ADAMTS9 - ADAM metallopeptidase with thrombospondin type 1 motif 9 | Elisa - Clia - Antibody - Protein

Background

ADAMTS9 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs 9) is a member of the ADAMTS family of proteases. Like other members of the ADAMTS family, ADAMTS9 contains characteristic domains, including a metalloproteinase domain, a disintegrin-like domain, and thrombospondin type-1 (TSP-1) motifs. ADAMTS9 is expressed in various tissues, including the brain, heart, kidney, cartilage, and skeletal muscle. Its expression pattern suggests potential roles in tissue development, maintenance, and remodeling.ADAMTS9 is involved in various physiological processes, particularly in extracellular matrix (ECM) remodeling. It plays a role in the turnover and organization of ECM components, such as proteoglycans and collagens. Additionally, ADAMTS9 has been implicated in angiogenesis, wound healing, and inflammation.Dysregulation of ADAMTS9 has been associated with several diseases and conditions. For instance, ADAMTS9 has been linked to cancer, where it may affect tumor growth, invasion, and metastasis by influencing the ECM and angiogenesis. Moreover, mutations in the ADAMTS9 gene have been associated with certain developmental disorders and connective tissue diseases.

Protein Structure

ADAMTS9 exhibits 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): ADAMTS9 contains multiple 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.
• Gon-1 Domain: Unique to ADAMTS9 and its close homologs, this domain contributes to its specific functional properties.

Classification and Subtypes

ADAMTS9 is classified within the ADAMTS family, characterized by the presence of TSP1 motifs and metalloprotease domains. It does not have distinct subtypes but shares functional and structural characteristics with other ADAMTS enzymes involved in ECM degradation and remodeling.

Function and Biological Significance

ADAMTS9 is involved in several key biological processes:

1. Extracellular Matrix Remodeling: Cleaves ECM components, facilitating tissue remodeling and repair.
2. Developmental Processes: Essential for normal embryonic development, including organogenesis and morphogenesis.
3. Angiogenesis Regulation: Involved in the regulation of new blood vessel formation, potentially acting as an anti-angiogenic factor.
4. Cell Migration and Adhesion: Influences cell migration and adhesion by modulating ECM composition and interactions with cell surface receptors.

Interactions

ADAMTS9 interacts with various proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves specific ECM components, such as aggrecan and versican, contributing to ECM turnover and 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

ADAMTS9 has significant clinical implications:

1. Cancer: Due to its role in ECM remodeling and angiogenesis regulation, ADAMTS9 may influence tumor progression and metastasis. Both upregulation and downregulation of ADAMTS9 expression have been observed in different types of cancers, suggesting a context-dependent role.
2. Cardiovascular Diseases: Involved in vascular remodeling and ECM dynamics, ADAMTS9 may play a role in the pathogenesis of atherosclerosis and other cardiovascular diseases.
3. Developmental Disorders: Mutations or dysregulation of ADAMTS9 can lead to developmental abnormalities, reflecting its crucial role in embryogenesis and organ development.

Summary

ADAMTS9 is a critical enzyme in the ADAMTS family, primarily involved in ECM remodeling, developmental processes, and the regulation of angiogenesis. Its multi-domain structure, including the metalloprotease and TSP1 domains, enables it to interact with various ECM components and cellular receptors. ADAMTS9 plays essential roles in maintaining tissue integrity and regulating angiogenesis, development, and possibly tumor progression. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.