NDEL1

NDEL1
Identifiers
Aliases	NDEL1, EOPA, MITAP1, NDE1L1, NDE2, NUDEL, nudE neurodevelopment protein 1 like 1
External IDs	OMIM: 607538; MGI: 1932915; GeneCards: NDEL1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2V66
Gene location (Human)
Chr.	Chromosome 17 (human)
End	8,490,411 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	68,762,684 bp
RNA expression pattern
	Top expressed in
	skin of leg; ; secondary oocyte; ; skin of abdomen; ; blood; ; right lung; ; Achilles tendon; ; bone marrow cell; ; ascending aorta; ; epithelium of colon; ; Descending thoracic aorta;
	Top expressed in
	seminal vesicula; ; molar; ; granulocyte; ; calvaria; ; lip; ; vastus lateralis muscle; ; esophagus; ; triceps brachii muscle; ; skin of external ear; ; sternocleidomastoid muscle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	alpha-tubulin binding; protein binding; beta-tubulin binding; oligopeptidase activity; microtubule binding; identical protein binding; protein-containing complex binding;
Cellular component	cytoplasm; cell body; neurofilament cytoskeleton; nuclear envelope; synaptic vesicle; spindle; chromosome; microtubule organizing center; microtubule associated complex; axon; cell leading edge; axon hillock; microtubule; chromosome, centromeric region; cytoskeleton; kinetochore; axon cytoplasm; cytosol; central region of growth cone; centrosome; kinesin complex;
Biological process	retrograde axonal transport; cell differentiation; activation of GTPase activity; chromosome segregation; neuron migration; positive regulation of axon regeneration; nervous system development; proteolysis; neuron projection extension; inner cell mass cell proliferation; multicellular organism development; regulation of intracellular protein transport; positive regulation of GTPase activity; nuclear membrane disassembly; positive regulation of axon extension; neurofilament cytoskeleton organization; cerebral cortex radially oriented cell migration; neuron projection development; microtubule cytoskeleton organization; central nervous system neuron axonogenesis; insulin receptor signaling pathway; establishment of mitotic spindle orientation; microtubule nucleation; mitotic centrosome separation; regulation of neuron projection development; cell migration; vesicle transport along microtubule; establishment of chromosome localization; centrosome localization; lysosome localization; positive regulation of ruffle assembly;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	81565
	83431
	ENSG00000166579
	ENSMUSG00000018736
	Q9GZM8
	Q9ERR1
	NM_001025579; NM_030808; NM_001330129
	NM_023668; NM_001363304; NM_001363305
	NP_001020750; NP_001317058; NP_110435
	NP_076157; NP_001350233; NP_001350234
	Wikidata
View/Edit Human	View/Edit Mouse

Nuclear distribution protein nudE-like 1 is a protein that in humans is encoded by the NDEL1 gene.

Gene

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

Structure

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. 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. 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.

Function

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. 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. Nde1 and Ndel1 were in the past referred to as NudE and NudEL respectively. The Nde1 protein is involved in nuclear migration throughout the process of neurogenesis. Studies have revealed that Ndel1 is structurally similar to Nde1 which both play a role in microtubule-based transport. Ndel1 and Nde1 are also thought to be associated with neurodevelopmental and psychiatric disorders.

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.

Other interactions

NDEL1 has been shown to interact with Cyclin-dependent kinase 5, YWHAE, PAFAH1B1 and DISC1.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000166579 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018736 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
↑ 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.
1 2 3 "Entrez Gene: NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1".
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.
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.
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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
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.
↑ 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.
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.
↑ 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.
↑ 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.

Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–358. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, et al. (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–3496. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
Feng Y, Olson EC, Stukenberg PT, Flanagan LA, Kirschner MW, Walsh CA (December 2000). "LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome". Neuron. 28 (3): 665–679. doi:10.1016/S0896-6273(00)00145-8. PMID 11163258. S2CID 15923472.
Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q, et al. (February 2003). "Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle". Molecular and Cellular Biology. 23 (4): 1239–1250. doi:10.1128/MCB.23.4.1239-1250.2003. PMC 141156. PMID 12556484.
Cardoso C, Leventer RJ, Ward HL, Toyo-Oka K, Chung J, Gross A, et al. (April 2003). "Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3". American Journal of Human Genetics. 72 (4): 918–930. doi:10.1086/374320. PMC 1180354. PMID 12621583.
Brandon NJ, Handford EJ, Schurov I, Rain JC, Pelling M, Duran-Jimeniz B, et al. (January 2004). "Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders". Molecular and Cellular Neurosciences. 25 (1): 42–55. doi:10.1016/j.mcn.2003.09.009. PMID 14962739. S2CID 21261573.
Liang Y, Yu W, Li Y, Yang Z, Yan X, Huang Q, et al. (February 2004). "Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein". The Journal of Cell Biology. 164 (4): 557–566. doi:10.1083/jcb.200308058. PMC 2171987. PMID 14970193.
Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (September 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–1718. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim MH, Derewenda ZS, et al. (December 2004). "Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase". Neuron. 44 (5): 809–821. doi:10.1016/j.neuron.2004.11.019. PMID 15572112.
Hayashi MA, Portaro FC, Bastos MF, Guerreiro JR, Oliveira V, Gorrão SS, et al. (March 2005). "Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity by disrupted-in-schizophrenia 1". Proceedings of the National Academy of Sciences of the United States of America. 102 (10): 3828–3833. Bibcode:2005PNAS..102.3828H. doi:10.1073/pnas.0500330102. PMC 553309. PMID 15728732.
Guerreiro JR, Winnischofer SM, Bastos MF, Portaro FC, Sogayar MC, de Camargo AC, et al. (July 2005). "Cloning and characterization of the human and rabbit NUDEL-oligopeptidase promoters and their negative regulation". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1730 (1): 77–84. doi:10.1016/j.bbaexp.2005.06.001. PMID 16005531.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000166579 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[Niethammer_2000-5] 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.

[Sasaki_2000-6] 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.

[entrez-7] 1 2 3 "Entrez Gene: NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1".

[Derewenda_2007-8] 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.

[Zyłkiewicz_2011-9] 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.

[Garrott_2023-10] 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.

[Soto-Perez_2020-15] 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.

[Toyo-oka_2003-17] 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.

[Morris_2003-18] 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.

[Ozeki_2003-19] 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.