Qinghaienin, a novel anticoagulation protein from the hard tick Haemaphysalis qinghaiensis, inhibits the activation of factor XII by competing for anionic surfaces.

Salivary proteins of ticks can inhibit host hemostatic and inflammatory responses during the blood-sucking process of the parasites. A cDNA sequence, Hq021, was identified from a cDNA library of Haemaphysalis qinghaiensis. Hq021 encodes a mature protein containing 182 amino acids with a molecular mass of 20.5 kDa. The protein is rich in basic amino acids (lysine and arginine) at its C-terminus. Identification of no homologous proteins in databases suggested its novelty. A recombinant protein expressed with the cDNA in Escherichia coli could prolong the activated partial thromboplastin time (aPTT) of human plasma. We designated this basic tail-protein as Qinghaienin. Although Qinghaienin did not inhibit the amidolytic activities of some coagulation factors, it dose-dependently inhibited the generation of FXIIa, FXIa and kallikrein in plasma in the presence of silica-based aPTT reagent. By competing with FXII for the negatively-charged binding sites, Qinghaienin inhibited the activation of the zymogen and the coagulation processes. These findings suggest that Qinghaienin plays a critical role in both anticoagulation and anti-inflammatory processes during tick feeding and could serve as a potential candidate for the developing tick-derived anticoagulants.