ADAMTS3

ADAMTS3, or A Disintegrin And Metalloproteinase with Thrombospondin Motifs 3, is a zinc-dependent metalloproteinase enzyme belonging to the ADAMTS family. These enzymes are involved in a variety of biological processes, including extracellular matrix (ECM) remodeling, angiogenesis, coagulation, inflammation, and arthritis.

ADAMTS3 specifically functions as a procollagen N-propeptidase, cleaving the N-propeptide from type II collagen (procollagen II) and type XI collagen. This cleavage is a critical step in the maturation of these collagens, allowing them to assemble into stable fibrils. Defective processing of procollagen II due to mutations in the ADAMTS3 gene or other related genes can lead to skeletal dysplasias and other connective tissue disorders.

The structure of ADAMTS3, like other ADAMTS family members, includes a prodomain, a metalloproteinase domain containing a zinc-binding motif, a disintegrin domain, a thrombospondin type 1 motif (TSP1), a cysteine-rich domain, and a spacer domain. The TSP1 motif is thought to mediate interactions with other ECM components and cellular receptors, influencing the enzyme's localization and activity.

ADAMTS3 has been implicated in several developmental and pathological processes. Its role in collagen processing makes it important for cartilage development and skeletal integrity. Abnormal ADAMTS3 activity has been linked to conditions such as osteoarthritis and certain types of dwarfism. Further research is ongoing to fully elucidate the roles of ADAMTS3 in health and disease, and to explore its potential as a therapeutic target.