ADAMTS4 - ADAM metallopeptidase with thrombospondin type 1 motif 4 | Elisa - Clia - Antibody - Protein

Background

ADAMTS4, also known as A Disintegrin And Metalloproteinase with Thrombospondin Motifs 4, is a member of the ADAMTS protein family. ADAMTS4 contains multiple domains, including a metalloproteinase domain responsible for its enzymatic activity, as well as thrombospondin type-1 (TSP-1) motifs. ADAMTS4 is primarily known for its role in extracellular matrix remodeling, particularly in the breakdown of aggrecan, a large proteoglycan found in cartilage. ADAMTS4 cleaves aggrecan at specific sites, leading to the degradation of cartilage matrix and contributing to the pathogenesis of osteoarthritis and other joint-related disorders. It is one of the key enzymes involved in cartilage degradation in osteoarthritis.ADAMTS4 has been implicated in various diseases, particularly osteoarthritis. Elevated levels of ADAMTS4 expression have been observed in osteoarthritic cartilage, synovial fluid, and serum, suggesting its involvement in the disease process. Inhibition of ADAMTS4 activity has been explored as a potential therapeutic strategy for osteoarthritis to prevent cartilage degradation.Research on ADAMTS4 has implications for understanding the pathogenesis of osteoarthritis and other joint-related disorders. Targeting ADAMTS4 activity or expression may represent a promising therapeutic approach for these conditions. Additionally, further research into the regulation and function of ADAMTS4 may provide insights into its roles in normal physiology and other diseases.

Protein Structure

ADAMTS4 has a complex multi-domain structure typical of the ADAMTS family:

• Signal Peptide: Directs the nascent 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): ADAMTS4 has TSP1 motifs involved in binding to ECM components and other proteins, aiding in 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

ADAMTS4 belongs to the ADAMTS family, which includes enzymes characterized by their TSP1 motifs and metalloprotease domains. ADAMTS4 does not have distinct subtypes but shares functional and structural characteristics with other members of the ADAMTS family, particularly those involved in ECM degradation.

Function and Biological Significance

ADAMTS4 is involved in several key biological processes:

1. Extracellular Matrix Remodeling: Cleaves major components of the ECM, such as aggrecan, a large proteoglycan in cartilage. This activity is crucial for maintaining cartilage structure and function.
2. Joint Health: Plays a significant role in the degradation of aggrecan in cartilage, which is an important process in the normal turnover and repair of joint tissues.
3. Inflammatory Response: Involved in inflammatory processes, especially in diseases like osteoarthritis and rheumatoid arthritis where ECM degradation is a major pathological feature.

Interactions

ADAMTS4 interacts with several proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves aggrecan and other proteoglycans, participating in ECM turnover and remodeling.
2. Integrins: The disintegrin-like domain facilitates interactions with integrins, affecting cell adhesion, signaling, and migration.
3. Thrombospondins: The TSP1 motifs mediate interactions with thrombospondins and other ECM proteins, playing a role 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

ADAMTS4 has significant clinical implications, especially in the context of joint health and inflammatory diseases:

1. Osteoarthritis and Rheumatoid Arthritis: Elevated levels of ADAMTS4 are associated with the degradation of cartilage in these conditions, leading to joint pain and dysfunction. Inhibiting ADAMTS4 activity is a potential therapeutic strategy for these diseases.
2. Intervertebral Disc Degeneration: ADAMTS4 is implicated in the breakdown of aggrecan in intervertebral discs, contributing to disc degeneration and associated back pain.
3. Cancer: Altered expression of ADAMTS4 has been observed in certain cancers, suggesting a role in tumor progression and metastasis, although its precise function in cancer biology requires further investigation.

Summary

ADAMTS4 is a crucial enzyme in the ADAMTS family, primarily involved in ECM remodeling and degradation, particularly in cartilage. Its multi-domain structure, including the metalloprotease and TSP1 domains, enables it to interact with various ECM components and cellular receptors. ADAMTS4 plays essential roles in maintaining joint health and is implicated in diseases such as osteoarthritis and rheumatoid arthritis. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.