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]
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
- GRCh38: Ensembl release 89: ENSG00000197594 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000037370 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 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.
- "Entrez Gene: ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1".
- 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. hdl:2318/134656. PMID 23576305. S2CID 205732787.
- 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.
- 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.
- 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. S2CID 59250501.
- 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.
- 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
- Abate N, Chandalia M, Di Paola R, Foster DW, Grundy SM, Trischitta V (2007). "Mechanisms of disease: Ectonucleotide pyrophosphatase phosphodiesterase 1 as a 'gatekeeper' of insulin receptors". Nature Clinical Practice Endocrinology & Metabolism. 2 (12): 694–701. doi:10.1038/ncpendmet0367. PMID 17143316. S2CID 8907895.
- Bacci S, De Cosmo S, Prudente S, Trischitta V (2007). "ENPP1 gene, insulin resistance and related clinical outcomes". Current Opinion in Clinical Nutrition and Metabolic Care. 10 (4): 403–9. doi:10.1097/MCO.0b013e3281e386c9. PMID 17563456. S2CID 13172655.
- Fadini GP, Pauletto P, Avogaro A, Rattazzi M (2007). "The good and the bad in the link between insulin resistance and vascular calcification". Atherosclerosis. 193 (2): 241–4. doi:10.1016/j.atherosclerosis.2007.05.015. PMID 17606264.
- Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW (1990). "Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location". J. Biol. Chem. 265 (29): 17506–11. doi:10.1016/S0021-9258(18)38193-6. PMID 2211644.
- Belli SI, Mercuri FA, Sali A, Goding JW (1995). "Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site". Eur. J. Biochem. 228 (3): 669–76. doi:10.1111/j.1432-1033.1995.tb20308.x. PMID 7737162.
- Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA (1995). "Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus". Nature. 373 (6513): 448–51. Bibcode:1995Natur.373..448M. doi:10.1038/373448a0. PMID 7830796. S2CID 4359358.
- Belli SI, Goding JW (1995). "Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities". Eur. J. Biochem. 226 (2): 433–43. doi:10.1111/j.1432-1033.1994.tb20068.x. PMID 8001561.
- Huang R, Rosenbach M, Vaughn R, Provvedini D, Rebbe N, Hickman S, Goding J, Terkeltaub R (1994). "Expression of the murine plasma cell nucleotide pyrophosphohydrolase PC-1 is shared by human liver, bone, and cartilage cells. Regulation of PC-1 expression in osteosarcoma cells by transforming growth factor-beta". J. Clin. Invest. 94 (2): 560–7. doi:10.1172/JCI117370. PMC 296131. PMID 8040311.
- Jin-Hua P, Goding JW, Nakamura H, Sano K (1998). "Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes". Genomics. 45 (2): 412–5. doi:10.1006/geno.1997.4949. PMID 9344668.
- Nakamura I, Ikegawa S, Okawa A, Okuda S, Koshizuka Y, Kawaguchi H, Nakamura K, Koyama T, Goto S, Toguchida J, Matsushita M, Ochi T, Takaoka K, Nakamura Y (1999). "Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL)". Hum. Genet. 104 (6): 492–7. doi:10.1007/s004390050993. PMID 10453738. S2CID 238056.
- Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine ID, Bozzali M, Ercolino T, Scarlato G, Iacoviello L, Vigneri R, Tassi V, Trischitta V (1999). "A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance". Diabetes. 48 (9): 1881–4. doi:10.2337/diabetes.48.9.1881. PMID 10480624.
- Andoh K, Piao JH, Terashima K, Nakamura H, Sano K (1999). "Genomic structure and promoter analysis of the ecto-phosphodiesterase I gene (PDNP3) expressed in glial cells". Biochim. Biophys. Acta. 1446 (3): 213–24. doi:10.1016/s0167-4781(99)00090-1. PMID 10524196.
- Maddux BA, Goldfine ID (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.
- Rutsch F, Vaingankar S, Johnson K, Goldfine I, Maddux B, Schauerte P, Kalhoff H, Sano K, Boisvert WA, Superti-Furga A, Terkeltaub R (2001). "PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification". Am. J. Pathol. 158 (2): 543–54. doi:10.1016/S0002-9440(10)63996-X. PMC 1850320. PMID 11159191.
- Frittitta L, Baratta R, Spampinato D, Di Paola R, Pizzuti A, Vigneri R, Trischitta V (2001). "The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance". J. Clin. Endocrinol. Metab. 86 (12): 5888–91. doi:10.1210/jcem.86.12.8108. PMID 11739459.
- Koshizuka Y, Kawaguchi H, Ogata N, Ikeda T, Mabuchi A, Seichi A, Nakamura Y, Nakamura K, Ikegawa S (2002). "Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine". J. Bone Miner. Res. 17 (1): 138–44. doi:10.1359/jbmr.2002.17.1.138. PMID 11771660. S2CID 20481601.
- de Azevedo MJ, Dalmáz CA, Caramori ML, Pecis M, Esteves JF, Maia AL, Gross JL (2003). "ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: a 10-year prospective study". J. Diabetes Complicat. 16 (4): 255–62. doi:10.1016/s1056-8727(01)00185-4. PMID 12126783.
- De Cosmo S, Miscio G, Zucaro L, Margaglione M, Argiolas A, Thomas S, Piras G, Trevisan R, Perin PC, Bacci S, Frittitta L, Pizzuti A, Tassi V, Di Minno G, Viberti G, Trischitta V (2003). "The role of PC-1 and ACE genes in diabetic nephropathy in type 1 diabetic patients: evidence for a polygenic control of kidney disease progression". Nephrol. Dial. Transplant. 17 (8): 1402–7. doi:10.1093/ndt/17.8.1402. PMID 12147786.
- Jacobsen P, Grarup N, Tarnow L, Parving HH, Pedersen O (2003). "PC-1 amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients". Nephrol. Dial. Transplant. 17 (8): 1408–12. doi:10.1093/ndt/17.8.1408. PMID 12147787.
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