InterPro: IPR000240 Serpin B9/maspin

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.

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 (IPR001254, IPR003966) [1]. The majority of the members are serpin B9, which is an inhibitor of the granzyme B/perforin lytic pathway [2]. Others members of this family include plasminogen activator inhibitor 2, serpin B8, serpin B13, proteinase inhibitor 3 and maspin

Maspin is a non-inhibitory member of family I4 [3, 1]. Maspin is expressed in normal mammary epithelial cells but not in most mammary carcinoma cell lines. Analysis of human breast cancer specimens has revealed that loss of maspin expression occurs most frequently in advanced cancers, supporting the hypothesis that maspin functions as a tumour suppressor [3].