Importance of individual residues in hydrophobic patch PLVIVGL (1481-1487) in FV-Short for synergistic TFPIα-cofactor activity with protein S, an alanine-scanning study. AlphaFold-mediated prediction of FV-Short/TFPIα/protein S tri-molecular complex structure.

In the splice variant Factor V-Short, 702 residues are deleted from the B domain, resulting in exposure of an acid region (AR2; 1493-1537) that binds TFPIα. FV-Short and protein S serve as synergistic TFPIα cofactors in inhibition of FXa. In the preAR2 region, a hydrophobic patch PLVIVGL (1481-1487) is crucial for synergistic TFPIα-cofactor activity and assembly of FV-Short, TFPIα and protein S.