ADAMTS1 - ADAM metallopeptidase with thrombospondin type 1 motif 1| Elisa - Clia - Antibody - Protein

Background

ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1) is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS1 contains several distinct domains, including a signal peptide, a propeptide region, a metalloproteinase domain, a disintegrin-like domain, a thrombospondin type 1 (TSP1) motif, and a spacer region. ADAMTS1 is expressed in various tissues during development and in adulthood. It is found in tissues such as the heart, lungs, kidneys, blood vessels, and skeletal tissues. Its expression is often regulated in response to physiological cues and pathological conditions. ADAMTS1 plays a crucial 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. ADAMTS1 is also involved in angiogenesis, It can promote or inhibit angiogenesis depending on the context and interacting partners. ADAMTS1 influences endothelial cell migration, proliferation, and tube formation during blood vessel development and remodeling.ADAMTS1 has been implicated in modulating inflammation and immune responses. It can regulate the activity of cytokines, chemokines, and growth factors, influencing immune cell recruitment, activation, and function. ADAMTS1 expression is dysregulated in various cancers, including breast cancer, ovarian cancer, and prostate cancer. Its roles in ECM remodeling, angiogenesis, and inflammation contribute to tumor progression, invasion, metastasis, and angiogenesis.Dysregulation of ADAMTS1 activity has been associated with musculoskeletal disorders such as osteoarthritis and intervertebral disc degeneration. In these conditions, ADAMTS1 contributes to the degradation of ECM components within cartilage and intervertebral discs, leading to tissue degeneration and joint dysfunction. ADAMTS1 expression levels correlate with cancer progression and poor prognosis in several types of cancer. It promotes tumor growth, invasion, and metastasis by facilitating ECM remodeling, angiogenesis, and inflammation within the tumor microenvironment.

Protein Structure

ADAMTS1 has a complex multi-domain structure characteristic 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, playing roles in 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.

Classification and Subtypes

ADAMTS1 is part of the ADAMTS family, which includes multiple members characterized by the presence of TSP1 motifs and metalloprotease domains. While ADAMTS1 does not have subtypes, it is closely related to other ADAMTS proteins that share similar structural and functional properties.

Function and Biological Significance

ADAMTS1 is involved in several critical biological functions:

1. Proteolysis: The metalloprotease domain cleaves specific substrates within the ECM, including aggrecan and versican, playing a role in ECM remodeling.
2. Angiogenesis: Regulates the formation of new blood vessels by modulating the availability of angiogenic factors and ECM components.
3. Inflammation: Involved in inflammatory responses by processing cytokines and chemokines, influencing immune cell recruitment and activity.
4. Tissue Remodeling: Participates in the restructuring of tissues during development, wound healing, and pathological conditions such as fibrosis.
5. Cell Migration and Invasion: Modulates cell adhesion and motility by interacting with integrins and other ECM components.

Interactions

ADAMTS1 interacts with various proteins and cellular components:

1. Extracellular Matrix Proteins: Cleaves proteoglycans such as aggrecan and versican, contributing to ECM remodeling.
2. Integrins: The disintegrin-like domain facilitates interactions with integrins, affecting cell adhesion and migration.
3. Growth Factors and Cytokines: Modulates the activity of growth factors and cytokines by processing them or their binding proteins.
4. Thrombospondins: The TSP1 motifs mediate interactions with thrombospondins and other matrix proteins, influencing cell-matrix communication.

Clinical Significance

ADAMTS1 has significant implications in several clinical contexts:

1. Cancer: Overexpression of ADAMTS1 is associated with tumor progression and metastasis in various cancers, including breast, prostate, and colorectal cancers. It can influence the tumor microenvironment by remodeling the ECM and modulating angiogenesis.
2. Cardiovascular Diseases: ADAMTS1 is involved in the pathology of atherosclerosis and myocardial infarction through its roles in ECM remodeling and inflammation.
3. Arthritis: Contributes to the degradation of cartilage in osteoarthritis and rheumatoid arthritis by cleaving aggrecan and other matrix components.
4. Fibrosis: Plays a role in fibrotic diseases by regulating tissue remodeling and ECM deposition.
5. Angiogenesis-Related Disorders: Implicated in diseases characterized by abnormal blood vessel formation, such as diabetic retinopathy and age-related macular degeneration.

Summary

ADAMTS1, a member of the ADAMTS family, is crucial for ECM remodeling, angiogenesis, and inflammation. It has a complex multi-domain structure, including a metalloprotease domain and multiple TSP1 motifs. ADAMTS1 interacts with ECM proteins, integrins, growth factors, and thrombospondins, playing essential roles in cell migration, tissue remodeling, and pathological conditions. Clinically, ADAMTS1 is significant in cancer, cardiovascular diseases, arthritis, fibrosis, and angiogenesis-related disorders. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.