ADAMTS15 - ADAM metallopeptidase with thrombospondin type 1 motif 15 | Elisa - Clia - Antibody - Protein

Background

ADAMTS15 (ADAM metallopeptidase with thrombospondin type 1 motif 15) is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS15 contains several domains characteristic of the ADAMTS family, including a signal peptide, a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and multiple thrombospondin type 1 (TSP1) motifs. ADAMTS15 is expressed in various tissues during development and in adulthood. It is found in tissues such as the heart, lungs, kidneys, and skeletal tissues. ADAMTS15 plays a role in ECM remodeling by cleaving ECM proteins such as aggrecan, versican, and brevican. ADAMTS15 is implicated in various aspects of tissue development, particularly in skeletal development. It may play a role in processes such as chondrogenesis and osteogenesis , where it regulates ECM composition and structure. Specific functions related to inflammation and immunity are less well-characterized for ADAMTS15 compared to other members of the ADAMTS family, its expression patterns in certain immune cells and tissues suggest potential roles in modulating immune responses. ADAMTS15 expression levels have been found to be dysregulated in various cancers, including breast cancer, ovarian cancer, and prostate cancer. Dysregulation of ADAMTS15 activity has been associated with musculoskeletal disorders such as osteoarthritis and intervertebral disc degeneration. In these conditions, ADAMTS15 contributes to the degradation of ECM components within cartilage and intervertebral discs, leading to tissue degeneration and joint dysfunction. ADAMTS15 expression levels correlate with cancer progression and poor prognosis in several types of cancer. It may promote tumor growth, invasion, and metastasis by facilitating ECM remodeling within the tumor microenvironment.

Protein Structure

ADAMTS15 has a typical multi-domain structure characteristic of the ADAMTS family:

• Signal Peptide: Directs the enzyme to the secretory pathway.
• Propeptide Domain: Maintains the enzyme in an inactive state until proteolytic activation.
• Metalloprotease Domain: Contains the catalytic zinc-binding motif essential for proteolytic activity.
• Disintegrin-Like Domain: Facilitates interactions with integrins and other cell surface receptors.
• Thrombospondin Type 1 Repeats (TSP1): ADAMTS15 has multiple TSP1 repeats 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 the catalytic domain to other domains, influencing substrate specificity and binding.

Classification and Subtypes

ADAMTS15 is classified within the ADAMTS family, which includes various enzymes sharing similar structural domains. There are no specific subtypes of ADAMTS15, but it is closely related to other ADAMTS proteins, such as ADAMTS1 and ADAMTS5, which also play roles in ECM remodeling.

Function and Biological Significance

ADAMTS15 plays several critical roles in physiological processes:

1. Extracellular Matrix Remodeling: Cleaves various ECM components, contributing to tissue remodeling and homeostasis.
2. Development: Involved in the development of various tissues, including the cardiovascular system and skeletal structure.
3. Inflammation: Modulates inflammatory responses by processing cytokines and other signaling molecules.
4. Cancer: Implicated in cancer progression and metastasis by influencing the tumor microenvironment through ECM remodeling.

Interactions

ADAMTS15 interacts with several proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves proteoglycans such as aggrecan and versican, playing a role in ECM turnover.
2. Integrins: The disintegrin-like domain facilitates interactions with integrins, affecting cell adhesion and signaling.
3. Cytokines and Growth Factors: Modulates the activity of various cytokines and growth factors, influencing cell behavior and tissue responses.
4. Thrombospondins: The TSP1 motifs mediate interactions with thrombospondins and other ECM proteins, influencing cell-matrix communication.

Clinical Significance

ADAMTS15 has significant implications in several clinical contexts:

1. Cancer: Dysregulation of ADAMTS15 has been linked to cancer progression and metastasis. It can affect tumor growth by remodeling the ECM and influencing cell adhesion, migration, and invasion.
2. Inflammatory Diseases: Altered expression of ADAMTS15 is associated with inflammatory conditions, where it can modulate the inflammatory response and ECM integrity.
3. Cardiovascular Diseases: Involved in cardiovascular development and diseases, where its role in ECM remodeling is crucial for maintaining vascular structure and function.
4. Skeletal Disorders: Given its role in ECM turnover, ADAMTS15 may be implicated in skeletal disorders that involve abnormal ECM remodeling and homeostasis.

Summary

ADAMTS15 is a crucial enzyme in the ADAMTS family, involved in ECM remodeling, tissue development, inflammation, and cancer. Its multi-domain structure, including the metalloprotease and TSP1 domains, enables it to interact with various ECM components and cellular receptors. ADAMTS15 plays essential roles in maintaining tissue integrity, modulating inflammatory responses, and influencing cancer progression. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.