A disintegrin and metalloproteinase

A disintegrin and metalloproteinase
Identifiers
EC number	Various
CAS number	Various
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

A disintegrin and metalloproteinase (ADAM) is a family of enzymes classified under the peptidase M12 family, primarily known for their roles in cell signaling and adhesion. These enzymes are characterized by their ability to cleave specific protein substrates at the cell surface, a process crucial for various biological functions including cell migration, cellular adhesion, and protein processing.

Structure

ADAM enzymes are multi-domain proteins that typically include a pro-domain that maintains enzyme latency, a metalloprotease domain that performs the proteolytic activity, a disintegrin domain that mediates cell-cell and cell-matrix interactions, a cysteine-rich domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic tail. The metalloprotease domain contains a zinc-binding site essential for its proteolytic activity.

Function

ADAMs are involved in a variety of cellular processes. One of their primary functions is the shedding of membrane-bound protein ectodomains, a regulatory process in the modulation of cell surface protein levels, including growth factors, cytokines, and receptors. This activity is crucial in processes such as cell signaling, immune response, and neural development.

ADAMs also play a significant role in the regulation of the Notch signaling pathway, which is essential for proper cell differentiation, proliferation, and apoptosis. By cleaving the extracellular domain of Notch receptors, ADAMs facilitate the activation of the pathway, influencing cell fate determination.

Clinical Significance

Alterations in the expression or activity of ADAM proteins have been linked to various diseases, including cancer, inflammatory diseases, and neurodegenerative diseases. For instance, overexpression of certain ADAMs has been observed in various cancers, where they may contribute to tumor progression by enhancing tumor cell proliferation, migration, and invasion.

In the context of inflammation, ADAMs can regulate the release of inflammatory cytokines and growth factors, thereby influencing inflammatory responses. In neurodegenerative diseases, such as Alzheimer's disease, ADAM10, for example, is known to play a role in the processing of the amyloid precursor protein, which is central to the pathogenesis of the disease.

Research

Research on ADAMs continues to explore their potential as therapeutic targets. Inhibitors of specific ADAMs are being studied for their potential to treat pathological conditions related to excessive protease activity, including cancer and inflammatory diseases.

See Also

• Metalloproteinase
• Enzyme
• Cell signaling
• Protein processing