Protease, factor vii activating

In 1996, a so-called "plasmahyaluron-binding serine protease" was isolated for the first time, which is encoded on the X chromosome in humans. This factor has a high homology with the "hepatocyte growth factor activator".
The molecular weight is 64 kD. Only later was its biological function recognised. It was possible to sequence two main fragments, a heavy chain with 45 kD and a light chain with 28 kD. FSAP is activated by cleavage of the FSAP peptide chain, whereby the molecule is split into the light and heavy chain.

Romisch was able to show that FSAP can activate factor VII without the tissue factor. Further analyses showed that FSAP has other activities as well: The factor VII activating protease activates the urokinase and the tissue plasminogen activator (t-PA) by splitting into the active form. In addition, it was shown that FSAP binds to the extracellular matrix and participates in the interaction with fibrinogen and fibronectin. One inhibitor of FSAP is the C1 esterase inhibitor, which forms a complex with FSAP that can be detected in plasma.

The F-VII activating protease is activated by glucosamine glycans such as heparin or dextran sulphate. Nazakawa and his research group were able to show that extracellular RNA is an important cofactor for the activation of FSAP. The activation of FSAP is in turn antagonised by RNA-ase-A. Furthermore, they were able to show that different forms of natural RNA such as rRNA, tRNA and viral RNA can activate FSAP.
It could be shown that a specific binding between FSAP and RNA, but not to DNA, is possible. The effect of RNA as a cofactor is only effective in the area of tissue damage. Thus, a new coagulation-activating mechanism was discovered through the FSAP-RNA system.

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin S. 58f.