Serine protease HTRA1 (HTRA1)

Serine protease HTRA1 is a secreted, homotrimeric enzyme belonging to the trypsin family of serine proteases, featuring an N-terminal IGFBP-like and Kazal-like domain, a central trypsin-like catalytic domain, and a C-terminal PDZ domain for substrate recognition. It performs ATP-independent proteolysis of misfolded proteins, extracellular matrix components like fibronectin, and IGF-binding proteins, while also exhibiting chaperone functions to maintain proteostasis. HTRA1 potently antagonizes TGF-β signaling by cleaving TGF-β family members and receptors, influencing tissue homeostasis, bone formation, and matrix turnover. In disease, HTRA1 variants at the 10q26 locus confer susceptibility to age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy through dysregulated extracellular milieu in ocular tissues, while mutations cause CARASIL, a hereditary cerebral arteriopathy with subcortical infarcts and leukoencephalopathy. Reduced expression links to impaired apoptosis and metastasis in ovarian and endometrial cancers, and it aids beta-amyloid clearance in Alzheimer's contexts. Though not yet clinically targeted, its multifaceted roles in proteolysis and signaling position it as a potential modulator in neurodegeneration, vascular diseases, and malignancies.

Other names

HtrA serine peptidase 1ARMD7CADASIL2CARASILHTRAL56ORF480PRSS11