ADAMTS7 - ADAM metallopeptidase with thrombospondin type 1 motif 7 | Elisa - Clia - Antibody - Protein

Background

ADAMTS7 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs 7) is another member of the ADAMTS family of proteases. Like other ADAMTS proteins, ADAMTS7 contains multiple domains, including a metalloproteinase domain, a disintegrin-like domain, and thrombospondin type-1 (TSP-1) motifs. ADAMTS7 is expressed in various tissues, including skeletal muscle, heart, brain, and cartilage. Its expression pattern suggests roles in tissue development, maintenance, and homeostasis. ADAMTS7 is implicated in various physiological processes, particularly in extracellular matrix (ECM) remodeling. It plays a role in the turnover and organization of ECM components, including proteoglycans and collagens. Additionally, ADAMTS7 has been linked to angiogenesis, inflammation, and wound healing.Dysregulation of ADAMTS7 has been associated with several diseases and conditions. In particular, ADAMTS7 has been implicated in osteoarthritis, where it may contribute to cartilage degradation and joint inflammation. Studies have also linked ADAMTS7 to atherosclerosis, where it may play a role in plaque formation and vascular remodeling.

Protein Structure

ADAMTS7 has a multi-domain structure typical of the ADAMTS family:

• Signal Peptide: Directs the enzyme to the secretory pathway.
• Propeptide Domain: Keeps the enzyme inactive until it is cleaved to activate the enzyme.
• Metalloprotease Domain: Contains the catalytic site with a zinc-binding motif essential for its proteolytic activity.
• Disintegrin-Like Domain: Facilitates interactions with integrins and other cell surface receptors.
• Thrombospondin Type 1 Repeats (TSP1): ADAMTS7 contains several TSP1 motifs that aid in binding to ECM components and other proteins, contributing to cell adhesion and signaling.
• Cysteine-Rich Domain: Contributes to the enzyme’s stability and interactions.
• Spacer Domain: Connects other domains and influences substrate specificity and binding.

Classification and Subtypes

ADAMTS7 belongs to the ADAMTS family, which includes enzymes characterized by TSP1 motifs and metalloprotease domains. While ADAMTS7 does not have distinct subtypes, it shares functional and structural characteristics with other ADAMTS enzymes involved in ECM degradation and remodeling.

Function and Biological Significance

ADAMTS7 is involved in several key biological processes:

1. Extracellular Matrix Remodeling: Cleaves and degrades ECM components, which is crucial for maintaining tissue structure and function.
2. Vascular Biology: ADAMTS7 has been particularly studied in the context of vascular smooth muscle cell migration and proliferation, processes that are essential for vascular remodeling and repair.
3. Atherosclerosis: Involved in the development of atherosclerotic lesions by degrading ECM components and influencing vascular cell behavior.

Interactions

ADAMTS7 interacts with several proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves cartilage oligomeric matrix protein (COMP), playing a role in ECM turnover and vascular remodeling.
2. Integrins: The disintegrin-like domain facilitates interactions with integrins, impacting cell adhesion, signaling, and migration.
3. Thrombospondins: The TSP1 motifs mediate interactions with thrombospondins and other ECM proteins, aiding in cell-matrix communication.
4. Growth Factors and Cytokines: Modulates the activity of various growth factors and cytokines, influencing cellular behavior and tissue responses.

Clinical Significance

ADAMTS7 has significant clinical implications, particularly in cardiovascular diseases:

1. Atherosclerosis: Elevated levels of ADAMTS7 are associated with the development of atherosclerotic plaques. Genetic studies have linked ADAMTS7 with increased risk of coronary artery disease.
2. Vascular Injury and Repair: Plays a role in vascular smooth muscle cell migration and proliferation, which are critical processes in response to vascular injury and during the formation of neointimal hyperplasia.
3. Potential Therapeutic Target: Due to its involvement in cardiovascular disease, ADAMTS7 is being investigated as a potential therapeutic target to prevent or treat atherosclerosis and related conditions.

Summary

ADAMTS7 is a crucial enzyme in the ADAMTS family, primarily involved in ECM remodeling and vascular biology. Its multi-domain structure, including the metalloprotease and TSP1 domains, enables it to interact with various ECM components and cellular receptors. ADAMTS7 plays essential roles in maintaining vascular health and is implicated in diseases such as atherosclerosis. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.