ENPP-2/Autotaxin: Proteins and Enzymes

ENPP-2, also known as Autotaxin, belongs to the ectonucleotide pyrophosphatase/phosphodiesterase (NPP) family. Some NPPs hydrolyze phosphates from nucleotides and their derivatives. ENPP-2 shares 40 - 50% identity to ENPP1 & 3, all of which contain a N-terminal intracellular domain, a single transmembrane domain and a large extracellular domain that includes a catalytic domain, two somatomedin-B-like domains, and a C-terminal nuclease-like domain. Unlike ENPP-1 and ENPP-3, ENPP-2 has weak activity against nucleotides, but exhibits a lysophospholipase D activity which allows the formation of lysophosphatidic acid (LPA) and choline from lysophosphatidylcholine. The hydrolysis of nucleotides and lysophospholipids by ENPP-2 is mediated by a single catalytic site. Evidence shows LPA and sphingosine 1-phosphate to be specific inhibitors of ENPP-2. ENPP-2 was originally found to stimulate tumor cell motility and has since been found to enhance tumor invasion and metastasis and to be up-regulated in several types of carcinomas including breast and lung.