• Purity

  >95%, by SDS-PAGE with silver staining

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by the ability of the immobilized protein to support the adhesion of C3H10T1/2 mouse embryonic fibroblast cells. The ED    ₅₀ for this effect is 1‑4 μg/mL.

• Source

  Chinese Hamster Ovary cell line, CHO-derived Arg17-Asn810, with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Arg17 (33%) & Phe22 (66%)

• Predicted Molecular Mass

  88.6 kDa & 88.1 kDa

• SDS-PAGE

  100-130 kDa, reducing conditions

Background: NELL1

NELL1 (neural EGF‑like like protein 1) is an approximately 140 kDa modular glycoprotein that plays an important role in bone physiology (1). NELL1 contains an N‑terminal Laminin G‑like domain and three vWF‑C domains interspersed with five tandem EGF‑like domains (2). Mature human NELL1 shares 93% aa identity with mouse and rat NELL1. Alternative splicing of human NELL1 generates a short isoform that lacks the fourth EGF‑like domain. NELL1 can be retained in the cytosol where it interacts with ARP3 (apoptosis‑related protein 3) and becomes phosphorylated by PKC (3, 4). NELL1 is secreted as an approximately 400 kDa noncovalent homotrimer of heavily glycosylated subunits (5). It is expressed in bone and in select B cell lines (6, 7). NELL1 promotes the osteogenic differentiation of adipose‑derived stromal/stem cells and inhibits adipogenic differentiation (8). It does not promote osteoblastic differentiation from myoblasts, but it does enhance the activity of BMP‑2 in that function (9). NELL1 interacts directly with osteoblasts   via Integrin alpha 3 beta 1 (10, 11) and promotes osteoblast differentiation and mineralization (3, 12, 13). It synergizes with BMP‑2 to increase phosphate uptake through the transporters Pit1 and Pit2 in pre‑osteoblasts (14).   In vivo, NELL1 expression in the cranium is localized at sites of suture closure (6). Its over‑expression induces multiple abnormalities in cranial development including premature suture closure (craniosyntosis) and overlapping sutures (12, 13). Experimental engrafting demonstrates the ability of NELL1 to promote new bone formation and the healing of calvarial defects (13, 15).

• References:

1. Zhang, X. et al. (2010) J. Dent. Res. 89:865.

2. Watanabe, T.K. et al. (1996) Genomics 38:273.

3. Zou, X. et al. (2011) FEBS Lett. 585:2410.

4. Kuroda, S. and K. Tanizawa (1999) Biochem. Biophys. Res. Commun. 265:752.

5. Kuroda, S. et al. (1999) Biochem. Biophys. Res. Commun. 265:79.

6. Ting, K. et al. (1999) J. Bone Miner. Res. 14:80.

7. Luce, M.J. and P.D. Burrows (1999) Gene 231:121.

8. James, A.W. et al. (2012) Stem Cells Dev. 21:2170.

9. Cowan, C.M. et al. (2007) J. Bone Miner. Res. 22:918.

10. Hasebe, A. et al. (2012) FEBS Lett. 586:2500.

11. Shen, J. et al. (2012) J. Cell. Biochem. 113:3620.

12. Zhang, X. et al. (2002) J. Clin. Invest. 110:861.

13. Aghaloo, T. et al. (2006) Am. J. Pathol. 169:903.

14. Cowan, C.M. et al. (2012) Biochem. Biophys. Res. Commun. 422:351.

15. Xue, J. et al. (2011) Bone 48:485.

• Long Name:

  NEL-like 1

• Entrez Gene IDs:

  4745 (Human); 338352 (Mouse)

• Alternate Names:

  FLJ45906; IDH3GL; nel (chicken)-like 1; NELL1; NEL-like 1 (chicken); NEL-like protein 1; Nel-related protein 1; neural epidermal growth factor-like 1; NRP1; protein kinase C-binding protein NELL1