NELL1 (neural EGF-like like protein 1) is an 89 kDa (predicted) member of the EGF-like domain containing family, Laminin G/N-TSP1/Pentraxin gene superfamily of molecules. When secreted, NELL1 exists as a phosphoglycoprotein that can add as much as 50 kDa to the calculated MW. NELL1 has restricted expression, being limited to pre-B cells and osteoblasts, where it apparently promotes osteoblast maturation and bone formation. In tumors, it is found in neuroblastoma-derived cells. NELL1 is both secreted and retained intracellularly where it is phosphorylated by PKC. The mouse NELL1 precursor is 810 amino acids (aa) in length. It contains a 16 aa signal sequence plus a 794 aa mature region. The mature region possesses an N-terminal TSP domain (aa 81-230), two VWFC domains (aa 271-390), six consecutive EGF-like domains (aa 391-631), and three additional C-terminal VWFC domains (aa 632-807). Secreted NELL1 forms a 400-420 kDa noncovalent homotrimer. Over aa #17-810, mouse NELL1 shares 98% and 93% aa identity with rat and human NELL1, respectively.
