ADAM28 - ADAM metallopeptidase domain 28 | Elisa - Clia - Antibody - Protein

Background

ADAM28 (A Disintegrin And Metalloproteinase domain-containing protein 28) is a member of the ADAM (a disintegrin and metalloproteinase) family of proteins. Like other members of this family, ADAM28 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 confer diverse functions to ADAM28, including proteolytic activity, cell adhesion, cell signaling, and regulation of protein-protein interactions.ADAM28 is primarily expressed in the testis, but it is also found in other tissues such as the spleen, lymph nodes, and thymus. In addition to its presence in normal tissues, ADAM28 expression has been detected in certain pathological conditions, including various cancers such as breast cancer, ovarian cancer, and prostate cancer. Its expression in these cancers suggests potential roles in tumor progression, invasion, and metastasis.ADAM28 has been implicated in immune responses and inflammatory processes. It is expressed in immune cells such as macrophages and dendritic cells, where it may participate in cell-cell interactions, cytokine signaling, and immune cell activation.

Protein Structure

ADAM28 has a complex multi-domain structure typical of the ADAM family:

• 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 (in membrane-bound isoforms).
• Cytoplasmic Tail: Participates in intracellular signaling and interactions with cytoskeletal elements.

Classification and Subtypes

ADAM28 belongs to the ADAM family and is categorized under metalloproteases due to its proteolytic activity. It exists in both membrane-bound and secreted isoforms, each with distinct biological functions.

Function and Biological Significance

ADAM28 is involved in several critical biological functions:

1. Immune Response: Plays a role in the regulation of immune cell functions and inflammatory responses.
2. Cancer: Involved in tumor progression, metastasis, and angiogenesis. ADAM28 can degrade extracellular matrix components, facilitating tumor cell invasion.
3. Reproductive Biology: Implicated in sperm maturation and fertilization processes.
4. Proteolysis: The metalloprotease domain is responsible for the cleavage of specific substrates, aiding in various cellular processes such as shedding of cell surface molecules.
5. Cell Adhesion: The disintegrin domain facilitates interactions with integrins, promoting cell-cell and cell-matrix adhesion.

Interactions

ADAM28 interacts with various proteins and cellular components:

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

Clinical Significance

The function and regulation of ADAM28 have significant implications in various diseases and conditions:

1. Cancer: Overexpression of ADAM28 is associated with poor prognosis in several cancers, including breast, lung, and prostate cancers. It facilitates tumor cell invasion and metastasis by degrading extracellular matrix components.
2. Inflammatory Diseases: Dysregulation of ADAM28 can lead to abnormal inflammatory responses, contributing to diseases such as rheumatoid arthritis and asthma.
3. Cardiovascular Diseases: ADAM28 may be involved in vascular remodeling and atherosclerosis, impacting cardiovascular health.
4. Reproductive Health: Impairment in ADAM28 function can affect fertility and reproductive processes.

Summary

ADAM28, a member of the ADAM family, is crucial for immune response, cancer progression, and reproductive biology. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM28 interacts with integrins, growth factors, receptors, extracellular matrix proteins, and immune cells. Clinically, ADAM28 is significant in the context of cancer, inflammatory diseases, cardiovascular diseases, and reproductive health. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes and potential as a therapeutic target.