ADAM21 - ADAM metallopeptidase domain 21 | Elisa - Clia - Antibody - Protein

Background

ADAM21 (A Disintegrin And Metalloproteinase domain-containing protein 21) is a member of the ADAM (A Disintegrin And Metalloproteinase) family. This family is involved in various biological processes such as cell adhesion, migration, proteolysis, and signaling. ADAM proteins are characterized by their multidomain structure, which includes a metalloproteinase domain responsible for proteolytic activity, a disintegrin domain involved in cell adhesion and signaling, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. ADAM21, specifically, is believed to play a role in fertilization. Studies have suggested its presence in sperm cells and involvement in sperm-egg interactions during fertilization. However, compared to other members of the ADAM family, relatively less is known about ADAM21, and further research is needed to fully understand its functions and mechanisms of action.

Protein Structure

ADAM21 possesses a multi-domain structure characteristic of the ADAM family:

• Signal Peptide: Directs the protein to the secretory pathway.
• Prodomain: Maintains the enzyme in an inactive form until it is processed and activated.
• 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

ADAM21 belongs to the ADAM family, which includes proteins with metalloprotease and disintegrin domains. It is classified under metalloproteases due to its catalytic activity.

Function and Biological Significance

ADAM21 is involved in several crucial biological functions:

1. Reproductive Function: Primarily expressed in reproductive tissues, ADAM21 plays roles in sperm maturation and fertilization.
2. Proteolysis: The metalloprotease domain is responsible for the cleavage of specific substrates, aiding in various cellular processes.
3. Cell Adhesion: The disintegrin domain facilitates interactions with integrins, contributing to cell-cell and cell-matrix adhesion.
4. Signal Transduction: Involved in signaling pathways that regulate cell migration, proliferation, and differentiation.

Interactions

ADAM21 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: Potentially involved in remodeling the extracellular matrix, important for tissue development and repair.
3. Sperm Surface Proteins: Interacts with other proteins on the sperm surface, aiding in sperm function and fertilization.
4. Growth Factors and Receptors: Can shed precursors of growth factors and receptors, modulating their activity.

Clinical Significance

The function and regulation of ADAM21 have potential implications in various diseases and conditions:

1. Male Infertility: Mutations or dysfunction in ADAM21 can impair sperm function and fertilization, potentially leading to male infertility.
2. Cancer: ADAM21 may play roles in cancer progression and metastasis through its involvement in cell adhesion, migration, and proteolysis.
3. Inflammatory Diseases: ADAM21’s role in shedding inflammatory mediators suggests it may be involved in the regulation of inflammatory responses.
4. Reproductive Technologies: Understanding the role of ADAM21 in fertilization can enhance assisted reproductive technologies (ART) such as in vitro fertilization (IVF).

Summary

ADAM21, a member of the ADAM family, is crucial for reproductive processes and cellular interactions, particularly in sperm maturation and fertilization. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM21 interacts with integrins, extracellular matrix proteins, sperm surface proteins, and growth factors. Clinically, ADAM21 is significant in the context of male infertility, cancer, inflammatory diseases, and reproductive technologies. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its role in fertilization and potential as a therapeutic target.