SERPINB3 and B4: from biochemistry to biology

Abstract

Human SERPINB3 and SERPINB4 are evolutionary duplicated serine/cysteine protease inhibitors. Genomic analysis indicates that these paralogous genes were encoded from independent loci arising from tandem gene duplication. Although the two molecules share 92% identity of their amino acid sequences, they are distinct in the Reactive Center Loop (RCL) including a hinge region and catalytic sequences which accounts for altered substrate specificity. Elevated expression of the two molecules have been reported to contribute to numerous pathological conditions such as inflammatory diseases and cancer. In this review, we focus on summarizing the biochemical features of SERPINB3/B4 and discussing the mechanistic basis for their biological functions and implications in human diseases.