Human Semaphorin 6B Biotinylated Antibody

Semaphorin 6B (Sema6B) is a 120 kDa member of the Semaphorin family of axon guidance molecules (1‑4). The four known Class 6 semaphorins are type I transmembrane glycoproteins with Sema domains but without other domains, making them most like Class 1 invertebrate semaphorins in structure (1‑4). Amino acid (aa) identity of Class 6 semaphorins is around 40% overall, but 53‑64% within the Sema domain. Sema6B is expressed developmentally in subregions of the nervous system and muscle, and at low levels in most adult tissues (3, 4). Human Sema6B cDNA encodes a 25 aa signal sequence, a 579 aa extracellular domain (ECD) including the Sema domain, a 20 aa transmembrane sequence and a 263 aa cytoplasmic portion. A cytoplasmic proline-rich sequence interacts with the SH3 domain of the c-src signaling protein (4). Full-length Sema6B is thought to form disulfide-linked homodimers (4). Alternate exon splicing creates a 492 aa (presumably) secreted form (Sema6B.1), and a 657 aa form with a shortened cytoplasmic tail (Sema6B.2) (3). Human Sema6B ECD shows 94%, 94%, 96% and 89% aa identity with corresponding mouse, rat, bovine and canine sequences, respectively. Crystal structures of semaphorins reveal that the 500 aa Sema domain forms an integrin-like seven-blade beta-propeller structure stabilized by 14 conserved cysteine residues (5). Sema6B is highly expressed in some glioblastoma and breast cancer cell lines. All-trans retinoic acid slows cancer cell growth and down‑regulates Sema6B expression, probably via dimerization with peroxisome proliferator-activated receptors (PPAR) that have a response element on the Sema6B gene (3, 6, 7). Semaphorins transduce signals through transmembrane plexins, either directly, or by binding associated neuropilin receptors. Plexin-A4 binds Sema6A (high affinity) and 6B (low affinity) and mediates sympathetic ganglion axon-repulsion, independent of neuropilin-1 (8).