Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1)

M6S1; NPP1; NPPS; PC-1; PCA1; PDNP1; Membrane component chromosome 6 surface marker 1; Alkaline phosphodiesterase I; Plasma-cell membrane glycoprotein PC-1

SPN	R582
HGNC	3356
MGI	97370
PubMed	23375129
RGD	628825
UniProt	P22413

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with 'idiopathic' infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance.

Reference

"Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location."
J. Biol. Chem. 265:17506-17511(1990) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase."
Arch. Biochem. Biophys. 295:180-187(1992) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and analysis of human chromosome 6."
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance."
Diabetes 48:1881-1884(1999) [PubMed] [Europe PMC] [Abstract]

"Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities."
Eur. J. Biochem. 226:433-443(1994) [PubMed] [Europe PMC] [Abstract]

"Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site."
Eur. J. Biochem. 228:669-676(1995) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes."
Genomics 45:412-415(1997) [PubMed] [Europe PMC] [Abstract]

"Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit."
Diabetes 49:13-19(2000) [PubMed] [Europe PMC] [Abstract]

"Characterization of a di-leucine-based signal in the cytoplasmic tail of the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not endocytosis."
Mol. Biol. Cell 12:3004-3015(2001) [PubMed] [Europe PMC] [Abstract]

"Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases."
Cancer Lett. 207:139-147(2004) [PubMed] [Europe PMC] [Abstract]

"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]

"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the somatomedin B domain of human ectonucleotide pyrophosphatase/phosphodiesterase family member."
Submitted (OCT-2007) to the PDB data bank

"Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL)."
Hum. Genet. 104:492-497(1999) [PubMed] [Europe PMC] [Abstract]

"Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification."
Nat. Genet. 34:379-381(2003) [PubMed] [Europe PMC] [Abstract]

"Generalized arterial calcification of infancy: different clinical courses in two affected siblings."
Am. J. Med. Genet. A 136:210-213(2005) [PubMed] [Europe PMC] [Abstract]

"The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction."
Diabetes 54:3021-3025(2005) [PubMed] [Europe PMC] [Abstract]

"The mutational spectrum oENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI)."
Hum. Mutat. 25:98-98(2005) [PubMed] [Europe PMC] [Abstract]

"Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets."
Am. J. Hum. Genet. 86:267-272(2010) [PubMed] [Europe PMC] [Abstract]

"Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene."
Am. J. Hum. Genet. 86:273-278(2010) [PubMed] [Europe PMC] [Abstract]

"An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy."
Am. J. Med. Genet. A 152:118-123(2010) [PubMed] [Europe PMC] [Abstract]

"Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6."
Am. J. Hum. Genet. 90:25-39(2012) [PubMed] [Europe PMC] [Abstract]

"Cole disease results from mutations in ENPP1."
Am. J. Hum. Genet. 93:752-757(2013) [PubMed] [Europe PMC] [Abstract]