Processing of C-terminal lysine and arginine residues of proteins isolated from mammalian cell culture.

C-terminal Lys or Arg residues whose presence was expected based on gene sequence information are often absent in proteins isolated from mammalian cell culture. This discrepancy is believed to be due to the activity of one or more basic carboxypeptidases. Internal Arg/Lys residues that become C-terminal upon proteolysis or zymogen activation, such as in the two-chain form of tissue plasminogen activator, may also be removed from the mature protein. Charge heterogeneity results when this type of processing is incomplete; such heterogeneity can be detected by isoelectric focusing or ion-exchange chromatography. The absence of C-terminal basic residues is not usually a regulatory concern, as plasma-derived proteins are often similarly processed.