Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity.
Szabo R, Netzel-Arnett S, Hobson JP, Antalis TM, Bugge TH
Biochemical Journal (2005)
Category: cancer, cell signaling, protein degradation ¤ Added: Jul 22, 2005 ¤ Rating: ◊◊
We report the bioinformatic identification, molecular cloning, and biological characterization of matriptase-3, a novel membrane-anchored serine protease that is phylogenetically preserved in fish, birds, rodents, canines and primates. The matriptase-3 gene is located on syntenic regions of human chromosome 3q13.2, mouse chromosome 16B5, rat chromosome 11q21, and chicken chromosome 1. Bioinformatic analysis combined with cDNA cloning predicts a functional type II transmembrane serine protease(TTSP) with 31 % amino acid identity to both matriptase/MT-SP1 and matriptase-2. The novel protease is composed of a short N-terminal cytoplasmic region that is followed by a transmembrane domain, a stem region with one SEA, two CUB, and three LDLRa domains, and a C-terminal catalytic serine protease domain. Transcript analysis revealed restricted, species-conserved expression of matriptase-3, with the highest mRNA levels in brain, skin, reproductive, and oro-pharyngeal tissues. The full-length matriptase-3 cDNA directed the expression of a 90-kDa N-glycosylated protein that localized to the cell surface, as assessed by cell-surface biotin labeling. The purified activated matriptase-3 serine protease domain expressed in insect cells hydrolyzed synthetic peptide substrates, with a strong preference for Arg in the P1 position, and showed proteolytic activity towards several macromolecular substrates, including gelatin, casein, and albumin. Interestingly, activated matriptase-3 formed stable inhibitor complexes with an array of serpins, including PAI-1, PCI, alpha1-proteinase inhibitor, alpha2-antiplasmin, and antithrombin III. Our study identifies matriptase-3 as a novel biologically active TTSP of the matriptase subfamily with a unique expression pattern and posttranslational regulation.