Annexin A4 inhibits sulfatide-induced activation of coagulation factor XII.

CONCLUSIONS: We found that ANXA3, ANXA4, and ANXA5 strongly inhibited sulfatide-induced plasma coagulation. Wild-type and mutated ANXA4 were used to clarify the molecular mechanism involved in inhibition. ANXA4 inhibited sulfatide-induced auto-activation of FXII to FXIIa and the conversion of its natural substrate FXI to FXIa but showed no effect on the protease activity of FXIIa or FXIa. Alanine scanning showed that substitution of the Ca2+ -binding amino acid residue in the fourth fold of the core domain of ANXA4 reduced anticoagulant activity, and deletion of the entire fourth fold of the core domain resulted in complete loss of anticoagulant activity.
PMID: 32145147 [PubMed - as supplied by publisher]

Source: Thrombosis and Haemostasis - March 6, 2020 Category: Hematology Authors: Nakayama M, Miyagawa H, Kuranami Y, Tsunooka-Ota M, Yamaguchi Y, Kojima-Aikawa K Tags: J Thromb Haemost Source Type: research