Screening of enzymes for cleavage of chem163S. (A) Separation of cleavage products of 10 μM chem163S after 30 minutes of incubation with 100 nM of the labeled proteases by SDS-PAGE followed by silver staining. Molecular weight markers are shown on the left. (B-D). Mass spectrometric analysis of input protein chem163S (B) and reaction mixtures of FXIa (C) and plasmin (D) described in panel A. (E) FXIa cleavage sequences. Alignments extracted from the MEROPS database⁵⁶  show the cleavage sites for FXIa marked within the chemerin C-terminal sequence with chemerin forms indicated (chem163S), β-2 glycoprotein 1 (β-2 GP),⁵⁷  FX, FXI, and FXII, the 2 FXIa cleavage sites in FIX and hepatocyte growth factor (HGF),^57,58  the 3 FXIa cleavage sites in FV and tissue factor pathway inhibitor (TFPI),⁵⁹  the 4 FXIa cleavage sites in FVIII, and the binding site from the FXIa inhibitor, protease nexin-2 (PN-2).⁶⁰  The basic amino acid at P1 is red and the black arrow indicates the FXIa cleavage site.