Entry into the ER requires a signal peptide

MRNAs that encode secreted proteins encode a 5’ signal sequence (SS) fused in frame to the sequence encoding the mature secretory protein: this signal sequence encodes an N-terminal signal peptide (SP). It seems that SPs are free to evolve rapidly, as long as they retain their overall features: a +ve charge towards the N’ terminus and a hydrophobic stretch. Do not bind the ER membrane directly: because the SP is recognised by signal recognition particle (SRP) in the cytosol – and this targets the SP to the translocon.