Ask about this productRelated genes to: NUDCD3 Blocking Peptide
- Gene:
- NUDCD3 NIH gene
- Name:
- NudC domain containing 3
- Previous symbol:
- -
- Synonyms:
- KIAA1068, NudCL
- Chromosome:
- 7p13
- Locus Type:
- gene with protein product
- Date approved:
- 2005-02-07
- Date modifiied:
- 2016-10-05
Related products to: NUDCD3 Blocking Peptide
Related articles to: NUDCD3 Blocking Peptide
- V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical non-homologous end-joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEI), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase (RAG1, RAG2, and the recently identified RAG co-chaperone NudC domain-containing 3, NUDCD3), end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development. - Source: PubMed
Publication date: 2026/03/28
Schim van der Loeff InaAhuja ManishaChen RuiPatane EleonoraHambleton Sophie - Gigaxonin is an intermediate filament (IF)-interacting partner belonging to the Kelch-like (KLHL) protein family. Gigaxonin is encoded by the KLHL16 gene, which is mutated in Giant Axonal Neuropathy (GAN). The lack of functional gigaxonin in GAN patient cells impairs IF proteostasis by affecting IF protein degradation and transport. This leads to focal abnormal accumulations of IFs and compromised cellular function, with neurons being most severely impacted. We hypothesized that gigaxonin forms molecular interactions via specific sequence motifs to regulate IF proteostasis. The goal of this study was to examine how distinct Kelch motifs on gigaxonin regulate IF protein degradation and filament morphology. We analyzed vimentin IFs in HEK293 cells overexpressing wild type (WT) gigaxonin, or gigaxonin lacking each of the six individual Kelch motifs, K1-K6. All six gigaxonin deletion mutants (ΔK1-ΔK6) promoted the degradation of soluble vimentin. Compared to WT-gigaxonin, ΔK3-gigaxonin exhibited increased soluble vimentin degradation and increased presence of thick bundles of vimentin IFs. The ΔK4 mutant showed similar, but milder phenotypes compared to ΔK3. Using mass spectrometry proteomics we found that, relative to WT gigaxonin, ΔK3 gigaxonin had increased associations with ubiquitination-associated and mitochondrial proteins but lost the association with the NudC domain-containing protein 3 (NUDCD3), a molecular chaperone enriched in the nervous system. AlphaFold modeling revealed loss of gigaxonin-NUDCD3 binding with ΔK3 and altered binding with ΔK4. Collectively, our cell biological data show the induction of an abnormal GAN-like IF phenotype in cells expressing ΔK3- and, to a lesser extent, ΔK4-gigaxonin, while our proteomic profiling links the loss of gigaxonin-NUDCD3 interactions with defective IF proteostasis. - Source: PubMed
Publication date: 2025/07/15
Phillips Cassandra LSo ChristinaGillis Meredith FHarrison JonathanHsu Chih-HsuanArmao DianeSnider Natasha T - Gigaxonin is an intermediate filament (IF)-interacting partner belonging to the Kelch-like (KLHL) protein family. Gigaxonin is encoded by the gene, which is mutated in Giant Axonal Neuropathy (GAN). The lack of functional gigaxonin in GAN patient cells impairs IF proteostasis, leading to focal abnormal accumulations of IFs and compromised neuronal function. We hypothesized that gigaxonin forms molecular interactions via specific sequence motifs to regulate IF proteostasis. The goal of this study was to examine how distinct Kelch motifs on gigaxonin regulate IF protein degradation and filament morphology. We analyzed vimentin IFs in HEK293 cells overexpressing wild type (WT) gigaxonin, or gigaxonin lacking each of the six individual Kelch motifs: K1 (aa274-326), K2 (aa327-374), K3 (aa376-421), K4 (aa422-468), K5 (aa470-522), and K6 (aa528-574). All six gigaxonin deletion mutants (ΔK1-ΔK6) promoted the degradation of soluble vimentin. The ΔK3 gigaxonin mutant exhibited soluble vimentin degradation and promoted the bundling of vimentin IFs relative to WT gigaxonin. Using mass spectrometry proteomic analysis we found that, relative to WT gigaxonin, ΔK3 gigaxonin had increased associations with ubiquitination-associated and mitochondrial proteins and lost the association with the NudC domain-containing protein 3 (NUDCD3), a molecular chaperone enriched in the nervous system. Collectively, our cell biological data show the induction of an abnormal GAN-like IF phenotype in cells expressing ΔK3-gigaxonin, while our mass spectrometry profiling links the loss of gigaxonin-NUDCD3 interactions with defective IF proteostasis, revealing NUDCD3 as a potential new target in GAN. - Source: PubMed
Publication date: 2025/03/13
Phillips Cassandra LSo ChristinaGillis Meredith FHarrison JonathanHsu Chih-HsuanArmao DianeSnider Natasha T - Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 () Two infants had severe combined immunodeficiency with the complete absence of T and B cells (TB SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans. - Source: PubMed
Publication date: 2024/05/24
Chen RuiLukianova ElenaSchim van der Loeff InaSpegarova Jarmila StremenovaWillet Joseph D PJames Kieran DRyder Edward JGriffin HelenIJspeert HannaGajbhiye AkshadaLamoliatte FredericMarin-Rubio Jose LWoodbine LisaLemos HenriqueSwan David JPintar ValeriaSayes KamalRuiz-Morales Elias REastham SimonDixon DavidPrete MartinPrigmore ElenaJeggo PennyBoyes JoanMellor AndrewHuang Leivan der Burg MirjamEngelhardt Karin RStray-Pedersen AsbjørgErichsen Hans ChristianGennery Andrew RTrost MatthiasAdams David JAnderson GrahamLorenc AnnaTrynka GosiaHambleton Sophie - The sea cucumber, , is one of the most valuable aquatic species. The color of body wall and appearance are important for the value of sea cucumbers. To examine expression pattern of (), (), and (), previously reported as differently expressed genes during the pigmentation of sea cucumber, we analyzed the temporal profiles of , , and mRNAs in LED-exposed and light-shielded . Real-time quantitative PCR revealed that the , , and mRNAs from the juveniles at 40-60 days post-fertilization (dpf) exhibited increasing patterns as compared to those of an early developmental larva (6-dpf). At 60-dpf juveniles, the and mRNA levels of LED-exposed individuals were higher than those of light-shielded ones, whereas at 40-dpf and 50-dpf juveniles, the mRNA expression was higher in the light-shielded condition (<0.05). In the pigmented juveniles (90-dpf), the and mRNA levels tended to show higher levels in red individuals than those in green ones, but there was a conversely higher level of mRNA in green larva. examination of and mRNAs in light-shielded 6-dpf larva revealed that both genes are mainly expressed in the internal organs compared to the body surface. Together, these results may provide insights into the differential gene expression of , , and during pigmentation process of the sea cucumber. - Source: PubMed
Publication date: 2023/06/30
Kim SehwanLee SeungheonKim Gil JungSohn Young Chang