Post‑Targeting Functions of Signal Peptides
Katja Kapp, Sabrina Schrempf, Marius K. Lemberg and Bernhard Dobberstein
Signal sequences are N‑terminal extensions of newly synthesized secretory and membrane proteins. They are usually 16 to 30 amino acid residues in length and comprised of a hydrophilic, usually positively charged N‑terminal region, a central hydrophobic domain and a C‑terminal region with the cleavage site for signal peptidase. Besides these common characteristics, signal sequences do not share sequence similarity and some are more than 50 amino acid residues long. In eukaryotes, signal sequences direct the insertion of proteins into the membrane of the endoplasmic reticulum and are usually cleaved off by signal peptidase. The resulting signal peptides are presumably rapidly degraded, but some still have functions on their own. Here, we describe examples of post-targeting functions of membrane‑integral signal peptides, of signal peptides released from the membrane into either the cytosol or endoplasmic reticulum lumen and of signal peptide fragments generated by intramembrane cleavage. Thus, signal peptides must be considered as an additional resource in the context of the function of secretory and membrane proteins.