Эктонуклеотидпирофосфатаза/фосфодиэстераза 1

Enpp1
Доступные структуры
PDB	Поиск ортолога: PDBE RCSB
showСписок кодов идентификаторов PDB
	2YS0
Идентификаторы
Псевдонимы	Enpp1 , Arhr2, Coled, M6S1, NPP1, NPPS, PC-1, PCA1, PDNP1, эктонуклеотидпирофосфатаза/фосфодиэстераза 1, CD203A
Внешние идентификаторы	Омим : 173335 ; MGI : 97370 ; Гомологен : 38151 ; GeneCards : Enpp1 ; OMA : ENPP1 - Ортологи
showМестоположение гена ( человек )
Chr.	Chromosome 6 (human)
End	131,895,155 bp
showМестоположение гена ( мышь )
Chr.	Chromosome 10 (mouse)
End	24,588,057 bp
showРНК -паттерн экспрессии
	Top expressed in
	tibia; ; decidua; ; cartilage tissue; ; tail of epididymis; ; Achilles tendon; ; tendon of biceps brachii; ; liver; ; right lobe of liver; ; synovial joint; ; corpus epididymis;
	Top expressed in
	epithelium of lens; ; fossa; ; condyle; ; transitional epithelium of urinary bladder; ; body of femur; ; right kidney; ; ankle; ; belly cord; ; ascending aorta; ; aortic valve;
	More reference expression data
	; ;
	More reference expression data
showДжин Онтология
Molecular function	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; protein binding; catalytic activity; nucleic acid binding; hydrolase activity; ATP binding; phosphodiesterase I activity; exonuclease activity; cyclic-GMP-AMP hydrolase activity;
Cellular component	integral component of membrane; membrane; plasma membrane; integral component of plasma membrane; extracellular region; cell surface; lysosomal membrane; basolateral plasma membrane; extracellular space;
Biological process	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; negative regulation of insulin receptor signaling pathway; negative regulation of cell growth; immune response; cellular response to insulin stimulus; phosphate-containing compound metabolic process; metabolism; 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; endocytosis;
	Sources:Amigo / QuickGO
hideOrthologs
	5167
	18605
	ENSG00000197594
	ENSMUSG00000037370
	P22413
	P06802
	NM_006208
	NM_008813; NM_001308327; NM_001308329
	NP_006199
	NP_001295256; NP_001295258; NP_032839
	Wikidata
View/Edit Human	View/Edit Mouse

Эктонуклеотидпирофосфатаза/фосфодиэстераза члена семейства 1 ( PC-1 , CD203A )-это фермент , который у людей кодируется ENPP1 геном . ^{[ 5 ]}^{[ 6 ]}^{[ 7 ]}

Структура

Этот ген является членом семейства экто-нуклеотидпофосфатазы/фосфодиэстеразы (ENPP). Кодированный белок представляет собой трансмембранный гликопротеин типа II, содержащий две идентичные субъединицы , связанные с дисульфидом .

Функция

ENPP1 имеет широкую специфичность и расщепляет различные субстраты, включая фосфодиэфирные связи нуклеотидов и нуклеотидных сахаров. Белок ENPP1 может функционировать с гидролизуемыми нуклеозидами 5'-трифосфатами до соответствующих монофосфатов , а также может также гидролизовать полифосфаты диаденозина.

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

^ Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000197594 – Ensembl, May 2017
^ Jump up to: ^a ^b ^c 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.
^ Jump up to: ^a ^b "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.
^ Jump up to: ^a ^b 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.
^ Jump up to: ^a ^b 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.

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.
Кошизука Ю., Кавагучи Х., Огата Н., Икеда Т., Мабучи А., Сейчи А., Накамура Ю., Накамура К., Икегава С. (2002). «Полиморфизм гена нуклеотидной пирофосфатазы, связанный с окостенением задней продольной связки позвоночника» . J. Bone Miner. Резерв 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). «Полиморфизмы генов ACE и PC-1 у нормоалбуминурических пациентов с диабетом 1 типа: 10-летнее проспективное исследование». J. Диабет усложняется . 16 (4): 255–62. doi : 10.1016/s1056-8727 (01) 00185-4 . PMID 12126783 .
De Cosmo S, Mistio G, Zucaro L, Margaglione M, Argiolas A, Thomas S, Piras G, Trevisan R, Perin PC, Bacci S, Friedittta L, Pizzuti A, Tassi V, Di Minno G, Viberti G, Trischitta V ( 2003). «Роль генов PC-1 и ACE в диабетической нефропатии у пациента с диабетом 1 типа: свидетельство полигенного контроля прогрессирования заболевания почек» . Нефрол. Набрать Пересадка . 17 (8): 1402–7. Doi : 10.1093/ndt/17.8.1402 . PMID 12147786 .
Jacobsen P, Grarup N, Tarnow L, Parving HH, Pedersen O (2003). «Аминокислотный вариант PC-1 (K121Q) не влияет на прогрессирование диабетической нефропатии у пациентов с диабетом 1 типа» . Нефрол. Набрать Пересадка . 17 (8): 1408–12. doi : 10.1093/ndt/17.8.1408 . PMID 12147787 .

Эта статья о гене о хромосоме человека 6 является заглушкой . Вы можете помочь Википедии, расширив ее .

[refGRCh38Ensembl-1] Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000197594 – Ensembl, May 2017

[refGRCm38Ensembl-2] Jump up to: ^a ^b ^c 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.

[pmid1315502-5] 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.

[entrez-6] Jump up to: ^a ^b "Entrez Gene: ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1".

[pmid23576305-7] 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. hdl:2318/134656. PMID 23576305. S2CID 205732787.

[pmid30108800-8] Jump up to: ^a ^b 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.

[pmid24319640-9] Jump up to: ^a ^b 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.

[pmid30676821-10] 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. S2CID 59250501.

[pmid30513816-11] 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.

[pmid10615944-12] 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.

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