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

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

↑ ^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

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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.
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[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.

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