اکتونوکلئوتید پیروفسفاتاز/فسفودی‌استراز ۱

ENPP1
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	2YS0
معین‌کننده‌ها
نام‌های دیگر	ENPP1, ARHR2, COLED, M6S1, NPP1, NPPS, PC-1, PCA1, PDNP1, Ectonucleotide pyrophosphatase/phosphodiesterase 1, CD203a
شناسه‌های بیرونی	OMIM: 173335 MGI: 97370 HomoloGene: 38151 GeneCards: ENPP1
موقعیت ژن (موش)
کروموزوم	کروموزوم ۱۰ (موش)
پایان	24,588,057 bp
الگوی گسترش RNA
	; ;
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• nucleoside-triphosphate diphosphatase activity; • calcium ion binding; • nucleotide diphosphatase activity; • protein homodimerization activity; • insulin receptor binding; • zinc ion binding; • polysaccharide binding; • 3'-phosphoadenosine 5'-phosphosulfate binding; • metal ion binding; • scavenger receptor activity; • NADH pyrophosphatase activity; • GO:0001948، GO:0016582 پیوند پروتئینی; • catalytic activity; • nucleic acid binding; • hydrolase activity; • ATP binding; • phosphodiesterase I activity; • exonuclease activity; • cyclic-GMP-AMP hydrolase activity;
ترکیبات سلولی	• integral component of membrane; • membrane; • پوسته یاخته; • integral component of plasma membrane; • extracellular region; • cell surface; • lysosomal membrane; • basolateral plasma membrane; • extracellular space;
فرایند زیستی	• negative regulation of fat cell differentiation; • negative regulation of protein autophosphorylation; • regulation of bone mineralization; • riboflavin metabolic process; • biomineral tissue development; • nucleoside triphosphate catabolic process; • cellular phosphate ion homeostasis; • negative regulation of glycogen biosynthetic process; • receptor-mediated endocytosis; • generation of precursor metabolites and energy; • 3'-phosphoadenosine 5'-phosphosulfate metabolic process; • negative regulation of glucose import; • GO:1903105 negative regulation of insulin receptor signaling pathway; • negative regulation of cell growth; • GO:0046730، GO:0046737، GO:0046738، GO:0046736 پاسخ ایمنی; • cellular response to insulin stimulus; • phosphate-containing compound metabolic process; • دگرگشت; • inorganic diphosphate transport; • sequestering of triglyceride; • ATP metabolic process; • nucleic acid phosphodiester bond hydrolysis; • vesicle-mediated transport; • melanocyte differentiation; • negative regulation of bone mineralization; • negative regulation of hh target transcription factor activity; • اندوسیتوز;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	5167
	18605
	ENSG00000197594
	ENSMUSG00000037370
	P22413
	P06802
	NM_006208
	XM_006512598، XM_006512599، NM_001308327، NM_001308329 NM_008813، XM_006512598، XM_006512599، NM_001308327، NM_001308329
	NP_006199
	NP_001295258، NP_032839، XP_006512661، XP_006512662 NP_001295256، NP_001295258، NP_032839، XP_006512661، XP_006512662
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

اکتونوکلئوتید پیروفسفاتاز/فسفودی‌استراز ۱ (انگلیسی: Ectonucleotide pyrophosphatase/phosphodiesterase 1) یک آنزیم است که در انسان توسط ژن «ENPP1» کُدگذاری می‌شود.^[۴]^[۵]^[۶]

سوبسترای اصلی این آنزیم آدنوزین تری‌فسفات است که پس از تجزیه به آدنوزین مونوفسفات و پیروفسفات مبدل می‌گردد.^[۷] یکی دیگر از سوبستراهای این آنزیم نیکوتین‌آمید آدنین دی‌نوکلئوتید است که پس از هیدرولیز منجر به تشکیل آدنوزین مونوفسفات می‌گردد.^[۷] این آنزیم حتی قادر است سیکلیک ای دی پی-ریبوز را هیدرولیز کند و آدنوزین مونوفسفات ایجاد نماید.^[۸]

اهمیت بالینی[ویرایش]

جهش در ژن «ENPP1» سبب بروز کلسیفیکاسیون گسترده شریانی نوزادی، استخوانی شدن رباط طولی پشتی ستون فقرات، نرمی استخوان هیپوفسفاتمیک اتوزومال مغلوب ۲ و مقاومت به انسولین می‌گردد.^[۵]

در ریزمحیط تومور آدنوزین مونوفسفات حاصل از اثر این آنزیم منجر به تولید آدنوزین می‌شود که عملکرد ضد سرطانی دستگاه ایمنی بدن را سرکوب می‌کند.^[۸]^[۹]^[۱۰]

این مولکول با گیرنده انسولین تعامل پروتئین-پروتئین دارد.^[۱۱]

منابع[ویرایش]

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ 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.
↑ ^۵٫۰ ^۵٫۱ "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. PMID 23576305. S2CID 205732787.
↑ ^۷٫۰ ^۷٫۱ 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.
↑ ^۸٫۰ ^۸٫۱ 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.

برای مطالعهٔ بیشتر[ویرایش]

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.

[refGRCm38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000037370 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1315502-4] 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-5] ۵٫۰ ^۵٫۱ "Entrez Gene: ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1".

[pmid23576305-6] 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.

[pmid30108800-7] ۷٫۰ ^۷٫۱ 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.

[pmid24319640-8] ۸٫۰ ^۸٫۱ 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.

[pmid30676821-9] 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.

[pmid30513816-10] 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.

[pmid10615944-11] 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.

[۱]

[۲]

[۳]

[۴]

[۵]

[۶]

[۷]

[۸]

[۹]

[۱۰]

[۱۱]