ectonucleotide pyrophosphatase/phosphodiesterase family member 1; E-NPP 1; membrane component chromosome 6 surface marker 1; phosphodiesterase I/nucleotide pyrophosphatase 1; plasma-cell membrane glycoprotein PC-1; includes: alkaline phosphodiesterase I; nucleotide pyrophosphatase; NPPase (ENPP1, M6S1, NPPS, PC1, PDNP1)

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Function

role primarily in ATP hydrolysis at the plasma membrane
role in regulating pyrophosphate levels
functions in bone mineralization
in vitro, has a broad specificity, hydrolyzing other nucleoside 5' triphosphates including as GTP, CTP, TTP & UTP to their corresponding monophosphates with release of pyrophosphate & diadenosine polyphosphates
hydrolyzes 3',5'-cAMP to AMP
may also be involved in regulation of availability of nucleotide sugars in the endoplasmic reticulum & Golgi, & the regulation of purinergic signaling
appears to modulate insulin sensitivity
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
at low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis
autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity

Cofactor:

binds 2 divalent metal cations per subunit (probable) homodimer; disulfide-linked

N-glycosylated
the di-leucine motif is required for basolateral targeting in epithelial cells, & for targeting to matrix vesicles derived from mineralizing cells (putative)
contains 2 SMB (somatomedin-B) domains
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
belongs to the nucleotide pyrophosphatase/phosphodiesterase family

membrane; single-pass type 2 membrane protein
basolateral cell membrane
targeted to the basolateral membrane in polarized epithelial cells & in hepatocytes, & to matrix vesicles in osteoblasts
in bile duct cells & cancer cells, located to the apical cytoplasmic side

expressed in plasma cells & also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes & epididymis

role in soft tissue calcification
defects in ENPP1 are a cause of
- increased susceptibility for ossification of the posterior longitudinal ligament of the spine
- idiopathic infantile arterial calcification
defects in ENPP1 are associated with metabolic syndrome X
defects in ENPP1 are the cause of hypophosphatemic rickets, autosomal recessive type 2