ADAMTS10

= ADAMTS10 =

ADAMTS10 is a member of the ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family of zinc-dependent proteases. These enzymes are involved in a variety of biological processes, including the processing of procollagens, the cleavage of proteoglycans, and the modulation of cell-matrix interactions.

Structure

ADAMTS10, like other members of the ADAMTS family, is characterized by a multi-domain structure. It typically includes a signal peptide, a propeptide region, a metalloproteinase domain, a disintegrin-like domain, a thrombospondin type 1 (TSP1) motif, and a cysteine-rich domain. The presence of multiple TSP1 motifs is a hallmark of the ADAMTS family, contributing to their interaction with extracellular matrix components.

Function

ADAMTS10 is primarily known for its role in the development and maintenance of connective tissues. It is involved in the processing of fibrillin-1, a major component of microfibrils in the extracellular matrix. This processing is crucial for the proper assembly and function of microfibrils, which are important for the structural integrity of tissues such as skin, blood vessels, and the eye.

Clinical Significance

Mutations in the ADAMTS10 gene have been associated with Weill-Marchesani syndrome, a rare genetic disorder characterized by short stature, brachydactyly (short fingers), joint stiffness, and ocular abnormalities such as microspherophakia (small, spherical lenses) and ectopia lentis (dislocation of the lens). The syndrome highlights the importance of ADAMTS10 in ocular and skeletal development.

Genetic Information

The ADAMTS10 gene is located on chromosome 19p13.2. It is expressed in various tissues, with significant expression in the eye, heart, and skeletal tissues. The gene undergoes alternative splicing, resulting in multiple transcript variants that encode different isoforms of the protein.

Research and Future Directions

Research into ADAMTS10 continues to explore its broader role in connective tissue disorders and its potential involvement in other diseases. Understanding the precise mechanisms by which ADAMTS10 interacts with fibrillin-1 and other matrix components could lead to new therapeutic approaches for conditions like Weill-Marchesani syndrome and other connective tissue disorders.

References

• Apte, S. S. (2009). A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: Functions and mechanisms. Journal of Biological Chemistry, 284(46), 31493-31497.
• Morales, J., Al-Sharif, L., Khalil, D. S., Shinwari, J. M., Bavi, P., Al-Mahrouqi, R. A., ... & Alkuraya, F. S. (2009). Homozygous mutations in ADAMTS10 cause Weill-Marchesani syndrome. American Journal of Human Genetics, 85(5), 558-564.

External Links

• [OMIM Entry on ADAMTS10](https://www.omim.org/entry/608990)
• [GeneCards: ADAMTS10](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADAMTS10)