Human HtrA1 (His-tagged), Recombinant

Secreted human HtrA1 serine protease is supposed to form oligomers of identical protein chains as revealed by X-ray analysis for the bacterial HtrA protein DegP. Polypeptide chains of human HtrA1 consist of several domains: An N-terminal insulin-like growth factor domain is followed by a Kazal-type serine protease inhibitor domain, a linker region, a trypsin-like protease domain and a PDZ domain. The function of HtrA1 appears closely linked to signaling by proteins of the TGFBeta family. During mouse embryo development HtrA1 is localized in specific areas where signaling by TGFBeat family proteins occurs. HtrA1 binds TGFBeta, BMP4, Gdf5 and activin. It inhibits signaling by these factors. For inhibition serine protease activity of HtrA1 is essential. HtrA1 is upregulated in osteoarthritic cartilage. Increased cartilage HtrA1 may possibly aggravate osteoarthritis by antagonizing TGFBeta and thereby promoting terminal differentiation of articular chondrocytes. In later stages of tumor progression HtrA1 is downregulated. As a protease HtrA1 hydrolyzes type II procollagen alpha1 C-propeptide, decorin and biglycan. Proteolytic activity of HtrA1 is regulated by ligand binding to the PDZ domain.