A disintegrin and metalloproteinase domain-containing protein 15 (ADAM15)

A disintegrin and metalloproteinase domain-containing protein 15 (ADAM15) is a unique member of the ADAM family, notable for being the only human ADAM containing an Arg-Gly-Asp (RGD) motif in its disintegrin-like domain. This dual-function transmembrane protein acts both as a zinc-dependent metalloprotease involved in the 'shedding' of cell-surface proteins and as an adhesion molecule that interacts with integrins such as alpha-v/beta-3 and alpha-5/beta-1. These activities allow ADAM15 to modulate critical cellular processes, including extracellular matrix remodeling, angiogenesis, and cell-cell signaling [1][9]. In pathological contexts, ADAM15 is significantly upregulated in various cancers (including prostate and breast) and chronic inflammatory diseases like rheumatoid arthritis, where it promotes tumor invasion, neovascularization, and apoptosis resistance [2][7]. Although it represents an attractive therapeutic target, the development of clinical drugs has been challenged by the lack of selectivity in small-molecule inhibitors. Current research is largely focused on monoclonal antibodies and selective peptides designed to target its specific adhesive or catalytic domains to minimize off-target toxicity [3][13].

Other names

ADAM metallopeptidase domain 15MDC15MetargidinMetalloprotease RGD disintegrin proteinMetalloproteinase-like, disintegrin-like, and cysteine-rich protein 15

Inhibition of zinc-dependent catalytic activity, Antagonism of integrin-binding (RGD-motif blockade), Disruption of ERK/MEK signaling pathways, Inhibition of ectodomain shedding of pro-inflammatory or pro-oncogenic ligands.