ADAMTS18 - ADAM metallopeptidase with thrombospondin type 1 motif 18 | Elisa - Clia - Antibody - Protein

Background

ADAMTS18, also known as ADAM metallopeptidase with thrombospondin type 1 motif 18, is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteins. ADAMTS18 contains several distinct domains, including a metalloproteinase domain responsible for its proteolytic activity, as well as multiple thrombospondin type-1 (TSP-1) motifs. These motifs are believed to be involved in protein-protein interactions and may mediate interactions with other extracellular matrix components.ADAMTS18 is expressed in various tissues throughout the body, including the brain, heart, lung, liver, and kidney, suggesting its involvement in multiple physiological processes.Mutations or dysregulation of ADAMTS18 have been implicated in various diseases and disorders. For example, mutations in the ADAMTS18 gene have been linked to autosomal recessive congenital myopia, a condition characterized by severe nearsightedness present from birth. Additionally, alterations in ADAMTS18 expression have been observed in cancers, such as breast cancer and colorectal cancer, suggesting a potential role in tumorigenesis and tumor progression.

Protein Structure

ADAMTS18 features 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 proteolytic activity.
• Disintegrin-Like Domain: Facilitates interactions with integrins and other cell surface receptors.
• Thrombospondin Type 1 Repeats (TSP1): ADAMTS18 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

ADAMTS18 belongs to the ADAMTS family, which includes several enzymes characterized by their TSP1 motifs and metalloprotease domains. It shares structural and functional similarities with other ADAMTS proteins but does not have distinct subtypes.

Function and Biological Significance

ADAMTS18 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, including the cardiovascular system and ocular structures.
3. Homeostasis: Involved in maintaining tissue homeostasis by regulating ECM turnover.
4. Cancer: Emerging evidence suggests that ADAMTS18 may play a role in tumor suppression and cancer progression.

Interactions

ADAMTS18 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.

Clinical Significance

ADAMTS18 has significant clinical implications in various contexts:

1. Cancer: Altered expression of ADAMTS18 has been associated with various cancers. Studies suggest it may function as a tumor suppressor, and loss of ADAMTS18 expression could contribute to cancer progression and metastasis.
2. Ocular Diseases: Given its role in ocular development, abnormalities in ADAMTS18 can lead to various eye conditions, though specific diseases linked directly to ADAMTS18 mutations are still under investigation.
3. Cardiovascular Diseases: Its involvement in cardiovascular development and ECM remodeling indicates potential implications in cardiovascular diseases where ECM integrity and remodeling are critical.

Summary

ADAMTS18 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. ADAMTS18 plays essential roles in maintaining tissue integrity and influencing cancer and cardiovascular health. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.