The cystatin superfamily consists of a large group of cystatin domain-containing proteins, most of which are reversible and tight-binding inhibitors of the papain (C1) and legumain (C13) families of cysteine proteases [1,E1]. Kininogens are multifunctional and multidomain glycoproteins related to cystatins. Kininogens ubiquitously exist in vertebrates, including mammals, birds, amphibians, and fishes. They vary extremely in both structure and function among different taxa of animals, in particular between mammals and amphibians. Kininogens contain a bradykinin domain and one (in lampreys), two (in fishes) or three (in mammals, birds, and amphibians) cystatin domain(s). Although mammalian kininogens harbor three cystatin domains only two of them are tight-binding inhibitors of cysteine cathepsins, which belong to the papain-like cysteine proteases. A Q-x-V-x-G motif is the canonical binding site for cysteine proteinases in mammals [2,3,4].

The profile we developed cover the entire kininogen-type cystatin domain.