Fig. 4.

Scheme of the generalized workflow of labeling approaches for the identification of substrates of proteases. A, B: proteins; C, D: proteolysis products of the protein A. a, b, c, d: Peptides resulting from enzymatic digestion of the proteins A, B, C, D. Label I (black dots, heavy label) and label II (open circles, light label) belong to the same group of label reagents (e.g., ICAT, ITRAQ or SILAC) but differ in their molecular masses because of the application of stable isotopes (ICAT, SILAC), or in the case of ITRAQ because of the integration of reporter groups, which differ in their molecular masses because of their different chemical compositions. MS, mass spectrometry; MS/MS, tandem mass spectrometry