Semaphorins are a large and diverse family of proteins, widely expressed across divergent animal phyla, divided into eight classes (1-7 and V) which are structurally and functionally conserved. These proteins are critical in neural development and adult brain plasticity being involved in axon guidance, neural connectivity, angiogenesis, immunoregulation, and also in cancer [, , ].This entry represents the C-terminal domain of the transmembrane Semaphorin 4F (Sema4F, also known as Semaphorin-W), which plays a role in visual system development and in oligodendrocyte precursor migration and differentiation. Like other Semaphorin 4 members, it includes a Ig-like domain, adjacent the PSI domain (plexin-semaphorin-integrin domain, conserved across all semaphorins) [], a transmembrane region and a short intracellular tail. The latter is rich in proline residues similar to other transmembrane semaphorins suggesting that it may interact with cytoskeletal or signalling proteins. It also contains a cyclic nucleotide-dependent protein kinase phosphorylation site, involved in signal transduction into the cell. Sema4F is found in glutamatergic synapses, preferentially in postsynaptic dendrites, attached to SAP90/PSD-95-scaffolding protein. Sema4F interacts with SAP90/PSD-95 PDZ domains through the critical last three C-terminal amino acids [, ].
