This entry represents a C-terminal domain of approximately 60 residues found in NELL1 and NELL2 (NEL-like proteins) in vertebrates. This domain is located after the VWC domains () and multiple EGF-like domains (). NELL proteins are secreted glycoproteins that form homotrimers and function as PKC-binding proteins. NELL1 promotes osteoblast differentiation while NELL2 functions in axon guidance through binding to ROBO3 receptor.
This family represents the NELL (neural EGFL-like) family of proteins, which includes protein kinase C-binding proteins NELL1 and NELL2. Members of this family are large glycoproteins that form homotrimers and interact with protein kinase C [, ]. NELL1 plays a role in the control of cell growth and differentiation, specifically promoting osteoblast cell differentiation and terminal mineralization [, ]. NELL2 plays multiple roles in neural tissues, regulating neuronal proliferation, survival, differentiation, polarization, and axon guidance [, , ]. NELL2 functions as a repulsive axon guidance cue by binding to the ROBO3 receptor [, ]. Furthermore, NELL2 is secreted in the epididymis and signals through the ROS1 receptor tyrosine kinase pathway to regulate sperm maturation and male fertility [, , , ]. Structurally, NELL proteins typically consist of an N-terminal thrombospondin-like domain, several von Willebrand factor type C domains, and multiple epidermal growth factor-like domains.
This entry represents the heparin-binding and cell adhesion domain of thrombospondin and related proteins such as protein kinase C-binding protein NELL1 and NELL2, and collagen alpha.Thrombospondins (TSPs) are secreted, calcium-binding glycoproteins that play an essential role in regulating cell-cell and cell-matrix interactions. They are divided into trimeric subgroup A (TSP-1 and TSP-2) and pentameric subgroup B (TSP-3-5). The actions of TSPs depend on their binding partners in a given environment. The N-terminal domain of TSPs plays an integral role in the interaction of TSPs with other secreted and transmembrane proteins, and proteoglycans. This domain folds into a ��-sandwich typical for concanavalin A-like lectins/glucanases superfamily () [, ].
