ADAM18 - ADAM metallopeptidase domain 18 | Elisa - Clia - Antibody - Protein

Background

The protein encoded by the ADAM18 gene contains the disintegrin and metalloprotease domain and is an enzyme in humans. It is a protein found on the surface membrane of sperm that may be involved in spermatogenesis and fertilization. This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in various biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature sperm surface protein. It is also known as Transmembrane metalloproteinase-like, disintegrin-like, and cysteine-rich protein III (tMDC III).

Protein Structure

ADAM18 has 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 properly localized and processed.
• 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 and signaling.
• Cysteine-Rich Domain: Contributes to protein 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

ADAM18 belongs to the ADAM family, which includes proteins with metalloprotease and disintegrin domains. It is specifically classified under metalloproteases due to its catalytic activity in proteolysis.

Function and Biological Significance

ADAM18 has several critical functions:

1. Reproduction: ADAM18 is predominantly expressed in the testis and is believed to play roles in sperm maturation and function.
2. Cell Adhesion: The disintegrin domain interacts with integrins, mediating cell-cell and cell-matrix adhesion.
3. Proteolysis: The metalloprotease domain is involved in the cleavage of specific substrates, though the exact physiological substrates of ADAM18 are less well-defined compared to other ADAM proteins.

Interactions

ADAM18 interacts with a variety of proteins and cellular components:

1. Integrins: The disintegrin domain interacts with integrins, affecting cell adhesion and signaling.
2. Extracellular Matrix Proteins: Potentially involved in remodeling the extracellular matrix, though specific interactions are not well-characterized.
3. Sperm Surface Proteins: Involved in interactions necessary for sperm function and fertilization.

Clinical Significance

The function and regulation of ADAM18 have potential implications in reproductive health:

1. Male Fertility: Given its expression in the testis and role in sperm function, ADAM18 may be important in male fertility. Mutations or dysregulation of ADAM18 could potentially contribute to male infertility.
2. Reproductive Diseases: Aberrations in ADAM18 function could impact reproductive processes, though direct links to specific diseases are not well-established.
3. Cancer: While ADAM18 is primarily associated with reproductive functions, like other ADAM family members, it may have roles in cancer progression, particularly in tumors of reproductive organs.

Summary

ADAM18, a member of the ADAM family, is essential for processes such as proteolysis, cell adhesion, and reproductive functions. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM18 interacts with integrins, extracellular matrix proteins, and sperm surface proteins. Clinically, ADAM18 is significant in the context of male fertility and potentially reproductive diseases and cancer. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its role in cellular processes and potential as a therapeutic target.