NDEL1 (nudE neurodevelopment protein 1-like 1) is a cytoplasmic coiled-coil protein of the NudE family. Its N-terminal coiled coil forms parallel homodimers and binds the LIS1 (PAFAH1B1) dimer, and its C-terminal region binds the cytoplasmic dynein-1 intermediate chain, DISC1, katanin and CENP-F. By recruiting LIS1 to dynein and modulating dynein-dynactin-adaptor assembly, NDEL1 regulates the minus-end-directed motor and is needed for dynein-dependent processes: nuclear translocation and nucleus-centrosome coupling in radially migrating cortical neurons, minus-end transport of lysosomes, late endosomes and secretory vesicles, Golgi integrity, and kinetochore function in mitosis. At the mother centriole it tethers dynein/dynactin and helps anchor microtubules; it is also found at kinetochores, the mitotic spindle and axons, where it promotes neurofilament assembly. Its activity is regulated by CDK5/CDK1 phosphorylation and palmitoylation. This donkey gene model matches human NDEL1 isoform 1 through residue 338 and ends in a 143-residue C-terminal tail of unknown significance in place of the last seven human residues.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0000132 establishment of mitotic spindle orientation
IEA GO_REF:0000118
KEEP AS NON CORE
Summary: NudE/LIS1/dynein act at the cortex and kinetochore in mitosis; NDEL1 localizes to the spindle.
Reason: The PAINT node places this NudE-family mitotic function at the family root; it is plausible for NDEL1, which localizes to the spindle and is required for mitosis in some cell types, but NDE1 is the paralog that carries most of this function in neural progenitors. Kept as non-core, matching the human NDEL1 review. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Supporting Evidence:
file:human/NDEL1/NDEL1-uniprot.txt
Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1.
file:human/NDEL1/NDEL1-uniprot.txt
Localizes to the interphase centrosome and the mitotic spindle.
file:EQUAS/NDEL1/NDEL1-bioinformatics/RESULTS.md
The donkey sequence A0A9L0IJ72 (481 residues) aligns to human Q9GZM8 (345 residues) with 97.1% identity across 345 paired residues.
Summary: NDEL1 is recruited to kinetochores by CENP-F.
Reason: Kinetochore localization is documented for human NDEL1 (IDA) via CENP-F, and the CENP-F-binding C-terminal region is conserved in the donkey protein. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Summary: NDEL1 binds the interphase centrosome (mother centriole) and anchors microtubules there.
Reason: Centrosomal localization is supported by several human and rodent studies and is assessed by the PTHR10921 family review as applicable to the vertebrate NDEL1 subfamily. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Summary: Correct, but centrosome is the specific supported location.
Reason: Ensembl projection from mouse Ndel1. The location is true but general; the specific supported MTOC is the centrosome (mother centriole), which this gene already carries (GO:0005813), so the row is refined to that term.
Reason: Spindle localization is recorded for human NDEL1. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Supporting Evidence:
file:human/NDEL1/NDEL1-uniprot.txt
Localizes to the interphase centrosome and the mitotic spindle.
Summary: NDEL1 is kinesin-1 cargo, not a kinesin complex subunit.
Reason: The PANTHER node was seeded by a rat study in which NUDEL/LIS1 is transported by kinesin-1 via DISC1; being cargo does not make NDEL1 part of the kinesin complex. The PTHR10921 family review judges the term not applicable to any member and the human NDEL1 review removes the IBA, so the TreeGrafter copy is removed for consistency.
Summary: NDEL1 forms complexes with LIS1 and dynein on microtubules.
Reason: NDEL1 associates with LIS1 and cytoplasmic dynein on microtubules but is not a stable subunit of the dynein complex, so no more specific complex term applies; the general term is as precise as warranted but describes a transient association rather than the core activity, which is captured by cytoskeletal motor regulator activity.
Reason: NDEL1 does not nucleate microtubules; it helps recruit pericentriolar proteins and katanin to the centrosome, so the effect is indirect (the family review leaves the term unresolved and vertebrate-specific). Kept as non-core, matching the human review.
inhibition of Ndel1 results in malorientations that are not detected by the spindle checkpoint; Ndel1-deficient cells consequently enter anaphase in a timely manner but lagging chromosomes then manifest
file:human/NDEL1/NDEL1-uniprot.txt
Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1.
file:human/NDEL1/NDEL1-uniprot.txt
Localizes to the kinetochore in a CENPF-dependent manner.
Reason: Microtubule interaction is reported for rodent NDEL1 and the protein decorates centrosomal and spindle microtubules; binding may be partly through dynein/LIS1. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Summary: No functional evidence places NDEL1 on synaptic vesicles.
Reason: NDEL1 is a cytosolic dynein regulator at centrosomes, axons and growth cones; the Ensembl projection rests on a rodent fractionation observation and does not represent a functional location. Matches the human review.
Supporting Evidence:
file:human/NDEL1/NDEL1-uniprot.txt
Localizes to the cell body of the motor neurons and colocalizes with assembled neurofilaments within axonal processes.
Summary: NDEL1 is not a component of insulin receptor signalling.
Reason: At most NDEL1 is a downstream effector whose interactions are modulated by insulin-regulated kinases; it does not transduce the signal. Matches the human review.
Supporting Evidence:
file:human/NDEL1/NDEL1-uniprot.txt
Also positively regulates the activity of the minus-end directed microtubule motor protein dynein.
GO:0010975 regulation of neuron projection development
a specific interaction between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for neurite outgrowth in differentiating PC12 cells
Summary: NDEL1 is required for neuronal migration and for adhesion-dependent migration of other cells.
Reason: Consistent with the family-level node and with the specific cortical migration row; matches the human review. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Summary: NDEL1 is required for radial migration of newborn cortical neurons.
Reason: Loss of Ndel1 impairs nucleus-centrosome coupling and radial positioning of cortical neurons; this is a core NDEL1 role through dynein regulation. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Loss of function of Ndel1, LIS1, or dynein in developing neocortex impairs neuronal positioning and causes the uncoupling of the centrosome and nucleus
p.R105P expression alone strongly disrupted neuronal migration, increased the length of the leading process, and impaired nucleus-centrosome coupling, suggesting a failure in nucleokinesis
file:human/NDEL1/NDEL1-uniprot.txt
Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate.
file:human/NDEL1/NDEL1-uniprot.txt
Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome.
Time-lapse microscopy for lysosomes reveals significant reduction in both frequencies and velocities of their minus end-directed motions in cells expressing the dynein-binding defective mutant
file:human/NDEL1/NDEL1-uniprot.txt
Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts
GO:0033157 regulation of intracellular protein transport
IEA GO_REF:0000107
KEEP AS NON CORE
Summary: NDEL1 affects the membrane distribution of a cargo protein.
Reason: Ensembl projection of a human IMP: Ndel1 gain and loss of function alter the intracellular distribution of the AMPA receptor subunit GluR1 through regulation of dynamin 2. A single-study, secondary role. (The previous review cited only the human record's own GO cross-reference, which restates the annotation and is not evidence; replaced by the primary paper.)
gain and loss of function of Ndel1 recapitulate the effects of overexpression of Dyn2 and Dyn2 dominant negative with reduced GTPase activity on the intracellular localization of GluR1
Summary: NDEL1 self-associates through its N-terminal coiled coil, forming parallel homodimers.
Reason: Identical protein binding is better expressed as protein homodimerization activity, matching the human NDEL1 review; the self-association is structural rather than a core activity.
Summary: NDEL1 is required, with LIS1 and dynein, for minus-end vesicle and organelle transport.
Reason: NDEL1 regulates the dynein motor that moves secretory vesicles, lysosomes and late endosomes; it contributes regulatory activity that the transport step depends on. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
Time-lapse microscopy for lysosomes reveals significant reduction in both frequencies and velocities of their minus end-directed motions in cells expressing the dynein-binding defective mutant
Phosphorylation of Ndel1 by Cdk5 not only reduces this inhibition but also allows Lis1 to further stimulate the cargo transport capacity of dynein.
file:human/NDEL1/NDEL1-uniprot.txt
Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome.
file:human/NDEL1/NDEL1-uniprot.txt
May act as a RAB9A/B effector that tethers RAB9-associated late endosomes to the dynein motor for their retrograde transport to the trans-Golgi network
file:EQUAS/NDEL1/NDEL1-bioinformatics/RESULTS.md
The donkey sequence A0A9L0IJ72 (481 residues) aligns to human Q9GZM8 (345 residues) with 97.1% identity across 345 paired residues.
Loss of function of Ndel1, LIS1, or dynein in developing neocortex impairs neuronal positioning and causes the uncoupling of the centrosome and nucleus
the percentage of migrating neurons with correctly polarized MTOC location was significantly reduced while nuclear-centrosomal distance was extended
file:human/NDEL1/NDEL1-uniprot.txt
Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome.
Summary: NDEL1 binds dynein and LIS1 and regulates the dynein motor.
Reason: The donkey GOA record has no informative molecular function. The defining activity of NDEL1 is regulation of cytoplasmic dynein through LIS1 recruitment; the PTHR10921 family review assesses cytoskeletal motor regulator activity as family-wide and the human NDEL1 review proposes it as core. Donkey NDEL1 is in PANTHER subfamily PTHR10921:SF0 with human and rodent NDEL1, and this gene model is collinear with human isoform 1 through residue 338, covering every mapped functional region, so the human/rodent evidence transfers.
ISS PMID:20007476 Distinct dose-dependent cortical neuronal migration and neur...
NEW
Summary: NDEL1, as a LIS1/dynein regulator, is required for dynein-driven nuclear translocation in migrating neurons.
Reason: Participation test: dynein does the pulling and NDEL1 contributes the regulatory activity (LIS1 recruitment to dynein) that the step depends on, the same role for which LIS1 carries nuclear migration terms. Complete loss of Ndel1 abolishes nuclear movement in mouse cortical slices. The human NDEL1 review proposes the same term; donkey NDEL1 is in the same PANTHER subfamily (SF0) and the LIS1-binding region is identical.
ISS PMID:16291865 Nudel contributes to microtubule anchoring at the mother cen...
NEW
Summary: NDEL1 tethers dynein/dynactin at the mother centriole and is needed for centrosomal microtubule anchoring.
Reason: Silencing NDEL1 in human cells represses centrosomal microtubule anchoring, and NDEL1 tethers dynactin and dynein to the mother centriole; it therefore contributes adaptor activity at the anchoring site rather than being merely required. The human review proposes the same term; the centrosome-targeting region (human 256-291) is identical in this donkey model.
ISS PMID:16291865 Nudel contributes to microtubule anchoring at the mother cen...
NEW
Summary: NDEL1 links dynein/dynactin and pericentriolar proteins to the mother centriole.
Reason: NDEL1 depletion in human cells displaces dynactin, LIS1, PCM-1, pericentrin and gamma-tubulin from the centrosome, and NDEL1 appears to tether dynactin and dynein to the mother centriole for microtubule anchoring: a bridging rather than catalytic role, best expressed as molecular adaptor activity. This matches the second core function of the human NDEL1 review. The evidence is from human cells; the donkey model is in the same PANTHER subfamily (PTHR10921:SF0) and is identical in the centrosome-targeting region. The term is kept to the centrosomal role; the dynein-regulatory activity is captured separately by cytoskeletal motor regulator activity.
Silencing Nudel also represses centrosomal MT nucleation and anchoring.
Core Functions
Binds LIS1 and the dynein-1 intermediate chain and regulates dynein activity, driving dynein-dependent nuclear translocation in migrating cortical neurons and minus-end organelle and vesicle transport.
Time-lapse microscopy for lysosomes reveals significant reduction in both frequencies and velocities of their minus end-directed motions in cells expressing the dynein-binding defective mutant
file:human/NDEL1/NDEL1-uniprot.txt
Also positively regulates the activity of the minus-end directed microtubule motor protein dynein.
file:human/NDEL1/NDEL1-uniprot.txt
Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate.
file:human/NDEL1/NDEL1-uniprot.txt
Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome.
At the mother centriole NDEL1 tethers dynein/dynactin and targets pericentriolar proteins, supporting microtubule anchoring at the centrosome.
Q: Is the donkey NDEL1 C-terminal tail (donkey residues 339-481, replacing human GMLPLSV 339-345 and absent from all three human isoforms) expressed, or is it a gene-model artefact? If expressed, does it alter the disordered C-terminal region that controls dynein and LIS1 binding?
Suggested Experiments
Experiment: RT-PCR and long-read sequencing of donkey NDEL1 transcripts to determine whether the C-terminal extension is a real exon or a gene-model artefact, followed by LIS1/dynein pull-downs comparing the extended and canonical forms.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Assessment of 3 ProtNLM2 GO predictions for donkey NDEL1 (A0A9L0IJ72), using the human Swiss-Prot record and existing human NDEL1 review, the PTHR10921 family review, and a donkey-human comparison (97.1% identity over the entire human sequence, with a donkey-specific C-terminal extension). Microtubule organizing center is correct and already in the donkey GOA record (CNN); cytoplasm is correct but less precise than the centrosome, spindle and axon annotations already present (LSP); cell differentiation is a generic process that the evidence neither supports nor refutes for NDEL1 (UNC). ProtNLM2 emitted no non-GO function-text or subcellular-location output for this accession in the frozen snapshot.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
Review rationale: NDEL1 binds the interphase centrosome, the principal microtubule organizing center of animal cells, where it anchors microtubules. The exact term is present in the donkey GOA record (Ensembl projection from mouse), alongside the more specific centrosome annotation. The donkey protein is 97.1% identical to human NDEL1 across the full human sequence. Training-set membership is unknown.
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
Review rationale: NDEL1 is a soluble cytoplasmic and cytoskeletal protein, so cytoplasm is correct. The donkey GOA record already has more specific cytoplasmic locations (centrosome, microtubule organizing center, spindle, axon), each part of the cytoplasm, so the prediction is less precise than existing annotations.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
Review rationale: NDEL1 is required for radial migration of newborn cortical neurons and, with DISC1, for regulation of neurite outgrowth; neither is an act of cell differentiation as such, and neither the human NDEL1 review nor the PTHR10921 family review assigns NDEL1 a differentiation role. The term is absent from the donkey GOA record. Literature linking Ndel1 to neural stem cell differentiation is indirect (lentiviral overexpression in cultured neural stem cells, and a mitotic kinetochore role in radial glial cell-cycle progression that affects neurogenesis secondarily); it shows an effect on the outcome, not participation in differentiation. The generic prediction can be neither supported nor refuted.
Supporting Evidence:
file:human/NDEL1/NDEL1-uniprot.txt: "Also required during brain CC development for the migration of newly formed neurons from the CC ventricular/subventricular zone toward the cortical plate."
PMID:34269216: "Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation"