Serine protease HtrA3 (HTRA3)

Serine protease HtrA3 (HTRA3) is a member of the HtrA family of homo-oligomeric serine proteases, featuring an N-terminal domain, a central serine protease domain with chymotrypsin-like properties, and a C-terminal PDZ domain (absent in the short isoform HtrA3S)[1][2][3]. HTRA3 is involved in protein quality control and induces mitochondria-mediated apoptosis, acting as a tumor suppressor and regulator of trophoblast invasion during placenta development; it has documented roles in cancer (e.g., lung, endometrial), preeclampsia, and possibly ovarian physiology[1][3][4]. HTRA3’s enzymatic activity includes cleavage of beta-casein and several extracellular matrix proteoglycans such as decorin, biglycan, and fibronectin, thus modulating TGF-beta signaling indirectly. HTRA3 may exist as a trimer stabilized by its PDZ domain, and deletion or mutation of the active site abrogates its proteolytic and pro-apoptotic functions[1][2]. No approved drugs selectively target HTRA3, but its role in apoptosis and tumor suppression makes it a molecule of pharmacological interest.

Other names

HtrA serine peptidase 3Serine protease HTRA3PRSPTaspHigh-temperature requirement factor A3Pregnancy-related serine proteaseprobable serine protease HTRA3Prsp

Proteolytic cleavage of ECM proteins and involvement in apoptosis (no clinically established inhibitors/activators)