Classical serine proteases use the conserved Ser/His/Asp catalytic triad to hydrolyze
substrates. Here, we show that longistatin, a salivary gland protein with two EF-hand
domains from the vector tick Haemaphysalis longicornis, does not have the conserved
catalytic triad, but still functions as a serine protease. Longistatin was synthesized in and
secreted from the salivary glands of ticks, and is injected into host tissues during the
acquisition of blood-meals. Longistatin hydrolyzed fibrinogen, an essential plasma protein in …