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Aliases for ENPP1 Gene

Aliases for ENPP1 Gene

  • Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 2 3
  • PDNP1 3 4 6
  • M6S1 3 4 6
  • NPPS 3 4 6
  • Membrane Component Chromosome 6 Surface Marker 1 3 4
  • Phosphodiesterase I/Nucleotide Pyrophosphatase 1 3 4
  • Plasma-Cell Membrane Glycoprotein PC-1 3 4
  • E-NPP 1 3 4
  • ARHR2 3 6
  • COLED 3 6
  • PCA1 3 6
  • Ectonucleotide Pyrophosphatase/Phosphodiesterase Family Member 1 3
  • Membrane Component, Chromosome 6, Surface Marker 1 3
  • Plasma-Cell Membrane Glycoprotein 1 3
  • Alkaline Phosphodiesterase 1 3
  • Ly-41 Antigen 3
  • NPP1 3
  • PC-1 3
  • PC1 4

External Ids for ENPP1 Gene

Previous Symbols for ENPP1 Gene

  • NPPS
  • M6S1
  • PDNP1

Summaries for ENPP1 Gene

Entrez Gene Summary for ENPP1 Gene

  • This gene 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. [provided by RefSeq, Jul 2008]

GeneCards Summary for ENPP1 Gene

ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) is a Protein Coding gene. Diseases associated with ENPP1 include hypophosphatemic rickets, autosomal recessive, 2 and cole disease. Among its related pathways are Disease and Endochondral Ossification. GO annotations related to this gene include protein homodimerization activity and scavenger receptor activity. An important paralog of this gene is ENPP3.

UniProtKB/Swiss-Prot for ENPP1 Gene

  • 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.

Gene Wiki entry for ENPP1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ENPP1 Gene

Genomics for ENPP1 Gene

Genomic Location for ENPP1 Gene

Start:
131,808,016 bp from pter
End:
131,895,155 bp from pter
Size:
87,140 bases
Orientation:
Plus strand

Genomic View for ENPP1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ENPP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ENPP1 Gene

Regulatory Elements for ENPP1 Gene

Proteins for ENPP1 Gene

  • Protein details for ENPP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P22413-ENPP1_HUMAN
    Recommended name:
    Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
    Protein Accession:
    P22413
    Secondary Accessions:
    • Q5T9R6
    • Q9NPZ3
    • Q9P1P6
    • Q9UP61
    • Q9Y6K3

    Protein attributes for ENPP1 Gene

    Size:
    925 amino acids
    Molecular mass:
    104924 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 2 Zn(2+) ions per subunit.;
    Quaternary structure:
    • The secreted form is monomeric (By similarity). Homodimer. Interacts with INSR.
    SequenceCaution:
    • Sequence=AAA63237.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAH59375.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA02054.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ENPP1 Gene

neXtProt entry for ENPP1 Gene

Proteomics data for ENPP1 Gene at MOPED

Post-translational modifications for ENPP1 Gene

  • A secreted form is produced through cleavage at Lys-103 by intracellular processing.
  • Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity
  • N-glycosylated.
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn179, Asn285, Asn341, Asn477, Asn585, Asn643, Asn700, Asn731, and Asn748

Other Protein References for ENPP1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for ENPP1 Gene

Domains for ENPP1 Gene

UniProtKB/Swiss-Prot:

ENPP1_HUMAN
Domain:
  • The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.:
    • P22413
  • Contains 2 SMB (somatomedin-B) domains.:
    • P22413
Family:
  • Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.:
    • P22413
genes like me logo Genes that share domains with ENPP1: view

No data available for Gene Families for ENPP1 Gene

Function for ENPP1 Gene

Molecular function for ENPP1 Gene

UniProtKB/Swiss-Prot CatalyticActivity: Hydrolytically removes 5-nucleotides successively from the 3-hydroxy termini of 3-hydroxy-terminated oligonucleotides.
UniProtKB/Swiss-Prot CatalyticActivity: A dinucleotide + H(2)O = 2 mononucleotides.
UniProtKB/Swiss-Prot EnzymeRegulation: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis
UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for ENPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003824 catalytic activity --
GO:0004528 phosphodiesterase I activity ISS --
GO:0004551 nucleotide diphosphatase activity TAS --
GO:0005044 scavenger receptor activity IEA --
genes like me logo Genes that share ontologies with ENPP1: view
genes like me logo Genes that share phenotypes with ENPP1: view

Animal Models for ENPP1 Gene

MGI Knock Outs for ENPP1:

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for ENPP1 Gene

Localization for ENPP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ENPP1 Gene

Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Secreted. Note=The proteolytically processed form is secreted (By similarity). 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. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ENPP1 Gene COMPARTMENTS Subcellular localization image for ENPP1 gene
Compartment Confidence
plasma membrane 5
extracellular 4
cytosol 2
mitochondrion 1
nucleus 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for ENPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 11159191
GO:0005765 lysosomal membrane IDA 17897319
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane ISS --
GO:0009986 cell surface IDA 10513816
genes like me logo Genes that share ontologies with ENPP1: view

Pathways for ENPP1 Gene

SuperPathways for ENPP1 Gene

Superpath Contained pathways
1 Defective BTD causes biotidinase deficiency
2 Metabolism
3 Nicotinate and nicotinamide metabolism
4 Disease
5 Endochondral Ossification
genes like me logo Genes that share pathways with ENPP1: view

Pathways by source for ENPP1 Gene

1 GeneGo (Thomson Reuters Life Sciences Research) pathway for ENPP1 Gene
1 Cell Signaling Technology pathway for ENPP1 Gene
2 BioSystems pathways for ENPP1 Gene

Gene Ontology (GO) - Biological Process for ENPP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006091 generation of precursor metabolites and energy IDA 12746903
GO:0006200 obsolete ATP catabolic process --
GO:0006766 vitamin metabolic process TAS --
GO:0006767 water-soluble vitamin metabolic process TAS --
GO:0006771 riboflavin metabolic process TAS --
genes like me logo Genes that share ontologies with ENPP1: view

Compounds for ENPP1 Gene

(20) HMDB Compounds for ENPP1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine 3',5'-diphosphate
  • 3,5-Diphosphoadenosine
1053-73-2
Adenosine monophosphate
  • 5'-AMP
61-19-8
Alpha-D-Glucose
  • Hexopyranose
492-62-6
Cyclic AMP
  • Cyclic AMP
60-92-4
Dephospho-CoA
  • 3'-O-dephosphono-Coenzyme A
3633-59-8

(2) Drugbank Compounds for ENPP1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Amifostine
  • Amifostine Ethiofos
20537-88-6 target inducer
Ribavirin
  • RBV
36791-04-5 target inhibitor

(21) Novoseek inferred chemical compound relationships for ENPP1 Gene

Compound -log(P) Hits PubMed IDs
npps 90.2 32
pdnp 79.7 2
pyrophosphate 79.7 21
5-nucleotide 79.6 5
glucose 46 26
genes like me logo Genes that share compounds with ENPP1: view

Transcripts for ENPP1 Gene

Unigene Clusters for ENPP1 Gene

Ectonucleotide pyrophosphatase/phosphodiesterase 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ENPP1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
SP1: -
SP2: -

ExUns: 24 ^ 25
SP1:
SP2:

Relevant External Links for ENPP1 Gene

GeneLoc Exon Structure for
ENPP1
ECgene alternative splicing isoforms for
ENPP1

Expression for ENPP1 Gene

mRNA expression in normal human tissues for ENPP1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ENPP1 Gene

This gene is overexpressed in Liver (6.3) and Uterus (5.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for ENPP1 Gene

SOURCE GeneReport for Unigene cluster for ENPP1 Gene Hs.527295

mRNA Expression by UniProt/SwissProt for ENPP1 Gene

P22413-ENPP1_HUMAN
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.
genes like me logo Genes that share expressions with ENPP1: view

Orthologs for ENPP1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ENPP1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ENPP1 36
  • 99.57 (n)
  • 99.24 (a)
ENPP1 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ENPP1 36
  • 88.49 (n)
  • 87.12 (a)
ENPP1 37
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ENPP1 36
  • 88.73 (n)
  • 86.76 (a)
ENPP1 37
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Enpp1 36
  • 81.15 (n)
  • 80.78 (a)
Enpp1 16
Enpp1 37
  • 80 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ENPP1 37
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ENPP1 37
  • 50 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Enpp1 36
  • 80.43 (n)
  • 80.25 (a)
chicken
(Gallus gallus)
Aves ENPP1 36
  • 70.9 (n)
  • 66.93 (a)
ENPP1 37
  • 65 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ENPP1 37
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia enpp1 36
  • 64.53 (n)
  • 60.87 (a)
zebrafish
(Danio rerio)
Actinopterygii enpp1 36
  • 59.85 (n)
  • 56.58 (a)
enpp1 37
  • 53 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea C27A7.3 37
  • 26 (a)
ManyToMany
CELE_C27A7.1 36
  • 46.27 (n)
  • 35.38 (a)
C27A7.3 38
  • 26 (a)
C27A7.1 38
  • 28 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NPP1 37
  • 21 (a)
ManyToMany
NPP2 37
  • 23 (a)
ManyToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G29680 36
  • 50.54 (n)
  • 42.7 (a)
rice
(Oryza sativa)
Liliopsida Os01g0196600 36
  • 50.54 (n)
  • 45.14 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 37 (a)
ManyToMany
Species with no ortholog for ENPP1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ENPP1 Gene

ENSEMBL:
Gene Tree for ENPP1 (if available)
TreeFam:
Gene Tree for ENPP1 (if available)

Paralogs for ENPP1 Gene

Paralogs for ENPP1 Gene

Selected SIMAP similar genes for ENPP1 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with ENPP1: view

Variants for ENPP1 Gene

Sequence variations from dbSNP and Humsavar for ENPP1 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs553 -- 131,890,900(+) GTAGG(A/G)TTGGG utr-variant-3-prime
rs1510 -- 131,893,782(-) TATCT(C/G)TTTAA utr-variant-3-prime
rs703184 -- 131,833,855(-) AATAT(C/G)CACTC intron-variant
rs766592 -- 131,810,461(+) CCCAA(A/G)AACTT intron-variant
rs858334 -- 131,830,836(+) ccagg(C/G)tgggt intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ENPP1 Gene

Variant ID Type Subtype PubMed ID
nsv7968 CNV Loss 18304495
dgv88n68 CNV Loss 17160897
dgv6993n71 CNV Gain 21882294
nsv5479 CNV Loss 18451855

Relevant External Links for ENPP1 Gene

HapMap Linkage Disequilibrium report
ENPP1
Human Gene Mutation Database (HGMD)
ENPP1

Disorders for ENPP1 Gene

(6) OMIM Diseases for ENPP1 Gene (173335)

UniProtKB/Swiss-Prot

ENPP1_HUMAN
  • Ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]: A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis. {ECO:0000269 PubMed:10453738}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Arterial calcification of infancy, generalized, 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. {ECO:0000269 PubMed:12881724, ECO:0000269 PubMed:15605415, ECO:0000269 PubMed:15940697, ECO:0000269 PubMed:22209248}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the bodys own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2) [MIM:613312]: 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. {ECO:0000269 PubMed:20137772, ECO:0000269 PubMed:20137773}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cole disease (COLED) [MIM:615522]: A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy. {ECO:0000269 PubMed:24075184}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(36) Novoseek inferred disease relationships for ENPP1 Gene

Disease -log(P) Hits PubMed IDs
adpkd 83.6 40
insulin resistance 76.6 97
chondrocalcinosis 74.7 3
polycystic kidney diseases 71.8 8
insulin sensitivity 64 18

Relevant External Links for ENPP1

Genetic Association Database (GAD)
ENPP1
Human Genome Epidemiology (HuGE) Navigator
ENPP1
genes like me logo Genes that share disorders with ENPP1: view

Publications for ENPP1 Gene

  1. Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). (PMID: 10453738) Nakamura I. … Nakamura Y. (Hum. Genet. 1999) 3 4 23 49
  2. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. (PMID: 10480624) Pizzuti A. … Trischitta V. (Diabetes 1999) 3 4 23
  3. A cluster of three single nucleotide polymorphisms in the 3'-untranslated region of human glycoprotein PC-1 gene stabilizes PC-1 mRNA and is associated with increased PC-1 protein content and insulin resistance-related abnormalities. (PMID: 11473061) Frittitta L. … Trischitta V. (Diabetes 2001) 3 23 49
  4. The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. (PMID: 11739459) Frittitta L. … Trischitta V. (J. Clin. Endocrinol. Metab. 2001) 3 23 49
  5. Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine. (PMID: 11771660) Koshizuka Y. … Ikegawa S. (J. Bone Miner. Res. 2002) 3 23 49

Products for ENPP1 Gene

Sources for ENPP1 Gene

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