Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for cytoplasmic localization, inferred phylogenetically from multiple orthologs including Drosophila, Arabidopsis, and human NudC proteins. Consistent with UniProt subcellular location annotation (Cytoplasm) and the known biology of NudC family proteins as cytoplasmic, microtubule-associated proteins. NUD-1::GFP fusion shows cytoplasmic expression in sensory neurons, embryos, gonad, gut, vulva, ventral cord, and hypodermal seam cells (PMID:11685578). Reason: Cytoplasmic localization is well-established for NUD-1 and the NudC family. The IBA inference is consistent with UniProt annotation and direct GFP expression data in C. elegans (PMID:11685578). Supporting Evidence: PMID:11685578 A C. elegans nud-1::GFP fusion produces sustained fluorescence in sensory neurons and embryos, and transient fluorescence in the gonad, gut, vulva, ventral cord, and hypodermal seam cells.
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for involvement in protein folding, inferred phylogenetically. NUD-1 has been demonstrated to exhibit chaperone activity in vitro (PMID:18626791), preventing aggregation of citrate synthase and luciferase. However, NUD-1 functions as a holdase rather than a foldase -- it prevents aggregation of unfolded substrates, which can then be refolded by ATP-dependent chaperones. The IBA annotation is consistent with the experimental evidence from PMID:18626791. Reason: Protein folding is appropriate as a biological process annotation for a holdase chaperone, as NUD-1 maintains unfolded intermediates in a refolding-competent state that can be subsequently refolded by the cellular chaperone machinery (PMID:18626791). The IBA inference is supported by direct experimental evidence. Supporting Evidence: PMID:18626791 In the presence of NUD-1, nearly all of the luciferase activity was regained, indicating that unfolded intermediates complexed with NUD-1 could be refolded.
GO:0051082 unfolded protein binding	IBA GO_REF:0000033	MODIFY	Summary: IBA annotation for unfolded protein binding, inferred phylogenetically from NUD-1 itself (WB:WBGene00003829) and other orthologs. GO:0051082 is proposed for obsoletion. NUD-1 has been directly demonstrated to prevent aggregation of denaturing citrate synthase and luciferase (PMID:18626791), functioning as an ATP-independent holdase chaperone. However, NUD-1 is not a classical sHSP -- it is a NudC family protein with an HSP20-like fold (CS domain) whose primary role is in nuclear migration and cytoskeletal dynamics. The chaperone activity may be secondary to its role in mitotic complex assembly. Reason: GO:0051082 is proposed for obsoletion. NUD-1 demonstrates holdase activity in vitro (PMID:18626791), preventing aggregation of denaturing substrates and maintaining them in a refolding-competent state. GO:0140309 (unfolded protein carrier activity) is not appropriate because it is carrier-specific (per go-ontology#30552). Retain until a holdase chaperone activity NTR is created. Proposed replacements: unfolded protein binding (retain until holdase NTR is created) Supporting Evidence: PMID:18626791 We demonstrate that nematode NUD-1 is able to prevent the aggregation of two substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric concentrations.
GO:0045202 synapse	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: IEA annotation for synaptic localization, inferred automatically from the GO:0051932 (synaptic transmission, GABAergic) annotation via inter-ontology logical inference. NUD-1 depletion causes defective GABA synaptic vesicle trafficking (PMID:16996038), which supports a role at synapses. However, this is an indirect inference -- NUD-1 may affect synaptic vesicle trafficking through its role in cytoskeletal dynamics (dynein/microtubule-dependent transport) rather than being a resident synaptic protein. Reason: The inference from GABAergic synaptic transmission to synaptic localization is logically valid. NUD-1 depletion disrupts GABA synaptic vesicle trafficking (PMID:16996038), suggesting functional involvement at synapses. However, NUD-1 is primarily a cytoplasmic, microtubule-associated protein and its synaptic role is secondary to its core function in nuclear migration and chaperone activity.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for cytoplasmic localization based on UniProt subcellular location mapping. Consistent with the IBA annotation for the same term and direct GFP expression data (PMID:11685578). Reason: Cytoplasmic localization is well-established. This IEA annotation is consistent with the IBA annotation and experimental evidence. Acceptable as automated confirmation.
GO:0006457 protein folding	IDA PMID:18626791 The microtubule-associated protein, NUD-1, exhibits chaperon...	ACCEPT	Summary: IDA annotation for involvement in protein folding based on Faircloth et al. 2009 (PMID:18626791). The study demonstrated that recombinant NUD-1 prevents aggregation of citrate synthase and luciferase, protects native CS from thermal inactivation, and maintains unfolded luciferase intermediates in a refolding-competent state. This is directly supported by the luciferase refolding assay showing that unfolded intermediates complexed with NUD-1 could be refolded by rabbit reticulocyte lysate plus ATP. Reason: Strong experimental evidence directly in C. elegans NUD-1 demonstrating chaperone activity that facilitates the protein folding process. NUD-1 acts as a holdase maintaining substrates in a refolding-competent state, which is part of the protein folding pathway (PMID:18626791). Supporting Evidence: PMID:18626791 In the presence of NUD-1, nearly all of the luciferase activity was regained, indicating that unfolded intermediates complexed with NUD-1 could be refolded. PMID:18626791 NUD-1 also protects the native state of CS from thermal inactivation by significantly reducing the inactivation rate of this enzyme.
GO:0044183 protein folding chaperone	IDA PMID:18626791 The microtubule-associated protein, NUD-1, exhibits chaperon...	ACCEPT	Summary: IDA annotation for protein folding chaperone molecular function based on Faircloth et al. 2009 (PMID:18626791). The study directly demonstrated that NUD-1 possesses ATP-independent chaperone activity comparable to small heat shock proteins and cochaperones. NUD-1 prevents aggregation of denaturing citrate synthase and luciferase at stoichiometric concentrations, and maintains substrates in a refolding-competent state. This is a more informative molecular function annotation than GO:0051082 (unfolded protein binding), as it captures the active chaperone function. Reason: GO:0044183 (protein folding chaperone) accurately describes the molecular function of NUD-1 as demonstrated by in vitro chaperone assays (PMID:18626791). The term captures the holdase activity, including prevention of aggregation and maintenance of refolding-competent intermediates. This is a well-supported core molecular function annotation. Supporting Evidence: PMID:18626791 NUD-1 possesses ATP-independent chaperone activity comparable to that of small heat shock proteins and cochaperones and that changes in phosphorylation state functionally alter chaperone activity in a phosphomimetic NUD-1 mutant. PMID:18626791 We demonstrate that nematode NUD-1 is able to prevent the aggregation of two substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric concentrations. file:worm/nud-1/nud-1-deep-research-falcon.md NUD-1 is described as a microtubule-associated protein with in vitro chaperone activity, preventing heat-induced aggregation of citrate synthase and luciferase
GO:0051082 unfolded protein binding	IDA PMID:18626791 The microtubule-associated protein, NUD-1, exhibits chaperon...	MODIFY	Summary: IDA annotation for unfolded protein binding based on Faircloth et al. 2009 (PMID:18626791). The study demonstrated that NUD-1 binds denaturing proteins (citrate synthase and luciferase) and prevents their aggregation. GO:0051082 is proposed for obsoletion. The more informative annotation GO:0044183 (protein folding chaperone) is already annotated with IDA evidence from the same publication, and GO:0140309 (unfolded protein carrier activity) would be the recommended replacement for the holdase function. Reason: GO:0051082 is proposed for obsoletion. The holdase activity demonstrated in PMID:18626791 is not well captured by GO:0140309 (carrier-specific, per go-ontology#30552). GO:0044183 (protein folding chaperone) is already annotated from the same evidence. Retain until a holdase chaperone activity NTR is created. Proposed replacements: unfolded protein binding (retain until holdase NTR is created) Supporting Evidence: PMID:18626791 We demonstrate that nematode NUD-1 is able to prevent the aggregation of two substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric concentrations.
GO:0048489 synaptic vesicle transport	IMP PMID:16996038 Genetic interactions among cortical malformation genes that ...	KEEP AS NON CORE	Summary: IMP annotation for involvement in synaptic vesicle transport based on Locke et al. 2006 (PMID:16996038). The study used fluorescent markers for synaptic vesicle trafficking and found that depletion of NUD-1 (along with other LIS1 pathway components) resulted in defective GABA synaptic vesicle trafficking. This is consistent with NUD-1's role in dynein-dependent transport along microtubules. Reason: The experimental evidence from PMID:16996038 supports involvement in synaptic vesicle transport, likely through NUD-1's role in the dynein motor complex and microtubule-based transport. However, this is a secondary consequence of NUD-1's core function in cytoskeletal dynamics rather than a specialized role in synaptic vesicle trafficking per se. Retained as non-core. Supporting Evidence: PMID:16996038 We found that depletion of LIS1 pathway components resulted in defective GABA synaptic vesicle trafficking.
GO:0051932 synaptic transmission, GABAergic	IGI PMID:16996038 Genetic interactions among cortical malformation genes that ...	KEEP AS NON CORE	Summary: IGI annotation for involvement in GABAergic synaptic transmission based on Locke et al. 2006 (PMID:16996038). The study used genetic interaction experiments with LIS-1 pathway components (indicated by with/from WB:WBGene00003047) and pentylenetetrazole exposure to demonstrate that NUD-1 depletion affects GABAergic neurotransmission, resulting in convulsion susceptibility. Reason: The genetic interaction evidence supports a role in GABAergic synaptic transmission, likely secondary to NUD-1's role in microtubule-dependent transport of synaptic vesicles. This is a non-core function reflecting the downstream effects of disrupted cytoskeletal dynamics on neuronal function. Supporting Evidence: PMID:16996038 Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5, and CDKA-1) exhibited significant convulsions following PTZ and RNAi treatment.
GO:0040011 locomotion	IMP PMID:11685578 Evolutionarily conserved nuclear migration genes required fo...	KEEP AS NON CORE	Summary: IMP annotation for involvement in locomotion based on Dawe et al. 2001 (PMID:11685578). RNAi knockdown of nud-1 resulted in uncoordinated movement, one of several pleiotropic phenotypes observed. This is a downstream consequence of NUD-1's role in neuronal development and function rather than a direct role in locomotion. Reason: The uncoordinated movement phenotype from nud-1 RNAi (PMID:11685578) is a pleiotropic effect of disrupting this broadly required nuclear migration/ cytoskeletal dynamics gene, not a specific role in locomotion. Retained as non-core. Supporting Evidence: PMID:11685578 Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded similar phenotypes, including embryonic lethality, sterility, altered vulval morphology, and uncoordinated movement.
GO:0040025 vulval development	IMP PMID:11685578 Evolutionarily conserved nuclear migration genes required fo...	KEEP AS NON CORE	Summary: IMP annotation for involvement in vulval development based on Dawe et al. 2001 (PMID:11685578). RNAi knockdown of nud-1 resulted in altered vulval morphology. nud-1::GFP shows expression in the vulva, and vulval development requires proper cell division and nuclear migration, consistent with NUD-1's core function. Reason: Altered vulval morphology from nud-1 RNAi (PMID:11685578) is a pleiotropic phenotype consistent with disruption of nuclear migration and cell division in vulval precursor cells. nud-1::GFP is expressed in the vulva. Retained as non-core since vulval development is not the primary function of NUD-1. Supporting Evidence: PMID:11685578 Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded similar phenotypes, including embryonic lethality, sterility, altered vulval morphology, and uncoordinated movement.
GO:0009792 embryo development ending in birth or egg hatching	IMP PMID:11685578 Evolutionarily conserved nuclear migration genes required fo...	ACCEPT	Summary: IMP annotation for involvement in embryo development based on Dawe et al. 2001 (PMID:11685578). RNAi knockdown of nud-1 caused embryonic lethality and nuclear positioning defects in early embryonic cell division similar to dynein/dynactin depletion. This is a core biological process for NUD-1 given its essential role in nuclear migration during cell division. Reason: Embryonic lethality from nud-1 RNAi represents a core phenotype (PMID:11685578). NUD-1 is essential for proper nuclear positioning during early embryonic cell division, and its requirement for embryo development is a direct consequence of its core function in nuclear migration and mitotic progression. Supporting Evidence: PMID:11685578 Digital time-lapse video microscopy was used to determine that RNAi-treated embryos exhibited nuclear positioning defects in early embryonic cell division similar to those reported for dynein/dynactin depletion. file:worm/nud-1/nud-1-deep-research-falcon.md embryos usually arrested between comma and one-fold stages
GO:0035046 pronuclear migration	IMP PMID:11685578 Evolutionarily conserved nuclear migration genes required fo...	ACCEPT	Summary: IMP annotation for involvement in pronuclear migration based on Dawe et al. 2001 (PMID:11685578). RNAi knockdown of nud-1 caused nuclear positioning defects in early embryonic cell division. Pronuclear migration is a dynein-dependent process, and NUD-1 functions with the dynein motor complex. This is a core biological process directly reflecting NUD-1's primary molecular role in nuclear migration. Reason: Pronuclear migration is a core function of NUD-1, directly reflecting its primary role in nuclear migration via the dynein motor complex. The nuclear positioning defects observed after nud-1 RNAi (PMID:11685578) are consistent with the conserved role of NudC family proteins in nuclear migration from fungi to humans. The gene name itself (nuclear distribution) reflects this function. Supporting Evidence: PMID:11685578 Digital time-lapse video microscopy was used to determine that RNAi-treated embryos exhibited nuclear positioning defects in early embryonic cell division similar to those reported for dynein/dynactin depletion. PMID:11685578 Heterologous expression of the C. elegans nudC ortholog, nud-1, complements the A. nidulans nudC3 mutant, demonstrating evolutionary conservation of function. file:worm/nud-1/nud-1-deep-research-falcon.md pronuclei moved inward but failed to rotate onto the anterior-posterior axis; nuclear envelope breakdown occurred on the dorsal-ventral axis
GO:0051932 synaptic transmission, GABAergic	IMP PMID:16996038 Genetic interactions among cortical malformation genes that ...	KEEP AS NON CORE	Summary: IMP annotation for involvement in GABAergic synaptic transmission based on Locke et al. 2006 (PMID:16996038). NUD-1-depleted worms exhibited significant convulsions following PTZ treatment, and fluorescent markers showed defective GABA synaptic vesicle trafficking. This is a separate evidence line (IMP vs IGI) from the other GO:0051932 annotation for the same gene from the same paper. Reason: This IMP annotation provides independent evidence from the IGI annotation for the same term. The convulsion susceptibility phenotype after NUD-1 depletion (PMID:16996038) supports involvement in GABAergic signaling, but this is a secondary function stemming from NUD-1's role in microtubule-based transport. Retained as non-core. Supporting Evidence: PMID:16996038 Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5, and CDKA-1) exhibited significant convulsions following PTZ and RNAi treatment.
GO:0000281 mitotic cytokinesis	IMP PMID:12679384 Role for NudC, a dynein-associated nuclear movement protein,...	NEW	Summary: NEW annotation proposed from Aumais et al. 2003 (PMID:12679384), which was not represented in the original GOA/UniProt set. RNAi gene silencing of nud-1 in C. elegans caused loss of midzone microtubules and rapid regression of the cleavage furrow, producing one-celled embryos containing two nuclei - a defining cytokinesis-failure phenotype. The falcon deep research synthesis further quantifies this (midzone microtubules absent in 26% and weak in 74% of one-cell embryos) and frames NUD-1 as required for late cytokinesis via midzone microtubule organization, mechanistically consistent with the conserved NudC-family role in midzone/midbody microtubule organization during cell division. Reason: Aumais et al. (PMID:12679384) provide direct experimental (RNAi) evidence in C. elegans that NUD-1 is required for completion of the first embryonic cytokinesis: its depletion blocks midzone microtubule formation and causes cleavage-furrow regression, yielding binucleate one-cell embryos. The phenotype occurs in the early embryonic mitotic division, so the directly-annotatable term GO:0000281 (mitotic cytokinesis) is appropriate. IMP with a verified primary PMID is a valid evidence/reference pairing for this RNAi loss-of-function phenotype. This complements the existing pronuclear-migration/nuclear-positioning annotations and captures the second worm-established arm of NUD-1 function. Supporting Evidence: PMID:12679384 Gene silencing of nud-1, the Caenorhabditis elegans ortholog of NudC, led to a loss of midzone microtubules and the rapid regression of the cleavage furrow, which resulted in one-celled embryos containing two nuclei. file:worm/nud-1/nud-1-deep-research-falcon.md cleavage furrows stalled or regressed, producing multinucleated one-cell embryos file:worm/nud-1/nud-1-deep-research-falcon.md Midzone microtubules were absent in 26% (10/39) of one-cell embryos and weak/poorly defined in 74% (29/39)

Core Functions

NUD-1 is a conserved cytoplasmic NudC-family protein whose most defensible worm-established role is as an essential microtubule-based nuclear-positioning and cell-division factor. In the early C. elegans embryo it is required for dynein-pathway pronuclear/centrosome rotation onto the anterior-posterior axis (PMID:11685578) and for completion of the first mitotic cytokinesis via midzone microtubule organization and cleavage-furrow stabilization (PMID:12679384). At the biochemical level it has demonstrated ATP-independent holdase chaperone activity, preventing aggregation of denaturing substrates (citrate synthase, luciferase) and maintaining them in a refolding-competent state (PMID:18626791); this CS (p23/HSP20-like) domain-mediated chaperone/co-chaperone activity provides a plausible mechanism for stabilizing the cytoskeletal regulators (e.g. dynein/LIS-1 pathway components) underlying its nuclear-positioning and cytokinesis functions, though the specific in vivo worm clients remain to be defined.

Molecular Function:

protein folding chaperone

Directly Involved In:

protein folding pronuclear migration mitotic cytokinesis embryo development ending in birth or egg hatching

Cellular Locations:

cytoplasm

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

PMID:11685578

Evolutionarily conserved nuclear migration genes required for early embryonic development in Caenorhabditis elegans.

RNAi knockdown of nud-1 causes embryonic lethality, sterility, altered vulval morphology, uncoordinated movement, and nuclear positioning defects in early embryonic cell division similar to dynein/dynactin depletion.

"Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded similar phenotypes, including embryonic lethality, sterility, altered vulval morphology, and uncoordinated movement."

PMID:16996038

Genetic interactions among cortical malformation genes that influence susceptibility to convulsions in C. elegans.

Depletion of NUD-1 and other LIS1 pathway components caused defective GABA synaptic vesicle trafficking and significant convulsions following pentylenetetrazole treatment.

"Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5, and CDKA-1) exhibited significant convulsions following PTZ and RNAi treatment."

PMID:18626791

The microtubule-associated protein, NUD-1, exhibits chaperone activity in vitro.

Recombinant C. elegans NUD-1 prevents aggregation of citrate synthase and luciferase at stoichiometric concentrations, protects native CS from thermal inactivation, and maintains unfolded intermediates in a refolding-competent state. NUD-1 possesses ATP-independent chaperone activity comparable to small heat shock proteins.

"We demonstrate that nematode NUD-1 is able to prevent the aggregation of two substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric concentrations."

PMID:12679384

Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis.

RNAi gene silencing of nud-1, the C. elegans ortholog of NudC, caused loss of midzone microtubules and rapid regression of the cleavage furrow, yielding one-celled embryos containing two nuclei - establishing a direct, worm-specific requirement for NUD-1 in midzone microtubule organization and completion of mitotic cytokinesis. In parallel mammalian cells, NudC depletion or overexpression caused multinucleation and disorganized midzone/midbody matrix and mislocalized polo-like kinase.

"Gene silencing of nud-1, the Caenorhabditis elegans ortholog of NudC, led to a loss of midzone microtubules and the rapid regression of the cleavage furrow, which resulted in one-celled embryos containing two nuclei."

file:worm/nud-1/nud-1-deep-research-falcon.md

Falcon deep research report on nud-1 (C. elegans)

The most defensible primary function of C. elegans NUD-1 is as an essential microtubule-based nuclear-positioning and cell-division factor acting in (i) pronuclear-centrosome rotation/positioning during the first embryonic division and (ii) midzone assembly and cleavage-furrow stabilization in cytokinesis. The nuclear-positioning phenotypes resemble dynein/dynactin perturbation, placing NUD-1 in the LIS-1/dynein nuclear-positioning pathway.

"essential microtubule-based cell division and nuclear-positioning factor"
In nud-1(RNAi) embryos, pronuclei moved inward but failed to rotate onto the anterior-posterior axis and nuclear envelope breakdown occurred on the dorsal-ventral axis, consistent with a dynein-associated role in pronuclear rotation/nuclear positioning rather than in initiating spindle elongation.

"pronuclei moved inward but failed to rotate onto the anterior-posterior axis; nuclear envelope breakdown occurred on the dorsal-ventral axis"
In nud-1 RNAi embryos, spindle elongation and pronuclear fusion proceeded but cleavage furrows stalled/regressed, producing multinucleated one-cell embryos; midzone microtubules were absent in 26% (10/39) and weak in 74% (29/39) of one-cell embryos, supporting a requirement for NUD-1 in late cytokinesis via midzone microtubule organization.

"Midzone microtubules were absent in 26% (10/39) of one-cell embryos and weak/poorly defined in 74% (29/39)"
nud-1 is the C. elegans nudC ortholog (cosmid F53A2, ORF F53A2.4); full-length nud-1, and especially its C-terminal 173 aa, complements the A. nidulans nudC3 mutant (47% identity / 67% similarity to A. nidulans NUDC), demonstrating deep functional conservation of the NudC family.

"Full-length `nud-1`, and especially its C-terminal 173 aa, complemented the *A. nidulans nudC3* mutant, restoring hyphal growth and nuclear migration"
NudC-family proteins have an N-terminal coiled-coil plus a conserved CS domain (related to p23 and HSP20/sHSP chaperones) and can function as Hsp70/Hsp90 co-chaperones that accelerate client transfer from Hsp70 to Hsp90. C. elegans NUD-1 specifically shows in vitro chaperone activity, preventing heat-induced aggregation of citrate synthase and luciferase. The co-chaperone/client biology is a family-level mechanistic model and is not directly demonstrated in vivo for the worm protein.

"NUD-1 is described as a microtubule-associated protein with in vitro chaperone activity, preventing heat-induced aggregation of citrate synthase and luciferase"

Deep Research

Falcon

(nud-1-deep-research-falcon.md)

Functional annotation research report: *Caenorhabditis elegans* **nud-1** (UniProt G5EE74; ORF **F53A2.4**) Falcon Edison Scientific Literature 29 citations 2 artifacts 2026-05-30T18:08:34.133091

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000015 Figure 3 illustrates the expression and localization of NUD-1::GFP in C. elegans at various life stages: - **Panel A**: Shows an L2 (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Functional annotation research report: Caenorhabditis elegans nud-1 (UniProt G5EE74; ORF F53A2.4)

0. Target identity verification (critical)

The target gene nud-1 in C. elegans corresponds to the fungal nudC ortholog located on cosmid F53A2 (ORF F53A2.4), consistent with the UniProt entry G5EE74 (NudC family). Dawe et al. explicitly identify nud-1 as the C. elegans nudC ortholog and demonstrate functional conservation by complementation in Aspergillus nidulans (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 2-3). Aumais et al. subsequently describe nud-1 as the C. elegans ortholog of mammalian NudC and assay its function via RNAi in embryos (aumais2003rolefornudc pages 2-3).

Conclusion: The literature summarized below refers to the C. elegans gene nud-1/F53A2.4 in the conserved NudC family, not to unrelated “nud-1” usages in other organisms (dawe2001evolutionarilyconservednuclear pages 1-2, aumais2003rolefornudc pages 2-3).

1. Key concepts and definitions (current understanding)

1.1 What is a NudC-family protein?

Nuclear distribution C (NudC) proteins are evolutionarily conserved eukaryotic proteins originally discovered in fungal nuclear migration genetics and now recognized as multifunctional regulators of nuclear migration/positioning, intracellular transport, and cell division (vassileva2023smallsizedyet pages 1-3, vassileva2023smallsizedyet pages 3-5). Reviews emphasize their tight connection to dynein–dynactin-mediated processes and to the broader “NUD” pathway that includes LIS1/NUDF and NUDE/NudE-family factors that modulate dynein force production and cargo/nuclear positioning (vassileva2023smallsizedyet pages 1-3, vassileva2023smallsizedyet pages 12-13).

1.2 Domain architecture relevant to annotation of worm NUD-1

Recent synthesis (2023) describes a characteristic NudC-family architecture: an N-terminal coiled-coil implicated in dimerization, paired with a conserved CS domain (related to p23 and small heat-shock proteins such as HSP20/α-crystallin), plus conserved C-terminal helices (vassileva2023smallsizedyet pages 3-5). The CS-domain link motivates a mechanistic model in which NudC-family proteins can have intrinsic chaperone activity and/or act as co-chaperones (vassileva2023smallsizedyet pages 5-7, vassileva2023smallsizedyet pages 13-14).

1.3 Chaperone/co-chaperone concept for NudC family

A 2024 review of molecular chaperones in barrier biology describes the NUDC family as Hsp70/Hsp90 co-chaperones that can accelerate client transfer from Hsp70 to Hsp90, with different family members showing preferences for distinct client domains (e.g., WD40, RCC1, Kelch) (lechuga2024regulationofepithelial pages 13-14). A 2023 NudC-family review similarly links the CS domain to co-chaperone function and highlights that NudC proteins can interface with Hsp90-centered proteostasis, including stabilization of LIS1 in mammalian systems (vassileva2023smallsizedyet pages 5-7, vassileva2023smallsizedyet pages 13-14).

Relevance for C. elegans nud-1: This provides a plausible mechanistic explanation for how NUD-1 could support dynein/LIS-1-dependent microtubule-based events in embryos—by helping stabilize or assemble key cytoskeletal regulators—while noting that much of the detailed client biology is best established in non-worm systems (vassileva2023smallsizedyet pages 13-14, lechuga2024regulationofepithelial pages 13-14).

2. Worm-specific experimental evidence for nud-1 function

2.1 Expression and localization in the animal

Dawe et al. generated a NUD-1::GFP reporter and observed:
- Diffuse embryonic expression
- Sustained expression in amphid and phasmid sensory neurons and the nerve ring
- Additional transient expression in tissues including the gonadal primordium and diffuse intestinal signal in adults (dawe2001evolutionarilyconservednuclear pages 4-7).

The corresponding Figure 3 images provide visual evidence of these expression patterns across embryo, larva, and adult (dawe2001evolutionarilyconservednuclear media febc75e2).

Functional interpretation: Expression in embryos and neurons is consistent with a protein required for early embryonic cell division/nuclear positioning and potentially neuronal development/function, matching the phenotypes described below (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 1-2).

2.2 Essential role in early embryonic nuclear positioning (dynein-like phenotype)

Using RNAi, Dawe et al. report that nud-1 depletion disrupts pronuclear/centrosome positioning in early embryos:
- Pronuclei migrate toward the center but fail to rotate onto the anterior–posterior axis (“never rotate onto the a–p axis”) (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 3-4).
- Nuclear envelope breakdown and initial spindle assembly occur along an incorrect (dorsal–ventral) axis, with downstream abnormal nuclear positioning at the two-cell stage (dawe2001evolutionarilyconservednuclear pages 4-7).
- Later (more severe) timepoints show pronuclei conjoining at variable embryo positions rather than the typical ~70% egg length (dawe2001evolutionarilyconservednuclear pages 3-4).

The authors explicitly note these nuclear-positioning phenotypes resemble dynein/dynactin perturbation, placing nud-1 within dynein-linked nuclear positioning pathways (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 3-4).

2.3 Role in cytokinesis via midzone microtubule organization

Aumais et al. (2003) extended worm phenotyping to cytokinesis and midzone microtubules. In nud-1 RNAi embryos:
- Pronuclear fusion and spindle elongation proceed, but the cleavage furrow stalls/regresses, producing multinucleated one-cell embryos (aumais2003rolefornudc pages 9-11, aumais2003rolefornudc pages 8-9).
- Midzone microtubules are frequently defective: absent in 26% (10/39) of one-cell embryos and weak/poorly defined in 74% (29/39) (aumais2003rolefornudc pages 9-11).
- Among embryos with weak midzone MTs, 15/29 display chromatin bridges, indicating chromosome segregation problems associated with defective midzone structures (aumais2003rolefornudc pages 9-11).
- Embryos can continue cycling without successful cytokinesis, yielding extra DNA and multipolar spindles (aumais2003rolefornudc pages 9-11).

Functional interpretation: These data support that NUD-1 is required for late cytokinesis, likely through ensuring proper midzone microtubule formation/maintenance and cleavage-furrow stabilization (aumais2003rolefornudc pages 9-11).

2.4 Organismal phenotypes and penetrance statistics

Dawe et al. quantify severe RNAi outcomes:
- 94% of injected mothers laid eggs with mutant phenotypes
- 73% produced only dead embryos
- Embryos typically arrest between comma and one-fold stages (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 3-4).

Among rarer “escaper” progeny:
- >50% show everted vulva
- >75% are uncoordinated
- All are sterile with cuticle/hypodermal defects (dawe2001evolutionarilyconservednuclear pages 4-7).

Functional interpretation: While pleiotropic, these phenotypes are consistent with an essential, conserved cytoskeletal/nuclear-positioning factor rather than a tissue-restricted metabolic enzyme (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 1-2).

3. Mechanistic model and pathway placement

3.1 Placement in the LIS-1/dynein nuclear positioning pathway

Dawe et al. frame nud-1 and lis-1 as conserved nuclear migration genes and show that nud-1 RNAi produces nuclear positioning defects similar to dynein/dynactin depletion (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 3-4). This strongly supports annotating NUD-1 as a dynein-associated regulator of nuclear positioning during early embryonic divisions.

3.2 Connection to midzone/midbody microtubule regulation (cell division)

Aumais et al. provide direct worm evidence that nud-1 is required for midzone microtubule organization and successful cytokinesis (aumais2003rolefornudc pages 9-11). In the same study, mammalian NudC localizes to mitotic structures including the midbody and is regulated by mitotic kinase pathways, supporting a conserved role for NudC-family proteins in microtubule reorganization during division (aumais2003rolefornudc pages 2-3, aumais2003rolefornudc pages 8-9).

3.3 Chaperone/co-chaperone model (family-based inference; not worm-proven in vivo)

Recent reviews and primary studies outside the worm system support a model in which NudC-family proteins (including NudCL2) act as Hsp90-associated co-chaperones that stabilize key clients required for mitosis/cytokinesis (lechuga2024regulationofepithelial pages 13-14, xu2024nudcl2isrequired pages 17-17). This is consistent with the family’s conserved CS (p23/sHSP-like) domain architecture (vassileva2023smallsizedyet pages 3-5, vassileva2023smallsizedyet pages 5-7).

Caution for annotation: The C. elegans in vivo embryo phenotypes firmly establish roles in nuclear positioning and cytokinesis (Sections 2.2–2.3), but the specific client proteins and direct biochemical interactions (e.g., with LIS-1 or dynein components in worm) are not demonstrated in the retrieved worm primary texts and should be treated as a mechanistic hypothesis (dawe2001evolutionarilyconservednuclear pages 1-2, aumais2003rolefornudc pages 9-11).

4. Recent developments (prioritizing 2023–2024)

No 2023–2024 studies specifically interrogating C. elegans nud-1/F53A2.4 were retrieved here. However, relevant 2023–2024 advances that refine functional interpretation include:

2023 (Plants; review): Synthesis of NudC-family domain architecture (coiled-coil + CS domain), conserved dynein-linked roles in nuclear migration and cell division, and explicit mention that C. elegans NUD-1 has in vitro chaperone activity and that NudC homologs can complement fungal nudC mutants (https://doi.org/10.3390/plants13010119; published Dec 2023) (vassileva2023smallsizedyet pages 5-7, vassileva2023smallsizedyet pages 3-5).
2024 (Cells; review): Framing of the NUDC family as Hsp70/Hsp90 co-chaperones with client-transfer acceleration and emerging cytoskeletal roles (https://doi.org/10.3390/cells13050370; published Feb 2024) (lechuga2024regulationofepithelial pages 13-14).
2024 (Protein & Cell; primary): Demonstration that NudCL2 (NudC-family member) is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody, strengthening a conserved co-chaperone mechanism for midbody function (https://doi.org/10.1093/procel/pwae025; published May 2024) (xu2024nudcl2isrequired pages 17-17).

5. Current applications and real-world implementations

5.1 In C. elegans research (real-world use in cell biology)

The principal “application” of nud-1 knowledge is as a genetic entry point to study conserved mechanisms of:
- Pronuclear rotation/nuclear positioning in early embryos (a dynein-linked process) (dawe2001evolutionarilyconservednuclear pages 3-4).
- Midzone microtubule organization and cleavage furrow stabilization during cytokinesis (aumais2003rolefornudc pages 9-11).

The availability of a nud-1::GFP expression reporter supports experimental use in developmental expression studies and potentially as a context marker for where nud-1 is expressed during phenotypic analyses (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear media febc75e2).

5.2 Cross-species functional conservation as an implementation strategy

Dawe et al. demonstrate a practical functional assay: heterologous expression of C. elegans nud-1 complements a fungal nudC mutant, directly leveraging conservation to infer function (https://doi.org/10.1007/s004270100176; published Sep 2001) (dawe2001evolutionarilyconservednuclear pages 2-3). This kind of cross-species complementation remains a real-world strategy to validate orthology and conserved biological roles.

6. Expert opinions and analysis (authoritative synthesis)

Two key interpretive statements emerge from authoritative sources:

NudC proteins as conserved, multifunctional regulators: Reviews emphasize that NudC-family proteins integrate dynein-linked transport/nuclear positioning with cell division and proteostasis/chaperone functions via conserved domains (vassileva2023smallsizedyet pages 1-3, vassileva2023smallsizedyet pages 3-5).
Worm NUD-1 as a link between nuclear positioning and cell division: Dawe et al. conclude that LIS-1/NUDC-like proteins represent a link between nuclear positioning, cell division, and neuronal function, supported by embryo time-lapse phenotypes and expression patterns (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 4-7).

My synthesis of the primary worm data is that nud-1’s most defensible primary function in C. elegans is as an essential microtubule-based cell division and nuclear-positioning factor, acting during (i) pronuclear-centrosome rotation/positioning and (ii) midzone assembly/furrow stabilization in cytokinesis. The chaperone/co-chaperone role is a plausible mechanistic layer (supported by family biology) but is not yet directly demonstrated in vivo for the worm protein in the retrieved corpus (aumais2003rolefornudc pages 9-11, lechuga2024regulationofepithelial pages 13-14).

7. Key statistics and data points (from recent and foundational studies)

RNAi penetrance (Dawe 2001): 94% of injected mothers produced mutant eggs; 73% produced only dead embryos (dawe2001evolutionarilyconservednuclear pages 3-4).
Escaper phenotypes (Dawe 2001): among escapers, >50% everted vulva; >75% uncoordinated; all sterile (dawe2001evolutionarilyconservednuclear pages 4-7).
Midzone microtubule defects (Aumais 2003): midzone MT absent in 26% (10/39) and weak in 74% (29/39) of one-cell embryos; chromatin bridges in 15/29 among weak-midzone embryos (aumais2003rolefornudc pages 9-11).

8. Evidence summary table

Evidence type	Key findings (with quantitative stats when available)	Experimental approach	Developmental stage/tissue	Interpretation for functional annotation	Primary source (author year, journal, DOI URL)
Expression/localization	`nud-1::GFP` showed diffuse expression in early embryos; sustained expression in amphid and phasmid sensory neurons and nerve ring; additional transient signal in gonadal primordium and diffuse intestinal expression in adults. Figure 3 documents embryo, larval, and adult expression patterns (dawe2001evolutionarilyconservednuclear pages 7-8, dawe2001evolutionarilyconservednuclear media febc75e2, dawe2001evolutionarilyconservednuclear pages 4-7).	Transgenic `nud-1::GFP` reporter microscopy (dawe2001evolutionarilyconservednuclear pages 7-8, dawe2001evolutionarilyconservednuclear pages 2-3, dawe2001evolutionarilyconservednuclear media febc75e2).	Early embryos; larval/adult sensory neurons; gonadal primordium; intestine (dawe2001evolutionarilyconservednuclear pages 7-8, dawe2001evolutionarilyconservednuclear media febc75e2, dawe2001evolutionarilyconservednuclear pages 4-7).	Supports a broadly used cytoplasmic/neuronal developmental factor rather than a tissue-restricted enzyme; embryonic and neuronal expression fits roles in cell division, nuclear positioning, and nervous-system function (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 4-7).	Dawe et al. 2001, Development Genes and Evolution, https://doi.org/10.1007/s004270100176
Embryo nuclear positioning	`nud-1(RNAi)` embryos showed defective pronuclear migration/rotation: pronuclei moved inward but failed to rotate onto the anterior-posterior axis; nuclear envelope breakdown occurred on the dorsal-ventral axis; after first division, two-cell nuclei were centrally located. In later embryos, pronuclei conjoined at variable positions instead of the normal ~70% egg length (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 3-4).	dsRNA injection RNAi followed by digital time-lapse video microscopy of early embryos (dawe2001evolutionarilyconservednuclear pages 3-4).	One-cell and two-cell embryos during first mitosis (dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 3-4).	Strongly supports a primary role in dynein-related nuclear positioning/pronuclear-centrosome orientation during early embryonic division, not in general spindle elongation initiation (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 4-7, dawe2001evolutionarilyconservednuclear pages 3-4).	Dawe et al. 2001, Development Genes and Evolution, https://doi.org/10.1007/s004270100176
Cytokinesis/midzone MT	In `nud-1` RNAi embryos, spindle elongation and pronuclear fusion occurred, but cleavage furrows stalled or regressed, producing multinucleated one-cell embryos. Midzone microtubules were absent in 26% (10/39) of one-cell embryos and weak/poorly defined in 74% (29/39); among embryos with weak midzone MTs, 15/29 showed chromatin bridges. Older embryos formed multipolar spindles and accumulated extra DNA, indicating continued cell cycling without successful cytokinesis (aumais2003rolefornudc pages 9-11, aumais2003rolefornudc pages 8-9).	RNAi feeding; time-lapse Nomarski/live imaging; anti-tubulin/DAPI staining (aumais2003rolefornudc pages 9-11, aumais2003rolefornudc pages 3-4).	One-cell embryos and older embryos during/after first cytokinesis (aumais2003rolefornudc pages 9-11).	Indicates that NUD-1 is required for late cytokinesis, especially stabilization of the cleavage furrow and organization of midzone microtubules; function is consistent with a microtubule-associated dynein-pathway regulator (aumais2003rolefornudc pages 9-11).	Aumais et al. 2003, Journal of Cell Science, https://doi.org/10.1242/jcs.00412
Organismal phenotypes	RNAi caused high-penetrance developmental defects: 94% of injected mothers laid mutant eggs and 73% produced only dead embryos; embryos usually arrested between comma and one-fold stages. Among F1 escapers, >50% showed everted vulva, >75% were uncoordinated, all were sterile, and cuticle/hypodermal defects were observed (dawe2001evolutionarilyconservednuclear pages 3-4, dawe2001evolutionarilyconservednuclear pages 4-7).	dsRNA injection RNAi with phenotype scoring across progeny (dawe2001evolutionarilyconservednuclear pages 2-3, dawe2001evolutionarilyconservednuclear pages 3-4, dawe2001evolutionarilyconservednuclear pages 4-7).	Embryos; surviving larval/adult escapers; vulva, hypodermis, locomotor system, germ line (dawe2001evolutionarilyconservednuclear pages 7-8, dawe2001evolutionarilyconservednuclear pages 4-7).	These pleiotropic phenotypes are consistent with an essential cellular factor for embryogenesis and postembryonic tissue morphogenesis, likely through conserved cytoskeletal/nuclear-positioning functions rather than a narrowly specialized pathway (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 4-7).	Dawe et al. 2001, Development Genes and Evolution, https://doi.org/10.1007/s004270100176
Functional conservation/complementation	`nud-1` was identified as the C. elegans `nudC` ortholog on cosmid F53A2; sequence comparison showed 47% identity/67% similarity to A. nidulans NUDC. Full-length `nud-1`, and especially its C-terminal 173 aa, complemented the A. nidulans nudC3 mutant, restoring hyphal growth and nuclear migration (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 2-3). A later review notes that C. elegans NudC homologs can complement fungal `nudC3`, supporting deep functional conservation (vassileva2023smallsizedyet pages 3-5, vassileva2023smallsizedyet pages 5-7).	Sequence comparison; heterologous expression complementation in fungal mutant; DAPI-based nuclear migration assessment (dawe2001evolutionarilyconservednuclear pages 2-3).	Cross-species assay using worm gene in fungal nuclear migration system (dawe2001evolutionarilyconservednuclear pages 2-3).	Provides direct evidence that `nud-1` belongs to the conserved NudC family and supports annotation as a nuclear migration/cell division factor rather than an enzyme or transporter (dawe2001evolutionarilyconservednuclear pages 1-2, dawe2001evolutionarilyconservednuclear pages 2-3).	Dawe et al. 2001, Development Genes and Evolution, https://doi.org/10.1007/s004270100176; summarized in Vassileva et al. 2023, Plants, https://doi.org/10.3390/plants13010119
Biochemical/chaperone inference	Family-level evidence shows NudC proteins are dimeric/coiled-coil proteins with a conserved CS domain related to p23 and HSP20/sHSP proteins and can function as Hsp70/Hsp90 co-chaperones. For C. elegans specifically, NUD-1 is described as a microtubule-associated protein with in vitro chaperone activity, preventing heat-induced aggregation of citrate synthase and luciferase (vassileva2023smallsizedyet pages 13-14, vassileva2023smallsizedyet pages 5-7, vassileva2023smallsizedyet pages 3-5, lechuga2024regulationofepithelial pages 13-14). Recent 2024 primary work on the paralogous family member NudCL2 shows Hsp90-dependent stabilization of RCC2 at the midbody during cytokinesis, reinforcing a conserved co-chaperone model for NudC-family proteins in cell division (xu2024nudcl2isrequired pages 17-17).	In vitro chaperone assays for NUD-1 (reviewed); family/domain analyses; recent mammalian primary study of NudCL2/Hsp90/RCC2 (vassileva2023smallsizedyet pages 5-7, vassileva2023smallsizedyet pages 3-5, xu2024nudcl2isrequired pages 17-17, lechuga2024regulationofepithelial pages 13-14).	Protein/family level; inferred for worm embryonic microtubule-associated functions (vassileva2023smallsizedyet pages 13-14, vassileva2023smallsizedyet pages 5-7).	Best current mechanistic model is that worm NUD-1 acts as a conserved microtubule-associated dynein/LIS-1 pathway regulator with chaperone or co-chaperone properties that help maintain client proteins required for nuclear positioning and cytokinesis (vassileva2023smallsizedyet pages 13-14, xu2024nudcl2isrequired pages 17-17).	Vassileva et al. 2023, Plants, https://doi.org/10.3390/plants13010119; Lechuga et al. 2024, Cells, https://doi.org/10.3390/cells13050370; Xu et al. 2024, Protein & Cell, https://doi.org/10.1093/procel/pwae025

Table: This table compiles the main experimental and inference-based annotations for C. elegans nud-1/F53A2.4, separating direct worm evidence from family-level mechanistic interpretation. It is useful for functional annotation because it links phenotypes, localization, and conserved NudC-family biology to a coherent gene-function model.

9. Reference URLs (publication dates from retrieved metadata)

Dawe AL et al. “Evolutionarily conserved nuclear migration genes required for early embryonic development in Caenorhabditis elegans.” Development Genes and Evolution (Sep 2001). https://doi.org/10.1007/s004270100176 (dawe2001evolutionarilyconservednuclear pages 1-2)
Aumais JP et al. “Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis.” Journal of Cell Science (May 2003). https://doi.org/10.1242/jcs.00412 (aumais2003rolefornudc pages 2-3)
Vassileva V et al. “Small Sized Yet Powerful: Nuclear Distribution C Proteins in Plants.” Plants (Dec 2023). https://doi.org/10.3390/plants13010119 (vassileva2023smallsizedyet pages 1-3)
Lechuga S et al. “Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones.” Cells (Feb 2024). https://doi.org/10.3390/cells13050370 (lechuga2024regulationofepithelial pages 13-14)
Xu X et al. “NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody.” Protein & Cell (May 2024). https://doi.org/10.1093/procel/pwae025 (xu2024nudcl2isrequired pages 17-17)

10. Limitations and gaps

Direct interaction partners in worm (dynein/LIS-1 binding, client proteins): The retrieved C. elegans primary sources establish phenotypes and expression but do not provide direct biochemical interaction maps for NUD-1 (dawe2001evolutionarilyconservednuclear pages 1-2, aumais2003rolefornudc pages 9-11).
2023–2024 worm-specific updates: No recent C. elegans nud-1-focused papers were retrieved; recent advances are therefore used to refine mechanistic interpretation at the NudC-family level (lechuga2024regulationofepithelial pages 13-14, xu2024nudcl2isrequired pages 17-17, vassileva2023smallsizedyet pages 5-7).

References

(dawe2001evolutionarilyconservednuclear pages 1-2): Angus L. Dawe, Kim A. Caldwell, Phillip M. Harris, Ronald N. Morris, and Guy A. Caldwell. Evolutionarily conserved nuclear migration genes required for early embryonic development in caenorhabditiselegans. Development Genes and Evolution, 211:434-441, Sep 2001. URL: https://doi.org/10.1007/s004270100176, doi:10.1007/s004270100176. This article has 66 citations and is from a peer-reviewed journal.
(dawe2001evolutionarilyconservednuclear pages 2-3): Angus L. Dawe, Kim A. Caldwell, Phillip M. Harris, Ronald N. Morris, and Guy A. Caldwell. Evolutionarily conserved nuclear migration genes required for early embryonic development in caenorhabditiselegans. Development Genes and Evolution, 211:434-441, Sep 2001. URL: https://doi.org/10.1007/s004270100176, doi:10.1007/s004270100176. This article has 66 citations and is from a peer-reviewed journal.
(aumais2003rolefornudc pages 2-3): Jonathan P. Aumais, Shelli N. Williams, Weiping Luo, Michiya Nishino, Kim A. Caldwell, Guy A. Caldwell, Sue-Hwa Lin, and Li-yuan Yu-Lee. Role for nudc, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. Journal of Cell Science, 116:1991-2003, May 2003. URL: https://doi.org/10.1242/jcs.00412, doi:10.1242/jcs.00412. This article has 148 citations and is from a domain leading peer-reviewed journal.
(vassileva2023smallsizedyet pages 1-3): Valya Vassileva, Mariyana Georgieva, Dimitar Todorov, and Kiril Mishev. Small sized yet powerful: nuclear distribution c proteins in plants. Plants, 13:119, Dec 2023. URL: https://doi.org/10.3390/plants13010119, doi:10.3390/plants13010119. This article has 0 citations.
(vassileva2023smallsizedyet pages 3-5): Valya Vassileva, Mariyana Georgieva, Dimitar Todorov, and Kiril Mishev. Small sized yet powerful: nuclear distribution c proteins in plants. Plants, 13:119, Dec 2023. URL: https://doi.org/10.3390/plants13010119, doi:10.3390/plants13010119. This article has 0 citations.
(vassileva2023smallsizedyet pages 12-13): Valya Vassileva, Mariyana Georgieva, Dimitar Todorov, and Kiril Mishev. Small sized yet powerful: nuclear distribution c proteins in plants. Plants, 13:119, Dec 2023. URL: https://doi.org/10.3390/plants13010119, doi:10.3390/plants13010119. This article has 0 citations.
(vassileva2023smallsizedyet pages 5-7): Valya Vassileva, Mariyana Georgieva, Dimitar Todorov, and Kiril Mishev. Small sized yet powerful: nuclear distribution c proteins in plants. Plants, 13:119, Dec 2023. URL: https://doi.org/10.3390/plants13010119, doi:10.3390/plants13010119. This article has 0 citations.
(vassileva2023smallsizedyet pages 13-14): Valya Vassileva, Mariyana Georgieva, Dimitar Todorov, and Kiril Mishev. Small sized yet powerful: nuclear distribution c proteins in plants. Plants, 13:119, Dec 2023. URL: https://doi.org/10.3390/plants13010119, doi:10.3390/plants13010119. This article has 0 citations.
(lechuga2024regulationofepithelial pages 13-14): Susana Lechuga, Armando Marino-Melendez, Nayden G. Naydenov, Atif Zafar, Manuel B. Braga-Neto, and Andrei I. Ivanov. Regulation of epithelial and endothelial barriers by molecular chaperones. Cells, 13:370, Feb 2024. URL: https://doi.org/10.3390/cells13050370, doi:10.3390/cells13050370. This article has 14 citations.
(dawe2001evolutionarilyconservednuclear pages 4-7): Angus L. Dawe, Kim A. Caldwell, Phillip M. Harris, Ronald N. Morris, and Guy A. Caldwell. Evolutionarily conserved nuclear migration genes required for early embryonic development in caenorhabditiselegans. Development Genes and Evolution, 211:434-441, Sep 2001. URL: https://doi.org/10.1007/s004270100176, doi:10.1007/s004270100176. This article has 66 citations and is from a peer-reviewed journal.
(dawe2001evolutionarilyconservednuclear media febc75e2): Angus L. Dawe, Kim A. Caldwell, Phillip M. Harris, Ronald N. Morris, and Guy A. Caldwell. Evolutionarily conserved nuclear migration genes required for early embryonic development in caenorhabditiselegans. Development Genes and Evolution, 211:434-441, Sep 2001. URL: https://doi.org/10.1007/s004270100176, doi:10.1007/s004270100176. This article has 66 citations and is from a peer-reviewed journal.
(dawe2001evolutionarilyconservednuclear pages 3-4): Angus L. Dawe, Kim A. Caldwell, Phillip M. Harris, Ronald N. Morris, and Guy A. Caldwell. Evolutionarily conserved nuclear migration genes required for early embryonic development in caenorhabditiselegans. Development Genes and Evolution, 211:434-441, Sep 2001. URL: https://doi.org/10.1007/s004270100176, doi:10.1007/s004270100176. This article has 66 citations and is from a peer-reviewed journal.
(aumais2003rolefornudc pages 9-11): Jonathan P. Aumais, Shelli N. Williams, Weiping Luo, Michiya Nishino, Kim A. Caldwell, Guy A. Caldwell, Sue-Hwa Lin, and Li-yuan Yu-Lee. Role for nudc, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. Journal of Cell Science, 116:1991-2003, May 2003. URL: https://doi.org/10.1242/jcs.00412, doi:10.1242/jcs.00412. This article has 148 citations and is from a domain leading peer-reviewed journal.
(aumais2003rolefornudc pages 8-9): Jonathan P. Aumais, Shelli N. Williams, Weiping Luo, Michiya Nishino, Kim A. Caldwell, Guy A. Caldwell, Sue-Hwa Lin, and Li-yuan Yu-Lee. Role for nudc, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. Journal of Cell Science, 116:1991-2003, May 2003. URL: https://doi.org/10.1242/jcs.00412, doi:10.1242/jcs.00412. This article has 148 citations and is from a domain leading peer-reviewed journal.
(xu2024nudcl2isrequired pages 17-17): Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, and Yuehong Yang. Nudcl2 is required for cytokinesis by stabilizing rcc2 with hsp90 at the midbody. Protein & Cell, 15:766-782, May 2024. URL: https://doi.org/10.1093/procel/pwae025, doi:10.1093/procel/pwae025. This article has 4 citations and is from a peer-reviewed journal.
(dawe2001evolutionarilyconservednuclear pages 7-8): Angus L. Dawe, Kim A. Caldwell, Phillip M. Harris, Ronald N. Morris, and Guy A. Caldwell. Evolutionarily conserved nuclear migration genes required for early embryonic development in caenorhabditiselegans. Development Genes and Evolution, 211:434-441, Sep 2001. URL: https://doi.org/10.1007/s004270100176, doi:10.1007/s004270100176. This article has 66 citations and is from a peer-reviewed journal.
(aumais2003rolefornudc pages 3-4): Jonathan P. Aumais, Shelli N. Williams, Weiping Luo, Michiya Nishino, Kim A. Caldwell, Guy A. Caldwell, Sue-Hwa Lin, and Li-yuan Yu-Lee. Role for nudc, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. Journal of Cell Science, 116:1991-2003, May 2003. URL: https://doi.org/10.1242/jcs.00412, doi:10.1242/jcs.00412. This article has 148 citations and is from a domain leading peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

aumais2003rolefornudc pages 2-3
vassileva2023smallsizedyet pages 3-5
lechuga2024regulationofepithelial pages 13-14
dawe2001evolutionarilyconservednuclear pages 4-7
dawe2001evolutionarilyconservednuclear pages 3-4
aumais2003rolefornudc pages 9-11
dawe2001evolutionarilyconservednuclear pages 2-3
dawe2001evolutionarilyconservednuclear pages 1-2
vassileva2023smallsizedyet pages 1-3
vassileva2023smallsizedyet pages 12-13
vassileva2023smallsizedyet pages 5-7
vassileva2023smallsizedyet pages 13-14
aumais2003rolefornudc pages 8-9
dawe2001evolutionarilyconservednuclear pages 7-8
aumais2003rolefornudc pages 3-4
https://doi.org/10.3390/plants13010119;
https://doi.org/10.3390/cells13050370;
https://doi.org/10.1093/procel/pwae025;
https://doi.org/10.1007/s004270100176;
https://doi.org/10.1007/s004270100176
https://doi.org/10.1242/jcs.00412
https://doi.org/10.3390/plants13010119
https://doi.org/10.1093/procel/pwae025
https://doi.org/10.3390/cells13050370
https://doi.org/10.1007/s004270100176,
https://doi.org/10.1242/jcs.00412,
https://doi.org/10.3390/plants13010119,
https://doi.org/10.3390/cells13050370,
https://doi.org/10.1093/procel/pwae025,

📄 View Raw YAML

id: G5EE74
gene_symbol: nud-1
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  C. elegans NUD-1 (Nuclear migration protein nudC) is an evolutionarily conserved
  member of the NudC family that functions in nuclear migration, mitotic progression,
  and cytoskeletal dynamics. NUD-1 associates with microtubules and the dynein motor
  complex, working alongside LIS-1 to ensure proper cell division and nuclear positioning
  (PMID:11685578). The protein contains a conserved p23/HSP20-like domain (CS domain)
  and an N-terminal NudC domain. In vitro studies demonstrate that NUD-1 exhibits
  ATP-independent molecular chaperone (holdase) activity, preventing aggregation of
  citrate synthase and luciferase at stoichiometric concentrations, and protecting
  native enzyme activity from thermal inactivation (PMID:18626791). Importantly,
  NUD-1/substrate complexes are productive -- unfolded intermediates can be refolded
  by ATP-dependent chaperones, indicating NUD-1 acts as a holdase that maintains
  substrates in a refolding-competent state (PMID:18626791). NUD-1 is expressed in
  sensory neurons, embryos, gonad, gut, vulva, ventral cord, and hypodermal seam
  cells (PMID:11685578). RNAi knockdown causes embryonic lethality, sterility,
  altered vulval morphology, uncoordinated movement, and nuclear positioning defects
  in early embryonic cell division (PMID:11685578). NUD-1 is also required for
  completion of the first embryonic cytokinesis: its depletion causes loss of midzone
  microtubules and rapid regression of the cleavage furrow, producing binucleate
  one-cell embryos (PMID:12679384). Depletion of NUD-1 also leads to
  defective GABA synaptic vesicle trafficking and increased susceptibility to
  pentylenetetrazole-induced convulsions (PMID:16996038).
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for cytoplasmic localization, inferred phylogenetically from
      multiple orthologs including Drosophila, Arabidopsis, and human NudC proteins.
      Consistent with UniProt subcellular location annotation (Cytoplasm) and the
      known biology of NudC family proteins as cytoplasmic, microtubule-associated
      proteins. NUD-1::GFP fusion shows cytoplasmic expression in sensory neurons,
      embryos, gonad, gut, vulva, ventral cord, and hypodermal seam cells (PMID:11685578).
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is well-established for NUD-1 and the NudC family.
      The IBA inference is consistent with UniProt annotation and direct GFP expression
      data in C. elegans (PMID:11685578).
    supported_by:
      - reference_id: PMID:11685578
        supporting_text: >-
          A C. elegans nud-1::GFP fusion produces sustained fluorescence in sensory
          neurons and embryos, and transient fluorescence in the gonad, gut, vulva,
          ventral cord, and hypodermal seam cells.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for involvement in protein folding, inferred phylogenetically.
      NUD-1 has been demonstrated to exhibit chaperone activity in vitro
      (PMID:18626791), preventing aggregation of citrate synthase and luciferase.
      However, NUD-1 functions as a holdase rather than a foldase -- it prevents
      aggregation of unfolded substrates, which can then be refolded by ATP-dependent
      chaperones. The IBA annotation is consistent with the experimental evidence
      from PMID:18626791.
    action: ACCEPT
    reason: >-
      Protein folding is appropriate as a biological process annotation for a holdase
      chaperone, as NUD-1 maintains unfolded intermediates in a refolding-competent
      state that can be subsequently refolded by the cellular chaperone machinery
      (PMID:18626791). The IBA inference is supported by direct experimental evidence.
    supported_by:
      - reference_id: PMID:18626791
        supporting_text: >-
          In the presence of NUD-1, nearly all of the luciferase activity was regained,
          indicating that unfolded intermediates complexed with NUD-1 could be refolded.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for unfolded protein binding, inferred phylogenetically from
      NUD-1 itself (WB:WBGene00003829) and other orthologs. GO:0051082 is proposed
      for obsoletion. NUD-1 has been directly demonstrated to prevent aggregation of
      denaturing citrate synthase and luciferase (PMID:18626791), functioning as
      an ATP-independent holdase chaperone. However, NUD-1 is not a classical sHSP --
      it is a NudC family protein with an HSP20-like fold (CS domain) whose primary
      role is in nuclear migration and cytoskeletal dynamics. The chaperone activity
      may be secondary to its role in mitotic complex assembly.
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. NUD-1 demonstrates holdase activity in
      vitro (PMID:18626791), preventing aggregation of denaturing substrates and
      maintaining them in a refolding-competent state. GO:0140309 (unfolded protein
      carrier activity) is not appropriate because it is carrier-specific (per
      go-ontology#30552). Retain until a holdase chaperone activity NTR is created.
    proposed_replacement_terms:
      - id: GO:0051082
        label: unfolded protein binding (retain until holdase NTR is created)
    supported_by:
      - reference_id: PMID:18626791
        supporting_text: >-
          We demonstrate that nematode NUD-1 is able to prevent the aggregation of two
          substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric
          concentrations.
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: >-
      IEA annotation for synaptic localization, inferred automatically from
      the GO:0051932 (synaptic transmission, GABAergic) annotation via
      inter-ontology logical inference. NUD-1 depletion causes defective GABA
      synaptic vesicle trafficking (PMID:16996038), which supports a role at
      synapses. However, this is an indirect inference -- NUD-1 may affect
      synaptic vesicle trafficking through its role in cytoskeletal dynamics
      (dynein/microtubule-dependent transport) rather than being a resident
      synaptic protein.
    action: KEEP_AS_NON_CORE
    reason: >-
      The inference from GABAergic synaptic transmission to synaptic localization
      is logically valid. NUD-1 depletion disrupts GABA synaptic vesicle
      trafficking (PMID:16996038), suggesting functional involvement at synapses.
      However, NUD-1 is primarily a cytoplasmic, microtubule-associated protein
      and its synaptic role is secondary to its core function in nuclear migration
      and chaperone activity.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA annotation for cytoplasmic localization based on UniProt subcellular
      location mapping. Consistent with the IBA annotation for the same term and
      direct GFP expression data (PMID:11685578).
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is well-established. This IEA annotation is consistent
      with the IBA annotation and experimental evidence. Acceptable as automated
      confirmation.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:18626791
  review:
    summary: >-
      IDA annotation for involvement in protein folding based on Faircloth et al. 2009
      (PMID:18626791). The study demonstrated that recombinant NUD-1 prevents
      aggregation of citrate synthase and luciferase, protects native CS from thermal
      inactivation, and maintains unfolded luciferase intermediates in a
      refolding-competent state. This is directly supported by the luciferase refolding
      assay showing that unfolded intermediates complexed with NUD-1 could be refolded
      by rabbit reticulocyte lysate plus ATP.
    action: ACCEPT
    reason: >-
      Strong experimental evidence directly in C. elegans NUD-1 demonstrating
      chaperone activity that facilitates the protein folding process. NUD-1 acts as a
      holdase maintaining substrates in a refolding-competent state, which is part of
      the protein folding pathway (PMID:18626791).
    supported_by:
      - reference_id: PMID:18626791
        supporting_text: >-
          In the presence of NUD-1, nearly all of the luciferase activity was regained,
          indicating that unfolded intermediates complexed with NUD-1 could be refolded.
      - reference_id: PMID:18626791
        supporting_text: >-
          NUD-1 also protects the native state of CS from thermal inactivation by
          significantly reducing the inactivation rate of this enzyme.
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IDA
  original_reference_id: PMID:18626791
  review:
    summary: >-
      IDA annotation for protein folding chaperone molecular function based on
      Faircloth et al. 2009 (PMID:18626791). The study directly demonstrated that
      NUD-1 possesses ATP-independent chaperone activity comparable to small heat
      shock proteins and cochaperones. NUD-1 prevents aggregation of denaturing
      citrate synthase and luciferase at stoichiometric concentrations, and maintains
      substrates in a refolding-competent state. This is a more informative molecular
      function annotation than GO:0051082 (unfolded protein binding), as it captures
      the active chaperone function.
    action: ACCEPT
    reason: >-
      GO:0044183 (protein folding chaperone) accurately describes the molecular
      function of NUD-1 as demonstrated by in vitro chaperone assays (PMID:18626791).
      The term captures the holdase activity, including prevention of aggregation and
      maintenance of refolding-competent intermediates. This is a well-supported
      core molecular function annotation.
    supported_by:
      - reference_id: PMID:18626791
        supporting_text: >-
          NUD-1 possesses ATP-independent chaperone activity comparable to that of small
          heat shock proteins and cochaperones and that changes in phosphorylation state
          functionally alter chaperone activity in a phosphomimetic NUD-1 mutant.
      - reference_id: PMID:18626791
        supporting_text: >-
          We demonstrate that nematode NUD-1 is able to prevent the aggregation of two
          substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric
          concentrations.
      - reference_id: file:worm/nud-1/nud-1-deep-research-falcon.md
        supporting_text: |-
          NUD-1 is described as a microtubule-associated protein with in vitro chaperone activity, preventing heat-induced aggregation of citrate synthase and luciferase
        reference_section_type: OTHER
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:18626791
  review:
    summary: >-
      IDA annotation for unfolded protein binding based on Faircloth et al. 2009
      (PMID:18626791). The study demonstrated that NUD-1 binds denaturing proteins
      (citrate synthase and luciferase) and prevents their aggregation. GO:0051082
      is proposed for obsoletion. The more informative annotation GO:0044183
      (protein folding chaperone) is already annotated with IDA evidence from the
      same publication, and GO:0140309 (unfolded protein carrier activity) would
      be the recommended replacement for the holdase function.
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. The holdase activity demonstrated in
      PMID:18626791 is not well captured by GO:0140309 (carrier-specific, per
      go-ontology#30552). GO:0044183 (protein folding chaperone) is already
      annotated from the same evidence. Retain until a holdase chaperone activity
      NTR is created.
    proposed_replacement_terms:
      - id: GO:0051082
        label: unfolded protein binding (retain until holdase NTR is created)
    supported_by:
      - reference_id: PMID:18626791
        supporting_text: >-
          We demonstrate that nematode NUD-1 is able to prevent the aggregation of two
          substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric
          concentrations.
- term:
    id: GO:0048489
    label: synaptic vesicle transport
  evidence_type: IMP
  original_reference_id: PMID:16996038
  review:
    summary: >-
      IMP annotation for involvement in synaptic vesicle transport based on Locke
      et al. 2006 (PMID:16996038). The study used fluorescent markers for synaptic
      vesicle trafficking and found that depletion of NUD-1 (along with other LIS1
      pathway components) resulted in defective GABA synaptic vesicle trafficking.
      This is consistent with NUD-1's role in dynein-dependent transport along
      microtubules.
    action: KEEP_AS_NON_CORE
    reason: >-
      The experimental evidence from PMID:16996038 supports involvement in synaptic
      vesicle transport, likely through NUD-1's role in the dynein motor complex and
      microtubule-based transport. However, this is a secondary consequence of NUD-1's
      core function in cytoskeletal dynamics rather than a specialized role in synaptic
      vesicle trafficking per se. Retained as non-core.
    supported_by:
      - reference_id: PMID:16996038
        supporting_text: >-
          We found that depletion of LIS1 pathway components resulted in defective GABA
          synaptic vesicle trafficking.
- term:
    id: GO:0051932
    label: synaptic transmission, GABAergic
  evidence_type: IGI
  original_reference_id: PMID:16996038
  review:
    summary: >-
      IGI annotation for involvement in GABAergic synaptic transmission based on
      Locke et al. 2006 (PMID:16996038). The study used genetic interaction
      experiments with LIS-1 pathway components (indicated by with/from
      WB:WBGene00003047) and pentylenetetrazole exposure to demonstrate that NUD-1
      depletion affects GABAergic neurotransmission, resulting in convulsion
      susceptibility.
    action: KEEP_AS_NON_CORE
    reason: >-
      The genetic interaction evidence supports a role in GABAergic synaptic
      transmission, likely secondary to NUD-1's role in microtubule-dependent
      transport of synaptic vesicles. This is a non-core function reflecting the
      downstream effects of disrupted cytoskeletal dynamics on neuronal function.
    supported_by:
      - reference_id: PMID:16996038
        supporting_text: >-
          Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5,
          and CDKA-1) exhibited significant convulsions following PTZ and RNAi
          treatment.
- term:
    id: GO:0040011
    label: locomotion
  evidence_type: IMP
  original_reference_id: PMID:11685578
  review:
    summary: >-
      IMP annotation for involvement in locomotion based on Dawe et al. 2001
      (PMID:11685578). RNAi knockdown of nud-1 resulted in uncoordinated movement,
      one of several pleiotropic phenotypes observed. This is a downstream consequence
      of NUD-1's role in neuronal development and function rather than a direct role
      in locomotion.
    action: KEEP_AS_NON_CORE
    reason: >-
      The uncoordinated movement phenotype from nud-1 RNAi (PMID:11685578) is a
      pleiotropic effect of disrupting this broadly required nuclear migration/
      cytoskeletal dynamics gene, not a specific role in locomotion. Retained as
      non-core.
    supported_by:
      - reference_id: PMID:11685578
        supporting_text: >-
          Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded
          similar phenotypes, including embryonic lethality, sterility, altered vulval
          morphology, and uncoordinated movement.
- term:
    id: GO:0040025
    label: vulval development
  evidence_type: IMP
  original_reference_id: PMID:11685578
  review:
    summary: >-
      IMP annotation for involvement in vulval development based on Dawe et al. 2001
      (PMID:11685578). RNAi knockdown of nud-1 resulted in altered vulval morphology.
      nud-1::GFP shows expression in the vulva, and vulval development requires
      proper cell division and nuclear migration, consistent with NUD-1's core
      function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Altered vulval morphology from nud-1 RNAi (PMID:11685578) is a pleiotropic
      phenotype consistent with disruption of nuclear migration and cell division
      in vulval precursor cells. nud-1::GFP is expressed in the vulva. Retained as
      non-core since vulval development is not the primary function of NUD-1.
    supported_by:
      - reference_id: PMID:11685578
        supporting_text: >-
          Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded
          similar phenotypes, including embryonic lethality, sterility, altered vulval
          morphology, and uncoordinated movement.
- term:
    id: GO:0009792
    label: embryo development ending in birth or egg hatching
  evidence_type: IMP
  original_reference_id: PMID:11685578
  review:
    summary: >-
      IMP annotation for involvement in embryo development based on Dawe et al. 2001
      (PMID:11685578). RNAi knockdown of nud-1 caused embryonic lethality and nuclear
      positioning defects in early embryonic cell division similar to dynein/dynactin
      depletion. This is a core biological process for NUD-1 given its essential role
      in nuclear migration during cell division.
    action: ACCEPT
    reason: >-
      Embryonic lethality from nud-1 RNAi represents a core phenotype (PMID:11685578).
      NUD-1 is essential for proper nuclear positioning during early embryonic cell
      division, and its requirement for embryo development is a direct consequence of
      its core function in nuclear migration and mitotic progression.
    supported_by:
      - reference_id: PMID:11685578
        supporting_text: >-
          Digital time-lapse video microscopy was used to determine that RNAi-treated
          embryos exhibited nuclear positioning defects in early embryonic cell division
          similar to those reported for dynein/dynactin depletion.
      - reference_id: file:worm/nud-1/nud-1-deep-research-falcon.md
        supporting_text: |-
          embryos usually arrested between comma and one-fold stages
        reference_section_type: OTHER
- term:
    id: GO:0035046
    label: pronuclear migration
  evidence_type: IMP
  original_reference_id: PMID:11685578
  review:
    summary: >-
      IMP annotation for involvement in pronuclear migration based on Dawe et al.
      2001 (PMID:11685578). RNAi knockdown of nud-1 caused nuclear positioning
      defects in early embryonic cell division. Pronuclear migration is a
      dynein-dependent process, and NUD-1 functions with the dynein motor complex.
      This is a core biological process directly reflecting NUD-1's primary
      molecular role in nuclear migration.
    action: ACCEPT
    reason: >-
      Pronuclear migration is a core function of NUD-1, directly reflecting its
      primary role in nuclear migration via the dynein motor complex. The nuclear
      positioning defects observed after nud-1 RNAi (PMID:11685578) are consistent
      with the conserved role of NudC family proteins in nuclear migration from
      fungi to humans. The gene name itself (nuclear distribution) reflects this
      function.
    supported_by:
      - reference_id: PMID:11685578
        supporting_text: >-
          Digital time-lapse video microscopy was used to determine that RNAi-treated
          embryos exhibited nuclear positioning defects in early embryonic cell division
          similar to those reported for dynein/dynactin depletion.
      - reference_id: PMID:11685578
        supporting_text: >-
          Heterologous expression of the C. elegans nudC ortholog, nud-1, complements
          the A. nidulans nudC3 mutant, demonstrating evolutionary conservation of
          function.
      - reference_id: file:worm/nud-1/nud-1-deep-research-falcon.md
        supporting_text: |-
          pronuclei moved inward but failed to rotate onto the anterior-posterior axis; nuclear envelope breakdown occurred on the dorsal-ventral axis
        reference_section_type: OTHER
- term:
    id: GO:0051932
    label: synaptic transmission, GABAergic
  evidence_type: IMP
  original_reference_id: PMID:16996038
  review:
    summary: >-
      IMP annotation for involvement in GABAergic synaptic transmission based on
      Locke et al. 2006 (PMID:16996038). NUD-1-depleted worms exhibited significant
      convulsions following PTZ treatment, and fluorescent markers showed defective
      GABA synaptic vesicle trafficking. This is a separate evidence line (IMP vs IGI)
      from the other GO:0051932 annotation for the same gene from the same paper.
    action: KEEP_AS_NON_CORE
    reason: >-
      This IMP annotation provides independent evidence from the IGI annotation for
      the same term. The convulsion susceptibility phenotype after NUD-1 depletion
      (PMID:16996038) supports involvement in GABAergic signaling, but this is a
      secondary function stemming from NUD-1's role in microtubule-based transport.
      Retained as non-core.
    supported_by:
      - reference_id: PMID:16996038
        supporting_text: >-
          Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5,
          and CDKA-1) exhibited significant convulsions following PTZ and RNAi
          treatment.
- term:
    id: GO:0000281
    label: mitotic cytokinesis
  evidence_type: IMP
  original_reference_id: PMID:12679384
  review:
    summary: |-
      NEW annotation proposed from Aumais et al. 2003 (PMID:12679384), which was not
      represented in the original GOA/UniProt set. RNAi gene silencing of nud-1 in
      C. elegans caused loss of midzone microtubules and rapid regression of the
      cleavage furrow, producing one-celled embryos containing two nuclei - a defining
      cytokinesis-failure phenotype. The falcon deep research synthesis further
      quantifies this (midzone microtubules absent in 26% and weak in 74% of one-cell
      embryos) and frames NUD-1 as required for late cytokinesis via midzone
      microtubule organization, mechanistically consistent with the conserved
      NudC-family role in midzone/midbody microtubule organization during cell division.
    action: NEW
    reason: |-
      Aumais et al. (PMID:12679384) provide direct experimental (RNAi) evidence in
      C. elegans that NUD-1 is required for completion of the first embryonic
      cytokinesis: its depletion blocks midzone microtubule formation and causes
      cleavage-furrow regression, yielding binucleate one-cell embryos. The phenotype
      occurs in the early embryonic mitotic division, so the directly-annotatable term
      GO:0000281 (mitotic cytokinesis) is appropriate. IMP with a verified primary PMID
      is a valid evidence/reference pairing for this RNAi loss-of-function phenotype.
      This complements the existing pronuclear-migration/nuclear-positioning annotations
      and captures the second worm-established arm of NUD-1 function.
    supported_by:
      - reference_id: PMID:12679384
        supporting_text: |-
          Gene silencing of nud-1, the Caenorhabditis elegans ortholog of NudC, led to a loss of midzone microtubules and the rapid regression of the cleavage furrow, which resulted in one-celled embryos containing two nuclei.
        reference_section_type: ABSTRACT
      - reference_id: file:worm/nud-1/nud-1-deep-research-falcon.md
        supporting_text: |-
          cleavage furrows stalled or regressed, producing multinucleated one-cell embryos
        reference_section_type: OTHER
      - reference_id: file:worm/nud-1/nud-1-deep-research-falcon.md
        supporting_text: |-
          Midzone microtubules were absent in 26% (10/39) of one-cell embryos and weak/poorly defined in 74% (29/39)
        reference_section_type: OTHER
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  findings: []
- id: PMID:11685578
  title: Evolutionarily conserved nuclear migration genes required for early embryonic
    development in Caenorhabditis elegans.
  findings:
    - statement: >-
        RNAi knockdown of nud-1 causes embryonic lethality, sterility, altered vulval
        morphology, uncoordinated movement, and nuclear positioning defects in early
        embryonic cell division similar to dynein/dynactin depletion.
      supporting_text: >-
        Phenotypic analysis of either nud-1 and lis-1 by RNA interference yielded
        similar phenotypes, including embryonic lethality, sterility, altered vulval
        morphology, and uncoordinated movement.
- id: PMID:16996038
  title: Genetic interactions among cortical malformation genes that influence susceptibility
    to convulsions in C. elegans.
  findings:
    - statement: >-
        Depletion of NUD-1 and other LIS1 pathway components caused defective GABA
        synaptic vesicle trafficking and significant convulsions following
        pentylenetetrazole treatment.
      supporting_text: >-
        Worms depleted for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5,
        and CDKA-1) exhibited significant convulsions following PTZ and RNAi
        treatment.
- id: PMID:18626791
  title: The microtubule-associated protein, NUD-1, exhibits chaperone activity in
    vitro.
  findings:
    - statement: >-
        Recombinant C. elegans NUD-1 prevents aggregation of citrate synthase and
        luciferase at stoichiometric concentrations, protects native CS from thermal
        inactivation, and maintains unfolded intermediates in a refolding-competent
        state. NUD-1 possesses ATP-independent chaperone activity comparable to
        small heat shock proteins.
      supporting_text: >-
        We demonstrate that nematode NUD-1 is able to prevent the aggregation of two
        substrate proteins, citrate synthase (CS) and luciferase, at stoichiometric
        concentrations.
- id: PMID:12679384
  title: Role for NudC, a dynein-associated nuclear movement protein, in mitosis and
    cytokinesis.
  findings:
    - statement: |-
        RNAi gene silencing of nud-1, the C. elegans ortholog of NudC, caused loss
        of midzone microtubules and rapid regression of the cleavage furrow, yielding
        one-celled embryos containing two nuclei - establishing a direct, worm-specific
        requirement for NUD-1 in midzone microtubule organization and completion of
        mitotic cytokinesis. In parallel mammalian cells, NudC depletion or
        overexpression caused multinucleation and disorganized midzone/midbody matrix
        and mislocalized polo-like kinase.
      supporting_text: |-
        Gene silencing of nud-1, the Caenorhabditis elegans ortholog of NudC, led to a loss of midzone microtubules and the rapid regression of the cleavage furrow, which resulted in one-celled embryos containing two nuclei.
      reference_section_type: ABSTRACT
- id: file:worm/nud-1/nud-1-deep-research-falcon.md
  title: Falcon deep research report on nud-1 (C. elegans)
  findings:
    - statement: |-
        The most defensible primary function of C. elegans NUD-1 is as an essential
        microtubule-based nuclear-positioning and cell-division factor acting in
        (i) pronuclear-centrosome rotation/positioning during the first embryonic
        division and (ii) midzone assembly and cleavage-furrow stabilization in
        cytokinesis. The nuclear-positioning phenotypes resemble dynein/dynactin
        perturbation, placing NUD-1 in the LIS-1/dynein nuclear-positioning pathway.
      supporting_text: |-
        essential microtubule-based cell division and nuclear-positioning factor
      reference_section_type: OTHER
    - statement: |-
        In nud-1(RNAi) embryos, pronuclei moved inward but failed to rotate onto the
        anterior-posterior axis and nuclear envelope breakdown occurred on the
        dorsal-ventral axis, consistent with a dynein-associated role in pronuclear
        rotation/nuclear positioning rather than in initiating spindle elongation.
      supporting_text: |-
        pronuclei moved inward but failed to rotate onto the anterior-posterior axis; nuclear envelope breakdown occurred on the dorsal-ventral axis
      reference_section_type: OTHER
    - statement: |-
        In nud-1 RNAi embryos, spindle elongation and pronuclear fusion proceeded but
        cleavage furrows stalled/regressed, producing multinucleated one-cell embryos;
        midzone microtubules were absent in 26% (10/39) and weak in 74% (29/39) of
        one-cell embryos, supporting a requirement for NUD-1 in late cytokinesis via
        midzone microtubule organization.
      supporting_text: |-
        Midzone microtubules were absent in 26% (10/39) of one-cell embryos and weak/poorly defined in 74% (29/39)
      reference_section_type: OTHER
    - statement: |-
        nud-1 is the C. elegans nudC ortholog (cosmid F53A2, ORF F53A2.4); full-length
        nud-1, and especially its C-terminal 173 aa, complements the A. nidulans nudC3
        mutant (47% identity / 67% similarity to A. nidulans NUDC), demonstrating deep
        functional conservation of the NudC family.
      supporting_text: |-
        Full-length `nud-1`, and especially its C-terminal 173 aa, complemented the *A. nidulans nudC3* mutant, restoring hyphal growth and nuclear migration
      reference_section_type: OTHER
    - statement: |-
        NudC-family proteins have an N-terminal coiled-coil plus a conserved CS domain
        (related to p23 and HSP20/sHSP chaperones) and can function as Hsp70/Hsp90
        co-chaperones that accelerate client transfer from Hsp70 to Hsp90. C. elegans
        NUD-1 specifically shows in vitro chaperone activity, preventing heat-induced
        aggregation of citrate synthase and luciferase. The co-chaperone/client biology
        is a family-level mechanistic model and is not directly demonstrated in vivo for
        the worm protein.
      supporting_text: |-
        NUD-1 is described as a microtubule-associated protein with in vitro chaperone activity, preventing heat-induced aggregation of citrate synthase and luciferase
      reference_section_type: OTHER
core_functions:
  - molecular_function:
      id: GO:0044183
      label: protein folding chaperone
    directly_involved_in:
      - id: GO:0006457
        label: protein folding
      - id: GO:0035046
        label: pronuclear migration
      - id: GO:0000281
        label: mitotic cytokinesis
      - id: GO:0009792
        label: embryo development ending in birth or egg hatching
    locations:
      - id: GO:0005737
        label: cytoplasm
    description: |-
      NUD-1 is a conserved cytoplasmic NudC-family protein whose most defensible
      worm-established role is as an essential microtubule-based nuclear-positioning
      and cell-division factor. In the early C. elegans embryo it is required for
      dynein-pathway pronuclear/centrosome rotation onto the anterior-posterior axis
      (PMID:11685578) and for completion of the first mitotic cytokinesis via midzone
      microtubule organization and cleavage-furrow stabilization (PMID:12679384). At
      the biochemical level it has demonstrated ATP-independent holdase chaperone
      activity, preventing aggregation of denaturing substrates (citrate synthase,
      luciferase) and maintaining them in a refolding-competent state (PMID:18626791);
      this CS (p23/HSP20-like) domain-mediated chaperone/co-chaperone activity provides
      a plausible mechanism for stabilizing the cytoskeletal regulators (e.g.
      dynein/LIS-1 pathway components) underlying its nuclear-positioning and cytokinesis
      functions, though the specific in vivo worm clients remain to be defined.

nud-1

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Functional annotation research report: Caenorhabditis elegans nud-1 (UniProt G5EE74; ORF F53A2.4)

0. Target identity verification (critical)

1. Key concepts and definitions (current understanding)

1.1 What is a NudC-family protein?

1.2 Domain architecture relevant to annotation of worm NUD-1

1.3 Chaperone/co-chaperone concept for NudC family

2. Worm-specific experimental evidence for nud-1 function

2.1 Expression and localization in the animal

2.2 Essential role in early embryonic nuclear positioning (dynein-like phenotype)

2.3 Role in cytokinesis via midzone microtubule organization

2.4 Organismal phenotypes and penetrance statistics

3. Mechanistic model and pathway placement

3.1 Placement in the LIS-1/dynein nuclear positioning pathway

3.2 Connection to midzone/midbody microtubule regulation (cell division)

3.3 Chaperone/co-chaperone model (family-based inference; not worm-proven in vivo)

4. Recent developments (prioritizing 2023–2024)

5. Current applications and real-world implementations

5.1 In C. elegans research (real-world use in cell biology)

5.2 Cross-species functional conservation as an implementation strategy

6. Expert opinions and analysis (authoritative synthesis)

7. Key statistics and data points (from recent and foundational studies)

8. Evidence summary table

9. Reference URLs (publication dates from retrieved metadata)

10. Limitations and gaps

Artifacts

Citations

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