Ectonucleotide pyrophosphatase/phosphodiesterase 1

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (PC-1, CD203a) is an enzyme that in humans is encoded by the ENPP1 gene.[5][6][7]

ENPP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesENPP1, ARHR2, COLED, M6S1, NPP1, NPPS, PC-1, PCA1, PDNP1, Ectonucleotide pyrophosphatase/phosphodiesterase 1, CD203a
External IDsOMIM: 173335 MGI: 97370 HomoloGene: 38151 GeneCards: ENPP1
Gene location (Human)
Chr.Chromosome 6 (human)[1]
Band6q23.2Start131,808,016 bp[1]
End131,895,155 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

5167

18605

Ensembl

ENSG00000197594

ENSMUSG00000037370

UniProt

P22413

P06802

RefSeq (mRNA)

NM_006208

NM_008813
NM_001308327
NM_001308329

RefSeq (protein)

NP_006199

NP_001295256
NP_001295258
NP_032839

Location (UCSC)Chr 6: 131.81 – 131.9 MbChr 10: 24.64 – 24.71 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

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.

Function

ENPP1 has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars. ENPP1 protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates.

The main substrate of ENNP1 is adenosine triphosphate (ATP), which is cleaved into adenosine monophosphate (AMP) and diphosphate.[8] Another notable nucleotide substrate is nicotinamide adenine dinucleotide (NAD+) which can be hydrolyzed to produce AMP.[8] ADPR can also be hydrolyzed by ENNP1 to produce AMP.[9]

Clinical significance

Mutations in this gene have been associated with Generalized arterial calcification of infancy, ossification of the posterior longitudinal ligament of the spine (OPLL), Hypophosphatemic rickets autosomal recessive 2 (ARHR2), and insulin resistance.[6]

In a tumor microenvironment, AMP generated by ENNP1 can lead to production of adenosine, which suppresses the anti-cancer function of the immune system.[9][10][11]

Interactions

Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been shown to interact with Insulin receptor.[12]

References

  1. GRCh38: Ensembl release 89: ENSG00000197594 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000037370 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Funakoshi I, Kato H, Horie K, Yano T, Hori Y, Kobayashi H, Inoue T, Suzuki H, Fukui S, Tsukahara M (June 1992). "Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase". Arch Biochem Biophys. 295 (1): 180–7. doi:10.1016/0003-9861(92)90504-P. PMID 1315502.
  6. "Entrez Gene: ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1".
  7. Quarona V, Zaccarello G, Chillemi A (2013). "CD38 and CD157: a long journey from activation markers to multifunctional molecules". Cytometry Part B. 84 (4): 207–217. doi:10.1002/cyto.b.21092. PMID 23576305. S2CID 205732787.
  8. Lee S, Müller CE (2017). "Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) and its inhibitors". MedChemComm. 8 (5): 823–840. doi:10.1039/c7md00015d. PMC 6072468. PMID 30108800.
  9. Horenstein AL, Chillemi A, Zaccarello G, Bruzzone S (2013). "A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes". Oncoimmunology. 2 (9): e26246. doi:10.4161/onci.26246. PMC 3850273. PMID 24319640.
  10. Linden J, Koch-Nolte F, Dahl G (2019). "Purine Release, Metabolism, and Signaling in the Inflammatory Response". Annual Review of Immunology. 37: 325–347. doi:10.1146/annurev-immunol-051116-052406. PMID 30676821.
  11. Sek K, Mølck C, Stewart GD, Kats L (2018). "Targeting Adenosine Receptor Signaling in Cancer Immunotherapy". International Journal of Molecular Sciences. 19 (12): 3837. doi:10.3390/ijms19123837. PMC 6321150. PMID 30513816.
  12. Maddux BA, Goldfine ID (January 2000). "Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit". Diabetes. 49 (1): 13–9. doi:10.2337/diabetes.49.1.13. PMID 10615944.

Further reading


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