ADAMTS3
ADAMTS3, also known as aggrecanase-3, is a secreted metallopeptidase belonging to a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family. These enzymes play crucial roles in extracellular matrix (ECM) remodeling and homeostasis. ADAMTS3 is well-known for its primary role in aggrecan cleavage, a proteoglycan found in cartilage.
ADAMTS3 is a long and complex protein composed of multiple domains:
- An N-terminal signal peptide
- A propeptide
- A catalytic domain
- A disintegrin domain
- A thrombospondin-1 (TSP1) domain
The disintegrin and thrombospondin domains interact with matrix components and cell surface receptors, modulating cell signaling and promoting cell adhesion.
ADAMTS3 dysregulation has been implicated in various diseases, including:
- Osteoarthritis (OA): ADAMTS3 overexpression contributes to cartilage degradation and progression of OA.
- Spondyloarthritis: Increased ADAMTS3 activity is associated with spinal inflammation and joint damage in spondyloarthritis.
- Cancer: ADAMTS3 promotes tumor growth and metastasis by modifying the tumor microenvironment.
Did you Know ?
ADAMTS3 polymorphisms have been linked to an increased risk of developing OA. A meta-analysis of studies found that individuals with a specific genetic variant (SNP rs731236) had a 15% higher risk of OA.