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// Workers AI · dad joke modeWhat did NDEL1 gene say? I'm a little "undecided".

From Wikipedia, the free encyclopedia

NDEL1
Identifiers
AliasesNDEL1, EOPA, MITAP1, NDE1L1, NDE2, NUDEL, nudE neurodevelopment protein 1 like 1
External IDsOMIM: 607538; MGI: 1932915; HomoloGene: 32567; GeneCards: NDEL1; OMA:NDEL1 - orthologs
Available structures
PDBOrtholog search: PDBe RCSB
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001025579
NM_030808
NM_001330129

NM_023668
NM_001363304
NM_001363305

RefSeq (protein)

NP_001020750
NP_001317058
NP_110435

NP_076157
NP_001350233
NP_001350234

Location (UCSC)Chr 17: 8.41 – 8.49 MbChr 11: 68.71 – 68.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Nuclear distribution protein nudE-like 1 is a protein that in humans is encoded by the NDEL1 gene.[5][6][7]

Gene

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Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[7]

Structure

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Secondary structure of Ndel1 is composed of various distinct domains: a C-terminal region, and a 200 amino acid N-terminal coiled-coil domain. The coiled-coil domain of Ndel1 serves as a self-associating stable parallel homodimer.[8] Such structural components help with interactions between an array of binding partners, including the motor protein dynein and its cofactor protein, Lis1. Ndel1 forms a heterotetramer complex with Lis1 via the N-terminal coiled-coil domain.[8] The Ndel1 N-terminal coiled-coil domain mediates binding to dynein, whereas the C-terminal domain interacts with Lis1, regulating the activity of the dynein complex.[9]

Function

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NDEL1 plays a significant role in intracellular transport and the process of cellular division via regulation of the dynein motor protein and its cofactor protein, Lis1.[10] Ndel1 is a highly conserved protein and its human gene, NDEL1 is expressed in a wide variety of brain tissues which contributes to neuronal function and development.[11][12][13] Nde1 and Ndel1 were in the past referred to as NudE and NudEL respectively.[14][9] The Nde1 protein is involved in nuclear migration throughout the process of neurogenesis.[15] Studies have revealed that Ndel1 is structurally similar to Nde1 which both play a role in microtubule-based transport.[10] Ndel1 and Nde1 are also thought to be associated with neurodevelopmental and psychiatric disorders.[15][16]

This gene product is a thiol-activated oligopeptidase and is also known as Endooligopeptidase A in that context. It is phosphorylated in M phase of the cell cycle. Phosphorylation regulates the cell cycle-dependent distribution of this protein, with a fraction of the protein bound strongly to centrosomes in interphase and localized to mitotic spindles in early M phase. Overall, this protein plays a role in nervous system development.[7]

Other interactions

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NDEL1 has been shown to interact with Cyclin-dependent kinase 5,[5] YWHAE,[17] PAFAH1B1[5][17] and DISC1.[18][19]

References

[edit]
  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000166579 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018736 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee MS, et al. (December 2000). "NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein". Neuron. 28 (3): 697–711. doi:10.1016/S0896-6273(00)00147-1. PMID 11163260. S2CID 11154069.
  6. Sasaki S, Shionoya A, Ishida M, Gambello MJ, Yingling J, Wynshaw-Boris A, et al. (December 2000). "A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system". Neuron. 28 (3): 681–696. doi:10.1016/S0896-6273(00)00146-X. PMID 11163259. S2CID 17738599.
  7. 1 2 3 "Entrez Gene: NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1".
  8. 1 2 Derewenda U, Tarricone C, Choi WC, Cooper DR, Lukasik S, Perrina F, et al. (November 2007). "The structure of the coiled-coil domain of Ndel1 and the basis of its interaction with Lis1, the causal protein of Miller-Dieker lissencephaly". Structure. 15 (11). London: 1467–1481. doi:10.1016/j.str.2007.09.015. PMID 17997972.
  9. 1 2 Zyłkiewicz E, Kijańska M, Choi WC, Derewenda U, Derewenda ZS, Stukenberg PT (February 2011). "The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein". The Journal of Cell Biology. 192 (3): 433–445. doi:10.1083/jcb.201011142. PMC 3101096. PMID 21282465.
  10. 1 2 Garrott SR, Gillies JP, Siva A, Little SR, El Jbeily R, DeSantis ME (June 2023). "Ndel1 disfavors dynein-dynactin-adaptor complex formation in two distinct ways". The Journal of Biological Chemistry. 299 (6) 104735. doi:10.1016/j.jbc.2023.104735. PMC 10248797. PMID 37086789.
  11. Sasaki S, Mori D, Toyo-oka K, Chen A, Garrett-Beal L, Muramatsu M, et al. (September 2005). "Complete loss of Ndel1 results in neuronal migration defects and early embryonic lethality". Molecular and Cellular Biology. 25 (17): 7812–7827. doi:10.1128/MCB.25.17.7812-7827.2005. PMC 1190282. PMID 16107726.
  12. Shim SY, Samuels BA, Wang J, Neumayer G, Belzil C, Ayala R, et al. (May 2008). "Ndel1 controls the dynein-mediated transport of vimentin during neurite outgrowth". The Journal of Biological Chemistry. 283 (18): 12232–12240. doi:10.1074/jbc.m710200200. PMID 18303022.
  13. Shu T, Ayala R, Nguyen MD, Xie Z, Gleeson JG, Tsai LH (October 2004). "Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate cortical neuronal positioning". Neuron. 44 (2): 263–277. doi:10.1016/j.neuron.2004.09.030. PMID 15473966.
  14. McKenney RJ, Vershinin M, Kunwar A, Vallee RB, Gross SP (April 2010). "LIS1 and NudE induce a persistent dynein force-producing state". Cell. 141 (2): 304–314. doi:10.1016/j.cell.2010.02.035. PMC 2881166. PMID 20403325.
  15. 1 2 Soto-Perez J, Baumgartner M, Kanadia RN (2020). "Role of NDE1 in the Development and Evolution of the Gyrified Cortex". Frontiers in Neuroscience. 14 617513. doi:10.3389/fnins.2020.617513. PMC 7775536. PMID 33390896.
  16. Bradshaw NJ, Hennah W, Soares DC (October 2013). "NDE1 and NDEL1: twin neurodevelopmental proteins with similar 'nature' but different 'nurture'". Biomolecular Concepts. 4 (5): 447–464. doi:10.1515/bmc-2013-0023. PMC 3787581. PMID 24093049.
  17. 1 2 Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, et al. (July 2003). "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome". Nature Genetics. 34 (3): 274–285. doi:10.1038/ng1169. PMID 12796778. S2CID 10301633.
  18. Morris JA, Kandpal G, Ma L, Austin CP (July 2003). "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation". Human Molecular Genetics. 12 (13): 1591–1608. doi:10.1093/hmg/ddg162. PMID 12812986.
  19. Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, et al. (January 2003). "Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth". Proceedings of the National Academy of Sciences of the United States of America. 100 (1): 289–294. Bibcode:2003PNAS..100..289O. doi:10.1073/pnas.0136913100. PMC 140954. PMID 12506198.

Further reading

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