Recombinant Human UNC5H1 Fc Chimera Protein, CF

UNC5H1, also known as UNC5A, is a member of the UNC5 (Drosophila uncoordinated-5 homology) family of type I transmembrane proteins within the immunoglobulin (Ig) superfamily. UNC5H1-4 (UNC5A-D, respectively) have two Ig and one or two thrombospondin type 1 (TSP1) domains in their extracellular regions, and a ZU-5 domain, a DCC (Deleted in Colorectal Cancer)-binding domain (DB) and a C-terminal death domain (DD) in their cytoplasmic regions (1, 2). Human UNC5H1 cDNA encodes 842 amino acids (aa) including a 25 aa signal peptide, a 281 aa extracellular domain with one TSP1 domain, and a 515 aa cytoplasmic domain. Within the extracellular domain, human UNC5A shares approximately 99%, 99%, 98%, 98%, 97% and 96% aa sequence identity with mouse, equine, rat, canine, bovine and porcine one-TSP1 isoforms of UNC5H1. UNC5 proteins are receptors for the netrin/UNC6 family of laminin-related secreted axon guidance cues; UNC5H1 has been shown to bind netrin 1, 3 and 4 (2 ‑ 4). Netrins can act as a chemoattractant for some axons in the presence of DCC (Deleted in Colorectal Cancer) proteins. However, UNC5H1 association with netrins changes them to chemorepellents (1, 5, 6). UNC5H1 is expressed after developmental migration of motor neurons, presumably halting their migration (7). UNC5H1 can be removed from the cell surface via endocytosis following phosphorylation by protein kinase C (PKC) in complex with PICK1. In turn, PKC activity is regulated by the neuronal G protein-coupled adenosine receptor A2b R (6, 8, 9). The UNC5 and DCC families also act as dependence receptors, and are pro-apoptotic in the absence of netrins (10 ‑ 13). UNC5H1 transcription is enhanced by the tumor suppressor p53, allowing increased apoptosis of tumor cells in the absence of netrin and the presence of NRAGE (13, 14).