Cleavage of a tail‐anchored protein by signal peptidase

Tail‐anchored proteins are post‐translationally targeted and inserted into the endoplasmic reticulum membrane. They do not use the co‐translational signal‐recognition particle (SRP)‐dependent pathway, but rather utilize an ill‐defined, ATP‐dependent mechanism. Here, we show that a tail‐anchored protein can be cleaved by signal peptidase and that the sequence requirements for efficient cleavage seem to be the same as for cleavage of co‐translationally targeted SRP‐dependent proteins.