ADAM12 - ADAM metallopeptidase domain 12 | Elisa - Clia - Antibody - Protein

Background

ADAM12, also known as ADAM metallopeptidase domain 12, is another member of the ADAM (a disintegrin and metalloproteinase) family of proteins. Like ADAM10, it is a type I transmembrane glycoprotein encoded by the ADAM12 gene. ADAM12 is known to be involved in various biological processes, including cell adhesion, migration, proliferation, proteolysis, and signaling. It has been implicated in several pathological conditions, including cancer, inflammation, and developmental disorders. ADAM12 is its involved in extracellular matrix (ECM) remodeling. It can cleave ECM components such as fibronectin and type IV collagen, thereby facilitating tissue remodeling processes like wound healing and tissue repair. Additionally, ADAM12 has been shown to interact with integrins, which are cell surface receptors involved in cell adhesion and signaling, further implicating its role in cell-ECM interactions. ADAM 12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21. In cancer, ADAM12 expression levels have been found to be dysregulated in various tumor types, and its overexpression has been associated with tumor progression, invasion, and metastasis. It can promote cancer cell migration and invasion by cleaving ECM components, modulating cell adhesion, and facilitating epithelial-to-mesenchymal transition (EMT), a process implicated in cancer metastasis.

Protein Structure

ADAM12 has a complex multi-domain structure, characteristic of the ADAM family:

• Signal Peptide: Directs the protein to the secretory pathway.
• Prodomain: Involved in the folding and inhibition of protease activity until the protein is properly localized.
• Metalloprotease Domain: Contains the catalytic site with a zinc-binding motif essential for proteolytic activity.
• Disintegrin Domain: Facilitates interactions with integrins and other cell surface proteins, playing a key role in cell adhesion.
• Cysteine-Rich Domain: Important for protein stability and interactions.
• EGF-Like Domain: Contributes to protein-protein interactions.
• Transmembrane Domain: Anchors the membrane-bound form of the protein in the cell membrane.
• Cytoplasmic Tail: Involved in intracellular signaling and interactions with cytoskeletal elements.

Classification and Subtypes

ADAM12 is part of the larger ADAM family, which includes numerous members classified based on their structural domains and functional similarities. ADAM12 exists in two primary forms:

1. Membrane-Bound Form (ADAM12-L): Contains the transmembrane domain, anchoring it in the cell membrane.
2. Secreted Form (ADAM12-S): Lacks the transmembrane domain and is released into the extracellular space.

Function and Biological Significance

ADAM12 performs several critical functions:

1. Proteolysis: The metalloprotease domain is responsible for cleaving various substrates, including growth factors, cytokines, and extracellular matrix proteins.
2. Cell Adhesion: The disintegrin domain interacts with integrins, mediating cell-cell and cell-matrix adhesion.
3. Cell Signaling: Modulates signaling pathways by shedding membrane-bound precursors of signaling molecules, influencing cell proliferation, differentiation, and migration.
4. Tissue Remodeling: Involved in remodeling the extracellular matrix, which is essential during development, wound healing, and disease processes.

Interactions

ADAM12 interacts with a variety of proteins and cellular components:

1. Substrate Proteins: Cleaves substrates such as insulin-like growth factor-binding proteins (IGFBPs), facilitating the release of active growth factors.
2. Integrins: The disintegrin domain mediates interactions with integrins, affecting cell adhesion and migration.
3. Extracellular Matrix Proteins: Involved in the degradation and remodeling of extracellular matrix components.
4. Signaling Molecules: Modulates the activity of various signaling molecules, influencing pathways related to cell growth and differentiation.

Clinical Significance

The function and regulation of ADAM12 have significant implications in various diseases and conditions:

1. Cancer: ADAM12 is implicated in cancer progression and metastasis through its roles in cell adhesion, migration, and proteolysis. Overexpression of ADAM12 has been observed in several cancers, including breast, prostate, and liver cancers.
2. Fibrosis: ADAM12 contributes to tissue fibrosis by modulating extracellular matrix remodeling and influencing fibroblast activity.
3. Muscular Dystrophy: Altered expression of ADAM12 has been linked to muscle development and repair, with potential implications in muscular dystrophies.
4. Metabolic Diseases: Involved in the regulation of insulin-like growth factors, ADAM12 may play a role in metabolic disorders such as diabetes and obesity.

Summary

ADAM12, a member of the ADAM family, is integral to processes such as proteolysis, cell adhesion, signaling, and tissue remodeling. It exists in two forms: a membrane-bound form (ADAM12-L) and a secreted form (ADAM12-S). ADAM12 interacts with substrate proteins, integrins, extracellular matrix proteins, and signaling molecules. Clinically, ADAM12 is significant in the context of cancer, fibrosis, muscular dystrophy, and metabolic diseases. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its role in cellular processes and potential as a therapeutic target.