Hepsin

Hepsin is an enzyme that in humans is encoded by the HPN gene.

Hepsin is a type II transmembrane serine protease found on the cell surface of various mammalian tissues.  In humans, the HPN gene encodes hepsin and is located on chromosome 19. The enzyme belongs to the type II transmembrane serine protease (TTSP) family, a group of membrane-anchored serine proteases that regulate a variety of proteolytic functions at the cell surface. Hepsin is part of the hepsin/TMPRSS subfamily of TTSPs, which contain a scavenger receptor cysteine-rich (SRCR) domain that facilitates interactions with other proteins.  These proteases are conserved across vertebrates, highlighting their important roles in tissue stability, development and cellular processes.

Hepsin is found in multiple organs, with the liver, kidney, and prostate showing the highest expression levels. Other tissues, such as the pancreas, lung, and thyroid have shown lower levels of hepsin expression. The enzyme's structure includes a short cytoplasmic tail, a single transmembrane helix, and an extracellular domain that is responsible for its proteolytic function. Hepsin cleaves and activates pro-hepatocyte growth factor (pro-HGF) and coagulation factor VII, suggesting roles in both signaling pathways and the blood clotting process. Higher levels of hepsin expression are linked to various diseases, most notably prostate cancer in humans, where the enzyme can promote metastasis, tumor spread, and disruption of normal tissue structure.  Mouse model studies indicate that both over expression and under expression of hepsin can directly affect tumor growth, cell movement, and metastatic behavior.  Apart from its role in cancer, hepsin also contributes to kidney protein processing, liver metabolism and auditory function, demonstrating that the enzyme plays important and diverse physiological functions in different tissues.