ADAM8 - ADAM metallopeptidase domain 8 | Elisa - Clia - Antibody - Protein

Background

ADAM metallopeptidase domain 8 (ADAM8), also known as CD156a, is a member of the ADAM family of proteins, which are zinc-dependent transmembrane proteins involved in various biological processes such as cell adhesion, migration, proteolysis, and signaling. ADAM8 is primarily known for its role in inflammation, immune response, and cancer progression. ADAM8 consists of several domains, including a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. These domains enable ADAM8 to participate in cell-cell and cell-matrix interactions and to proteolytically process various substrates.ADAM8 is expressed in various tissues and cell types, including leukocytes (white blood cells), lung epithelial cells, and certain cancer cells. Its expression is often upregulated in response to inflammatory stimuli, suggesting a role in immune responses.ADAM8 is implicated in the regulation of inflammation and immune responses. It has been shown to modulate leukocyte migration, cytokine production, and antigen presentation.ADAM8 can mediate cell adhesion to extracellular matrix components such as fibronectin and collagen. It also plays a role in cell migration by cleaving cell surface proteins involved in cell adhesion and signaling.ADAM8 possesses metalloprotease activity and can cleave various substrates, including cytokines, cell surface receptors, and extracellular matrix proteins. This proteolytic activity can influence cell behavior and tissue remodeling.ADAM8 has been linked to inflammatory diseases such as asthma, rheumatoid arthritis, and multiple sclerosis. It contributes to the pathogenesis of these conditions by modulating immune cell function and inflammation. ADAM8 is also overexpressed in several cancers, including breast cancer, lung cancer, and glioblastoma. Its upregulation is associated with tumor progression, invasion, metastasis, and angiogenesis. ADAM8's proteolytic activity can facilitate cancer cell migration and invasion by cleaving extracellular matrix components and cell adhesion molecules.

Protein Structure

ADAM8 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

ADAM8 is classified under the ADAM family and is known for its proteolytic activity, mainly functioning as a membrane-bound protein. There are no subtypes of ADAM8, but it can exist in both membrane-bound and soluble forms.

Function and Biological Significance

ADAM8 is involved in several critical biological functions:

1. Proteolysis: The metalloprotease domain is responsible for the cleavage of specific substrates, aiding in the processing of proteins and shedding of cell surface molecules.
2. Cell Adhesion: The disintegrin domain facilitates interactions with integrins, promoting cell-cell and cell-matrix adhesion.
3. Immune Response: Plays a significant role in the migration and activation of immune cells, including neutrophils, macrophages, and dendritic cells.
4. Inflammation: Involved in the inflammatory response, particularly in diseases such as asthma, arthritis, and multiple sclerosis.
5. Bone Remodeling: ADAM8 is implicated in the differentiation and function of osteoclasts, cells involved in bone resorption.

Interactions

ADAM8 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 their activation and migration.

Clinical Significance

ADAM8 has significant implications in several clinical contexts:

1. Asthma: Increased expression of ADAM8 is associated with airway inflammation and remodeling in asthma.
2. Arthritis: Implicated in the pathogenesis of rheumatoid arthritis through its role in inflammatory processes and joint destruction.
3. Multiple Sclerosis: ADAM8 is involved in the migration of immune cells across the blood-brain barrier, contributing to the pathology of multiple sclerosis.
4. Cancer: Overexpression of ADAM8 is observed in various cancers, including breast, pancreatic, and gliomas, where it is associated with tumor progression and metastasis.
5. Bone Diseases: Plays a role in osteoclast differentiation and function, influencing conditions such as osteoporosis.

Summary

ADAM8, a member of the ADAM family, is crucial for proteolysis, cell adhesion, and immune responses. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM8 interacts with integrins, extracellular matrix proteins, growth factors, and immune cells. Clinically, ADAM8 is significant in asthma, arthritis, multiple sclerosis, cancer, and bone diseases. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.