NDEL1

NDEL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2V66
Identifiers
Aliases	NDEL1 , EOPA, MITAP1, NDE1L1, NDE2, NUDEL, nudE neurodevelopment protein 1 like 1
External IDs	OMIM: 607538; MGI: 1932915; HomoloGene: 32567; GeneCards: NDEL1; OMA:NDEL1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17p13.1 Start 8,413,131 bp [1] End 8,490,411 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 B3 Start 68,712,260 bp [2] End 68,762,684 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of leg secondary oocyte skin of abdomen blood right lung Achilles tendon bone marrow cells 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 BioGPS 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 Species Human Mouse Entrez 81565 83431 Ensembl ENSG00000166579 ENSMUSG00000018736 UniProt Q9GZM8 Q9ERR1 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 Mb Chr 11: 68.71 – 68.76 Mb PubMed search [3] [4]
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. ^{[5] [6] [7]}

It 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. ^[8] 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. ^{[9] [10] [11]} Nde1 and Ndel1 were in the past referred to as NudE and NudEL respectively. ^{[12] [13]} The Nde1 protein is involved in nuclear migration throughout the process of neurogenesis. ^[14] Studies have revealed that Ndel1 is structurally similar to Nde1 which both play a role in microtubule-based transport. ^[8] Ndel1 and Nde1 are also thought to be associated with neurodevelopmental and psychiatric disorders. ^{[14] [15]} 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. ^[16] 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. ^[16] 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. ^[13]

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

Other Interactions

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

References

1. GRCh38: Ensembl release 89: ENSG00000166579 – Ensembl, May 2017
2. 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. Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee MS, Morabito M, Tsai LH (Dec 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, Hirotsune S (Dec 2000). "A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system". Neuron. 28 (3): 681–96. doi: 10.1016/S0896-6273(00)00146-X . PMID   11163259. S2CID   17738599.
7. "Entrez Gene: NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1".
8. Garrott, Sharon R.; Gillies, John P.; Siva, Aravintha; Little, Saffron R.; El Jbeily, Rita; DeSantis, Morgan E. (June 2023). "Ndel1 disfavors dynein–dynactin–adaptor complex formation in two distinct ways". Journal of Biological Chemistry. 299 (6): 104735. doi: 10.1016/j.jbc.2023.104735 . ISSN   0021-9258. PMC   10248797 . PMID   37086789.
9. Sasaki, Shinji; Mori, Daisuke; Toyo-oka, Kazuhito; Chen, Amy; Garrett-Beal, Lisa; Muramatsu, Masami; Miyagawa, Shuji; Hiraiwa, Noriko; Yoshiki, Atsushi; Wynshaw-Boris, Anthony; Hirotsune, Shinji (2005-09-01). "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. ISSN   1098-5549. PMC   1190282 . PMID   16107726.
10. Shim, Su Yeon; Samuels, Benjamin Adam; Wang, Jian; Neumayer, Gernot; Belzil, Camille; Ayala, Ramses; Shi, Yang; Shi, Yujiang; Tsai, Li-Huei; Nguyen, Minh Dang (May 2008). "Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth". Journal of Biological Chemistry. 283 (18): 12232–12240. doi: 10.1074/jbc.m710200200 . ISSN   0021-9258. PMID   18303022.
11. Shu, Tianzhi; Ayala, Ramses; Nguyen, Minh-Dang; Xie, Zhigang; Gleeson, Joseph G.; Tsai, Li-Huei (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 . ISSN   0896-6273. PMID   15473966.
12. McKenney, Richard J.; Vershinin, Michael; Kunwar, Ambarish; Vallee, Richard B.; Gross, Steven P. (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. ISSN   0092-8674. PMC   2881166 . PMID   20403325.
13. Żyłkiewicz, Eliza; Kijańska, Monika; Choi, Won-Chan; Derewenda, Urszula; Derewenda, Zygmunt S.; Stukenberg, P. Todd (2011-01-31). "The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein". Journal of Cell Biology. 192 (3): 433–445. doi:10.1083/jcb.201011142. ISSN   1540-8140. PMC   3101096 . PMID   21282465.
14. Soto-Perez, Jaseph; Baumgartner, Marybeth; Kanadia, Rahul N. (2020). "Role of NDE1 in the Development and Evolution of the Gyrified Cortex". Frontiers in Neuroscience. 14. doi: 10.3389/fnins.2020.617513 . ISSN   1662-453X. PMC   7775536 . PMID   33390896.
15. Bradshaw, Nicholas J.; Hennah, William; Soares, Dinesh C. (2013-10-01). "NDE1 and NDEL1: twin neurodevelopmental proteins with similar 'nature' but different 'nurture'". BioMolecular Concepts. 4 (5): 447–464. doi:10.1515/bmc-2013-0023. ISSN   1868-503X. PMC   3787581 . PMID   24093049.
16. Derewenda, Urszula; Tarricone, Cataldo; Choi, Won Chan; Cooper, David R.; Lukasik, Steve; Perrina, Franco; Tripathy, Ashutosh; Kim, Myung Hee; Cafiso, David S.; Musacchio, Andrea; Derewenda, Zygmunt S. (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): 1467–1481. doi: 10.1016/j.str.2007.09.015 . ISSN   0969-2126. PMID   17997972.
17. Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A (Jul 2003). "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome". Nature Genetics. 34 (3): 274–85. doi:10.1038/ng1169. PMID   12796778. S2CID   10301633.
18. Morris JA, Kandpal G, Ma L, Austin CP (Jul 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): 1591–608. doi: 10.1093/hmg/ddg162 . PMID   12812986.
19. Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, Okawa M, Yamada N, Hatten ME, Snyder SH, Ross CA, Sawa A (Jan 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): 289–94. Bibcode:2003PNAS..100..289O. doi: 10.1073/pnas.0136913100 . PMC   140954 . PMID   12506198.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID   8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. 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, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (Mar 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): 3491–6. 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 (Dec 2000). "LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome". Neuron. 28 (3): 665–79. doi: 10.1016/S0896-6273(00)00145-8 . PMID   11163258. S2CID   15923472.
• Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, Okawa M, Yamada N, Hatten ME, Snyder SH, Ross CA, Sawa A (Jan 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): 289–94. Bibcode:2003PNAS..100..289O. doi: 10.1073/pnas.0136913100 . PMC   140954 . PMID   12506198.
• Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q, Zhu X (Feb 2003). "Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle". Molecular and Cellular Biology. 23 (4): 1239–50. 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, Martin CL, Allanson J, Pilz DT, Olney AH, Mutchinick OM, Hirotsune S, Wynshaw-Boris A, Dobyns WB, Ledbetter DH (Apr 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): 918–30. doi:10.1086/374320. PMC   1180354 . PMID   12621583.
• Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A (Jul 2003). "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome". Nature Genetics. 34 (3): 274–85. doi:10.1038/ng1169. PMID   12796778. S2CID   10301633.
• Morris JA, Kandpal G, Ma L, Austin CP (Jul 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): 1591–608. doi: 10.1093/hmg/ddg162 . PMID   12812986.
• Brandon NJ, Handford EJ, Schurov I, Rain JC, Pelling M, Duran-Jimeniz B, Camargo LM, Oliver KR, Beher D, Shearman MS, Whiting PJ (Jan 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, Zhu X (Feb 2004). "Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein". The Journal of Cell Biology. 164 (4): 557–66. doi:10.1083/jcb.200308058. PMC   2171987 . PMID   14970193.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (Sep 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC   515316 . PMID   15342556.
• Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim MH, Derewenda ZS, Knapp S, Tsai LH, Musacchio A (Dec 2004). "Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase". Neuron. 44 (5): 809–21. doi: 10.1016/j.neuron.2004.11.019 . PMID   15572112.
• Hayashi MA, Portaro FC, Bastos MF, Guerreiro JR, Oliveira V, Gorrão SS, Tambourgi DV, Sant'Anna OA, Whiting PJ, Camargo LM, Konno K, Brandon NJ, Camargo AC (Mar 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): 3828–33. 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, Hayashi MA (Jul 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.