ADAM33 - ADAM metallopeptidase domain 33 | Elisa - Clia - Antibody - Protein

Background

ADAM33, also known as ADAM metallopeptidase domain 33, is a member of the ADAM family of proteins. It is primarily associated with asthma and related respiratory conditions.ADAM33 is a transmembrane protein, meaning it spans the cell membrane. It contains several distinct domains, including a metalloproteinase domain, a disintegrin domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. These domains suggest roles in proteolysis, cell adhesion, and signaling. ADAM33 is primarily expressed in lung tissues, particularly in smooth muscle cells, fibroblasts, and airway epithelial cells. Its expression is upregulated in asthmatic individuals and has been linked to airway remodeling, a hallmark of chronic asthma.ADAM33 gene variants have been consistently associated with asthma susceptibility and severity in various populations. These genetic variations may influence ADAM33 expression levels or protein function, contributing to the pathogenesis of asthma. ADAM33 may serve as a potential biomarker for asthma diagnosis, prognosis, and treatment response.

Protein Structure

ADAM33 has the characteristic multi-domain structure of ADAM family proteins:

• Signal Peptide: Directs the nascent protein to the secretory pathway.
• Prodomain: Maintains the enzyme in an inactive form until it is cleaved off to activate the enzyme.
• Metalloprotease Domain: Contains the catalytic site with a zinc-binding motif essential for its proteolytic activity.
• Disintegrin Domain: Facilitates interactions with integrins and other cell surface receptors, contributing to cell adhesion.
• Cysteine-Rich Domain: Contributes to the protein’s stability and interactions.
• EGF-Like Domain: Involved in protein-protein interactions.
• Transmembrane Domain: Anchors the protein in the cell membrane.
• Cytoplasmic Tail: Participates in intracellular signaling and interactions with cytoskeletal elements.

Classification and Subtypes

ADAM33 belongs to the ADAM family and is classified as a proteolytic enzyme due to its active metalloprotease domain. It is primarily expressed as a membrane-bound protein but can also be found in a soluble form after proteolytic cleavage.

Function and Biological Significance

ADAM33 is involved in several critical biological functions:

1. Airway Remodeling: Plays a significant role in the remodeling of airway tissues, which is crucial in the pathogenesis of asthma.
2. Proteolysis: The metalloprotease domain is responsible for the cleavage of specific substrates, aiding in various cellular processes.
3. Cell Adhesion: The disintegrin domain facilitates interactions with integrins, promoting cell-cell and cell-matrix adhesion.
4. Signal Transduction: Participates in signaling pathways that regulate cell differentiation and development.

Interactions

ADAM33 interacts with various proteins and cellular components:

1. Integrins: The disintegrin domain mediates interactions with integrins, affecting cell adhesion and signaling.
2. Extracellular Matrix Proteins: Involved in remodeling the extracellular matrix, which is crucial for tissue development and repair.
3. Growth Factors and Receptors: Can modulate the activity of growth factors and their receptors by proteolytic processing.
4. Immune Cells: Interacts with immune cell surface proteins, influencing inflammatory responses.

Clinical Significance

ADAM33 has significant implications in respiratory diseases, particularly asthma:

1. Asthma: Polymorphisms in the ADAM33 gene are associated with an increased risk of asthma and bronchial hyperresponsiveness. It plays a role in airway remodeling, inflammation, and hyperresponsiveness.
2. Chronic Obstructive Pulmonary Disease (COPD): ADAM33 may contribute to the pathogenesis of COPD through its role in airway remodeling and inflammation.
3. Lung Cancer: Although primarily associated with respiratory diseases, aberrant expression of ADAM33 has been explored in the context of lung cancer.
4. Fibrosis: ADAM33 is implicated in fibrotic diseases due to its role in extracellular matrix remodeling.

Summary

ADAM33, a member of the ADAM family, is essential for airway remodeling and respiratory health. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM33 interacts with integrins, extracellular matrix proteins, growth factors, and immune cells. Clinically, ADAM33 is significant in the context of asthma, COPD, lung cancer, and fibrotic diseases. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its roles in respiratory diseases and potential as a therapeutic target.