Type II transmembrane serine proteases

Abstract

Analysis of genome and expressed sequence tag data bases at the turn of the millennium unveiled a new protease family named the type II transmembrane serine proteases (TTSPs) in a Journal of Biological Chemistry minireview (Hooper, J. D., Clements, J. A., Quigley, J. P., and Antalis, T. M. (2001) J. Biol. Chem. 276, 857-860). Since then, the number of known TTSPs has more than doubled, and more importantly, our understanding of the physiological functions of individual TTSPs and their contribution to human disease has greatly increased. Progress has also been made in identifying molecular substrates and endogenous inhibitors. This minireview summarizes the current knowledge of the rapidly advancing TTSP field.

FIGURE 1.

The TTSP family is composed of four subfamilies: HAT/DESC, hepsin/TMPRSS, matriptase, and corin. The structure of each TTSP is shown schematically. TTSPs consist of an N-terminal signal anchor domain (S.A.) and a C-terminal trypsin-like serine protease domain (Serine) that flank a stem region composed of 1–11 protein domains of six different types (see box at bottom). The location of each domain (amino acid numbering) is indicated above the domain (4). HAT-like 2 and HAT-like 3 are found in rodents but not in primates. Polyserase has three C-terminal serine protease domains, of which the third is catalytically inactive. Scavenger indicates the group A scavenger receptor domain.