ENPP3

Function

Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (PubMed:29717535, PubMed:9344668). 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 (PubMed:12846830). In addition, displays an alkaline phosphodiesterase activity in vitro (PubMed:11342463).

Post-translational modifications

N-glycosylated. N-glycosylation is necessary for normal transport to the cell membrane, but is not the apical targeting signal.

Sequence Similarities

Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

Tissue Specificity

Detected on bile ducts in liver, and in blood serum (at protein level) (PubMed:15072822). Detected in prostate and uterus (PubMed:9344668). Detected on basophils, but not neutrophils (PubMed:11342463).

Cellular localization

• Cell membrane
• Single-pass type II membrane protein
• Apical cell membrane
• Single-pass type II membrane protein
• Secreted
• Detected at the cell surface of basophils (PubMed:11342463). Detected at the apical plasma membrane of bile duct cells (PubMed:15072822). Located to the apical surface in intestinal and kidney epithelial cells. Secreted in serum, and in lumen of epithelial cells.

Alternative names

CD203c, PDNP3, ENPP3, Ectonucleotide pyrophosphatase/phosphodiesterase family member 3, E-NPP 3, NPP3, Alkaline phosphodiesterase I, Dinucleoside polyphosphatase, Nucleotide diphosphatase, Nucleotide pyrophosphatase, Phosphodiesterase I beta, Phosphodiesterase I/nucleotide pyrophosphatase 3, NPPase, PD-Ibeta

Database links

swissprot:O14638 entrezGene:5169 entrezGene:5167 swissprot:P22413 omim:602182