Recombinant Human Semaphorin 5B Fc Chimera Protein, CF

Semaphorin 5B (Sema5B, previously called SemG) is a ~150 kDa protein of the semaphorin family of axon guidance molecules (1, 2). Class 5 semaphorins are 1-pass transmembrane glycoproteins with an N-terminal Sema domain and multiple juxtamembrane type 1 thrombospondin (TSP) repeats within their extracellular domains (1, 2). Sema5B is expressed developmentally in the neuroepithelium along the anterior-posterior axis in a complimentary pattern with Sema5A (2, 3). It has been identified in oligodendrocytes and their precursors, neurons, dental mesenchyme and pre‑osteoblasts (1 ‑ 6). Sema5B expression may be up‑regulated in cancer cells such as renal carcinoma clear cells, where blocking Sema5B expression attenuates viability (7). The human Sema5B cDNA encodes a 1151 amino acid (aa) type III transmembrane protein with a 1036 aa extracellular domain (ECD), a 21 aa transmembrane sequence and a 94 aa cytoplasmic portion. Within aa 78 ‑ 834, which includes the sema domain and two of the five TSP repeats, human Sema5B shares 94 ‑ 95% aa identity with corresponding mouse, rat, equine and bovine sequences. An alternate start site at aa 59 and two splicing variations in the cytoplasmic domain may create isoforms of 1093, 1092 or 1130 aa, respectively (7, 8). In the hippocampus, either full-length or proteolytically created secreted Sema5B mediates neuronal synapse elimination (6). In the cortex, Sema5B appears to be inhibitory to cortical axons, but not to dorsal thalamic axons, indicating a role in corticothalamic axon guidance during development (3). Sema5B promotes the influx of extracellular calcium, which is necessary to induce neuronal growth cone collapse (9). Semaphorins typically transduce signals through transmembrane plexins, but additional molecules, such as heparin sulfate or chondroitin sulfate proteoglycans which bind TSP repeats on the class 5 family member Sema5A, can mediate midbrain axon attraction or repulsion (10).