Nucleotide Pyrophosphatase 1

From Anvita Health Wiki

Contents 1 Function 2 Structure 3 Compartment 4 Expression 5 Pathology 6 Notes 7 More General Terms 8 Internet Database 9 References

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

Structure

• 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

Compartment

• 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

Expression

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

Pathology

• 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

Notes

• uncertain whether Met-1 or Met-53 is the initiator

More General Terms

• phosphodiesterase I/nucleotide pyrophosphatase
• nucleotidase
• glycoprotein
• membrane protein

Internet Database

Entrez gene: 5167
Kegg: [1]
OMIM: 125853
OMIM: 173335
OMIM: 208000
OMIM: 602475
OMIM: 613312
Prosite: [2]
Prosite: [3]
UniProt: [4]

References

UniProt [5]

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)