SPINT1, also known as HAI-1, is a membrane-bound multidomain protein that is subsequently released from cell surface by shedding []. It contains a MANEC (motif at N terminus with eight cysteines) PAN/apple-like domain (MANEC or N), an internal PKD-like domain (I), a Kunitz domain 1 (K1), a low-density lipoprotein receptor class A (LDLRA) domain (L), and a Kunitz domain 2 (K2) followed by a C-terminal single-span transmembrane region [, ]. It is required for epithelial integrity of the zebrafish epidermis []. In mammals, it is essential to the integrity of the basement membrane during placental development and is involved in maintaining postnatal tissue homeostasis []. It has been demonstrated to inhibit a number of serine proteases, including matriptase, HGFA, hepsin, trypsin, and prostasin. The structure of HAI-1 has been revealed [].
