Serine pseudoproteases in physiology and disease

Serine proteases (SPs) constitute a very important family of enzymes, both physiologically and pathologically. The effects produced by these proteins have been explained by their proteolytic activity. However, the discovery of pharmacologically active SP molecules that show no enzymatic activity, as the so-called pseudo SPs or SP homologs (SPHs), has exposed a profoundly neglected possibility of nonenzymatic functions of these SP molecules. In this review, the most thoroughly described SPHs are presented. The main physiological domains in which SPHs operate appear to be in reproduction, embryonic development, immune response, host defense, and hemostasis. Hitherto unexplained actions of SPs should therefore be considered also as the result of the ligand-like attributes of SPs. The gain of a novel function by an SPH is a consequence of specific amino acid replacements that have resulted in a novel interaction interface or a 'catalytic trap'. Unraveling the SP/SPH interactome will provide a description of previously unknown physiological functions of SPs/SPHs, aiding the creation of innovative medical approaches.

Automated summary

Serine proteases play a crucial role in physiology and pathology. The discovery of nonenzymatic functions in pseudo serine proteases (SPHs) has expanded our understanding of the role of these proteins. SPHs have been found to be important in reproduction, embryonic development, immune response, host defense, and hemostasis. Investigating the interaction between SPs and SPHs can uncover new physiological functions and aid in the development of innovative medical approaches.