ADAMTS10 - ADAM metallopeptidase with thrombospondin type 1 motif 10 | Elisa - Clia - Antibody - Protein

Background

ADAMTS10 (ADAM metallopeptidase with thrombospondin type 1 motif 10) is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS10 contains several domains, including a signal peptide, a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and multiple thrombospondin type 1 (TSP1) motifs. ADAMTS10 plays a crucial role in ECM remodeling by cleaving ECM proteins such as aggrecan, versican, and brevican. ADAMTS10 is implicated in embryonic development, particularly in skeletal development. It is involved in processes such as chondrogenesis and osteogenesis , where it regulates ECM composition and structure. Mutations in the ADAMTS10 gene have been associated with human genetic disorders such as Weill-Marchesani syndrome (WMS) and geleophysic dysplasia (GD). These disorders are characterized by skeletal abnormalities, short stature, and other connective tissue abnormalities. ADAMTS10 gene mutations can also cause GD, another rare connective tissue disorder characterized by short stature, joint contractures, and cardiac abnormalities. Like in WMS, mutations in ADAMTS10 disrupt normal ECM remodeling and tissue development, leading to the characteristic features of GD.ADAMTS10 expression levels have been found to be dysregulated in various cancers, including breast cancer, colon cancer, and gastric cancer. Its roles in ECM remodeling and tissue development suggest potential contributions to tumor progression, invasion, and metastasis

Protein Structure

ADAMTS10 has a complex multi-domain structure typical of the ADAMTS family:

• Signal Peptide: Directs the nascent protein to the secretory pathway.
• Prodomain: Maintains the enzyme in an inactive form 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): Involved in binding to ECM components and other proteins, contributing to cell adhesion and signaling.
• Cysteine-Rich Domain: Contributes to the protein’s stability and interactions.
• Spacer Domain: Connects other domains and influences substrate specificity and binding.
• Additional TSP1 Repeats: ADAMTS10 has multiple TSP1 repeats that further facilitate interactions with the ECM and other proteins.

Classification and Subtypes

ADAMTS10 is part of the ADAMTS family, which includes several members characterized by the presence of TSP1 motifs and metalloprotease domains. There are no known subtypes of ADAMTS10, but it is closely related to other ADAMTS proteins, sharing similar structural and functional properties.

Function and Biological Significance

ADAMTS10 is involved in several critical biological functions:

1. Proteolysis: The metalloprotease domain cleaves specific substrates within the ECM, playing a role in ECM remodeling.
2. Development: Essential for the proper development and maintenance of connective tissues, including the eyes, cardiovascular system, and skeletal structures.
3. Cell Signaling: Participates in signaling pathways that regulate cell proliferation, differentiation, and migration.
4. Tissue Homeostasis: Involved in maintaining the structural integrity and function of various tissues through ECM remodeling and interaction with other cellular components.

Interactions

ADAMTS10 interacts with various proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves proteoglycans and other ECM components, contributing to ECM remodeling and tissue homeostasis.
2. Integrins: The disintegrin-like domain facilitates interactions with integrins, affecting cell adhesion and signaling.
3. Fibrillin-1: ADAMTS10 interacts with fibrillin-1, a critical component of microfibrils in the ECM, influencing tissue elasticity and integrity.
4. Growth Factors and Cytokines: Modulates the activity of growth factors and cytokines by processing them or their binding proteins, influencing cell behavior and tissue development.

Clinical Significance

ADAMTS10 has significant implications in several clinical contexts:

1. Weill-Marchesani Syndrome: Mutations in ADAMTS10 cause Weill-Marchesani syndrome, a genetic disorder characterized by short stature, brachydactyly, joint stiffness, and severe eye abnormalities such as ectopia lentis (dislocation of the lens).
2. Cardiovascular Diseases: Given its role in ECM remodeling and interaction with fibrillin-1, ADAMTS10 is implicated in cardiovascular diseases, potentially affecting vascular integrity and function.
3. Ocular Diseases: In addition to its role in Weill-Marchesani syndrome, ADAMTS10 may be involved in other ocular diseases due to its critical function in eye development and maintenance.
4. Connective Tissue Disorders: As a key player in connective tissue homeostasis, alterations in ADAMTS10 function can contribute to various connective tissue disorders.

Summary

ADAMTS10, a member of the ADAMTS family, is crucial for ECM remodeling, connective tissue development, and maintenance. It has a complex multi-domain structure, including a metalloprotease domain, disintegrin-like domain, and multiple TSP1 motifs. ADAMTS10 interacts with ECM proteins, integrins, fibrillin-1, and growth factors, playing essential roles in tissue homeostasis and development. Clinically, ADAMTS10 is significant in Weill-Marchesani syndrome, cardiovascular diseases, ocular diseases, and connective tissue disorders. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.