ADAMTS2

= ADAMTS2 =

ADAMTS2 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 2) is an enzyme that plays a crucial role in the processing of collagen, a fundamental component of the extracellular matrix in connective tissues. This enzyme is part of the ADAMTS family, which is characterized by a combination of metalloproteinase and disintegrin-like domains, along with thrombospondin type 1 motifs.

Structure

ADAMTS2 is a zinc-dependent metalloproteinase. The protein structure includes several distinct domains:

• A signal peptide that directs the enzyme to the secretory pathway.
• A propeptide region that is cleaved to activate the enzyme.
• A catalytic domain containing the zinc-binding motif essential for its proteolytic activity.
• A disintegrin-like domain that may be involved in substrate recognition or interaction with other proteins.
• A series of thrombospondin type 1 repeats, which are thought to mediate interactions with the extracellular matrix.

Function

The primary function of ADAMTS2 is the cleavage of the N-propeptide of type I, II, and III procollagens. This processing step is essential for the maturation of procollagen into collagen, which then assembles into fibrils that provide structural integrity to tissues such as skin, bone, and cartilage.

Clinical Significance

Mutations in the ADAMTS2 gene can lead to a rare genetic disorder known as Ehlers-Danlos syndrome type VIIC (also known as dermatosparaxis). This condition is characterized by extremely fragile and sagging skin, due to the improper processing of procollagen into collagen.

Ehlers-Danlos Syndrome Type VIIC

Ehlers-Danlos syndrome type VIIC is an autosomal recessive disorder. Patients with this condition exhibit symptoms such as:

• Skin that is soft, doughy, and easily bruised.
• Increased skin fragility, leading to tears and scarring.
• Joint hypermobility in some cases.

The underlying cause is the deficiency of ADAMTS2 activity, resulting in the accumulation of unprocessed procollagen and the formation of abnormal collagen fibrils.

Genetic Information

The ADAMTS2 gene is located on chromosome 5q23.2. It consists of multiple exons and encodes a protein of approximately 1200 amino acids. Various mutations, including missense, nonsense, and splice-site mutations, have been identified in patients with Ehlers-Danlos syndrome type VIIC.

Research and Therapeutic Implications

Understanding the role of ADAMTS2 in collagen processing has implications for developing therapies for connective tissue disorders. Research is ongoing to explore potential treatments that could compensate for the lack of ADAMTS2 activity or correct the underlying genetic defects.

References

• Colige, A., et al. (1999). "Human procollagen I N-proteinase: a proteinase with a C-terminal domain homologous to that of von Willebrand factor." Proceedings of the National Academy of Sciences, 96(12), 6842-6846.
• Malfait, F., et al. (2017). "The Ehlers-Danlos syndromes." Nature Reviews Disease Primers, 3, 17059.
• "ADAMTS2 gene." Genetics Home Reference. U.S. National Library of Medicine.

External Links

• [OMIM Entry on ADAMTS2](https://www.omim.org/entry/604539)
• [GeneCards: ADAMTS2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADAMTS2)