GLPG-1690

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

ENPP2 also known as Autotaxin (ATX) is a multifunctional enzyme with phosphodiesterase activity. It breaks down lysophosphatidylcholine into lysophosphatidic acid (LPA) and glycerol phosphate. With a molecular mass of approximately 100 kDa ENPP2 is secreted into extracellular environments. This protein is mainly expressed in adipose tissue but researchers found its presence in other tissues such as the brain and the liver as well.

Biological function summary

ENPP2/ATX plays an important role in processes like cell proliferation migration and survival by producing LPA a bioactive lysophospholipid. LPA acts as a signaling molecule by binding to its specific G-protein-coupled receptors. ENPP2 exists as a monomer and does not form a stable part of a larger protein structure. Its enzymatic activity in generating LPA influences various cellular responses and physiologic states.

Pathways

It is evident that ENPP2 is involved in the LPA signaling pathway and metabolic processes related to phospholipids. The LPA signaling pathway in particular links ENPP2 to proteins such as LPAR1 and LPAR2 which bind LPA and initiate downstream effects. ENPP2's enzymatic product LPA further participates in pathways influencing cellular responses like inflammation and angiogenesis.

Research highlights ENPP2's involvement in diseases such as cancer and fibrosis. ENPP2 activity is upregulated in several cancers leading to enhanced tumor cell motility and invasion. It is also linked to fibrosis particularly liver fibrosis due to its role in producing LPA which promotes fibrotic responses. In the context of these diseases ENPP2 interacts with proteins like MMPs (matrix metalloproteinases) in cancer invasion exemplifying its contribution to pathological conditions.