ENPP1: Involved primarily in ATP hydrolysis at the plasma membrane. Plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. In vitro, has a broad specificity, hydrolyzing 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. Appears to modulate insulin sensitivity. Homodimer; disulfide-linked. Interacts with INSR. Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis. At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis. Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
Protein type: Membrane protein, integral; EC 3.1.4.1; EC 3.6.1.9; Motility/polarity/chemotaxis; Carbohydrate Metabolism - starch and sucrose; Nucleotide Metabolism - purine; Phosphodiesterase; Cofactor and Vitamin Metabolism - riboflavin; Phosphatase (non-protein); Cofactor and Vitamin Metabolism - nicotinate and nicotinamide; Cofactor and Vitamin Metabolism - pantothenate and CoA biosynthesis
Chromosomal Location of Human Ortholog: 6q22-q23
Cellular Component: extracellular space; cell surface; basolateral plasma membrane; lysosomal membrane; integral to plasma membrane; integral to membrane; plasma membrane
Molecular Function: phosphodiesterase I activity; nucleotide diphosphatase activity; protein homodimerization activity; 3'-phosphoadenosine 5'-phosphosulfate binding; zinc ion binding; calcium ion binding; nucleoside-triphosphate diphosphatase activity; insulin receptor binding; polysaccharide binding; protein binding; nucleic acid binding; ATP binding; scavenger receptor activity
Biological Process: receptor-mediated endocytosis; generation of precursor metabolites and energy; sequestering of triacylglycerol; vitamin metabolic process; nucleoside triphosphate catabolic process; negative regulation of insulin receptor signaling pathway; negative regulation of fat cell differentiation; bone remodeling; phosphate metabolic process; 3'-phosphoadenosine 5'-phosphosulfate metabolic process; riboflavin metabolic process; negative regulation of glucose import; cellular phosphate ion homeostasis; cellular response to insulin stimulus; biomineral formation; negative regulation of ossification; negative regulation of protein amino acid autophosphorylation; immune response; negative regulation of cell growth; regulation of bone mineralization; water-soluble vitamin metabolic process; inorganic diphosphate transport; negative regulation of glycogen biosynthetic process
Disease: Obesity; Cole Disease; Arterial Calcification, Generalized, Of Infancy, 1; Hypophosphatemic Rickets, Autosomal Recessive, 2; Diabetes Mellitus, Noninsulin-dependent
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