Effects of protein S and protein S-C4BP on APC-mediated proteolysis of factor Va at R306 and R506. Both protein S and protein S-C4BP are cofactors for APC that stimulate APC-mediated proteolysis at R306 in factor Va 18-fold and 11-fold, respectively. While protein S has no effect on APC-mediated inactivation at R506 in factor Va, the protein S-C4BP complex specifically inhibits APC-mediated cleavage at R506 3- to 4-fold.