ENPP3

Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP. Also hydrolyzes extracellular 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production, and is therefore involved in the regulation of innate immune response. 2',3'-cGAMP appears to be further processed to GMP, AMP and inorganic phosphate. Limits mast cells and basophils response during inflammation and during the chronic phases of allergic responses by eliminating extracellular ATP, a signaling molecule activating these cells in an autocrine manner. Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (By similarity). Has a broad specificity and can also hydrolyze UDP-GlcNAc into UMP and GlcNAc-1-phosphate and potentially several other intracellular nucleotide sugars, including UDP-GalNAc, CMP-NeuAc, GDP-Fuc, and UDP-GlcA. Thereby, could modulate glycan biosynthesis and protein glycosylation (By similarity). Can hydrolyze extracellular dinucleoside polyphosphates, including the vasoactive adenosine polyphosphates as well. In addition, displays an alkaline phosphodiesterase activity in vitro..

Function from UniProtKB (O14638), read 2026-09-23. CC BY 4.0.