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Protein kinase C-binding protein NELL2 is a secreted glycoprotein that in humans is encoded by the NELL2gene.[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]
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]
↑Watanabe TK, Katagiri T, Suzuki M, Shimizu F, Fujiwara T, Kanemoto N, etal. (December 1996). "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. PMID8975702.
↑Miyaguchi M, Nakanishi Y, Maturana AD, Mizutani K, Niimi T (October 2022). "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. PMID35940226.
↑Jaworski A, Tom I, Tong RK, Gildea HK, Koch AW, Gonzalez LC, etal. (November 2015). "Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2". Science. 350 (6263). New York, N.Y.: 961–965. doi:10.1126/science.aad2615. PMID26586761.
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". Journal of Molecular Biology. 275 (5): 725–730. doi:10.1006/jmbi.1997.1510. PMID9480764.
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): 121–126. doi:10.1016/S0378-1119(99)00093-1. PMID10231576.
Kuroda S, Oyasu M, Kawakami M, Kanayama N, Tanizawa K, Saito N, etal. (November 1999). "Biochemical characterization and expression analysis of neural thrombospondin-1-like proteins NELL1 and NELL2". Biochemical and Biophysical Research Communications. 265 (1): 79–86. Bibcode:1999BBRC..265...79K. doi:10.1006/bbrc.1999.1638. PMID10548494.
