ADAMTS18

A Deep Dive into ADAMTS18: A Key Player in Human Health and Disease

Description

ADAMTS18 (A Disintegrin And Metalloprotease with Thrombospondin motif 18) is a secreted metalloprotease enzyme that plays crucial roles in various physiological and pathological processes. It belongs to the ADAMTS (A Disintegrin And Metalloprotease with Thrombospondin motif) family, which is known for its involvement in extracellular matrix (ECM) remodeling.

ADAMTS18 has a unique domain structure, consisting of a prodomain, a catalytic domain, and a thrombospondin type 1 (TSP1) domain. The prodomain regulates enzyme activity, while the catalytic domain contains the zinc-binding site required for proteolytic activity. The TSP1 domain facilitates interactions with ECM components and other proteins.

Associated Diseases

Mutations in the ADAMTS18 gene have been linked to several human diseases, including:

• Ehlers-Danlos Syndrome (EDS) Type VIIC: This rare connective tissue disorder is characterized by excessive joint flexibility, skin fragility, and easy bruising. Mutations in ADAMTS18 disrupt collagen processing, leading to defects in ECM structure and function.
• Bruising Propensity Disorder: This condition is characterized by excessive bruising with minimal trauma. Mutations in ADAMTS18 impair the proteolytic degradation of collagen VI, contributing to increased susceptibility to bruising.
• Articular Cartilage Diseases: ADAMTS18 is involved in the homeostasis of articular cartilage, the protective lining of joints. Dysregulation of ADAMTS18 activity can contribute to the development of osteoarthritis and other cartilage-related disorders.
• Cancer: ADAMTS18 has been implicated in the progression and metastasis of various cancers. It can promote tumor cell migration and invasion by degrading ECM components and modifying the microenvironment.

Did you Know ?

ADAMTS18 is the most potent collagenase among the ADAMTS family. It can cleave collagen VI and other ECM proteins at specific sites, playing a key role in the remodeling of the extracellular environment.