ADAMTS17 - ADAM metallopeptidase with thrombospondin type 1 motif 17 | Elisa - Clia - Antibody - Protein

Background

ADAMTS17 (ADAM metallopeptidase with thrombospondin type 1 motif 17) is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS17, like other members of the ADAMTS family, contains several characteristic domains, including a signal peptide, a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and multiple thrombospondin type 1 (TSP1) motifs. ADAMTS17 is expressed in various tissues during development and in adulthood. It is found in tissues such as the heart, lungs, kidneys, and skeletal tissues. ADAMTS17 plays a role in ECM remodeling by cleaving ECM proteins such as aggrecan, versican, and brevican. These proteolytic activities are essential for tissue development, maintenance, and repair.ADAMTS17 is implicated in various aspects of tissue development, particularly in skeletal development. It may play a role in processes such as chondrogenesis (cartilage formation) and osteogenesis (bone formation), where it regulates ECM composition and structure.While specific functions related to inflammation and immunity are less well-characterized for ADAMTS17 compared to other members of the ADAMTS family, its expression patterns in certain immune cells and tissues suggest potential roles in modulating immune responses. ADAMTS17 expression levels have been found to be dysregulated in various cancers, including breast cancer, ovarian cancer, and prostate cancer. Its roles in ECM remodeling and tissue development suggest potential contributions to tumor progression, invasion, and metastasis.

Protein Structure

ADAMTS17 exhibits a complex multi-domain structure typical of ADAMTS family members:

• 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): ADAMTS17 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

ADAMTS17 belongs to the ADAMTS family, which includes several enzymes characterized by their TSP1 motifs and metalloprotease domains. While there are no specific subtypes of ADAMTS17, it is closely related to other ADAMTS proteins involved in similar biological processes, such as ADAMTS10 and ADAMTS6.

Function and Biological Significance

ADAMTS17 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 connective tissues.
3. Homeostasis: Involved in maintaining tissue homeostasis by regulating ECM turnover.
4. Eye Development: ADAMTS17 has been particularly associated with the development and maintenance of ocular structures.

Interactions

ADAMTS17 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. Fibrillin: ADAMTS17 is known to interact with fibrillin, a component of microfibrils in the ECM, influencing connective tissue structure and function.
4. Thrombospondins: The TSP1 motifs mediate interactions with thrombospondins and other ECM proteins, playing a role in cell-matrix communication.

Clinical Significance

ADAMTS17 has significant clinical implications in various contexts:

1. Weill-Marchesani Syndrome: Mutations in ADAMTS17 are associated with Weill-Marchesani syndrome, a rare genetic disorder characterized by short stature, brachydactyly (short fingers and toes), joint stiffness, and ocular abnormalities such as microspherophakia (small, spherical lens).
2. Eye Diseases: Given its role in ocular development, abnormalities in ADAMTS17 can lead to various eye diseases and conditions, including lens dislocation and other structural defects.
3. Connective Tissue Disorders: Due to its involvement in ECM remodeling and interaction with fibrillin, mutations or dysregulation of ADAMTS17 can contribute to connective tissue disorders.

Summary

ADAMTS17 is a crucial enzyme in the ADAMTS family, contributing to ECM remodeling, tissue development, and maintenance of connective tissues. Its multi-domain structure, including the metalloprotease and TSP1 domains, enables it to interact with various ECM components and cellular receptors. ADAMTS17 plays essential roles in maintaining tissue integrity and influencing eye and connective tissue health. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.