Biology:NELL2
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Protein kinase C-binding protein NELL2 is a secreted glycoprotein that in humans is encoded by the NELL2 gene.[1] It is a homolog of Nel, which is a gene present in the neural tissues of chickens.[2]
This gene encodes a cytoplasmic protein that contains six epidermal growth factor (EGF) -like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. An alternative splice variant has been described but its full length sequence has not been determined.[1]
Function
NELL2 has been implicated to be involved in a variety of different functions including neuronal development, sperm maturation, cancer progression and bone development.[3][4][5][6]
NELL2 has been shown to have roles in neuronal polarization and axon growth.[7] NELL2 is a negative regulator of axon guidance in the SLIT-ROBO signalling pathway where it binds with the ROBO3/Rig-1 receptor.[8] It can also bind with ROBO2 under acidic conditions, where ROBO2 undergoes proteolytic cleavage.[4]
NELL2 expression has been linked to higher survival rates for female lung adenocarcinoma patients.[9]
References
- ↑ 1.0 1.1 "Entrez Gene: NELL2 NEL-like 2 (chicken)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=4753.
- ↑ Watanabe, Takeshi K.; Katagiri, Toyomasa; Suzuki, Mikio; Shimizu, Fumio; Fujiwara, Tsutomu; Kanemoto, Naohide; Nakamura, Yusuke; Hirai, Yoshikatsu et al. (1996-12-15). "Cloning and Characterization of Two Novel Human cDNAs (NELL1 and NELL2) Encoding Proteins with Six EGF-like Repeats". Genomics 38 (3): 273–276. doi:10.1006/geno.1996.0628. ISSN 0888-7543. https://www.sciencedirect.com/science/article/pii/S088875439690628X.
- ↑ Miyaguchi, Masaki; Nakanishi, Yoichi; Maturana, Andrés D.; Mizutani, Kimihiko; Niimi, Tomoaki (2022-10-15). "Conformational Change of the Hairpin-like-structured Robo2 Ectodomain Allows NELL1/2 Binding". Journal of Molecular Biology 434 (19). doi:10.1016/j.jmb.2022.167777. ISSN 0022-2836. https://www.sciencedirect.com/science/article/pii/S0022283622003795.
- ↑ 4.0 4.1 Yamamoto, Naoka; Kashiwagi, Manabu; Ishihara, Manami; Kojima, Takaaki; Maturana, Andrés D.; Kuroda, Shun'ichi; Niimi, Tomoaki (2019-03-22). "Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2" (in English). Journal of Biological Chemistry 294 (12): 4693–4703. doi:10.1074/jbc.RA118.005819. ISSN 0021-9258. PMID 30700556.
- ↑ Yuan, Hairui; Wang, Xinyu; Du, Shuanglin; Li, Mengyue; Zhu, Endong; Zhou, Jie; Dong, Yuan; Wang, Shuang et al. (2025-04-11). "NELL2, a novel osteoinductive factor, regulates osteoblast differentiation and bone homeostasis through fibronectin 1/integrin-mediated FAK/AKT signaling" (in en). Bone Research 13 (1): 46. doi:10.1038/s41413-025-00420-5. ISSN 2095-6231. PMID 40210857.
- ↑ Kiyozumi, Daiji; Noda, Taichi; Yamaguchi, Ryo; Tobita, Tomohiro; Matsumura, Takafumi; Shimada, Kentaro; Kodani, Mayo; Kohda, Takashi et al. (2020-06-05). "NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility". Science 368 (6495): 1132–1135. doi:10.1126/science.aay5134. PMID 32499443. Bibcode: 2020Sci...368.1132K.
- ↑ Kim, Han Rae; Kim, Dong Hee; An, Ji Young; Kang, Dasol; Park, Jeong Woo; Hwang, Eun Mi; Seo, Eun Jin; Jang, Il Ho et al. (2020-06-30). "NELL2 Function in Axon Development of Hippocampal Neurons". Molecules and Cells 43 (6): 581–589. doi:10.14348/molcells.2020.0032. ISSN 0219-1032. PMID 32597395.
- ↑ Jaworski, Alexander; Tom, Irene; Tong, Raymond K.; Gildea, Holly K.; Koch, Alexander W.; Gonzalez, Lino C.; Tessier-Lavigne, Marc (2015-11-20). "Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2". Science 350 (6263): 961–965. doi:10.1126/science.aad2615. https://www.science.org/doi/10.1126/science.aad2615.
- ↑ "Research update from the MCM team (October 2025)". World Community Grid. 28 October 2025. https://www.worldcommunitygrid.org/about_us/article.s?articleId=827.
Further reading
- "Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) encoding proteins with six EGF-like repeats.". Genomics 38 (3): 273–6. 1997. doi:10.1006/geno.1996.0628. PMID 8975702.
- "Merging extracellular domains: fold prediction for laminin G-like and amino-terminal thrombospondin-like modules based on homology to pentraxins.". J. Mol. Biol. 275 (5): 725–30. 1998. doi:10.1006/jmbi.1997.1510. PMID 9480764.
- "The neuronal EGF-related genes NELL1 and NELL2 are expressed in hemopoietic cells and developmentally regulated in the B lineage.". Gene 231 (1–2): 121–6. 1999. doi:10.1016/S0378-1119(99)00093-1. PMID 10231576.
- "Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2". Biochem. Biophys. Res. Commun. 265 (1): 79–86. 1999. doi:10.1006/bbrc.1999.1638. PMID 10548494. Bibcode: 1999BBRC..265...79K.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–24. 2005. doi:10.1110/ps.04682504. PMID 15340161.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
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