Protein secretion signal-peptide peptidase

The signal hypothesis postulates the existence of several proteins necessary for secretion. These include the components of the SRP, which is proposed to bind to the signal sequence and block further translation of the mRNA coding for the mature protein SRP receptor, or docking protein, which relieves the translation block imposed by the SRP ribophorins, which bind the ribosome to the ER membrane signal peptidase and signal-peptide peptidase, discussed above and other proteins, which form a pore or transport apparatus in the membrane. Some of these proteins, the SRP, SRP receptor, signal peptidase, and ribophorins, have been isolated from eukaryotic cell extracts and characterized. 

In addition to the destructive proteolysis processes in the proteasome and lysosome, many constructive proteolysis processes occur in cells. In both prokaryotes and eukaryotes, secreted proteins contain a signal peptide at the N-terminus that directs them to the secretary pathway. This signal peptide must be cleaved later by signal peptidases (typically serine proteases)... 

Factor XII is a secreted protein and would be expected to contain a signal peptide which functions in transport of the protein across the rough endoplasmic reticulum membrane (76). The cDNA sequence predicts that factor XII is synthesized as a precursor containing an amino-terminal extension of at least 19 amino acid residues. Cleavage of a Ser-Ile bond in the precursor would give rise to plasma factor XII. This bond cleavage is consistent with the specificity of signal peptidase (77). 

This enzyme [EC 3.4.21.89], also known as signal peptidase I and phage-procoat-leader peptidase, catalyzes the hydrolysis of N-terminal leader sequences from secreted and periplasmic protein precursors. It acts on a single bond Ala-Ala in the m-13 phage procoat protein and creates the signal (leader) peptide and coat protein. It is a member of the peptidase family S26 but is unaffected by inhibitors of most serine peptidases. 

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