All signal peptidases described so far are serine proteases. The active site that endoproteolytically cleaves signal peptides from translocated precursor proteins is located at the extracytoplasmic site of the membrane. The eukaryotic signal peptidase is an integral membrane protein complex. The first subunit, which was identified by yeast genetics is Sec11, a 17 kDa membrane protein that is associated with three subunits termed Spc3p (21 kDa), Spc2p (18 kDa) and Spc1p (11 kDa). Sec11 is the only essential factor for signal peptide processing as can be deduced from a growth defect upon its deletion. The functional signal peptidase complex was first purified from a canine ER membrane fraction. The five mammalian subunits are named SPC12, SPC18, SPC21, SPC22/23 and SPC25 according to their molecular weight.