Recombinant Human Semaphorin 4G Fc Chimera Protein, CF

Semaphorin 4G (Sema4G) is the least characterized of the seven known Class 4 transmembrane semaphorin glycoproteins (1). Class 4 semaphorins have multiple roles in cell attraction or repulsion. These include development of nerve pathways in the brain, promoting or inhibiting proliferation, and in some cases organizing immune cell interactions. Receptors include transmembrane plexins, but alternate receptors, such as CD72 for Sema4D and TIM-2 for Sema4A, have been identified (2, 3). The 838 amino acid (aa) human Sema4G precursor contains a 17 aa signal sequence, a 658 aa extracellular domain (ECD) containing sema and C2-type immunoglobulin domains, a 21 aa transmembrane domain, and a 142 aa cytoplasmic domain with one Ser/Thr phosphorylation site (4). The human Sema4G ECD shares 90%, 92%, 93%, 93% and 92% aa identity with mouse, rat, equine, bovine and canine Sema4G, respectively. It also shares 42% aa identity with Sema4C, the most closely related semaphorin. Two additional isoforms have been reported: an 843 aa form contains a 5 aa insert at aa 542, while a 458 aa form diverges at aa 450 near the end of the Sema domain (5). Sema4G mRNA is expressed early in development in the central and peripheral nervous systems and in sensory organs such as retina, cochlea, vomeronasal organ and olfactory epithelium. In adults, Sema4G mRNA is found in predominantly in the liver, but is also detected in the kidneys and brain. Elevated Sema4G mRNA expression was found in mouse kidney during Plasmodium yoelii infection (6). Sema4G was also identified in a screen for genes that are downregulated in human colorectal cancer (7).