ADAM9

= ADAM9 =

ADAM9 (A Disintegrin and Metalloproteinase domain-containing protein 9) is a member of the ADAM family of proteins, which are involved in a variety of biological processes including cell adhesion, cell fusion, and proteolysis. ADAM9 is encoded by the ADAM9 gene in humans.

Structure

ADAM9 is a type I transmembrane protein that consists of several distinct domains:

• Signal Peptide: Directs the nascent protein to the secretory pathway.
• Prodomain: Maintains the enzyme in an inactive form until it is cleaved.
• Metalloproteinase Domain: Contains the catalytic site responsible for proteolytic activity.
• Disintegrin Domain: Involved in cell adhesion by interacting with integrins.
• Cysteine-rich Domain: May play a role in substrate recognition.
• EGF-like Domain: Potentially involved in protein-protein interactions.
• Transmembrane Domain: Anchors the protein in the cell membrane.
• Cytoplasmic Tail: May be involved in intracellular signaling.

Function

ADAM9 is involved in several physiological and pathological processes:

• Proteolysis: ADAM9 can cleave a variety of substrates, including growth factors, cytokines, and cell surface receptors, thereby modulating their activity.
• Cell Adhesion: Through its disintegrin domain, ADAM9 can interact with integrins, influencing cell adhesion and migration.
• Cell Signaling: The shedding of membrane-bound precursors by ADAM9 can activate signaling pathways that regulate cell proliferation, differentiation, and survival.

Clinical Significance

ADAM9 has been implicated in several diseases:

• Cancer: Overexpression of ADAM9 has been observed in various cancers, including breast, prostate, and pancreatic cancer. It is thought to promote tumor progression by enhancing cell migration and invasion.
• Neurological Disorders: ADAM9 may play a role in neurodegenerative diseases by modulating the shedding of amyloid precursor protein (APP), which is involved in Alzheimer's disease.
• Inflammatory Diseases: ADAM9 can influence inflammatory responses by processing cytokines and their receptors.

Research and Therapeutic Potential

Due to its involvement in disease processes, ADAM9 is a potential target for therapeutic intervention. Inhibitors of ADAM9 are being investigated for their ability to block tumor growth and metastasis. Additionally, understanding the regulation of ADAM9 activity could lead to new strategies for treating inflammatory and neurodegenerative diseases.

References

• Seals, D. F., & Courtneidge, S. A. (2003). The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes & Development, 17(1), 7-30.
• Mochizuki, S., & Okada, Y. (2007). ADAMs in cancer cell proliferation and progression. Cancer Science, 98(5), 621-628.
• Edwards, D. R., & Handsley, M. M. (2008). Metalloproteinases in extracellular matrix remodeling during development and disease. Cellular and Molecular Life Sciences, 65(19), 3069-3093.

External Links

• [GeneCards: ADAM9](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADAM9)
• [UniProt: ADAM9](https://www.uniprot.org/uniprot/Q13443)