ADAM7 - ADAM metallopeptidase domain 7 | Elisa - Clia - Antibody - Protein

Background

ADAM7 is a member of the ADAMs family, a group distinguished by their zinc protease activity. These transmembrane proteins serve as pivotal players in a myriad of biological processes, orchestrating vital functions such as cell signaling, adhesion, and migration. Despite its classification as a zinc protease, the protein encoded by ADAM7 intriguingly lacks typical protease activity. Instead, it likely operates through mediating protein-protein interactions, thereby modulating essential cellular processes such as cell adhesion. Of particular interest is its potential involvement in facilitating protein-protein interactions and cell adhesion events, including the intricate process of sperm-egg fusion. Through its participation in these adhesive mechanisms, ADAM7 may act as a facilitator in the complex interplay between sperm and egg, ultimately contributing to successful fertilization. Moreover, emerging studies suggest a connection between mutations in the ADAM7 gene and the progression of melanoma, a highly aggressive form of skin cancer. These mutations are hypothesized to disrupt the protein's normal functioning, potentially leading to dysregulated cell adhesion processes and promoting the uncontrolled growth and metastasis of melanoma cells.

Protein Structure

ADAM7 has the characteristic multi-domain structure 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, although ADAM7 is considered catalytically inactive due to mutations in the active site.
• 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

ADAM7 is classified under the ADAM family, but it is considered catalytically inactive due to specific mutations in the metalloprotease domain that prevent proteolytic activity. It primarily functions as a membrane-bound protein.

Function and Biological Significance

ADAM7 is involved in several biological processes, despite its lack of proteolytic activity:

1. Reproductive Biology: Plays roles in sperm maturation and epididymal function.
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 differentiation and development.
4. Pancreatic Function: Implicated in pancreatic processes, although specific functions remain to be fully elucidated.

Interactions

ADAM7 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 interacting with cell surface molecules.
4. Immune Cells: Potential interactions with immune cell surface proteins, influencing inflammatory responses.

Clinical Significance

The clinical significance of ADAM7 is associated with several conditions:

1. Pancreatic Diseases: Altered expression of ADAM7 has been linked to pancreatic cancer and pancreatitis.
2. Reproductive Health: May play a role in male fertility due to its expression in the epididymis and involvement in sperm maturation.
3. Cancer: Aberrant expression of ADAM7 has been investigated in various cancers, including breast and prostate cancer, where it may influence tumor progression and metastasis.

Summary

ADAM7, a member of the ADAM family, is a catalytically inactive protein that plays roles in reproductive biology, cell adhesion, and signal transduction. It has a multi-domain structure, including a disintegrin domain for cell adhesion and interactions with integrins. ADAM7 interacts with extracellular matrix proteins, growth factors, and immune cells. Clinically, ADAM7 is significant in the context of pancreatic diseases, male fertility, and various cancers. Understanding its structure, functions, interactions, and clinical implications provides valuable insights into its roles in physiological and pathological processes.