Thyroglobulin (Tg) is a large glycoprotein specific to the thyroid gland and is the precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The N-terminal section of Tg contains 10 repeats of a domain of about 65 amino acids which is known as the Tg type-1 repeat [3595599, 8797845]. Such a domain has also been found as a single or repeated sequence in the HLA class II associated invariant chain ; human pancreatic carcinoma marker proteins GA733-1 and GA733-2 ; nidogen (entactin), a sulphated glycoprotein which is widely distributed in basement membranes and that is tightly associated with laminin; insulin-like growth factor binding proteins (IGFBP) ; saxiphilin, a transferrin-like protein from Rana catesbeiana (Bull frog) that binds specifically to the neurotoxin saxitoxin ; chum salmon egg cysteine proteinase inhibitor, and equistatin, a thiol-protease inhibitor from Actinia equina (sea anemone) . The existence of Thyr-1 domains in such a wide variety of proteins raises questions about their activity and function, and their interactions with neighbouring domains. The Thyr-1 and related domains belong to MEROPS proteinase inhibitor family I31, clan IX.
Equistatin from A. equina is composed of three Thyr-1 domains; as with other proteins that contains Thyr-1 domains, the thyropins, they bind reversibly and tightly to cysteine proteases (inhibitor family C1). In equistatin inhibition of papain is a function of domain-1. Unusually domain-2 inhibits cathepsin D, an aspartic protease (inhibitor family A1) and has no activity against papain. Domain-3, does not inhibit either papain or cathepsin D, and its function or its target peptidase has yet to be determined [9153250, 12650938].