Proteinase inhibitor I4, leuserpin 2 <p>Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties. </p><p>The members of this family are serpins (SERine Protease INhibitors) belonging to MEROPS inhibitor family I4, clan ID; they are active against serine proteinases of the S1 family (<db_xref db="INTERPRO" dbkey="IPR001254"/>, <db_xref db="INTERPRO" dbkey="IPR003966"/>) [<cite idref="PUB00014133"/>]. They include heparin cofactor II (HCII), alpha-1-antichymotrypsin, protein Z-dependent protease inhibitor, corticosteroid-binding globulin and thyroxin-binding globulin. Thyroxin-binding globulin and corticosteroid-binding globulin are non-inhibitory homologues that function as a hormone carriers [<cite idref="PUB00000298"/>, <cite idref="PUB00011889"/>].</p><p>Leuserpin 2 is a 5-element fingerprint that provides a signature for heparin cofactor II. Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin rapidly in the presence of dermatan sulphate or heparin [<cite idref="PUB00000399"/>]. In the presence of these glycosaminoglycans, HCII becomes the predominant thrombin inhibitor in place of antithrombin III (AT). It also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner. Not only does HCII function as a thrombin inhibitor, but limited proteolysis near its N- terminus yields biologically active peptide(s) that might participate in inflammation and in wound healing and tissue repair processes [<cite idref="PUB00002688"/>].The sequence of HCII contains a signal peptide of 19 amino acids and a mature protein of 480 amino acids [<cite idref="PUB00000298"/>]. The N-terminal portion of HCII contains two acidic repeats (EDDDYLD and EDDDYID) that may bind to anion- binding exosite I of thrombin to facilitate covalent complex formation [<cite idref="PUB00002662"/>].</p>