ADAM9 - ADAM metallopeptidase domain 9 | Elisa - Clia - Antibody - Protein

Background

ADAM metallopeptidase domain 9 (ADAM9) is another member of the ADAM family of proteins, sharing structural similarities and functional properties with ADAM8. Like other ADAM proteins, ADAM9 contains 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 ADAM9 to interact with other proteins and participate in various cellular processes.ADAM9 is widely expressed in various tissues and cell types, including the brain, heart, lungs, kidneys, and reproductive organs. Its expression pattern suggests diverse roles in physiological processes.ADAM9 plays a role in cell adhesion and migration by interacting with extracellular matrix components and cell surface receptors. It can promote cell migration by cleaving adhesion molecules and releasing cell-to-cell or cell-to-matrix contacts. As a metalloprotease, ADAM9 has the ability to cleave and process various substrates, including growth factors, cytokines, cell surface receptors, and extracellular matrix proteins. This proteolytic activity allows ADAM9 to regulate signaling pathways, cell behavior, and tissue remodeling. ADAM9 is often upregulated in various cancers, including breast cancer, lung cancer, prostate cancer, and pancreatic cancer. Its overexpression is associated with tumor progression, invasion, metastasis, and angiogenesis. ADAM9 promotes cancer cell migration and invasion by cleaving extracellular matrix proteins and cell adhesion molecules.ADAM9 has been implicated in neurological disorders such as Alzheimer's disease and multiple sclerosis. Its expression in the brain suggests potential roles in synaptic plasticity, neuronal migration, and myelination.ADAM9 has also been linked to cardiovascular diseases such as atherosclerosis and cardiac remodeling. Its involvement in cell adhesion, migration, and proteolysis may contribute to vascular remodeling and plaque formation

Protein Structure

ADAM9 has a characteristic 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 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

ADAM9 is classified under the ADAM family of proteins and is known for its proteolytic activity. It primarily exists as a membrane-bound protein, but can also be shed from the membrane to function in a soluble form.

Function and Biological Significance

ADAM9 is involved in several critical biological functions:

1. Proteolysis: The metalloprotease domain cleaves 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. Signal Transduction: Participates in signaling pathways that regulate cell proliferation, differentiation, and migration.
4. Development and Tissue Remodeling: Plays a role in developmental processes and tissue remodeling, including angiogenesis and wound healing.
5. Cancer: Involved in the progression and metastasis of various cancers through modulation of cell adhesion and migration.

Interactions

ADAM9 interacts with a variety of proteins and cellular components:

1. Integrins: The disintegrin domain mediates interactions with integrins, affecting cell adhesion and signaling.
2. Growth Factors and Receptors: Modulates the activity of growth factors and their receptors by proteolytic processing.
3. Extracellular Matrix Proteins: Involved in remodeling the extracellular matrix, which is crucial for tissue development and repair.
4. Signaling Pathway Proteins: Interacts with proteins involved in intracellular signaling pathways, influencing cell behavior.

Clinical Significance

ADAM9 has significant implications in several clinical contexts:

1. Cancer: Overexpression of ADAM9 is observed in various cancers, including breast, prostate, and pancreatic cancer, where it is associated with tumor progression, invasion, and metastasis.
2. Neurodegenerative Diseases: ADAM9 is implicated in Alzheimer's disease, where it may influence amyloid precursor protein processing.
3. Cardiovascular Diseases: Involved in processes such as atherosclerosis and myocardial infarction through its roles in cell adhesion and proteolysis.
4. Wound Healing: Plays a role in tissue repair and regeneration, making it relevant in wound healing and fibrotic diseases.
5. Inflammatory Diseases: Contributes to the regulation of inflammatory responses, impacting conditions such as rheumatoid arthritis.

Summary

ADAM9, a member of the ADAM family, is crucial for proteolysis, cell adhesion, and signal transduction. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM9 interacts with integrins, growth factors, extracellular matrix proteins, and signaling pathway proteins. Clinically, ADAM9 is significant in cancer, neurodegenerative diseases, cardiovascular diseases, wound healing, and inflammatory diseases. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in various physiological and pathological processes.