ID:ENPP1_HUMAN DESCRIPTION: RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 1; Short=E-NPP 1; AltName: Full=Membrane component chromosome 6 surface marker 1; AltName: Full=Phosphodiesterase I/nucleotide pyrophosphatase 1; AltName: Full=Plasma-cell membrane glycoprotein PC-1; Includes: RecName: Full=Alkaline phosphodiesterase I; EC=3.1.4.1; Includes: RecName: Full=Nucleotide pyrophosphatase; Short=NPPase; EC=3.6.1.9; FUNCTION: 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. CATALYTIC ACTIVITY: Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides. CATALYTIC ACTIVITY: A dinucleotide + H(2)O = 2 mononucleotides. COFACTOR: Binds 2 divalent metal cations per subunit (Probable). ENZYME REGULATION: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis. SUBUNIT: Homodimer; disulfide-linked. Interacts with INSR. SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Note=Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side. TISSUE SPECIFICITY: Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis. DOMAIN: The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells (By similarity). PTM: Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity. PTM: N-glycosylated. PTM: It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both. DISEASE: Defects in ENPP1 are a cause of increased susceptibility for ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]. OPLL is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups. DISEASE: Defects in ENPP1 are the cause of arterial calcification of infancy, generalized, type 1 (GACI1) [MIM:208000]. A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. DISEASE: Defects in ENPP1 are associated with obesity, glucose intolerance, and type II diabetes non-insulin dependent (NIDDM) [MIM:125853]. DISEASE: Defects in ENPP1 are the cause of rickets hypophosphatemic autosomal recessive type 2 (ARHR2) [MIM:613312]. ARHR2 is a hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities. SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family. SIMILARITY: Contains 2 SMB (somatomedin-B) domains. CAUTION: It is uncertain whether Met-1 or Met-53 is the initiator. SEQUENCE CAUTION: Sequence=AAA63237.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH59375.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA02054.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P22413
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006091 generation of precursor metabolites and energy GO:0006771 riboflavin metabolic process GO:0006796 phosphate-containing compound metabolic process GO:0006898 receptor-mediated endocytosis GO:0006955 immune response GO:0008152 metabolic process GO:0009143 nucleoside triphosphate catabolic process GO:0030308 negative regulation of cell growth GO:0030500 regulation of bone mineralization GO:0030505 inorganic diphosphate transport GO:0030643 cellular phosphate ion homeostasis GO:0030730 sequestering of triglyceride GO:0031214 biomineral tissue development GO:0031953 negative regulation of protein autophosphorylation GO:0032869 cellular response to insulin stimulus GO:0045599 negative regulation of fat cell differentiation GO:0045719 negative regulation of glycogen biosynthetic process GO:0046034 ATP metabolic process GO:0046325 negative regulation of glucose import GO:0046627 negative regulation of insulin receptor signaling pathway GO:0050427 3'-phosphoadenosine 5'-phosphosulfate metabolic process GO:0090305 nucleic acid phosphodiester bond hydrolysis
BioCyc Knowledge Library PWY-7184 - pyrimidine deoxyribonucleotides de novo biosynthesis PWY-7211 - superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
BioCarta from NCI Cancer Genome Anatomy Project h_npp1Pathway - Regulators of Bone Mineralization
Reactome (by CSHL, EBI, and GO)
Protein P22413 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
