HAI-1

HAI1 is a Kunitz-type serine protease inhibitor, identified as a strong inhibitor of HGF activator (HGFA) and matriptase. The membrane anchored HAI1 consists of two Kunitz domains, a LDL receptorlike domain, and a C-terminal transmembrane domain. Two soluble forms are generated by ectodomain shedding, one with a single Kunitz domain and the other with two Kunitz domains. HAI1 is not only an inhibitor but also a specific receptor of active HGFA, acting as a reservoir of this enzyme on the cell surface . The shedding of HAI1 and HGFA/HAI1 complex is enhanced by treatment with phorbol 12-myristate 13-acetate or IL1β. The regulated shedding is completely inhibited by a synthetic zinc metalloprotease inhibitor.