Recombinant Human Semaphorin 6C Fc Chimera Protein, CF

Semaphorin 6C (Sema6C; previously Sema Y) is a 120 kDa member of the Semaphorin family of axon guidance molecules (1 ‑ 3). The four known Class 6 semaphorins are type I transmembrane glycoproteins that are most like Class 1 invertebrate semaphorins in structure, and exhibit neuropilin-independent binding to specific plexin A receptors (1 ‑ 3). Amino acid (aa) identity of Class 6 semaphorins is around 40% overall, but 53 - 64% within the Sema domain. Sema6C is expressed developmentally in subregions of the central and peripheral nervous systems, heart, and kidney, and primarily in skeletal muscle in adults (3, 4). Human Sema6C cDNA encodes 930 aa, including a 24 aa signal sequence, a 579 aa extracellular domain (ECD) including the Sema domain, a 21 aa transmembrane sequence and a 306 aa cytoplasmic portion. Alternate exon splicing creates a 922 aa short form (Sema6C.3) that is lacking aa 184 - 223 within the Sema domain, but contains 32 unique aa inserted after aa 586; postnatally, this form predominates in muscle (2, 3). A 962 aa form contains only the insert. The 930 aa “long form” predominates in brain, especially in areas of increased plasticity (4). Human Sema6C ECD shares 92%, 93%, 94%, 94%, 95% and 87% aa identity with corresponding mouse, rat, porcine, bovine, equine and canine sequences, respectively. Sema6C, along with Sema6D, is co-expressed with and binds to Plexin A1 (5). This interaction is thought to guide proprioceptive peripheral neurons by repulsion, excluding them from the superficial dorsal horn of the spinal cord (5). Sema6C is down‑regulated and redistributed following denervation or axotomy, potentially promoting regrowth (4, 6). In muscle, Sema6C is concentrated at neuromuscular junctions (6).