HTRA1 Protein, Human (His, SUMO)

HTRA1, a serine protease, demonstrates a diverse range of targets, notably including extracellular matrix proteins like fibronectin. The generation of fibronectin fragments by HTRA1 further stimulates synovial cells to up-regulate MMP1 and MMP3 production, suggesting a role in extracellular matrix remodeling. Additionally, HTRA1 exhibits the capacity to degrade proteoglycans such as aggrecan, decorin, and fibromodulin, potentially releasing soluble FGF-glycosaminoglycan complexes that enhance FGF signaling in the extracellular space. This multifaceted enzyme regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins and inhibits signaling mediated by TGF-beta family members, influencing various physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Moreover, intracellularly, HTRA1 degrades TSC2, leading to the activation of downstream targets. The formation of homotrimers and potential higher-order multimers in the presence of substrate highlights the complex regulatory mechanisms of HTRA1, which also interacts with TGF-beta family members like BMP4, TGFB1, TGFB2, activin A, and GDF5.