ADAMs/ADAMTSs

ADAM (A Disintegrin and Metallo-proteinases) and ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs), which together are known as adamalysins, are the matrix zinc-dependent metalloproteinases. ADAM metalloproteinases are transmembrane and secreted proteins while ADAMTS are secretion forms. Adamalysins are mainly localized in the extracellular matrix (ECM), with which they can be linked by spacer domain (SD) or thrombospondin motif (TS). All adamalysins are initially synthesized as precursors, and most of them can be activated by furin. They play an important role in the cell phenotype regulation via their activities in signaling pathways, cell adhesion and migration. The ADAMs belongs to the metzincin superfamily. ADAMs consists of a prodomain, a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. ADAMs have essential functions in cell-cell interactions (such as adhesion and fusion), in signaling, and in proteolysis (also termed ectodomain shedding) of important cytokines, cytokine receptors, and other targets. Thus, ADAMs are fundamental to many control processes in development and homeostasis, and they are also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, Alzheimer’s disease. ADAMTSs (TS=thrombospondin motifs) is a related family of ADAMs that also belong to the metzincin protease superfamily. ADAMTS have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology.