Adam10

ADAM10, or a disintegrin and metalloprotease 10, is a membrane-anchored sheddase belonging to the ADAM family of zinc-dependent proteases. It functions primarily to proteolytically release the extracellular domains of various transmembrane proteins, a process known as ectodomain shedding, thereby modulating signaling, adhesion, and receptor activity. ADAM10 is widely expressed in many tissues and is particularly important during development and in the nervous system.

Structurally, ADAM10 is a type I transmembrane protein consisting of a prodomain, a metalloprotease catalytic domain with the zinc-binding HEXGH motif, a disintegrin-like domain, a cysteine-rich region, an epidermal growth factor (EGF)-like domain, and a short cytoplasmic tail. The prodomain maintains the enzyme in an inactive state until proteolytic removal by proprotein convertases such as furin. Maturation and trafficking to the cell surface are aided by tetraspanin proteins of the TSPANC8 family, which influence substrate selectivity.

ADAM10 cleaves a variety of substrates, including Notch ligands such as Delta-like and Jagged family members, and participates in the Notch signaling pathway by mediating the S2 proteolysis of the Notch receptor upon ligand engagement. It also acts as the principal alpha-secretase for the amyloid precursor protein (APP), promoting non-amyloidogenic processing. Other substrates include adhesion molecules such as E-cadherin and L1CAM, receptors, and cytokine or growth factor receptors, impacting cell adhesion and signaling.

Regulation of ADAM10 activity is responsive to cellular context and can be influenced by phosphorylation, calcium signaling, and interacting proteins. It is broadly expressed with important roles in development, neural function, and immune processes.

Deregulation of ADAM10 has been linked to diseases such as cancer and neurodegenerative disorders, and the enzyme is a subject of study as a potential therapeutic target to modulate Notch signaling or APP processing.