A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12)

A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) is an extracellular zinc-dependent metalloproteinase that is part of the ADAMTS family, characterized by a multidomain structure including a metalloprotease domain, disintegrin-like domain, thrombospondin type 1 motifs, and additional C-terminal domains. ADAMTS12 cleaves key extracellular matrix proteins such as cartilage oligomeric matrix protein (COMP), alpha-2 macroglobulin, and aggrecan, playing important roles in cartilage homeostasis, inflammation, cancer, and neurological disease. It is involved in both pro- and anti-inflammatory processes and has been described as having tumor suppressor properties in certain contexts; however, depending on biological environment, it may contribute to pathological tissue remodeling. ADAMTS12 activity and expression are regulated by cytokines, cell interactions, and may generate cleavage products with biomarker potential for arthritis and other diseases.

Other names

ADAM metallopeptidase with thrombospondin type 1 motif 12ADAMTS12ADAM-TS 12ADAM-TS12ADAMTS-12PRO4389UNQ1918/PRO4389a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 12

ADAMTS12 primarily acts through proteolytic cleavage of extracellular matrix substrates and inhibitors, including COMP, alpha-2 macroglobulin, and aggrecan. It also modulates inflammatory signaling pathways, such as the ERK pathway and Runx2 signaling, contributing to its anti-tumorigenic activity through ERK pathway modulation.