ADAMTS19 - ADAM metallopeptidase with thrombospondin type 1 motif 19 | Elisa - Clia - Antibody - Protein

Background

ADAMTS19, short for A Disintegrin And Metalloproteinase with Thrombospondin Motifs 19, is a member of the ADAMTS protein family. Like other members of the ADAMTS family, ADAMTS19 contains multiple domains, including a metalloproteinase domain responsible for its proteolytic activity, as well as thrombospondin type-1 (TSP-1) motifs. ADAMTS19 is expressed in various tissues and organs, including the brain, heart, lung, and skeletal muscle, suggesting its involvement in multiple physiological processes.The precise function of ADAMTS19 is not fully understood, but it is thought to be involved in ECM remodeling, cell adhesion, and tissue development. Studies have suggested potential roles for ADAMTS19 in heart development and function, as well as in skeletal muscle biology.Mutations or dysregulation of ADAMTS19 have been implicated in several diseases and disorders. For example, mutations in the ADAMTS19 gene have been linked to a rare genetic disorder known as geleophysic dysplasia. This condition is characterized by short stature, distinctive facial features, joint stiffness, and other skeletal abnormalities. Additionally, alterations in ADAMTS19 expression have been observed in certain types of cancer, although the significance of these findings is still being investigated.

Protein Structure

ADAMTS19 exhibits a complex multi-domain structure typical of ADAMTS family members:

• 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): ADAMTS19 has multiple 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

ADAMTS19 is classified within the ADAMTS family, which includes several enzymes sharing similar structural domains. While there are no specific subtypes of ADAMTS19, it shares functional and structural characteristics with other members of the ADAMTS family.

Function and Biological Significance

ADAMTS19 is involved in several key biological processes:

1. Extracellular Matrix Remodeling: Cleaves components of the ECM, contributing to tissue remodeling and maintenance.
2. Development: Plays a role in the development of various tissues, particularly the cardiovascular system.
3. Homeostasis: Involved in maintaining tissue homeostasis by regulating ECM turnover.
4. Cell Signaling: Participates in cell signaling pathways through interactions with ECM components and cell surface receptors.

Interactions

ADAMTS19 interacts with several proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves proteoglycans and other ECM components, 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

ADAMTS19 has significant clinical implications in various contexts:

1. Cardiovascular Diseases: Mutations in ADAMTS19 have been linked to congenital heart defects and other cardiovascular conditions, emphasizing its role in cardiovascular development and function.
2. Skeletal Abnormalities: Given its role in ECM remodeling, alterations in ADAMTS19 expression or function can contribute to skeletal abnormalities and connective tissue disorders.
3. Cancer: Dysregulation of ADAMTS19 expression has been observed in certain cancers, suggesting a role in tumor progression and metastasis.
4. Genetic Disorders: Mutations in ADAMTS19 have been associated with autosomal recessive conditions, including some characterized by developmental delays and physical malformations.

Summary

ADAMTS19 is a crucial enzyme in the ADAMTS family, contributing to ECM remodeling, tissue development, and maintenance of various tissues. Its multi-domain structure, including the metalloprotease and TSP1 domains, enables it to interact with various ECM components and cellular receptors. ADAMTS19 plays essential roles in maintaining tissue integrity and influencing cardiovascular health and disease. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.