in progenitors.
Type: in vitro reconstitution / TIRF
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