ENPP1 Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels. PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect. Appears to modulate insulin sensitivity and function. Also involved in melanogenesis. Also able to hydrolyze 2'-3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production. 2'-3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2'-3'-cGAMP hydrolysis is therefore unclear. Not able to hydrolyze the 2'-3'-cGAMP linkage isomer 3'-3'-cGAMP. Belongs to the nucleotide pyrophosphatase/phosphodiesterase family. Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis (PubMed:9344668). Expressed in melanocytes but not in keratinocytes (PubMed:28964717). Note: This description may include information from UniProtKB.
Protein type: Carbohydrate Metabolism - starch and sucrose; Cofactor and Vitamin Metabolism - nicotinate and nicotinamide; Cofactor and Vitamin Metabolism - pantothenate and CoA biosynthesis; Cofactor and Vitamin Metabolism - riboflavin; EC; EC; Membrane protein, integral; Motility/polarity/chemotaxis; Nucleotide Metabolism - purine; Phosphatase (non-protein); Phosphodiesterase
Chromosomal Location of mouse Ortholog: 10 A4|10 12.26 cM
Cellular Component:  apical dendrite; basal dendrite; cell body; cell projection; cell surface; extracellular region; extracellular space; membrane; neuron projection; neuronal cell body; plasma membrane; synapse
Molecular Function:  ATP binding; calcium ion binding; cyclic-GMP-AMP hydrolase activity; dinucleotide phosphatase activity; exonuclease activity; hydrolase activity; identical protein binding; insulin receptor binding; metal ion binding; nucleic acid binding; nucleoside triphosphate diphosphatase activity; phosphatase activity; phosphodiesterase I activity; phosphoric diester hydrolase activity; polysaccharide binding; protein homodimerization activity; scavenger receptor activity; zinc ion binding
Biological Process:  3'-phosphoadenosine 5'-phosphosulfate metabolic process; adipose tissue development; adult locomotory behavior; adult walking behavior; aging; aorta development; apoptotic process involved in development; artery development; articular cartilage development; ATP metabolic process; axon regeneration; B-1 B cell homeostasis; biomineral tissue development; biomineralization; bone development; bone growth; bone mineralization; bone mineralization involved in bone maturation; bone remodeling; bone resorption; bone trabecula formation; calcium ion homeostasis; cartilage development; cell morphogenesis involved in differentiation; cell population proliferation; cellular homeostasis; cellular phosphate ion homeostasis; cellular response to insulin stimulus; cellular response to sodium phosphate; cementum mineralization; central nervous system myelination; collagen-activated signaling pathway; defense response to protozoan; determination of adult lifespan; diphosphate metabolic process; endochondral bone morphogenesis; endochondral ossification; establishment of localization in cell; fat cell differentiation; fat pad development; fatty acid metabolic process; fibroblast growth factor receptor signaling pathway; gene expression; generation of precursor metabolites and energy; glucose homeostasis; glucose import; glycolytic process; heart development; hematopoietic stem cell migration to bone marrow; hormone metabolic process; immune response; immunoglobulin production involved in immunoglobulin-mediated immune response; inflammatory response to antigenic stimulus; inorganic diphosphate transport; kidney development; leukocyte activation involved in inflammatory response; ligamentous ossification; long-term synaptic potentiation; macrophage differentiation; magnesium ion homeostasis; melanocyte differentiation; microglia differentiation; microglial cell migration; middle ear morphogenesis; mitochondrion organization; morphogenesis of an epithelium; mRNA transcription by RNA polymerase II; mucus secretion; multicellular organism aging; multicellular organism growth; negative regulation of bone mineralization; negative regulation of cell growth; negative regulation of fat cell differentiation; negative regulation of glucose import; negative regulation of glycogen biosynthetic process; negative regulation of hh target transcription factor activity; negative regulation of insulin receptor signaling pathway; negative regulation of ossification; negative regulation of protein autophosphorylation; neuron apoptotic process; nitrogen compound metabolic process; nucleic acid phosphodiester bond hydrolysis; nucleoside triphosphate catabolic process; odontogenesis; oligodendrocyte apoptotic process; organic phosphonate metabolic process; ossification; osteoblast differentiation; osteoclast differentiation; phosphate ion homeostasis; phosphate-containing compound metabolic process; plasma cell differentiation; post-embryonic forelimb morphogenesis; protein poly-ADP-ribosylation; regulation of bone mineralization; response to ATP; response to dietary excess; response to Gram-positive bacterium; response to inorganic substance; response to insulin; response to L-ascorbic acid; response to magnesium ion; response to platelet-derived growth factor; response to sodium phosphate; response to vitamin B6; response to wounding; sensory perception of mechanical stimulus; sensory perception of sound; sensory perception of temperature stimulus; sequestering of triglyceride; skin development; smoothened signaling pathway; spinal cord development; T cell differentiation; tooth mineralization; type II interferon production; vascular associated smooth muscle cell migration; vascular associated smooth muscle cell proliferation; vasculogenesis; vitamin D3 metabolic process; Wnt signaling pathway
Reference #:  P06802 (UniProtKB)
Alt. Names/Synonyms: 1 ectonucleotide pyrophosphatase/phosphodiesterase 1; 4833416E15Rik; AI428932; Alkaline phosphodiesterase I; C76301; CD203c; E-N; E-NPP 1; E-NPP1; ectonucleotide pyrophosphatase/phosphodiesterase 1; Ectonucleotide pyrophosphatase/phosphodiesterase family member 1; Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form; Enpp1; Ly-4; Ly-41; Lymphocyte antigen 41; M6S1; NPP1; NPPase; Npps; Nucleotide diphosphatase; Nucleotide pyrophosphatase; OTTMUSP00000021307; PC-; PC-1; Pc1; Pca; Pca-1; Pdnp1; Phosphodiesterase I/nucleotide pyrophosphatase 1; Plasma-cell membrane glycoprotein PC-1; tiptoe walking; ttw; twy
Gene Symbols: Enpp1
Molecular weight: 103,176 Da
Basal Isoelectric point: 6.14  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein