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 Human Ortholog: 6q23.2
Cellular Component:  basolateral plasma membrane; cell surface; extracellular space; integral component of membrane; integral component of plasma membrane; plasma membrane
Molecular Function:  3'-phosphoadenosine 5'-phosphosulfate binding; ATP binding; calcium ion binding; exonuclease activity; insulin receptor binding; NADH pyrophosphatase activity; nucleic acid binding; nucleoside-triphosphate diphosphatase activity; nucleotide diphosphatase activity; phosphodiesterase I activity; polysaccharide binding; protein binding; protein homodimerization activity; scavenger receptor activity; zinc ion binding
Biological Process:  3'-phosphoadenosine 5'-phosphosulfate metabolic process; ATP metabolic process; biomineral tissue development; cellular phosphate ion homeostasis; cellular response to insulin stimulus; generation of precursor metabolites and energy; immune response; inorganic diphosphate transport; melanocyte differentiation; 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 protein autophosphorylation; nucleic acid phosphodiester bond hydrolysis; nucleoside triphosphate catabolic process; phosphate-containing compound metabolic process; regulation of bone mineralization; riboflavin metabolic process; sequestering of triglyceride; vesicle-mediated transport
Disease: Arterial Calcification, Generalized, Of Infancy, 1; Cole Disease; Diabetes Mellitus, Noninsulin-dependent; Hypophosphatemic Rickets, Autosomal Recessive, 2; Obesity
Reference #:  P22413 (UniProtKB)
Alt. Names/Synonyms: alkaline phosphodiesterase 1; Alkaline phosphodiesterase I; ARHR2; COLED; E-NPP 1; ectonucleotide pyrophosphatase/phosphodiesterase 1; Ectonucleotide pyrophosphatase/phosphodiesterase family member 1; Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form; ENPP1; Ly-41 antigen; M6S1; Membrane component chromosome 6 surface marker 1; membrane component, chromosome 6, surface marker 1; NPP1; NPPase; NPPS; Nucleotide diphosphatase; Nucleotide pyrophosphatase; PC-1; PC1; PCA1; PDNP1; Phosphodiesterase I/nucleotide pyrophosphatase 1; plasma-cell membrane glycoprotein 1; Plasma-cell membrane glycoprotein PC-1
Gene Symbols: ENPP1
Molecular weight: 104,924 Da
Basal Isoelectric point: 6.76  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene