Recombinant Human Semaphorin 3C Fc Chimera Protein, CF

Semaphorin 3C (Sema3C; previously SemaE) is one of six Class 3 secreted semaphorins which share 40 - 50% amino acid (aa) identity among themselves. Class 3 semaphorins are potent chemorepellents that function in axon and/or vascular guidance during development, and may be upregulated in tumor progression (1, 2). The 751 aa human Sema3C is highly modular. It contains a 20 aa signal sequence, an ~500 aa N-terminal Sema domain that forms a beta -propeller structure similar to that found in integrin molecules, a cysteine knot, a furin-type cleavage site, an Ig-like domain, and a C-terminal basic domain (1 - 3). Covalent dimerization plus cleavage at the C-terminus are required for activity of class 3 semaphorins (4). Human Sema3C shares at least 95% aa identity with mouse, rat, bovine and canine Sema3C, and 89% and 75% aa identity with chick and zebrafish Sema3C, respectively. Type 3 semaphorins transduce signals through transmembrane plexins, either directly, or by binding associated neuropilin receptors (1, 2). Sema3C signaling is transduced by Plexin-D1 indirectly via Neuropilin 1 or Neuropilin 2 (5). Sema3C is expressed in all somitic motor neurons, in lung buds, and in cardiac neural crest cells during development (1, 5 - 8). Sema3C activates integrins in certain cells, so in addition to its repulsive activities, it sometimes acts as a chemoattractant (6, 9). In the developing nervous system, this chemoattraction appears to complement Sema3A repulsion in adjacent cell layers (1, 6, 7). Sema3C also provides an attractive force opposing Sema6A and Sema6B to guide migration of neural crest endothelial cells to the cardiac outflow tract (10). Consequently, defects in aortic arch formation occur when Sema3C or Plexin D1 genes or Sema3C neuropilin interactions are disrupted (5, 11, 12).