NELL2
Protein kinase C-binding protein NELL2 is a secreted glycoprotein that in humans is encoded by the NELL2 gene. It is a homolog of Nel, which is a gene present in the neural tissues of chickens. 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.
| NELL2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | NELL2, NRP2, neural EGFL like 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602320; MGI: 1858510; HomoloGene: 4488; GeneCards: NELL2; OMA:NELL2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Protein kinase C-binding protein NELL2 is a secreted glycoprotein that in humans is encoded by the NELL2 gene.[5] It is a homolog of Nel, which is a gene present in the neural tissues of chickens.[6]
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.[5]
Function
[edit]NELL2 has been implicated to be involved in a variety of different functions including neuronal development, sperm maturation, cancer progression and bone development.[7][8][9][10]
NELL2 has been shown to have roles in neuronal polarization and axon growth.[11] NELL2 is a negative regulator of axon guidance in the SLIT-ROBO signalling pathway where it binds with the ROBO3/Rig-1 receptor.[12] It can also bind with ROBO2 under acidic conditions, where ROBO2 undergoes proteolytic cleavage.[8]
NELL2 expression has been linked to higher survival rates for female lung adenocarcinoma patients.[13]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000184613 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022454 – 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.
- ^ a b "Entrez Gene: NELL2 NEL-like 2 (chicken)".
- ^ Watanabe, Takeshi K.; Katagiri, Toyomasa; Suzuki, Mikio; Shimizu, Fumio; Fujiwara, Tsutomu; Kanemoto, Naohide; Nakamura, Yusuke; Hirai, Yoshikatsu; Maekawa, Hiroumi; Takahashi, Ei-ichi (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.
- ^ 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) 167777. doi:10.1016/j.jmb.2022.167777. ISSN 0022-2836.
- ^ a b 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". Journal of Biological Chemistry. 294 (12): 4693–4703. doi:10.1074/jbc.RA118.005819. ISSN 0021-9258. PMC 6433047. PMID 30700556.
- ^ Yuan, Hairui; Wang, Xinyu; Du, Shuanglin; Li, Mengyue; Zhu, Endong; Zhou, Jie; Dong, Yuan; Wang, Shuang; Shan, Liying; Liu, Qian; Wang, Baoli (2025-04-11). "NELL2, a novel osteoinductive factor, regulates osteoblast differentiation and bone homeostasis through fibronectin 1/integrin-mediated FAK/AKT signaling". Bone Research. 13 (1): 46. doi:10.1038/s41413-025-00420-5. ISSN 2095-6231. PMC 11986068. PMID 40210857.
- ^ Kiyozumi, Daiji; Noda, Taichi; Yamaguchi, Ryo; Tobita, Tomohiro; Matsumura, Takafumi; Shimada, Kentaro; Kodani, Mayo; Kohda, Takashi; Fujihara, Yoshitaka; Ozawa, Manabu; Yu, Zhifeng; Miklossy, Gabriella; Bohren, Kurt M.; Horie, Masato; Okabe, Masaru (2020-06-05). "NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility". Science. 368 (6495): 1132–1135. Bibcode:2020Sci...368.1132K. doi:10.1126/science.aay5134. PMC 7396227. PMID 32499443.
- ^ Kim, Han Rae; Kim, Dong Hee; An, Ji Young; Kang, Dasol; Park, Jeong Woo; Hwang, Eun Mi; Seo, Eun Jin; Jang, Il Ho; Ha, Chang Man; Lee, Byung Ju (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. PMC 7332358. 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.
- ^ "Research update from the MCM team (October 2025)". World Community Grid. 28 October 2025. Retrieved 29 October 2025.
Further reading
[edit]- Watanabe TK, Katagiri T, Suzuki M, et al. (1997). "Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) encoding proteins with six EGF-like repeats". Genomics. 38 (3): 273–6. doi:10.1006/geno.1996.0628. PMID 8975702.
- Beckmann G, Hanke J, Bork P, Reich JG (1998). "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. doi:10.1006/jmbi.1997.1510. PMID 9480764.
- Luce MJ, Burrows PD (1999). "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. doi:10.1016/S0378-1119(99)00093-1. PMID 10231576.
- Kuroda S, Oyasu M, Kawakami M, et al. (1999). "Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2". Biochem. Biophys. Res. Commun. 265 (1): 79–86. Bibcode:1999BBRC..265...79K. doi:10.1006/bbrc.1999.1638. PMID 10548494.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
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