Names & Taxonomy

Uniprot ID:
P22413
Entry Name:
ENPP1_HUMAN
Status:
reviewed
Protein Names:
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 (EC 3.1.4.1); Nucleotide pyrophosphatase (NPPase) (EC 3.6.1.9)]
Gene Names:
ENPP1 M6S1 NPPS PC1 PDNP1
Gene Names Primary:
ENPP1
Organism:
Homo sapiens (Human)

Structure

Length:
925
Sequence:
MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPLEKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNCRCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINYSSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKKCGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEWYKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLPKDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLILISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSCREPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNVFSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVYTPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYGRPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPLSPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTLLRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKDTSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSFYQQRKEPVSDILKLKTHLPTFSQED
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Secreted

Function

Function:
By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze 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 and function.
Catalytic Activity:
Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.
Cofactor:
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
Enzyme Regulation:
ENZYME REGULATION: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.
Active Site:
ACT_SITE 256 256 AMP-threonine intermediate.
Cross Reference Drug Bank:
DB01143 DB00811
Gene Ontology Go:
basolateral plasma membrane
cell surface
extracellular space
integral component of membrane
integral component of plasma membrane
lysosomal membrane
plasma membrane
3'-phosphoadenosine 5'-phosphosulfate binding
ATP binding
calcium ion binding
insulin receptor binding
NADH pyrophosphatase activity
nucleic acid binding
nucleoside-triphosphate diphosphatase activity
nucleotide diphosphatase activity
phosphodiesterase I activity
polysaccharide binding
protein homodimerization activity
scavenger receptor activity
zinc ion binding
3'-phosphoadenosine 5'-phosphosulfate metabolic process
biomineral tissue development
cellular phosphate ion homeostasis
cellular response to insulin stimulus
generation of precursor metabolites and energy
immune response
inorganic diphosphate transport
negative regulation of cell growth
negative regulation of fat cell differentiation
negative regulation of glucose import
negative regulation of glycogen biosynthetic process
negative regulation of insulin receptor signaling pathway
negative regulation of protein autophosphorylation
nucleic acid phosphodiester bond hydrolysis
nucleoside triphosphate catabolic process
phosphate-containing compound metabolic process
regulation of bone mineralization
riboflavin metabolic process
sequestering of triglyceride
small molecule metabolic process
vitamin metabolic process
water-soluble vitamin metabolic process
Gene Ontology Biological Process:
3'-phosphoadenosine 5'-phosphosulfate metabolic process
biomineral tissue development
cellular phosphate ion homeostasis
cellular response to insulin stimulus
generation of precursor metabolites and energy
immune response
inorganic diphosphate transport
negative regulation of cell growth
negative regulation of fat cell differentiation
negative regulation of glucose import
negative regulation of glycogen biosynthetic process
negative regulation of insulin receptor signaling pathway
negative regulation of protein autophosphorylation
nucleic acid phosphodiester bond hydrolysis
nucleoside triphosphate catabolic process
phosphate-containing compound metabolic process
regulation of bone mineralization
riboflavin metabolic process
sequestering of triglyceride
small molecule metabolic process
vitamin metabolic process
water-soluble vitamin metabolic process
Gene Ontology Molecular Function:
3'-phosphoadenosine 5'-phosphosulfate binding
ATP binding
calcium ion binding
insulin receptor binding
NADH pyrophosphatase activity
nucleic acid binding
nucleoside-triphosphate diphosphatase activity
nucleotide diphosphatase activity
phosphodiesterase I activity
polysaccharide binding
protein homodimerization activity
scavenger receptor activity
zinc ion binding
Gene Ontology Cellular Component:
basolateral plasma membrane
cell surface
extracellular space
integral component of membrane
integral component of plasma membrane
lysosomal membrane
plasma membrane
Keywords:
3D-structure
Biomineralization
Calcium
Cell membrane
Complete proteome
Diabetes mellitus
Direct protein sequencing
Disease mutation
Disulfide bond
Glycoprotein
Hydrolase
Membrane
Metal-binding
Obesity
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Secreted
Signal-anchor
Transmembrane
Transmembrane helix
Zinc
Interacts With:
P06213

Publication

PubMed ID:
2211644 1315502 14574404 15489334 10480624 8001561 7737162 9344668 10615944 11598187 15072822 19159218 19349973 24275569 10453738 12881724 15940697 16186408 15605415 20137773 20137772 20034067 22209248 24075184