1. Abstract 2. Introduction 3. Hepsin cDNA and gene structures 3.1. Cloning of hepsin cDNA 3.2. Hepsin gene structure 3.3. The promoter sequence of the mouse hepsin gene. 4. Hepsin protein 4.1. The domain structure of hepsin 4.2. Biochemical properties of hepsin 4.2.1. Molecular weight 4.2.2. Membrane topology 4.2.3. Substrate specificity 4.2.4. Effect of inhibitors 5. Functions of hepsin 5.1. ...

Hepsin is a membrane serine protease expressed in several human tissues including the liver, kidney, prostate, and thyroid. The physiological function of hepsin remains unknown. In vitro studies have shown that hepsin activates blood clotting factors VII, XII, and IX, pro-urokinase (pro-uPA), and pro-hepatocyte growth factor (pro-HGF). Recently, hepsin has been identified as one of the most up-...

Hepsin is a type II transmembrane serine protease highly expressed on the surface of hepatocytes. The physiological function of hepsin is not known, although in vitro studies indicate that hepsin plays a role in the initiation of blood coagulation and in hepatocyte growth. To determine the functional importance of hepsin, we generated hepsin-deficient mice by homologous recombination. Homozygou...

Expression of HEPSIN, a type II transmembrane serine protease in prostate cancer (CaP), has been highlighted by several studies analyzing CaP-specific gene expression alterations by cDNA microarray. Evaluations of the biological functions of HEPSIN in CaP cells are warranted for better assessment of its utility as a biomarker and/or therapeutic target. In stable clones of PC-3/HEPSIN transfecta...

Hepsin, a type II transmembrane serine protease, is strongly up-regulated in prostate cancer. Hepsin overexpression in a mouse prostate cancer model resulted in tumor progression and metastasis, associated with basement membrane disorganization. We investigated whether hepsin enzymatic activity was linked to the basement membrane defects by examining its ability to initiate the plasminogen/plas...

Hepsin is a membrane-anchored, trypsin-like serine protease with prominent expression in the human liver and tumours of the prostate and ovaries. To better understand the biological functions of hepsin, we identified macromolecular substrates employing a tetrapeptide PS-SCL (positional scanning-synthetic combinatorial library) screen that rapidly determines the P1-P4 substrate specificity. Heps...

Hepsin is a type II transmembrane serine protease overexpressed in the majority of human prostate cancers. We recently demonstrated that hepsin promotes prostate cancer progression and metastasis and thus represents a potential therapeutic target. Here we report the identification of novel small-molecule inhibitors of hepsin catalytic activity. We utilized purified human hepsin for high-through...

Hepsin, a type-II membrane-associated serine protease, has been implicated in cell growth and development as well as possible initiation of blood coagulation. Here, we report on the complete nucleotide sequence, functional characterization of key structural features and the promoter of the mouse hepsin gene. The gene has a size of approximately 17 kb, and is composed of 12, 13, or 14 exons depe...

The serine protease hepsin is highly upregulated in prostate cancer and is implicated in tumor progression. Therefore, specific inhibition of hepsin enzymatic activity by an antibody constitutes an attractive therapeutic approach. Here, we report the identification of the anti-hepsin antibody Fab25 by screening of a Fab phage display library with a restricted chemical diversity at the complemen...

Hepatitis B virus (HBV) X protein (HBx) is an important effector for HBV-associated pathogenesis. In this study, we identified hepsin as an HBx-interacting protein and investigated the effects of hepsin on HBx-mediated complement component 3 (C3) secretion in hepatocytes. In vivo and in vitro binding between HBx and hepsin was confirmed by co-immunoprecipitation and Glutathione S-transferase pu...