Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Details

Name
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Synonyms
  • E-NPP 1
  • M6S1
  • Membrane component chromosome 6 surface marker 1
  • NPPS
  • PC1
  • PDNP1
  • Phosphodiesterase I/nucleotide pyrophosphatase 1
  • Plasma-cell membrane glycoprotein PC-1
Gene Name
ENPP1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000911|Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPL
EKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNC
RCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINY
SSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKK
CGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEW
YKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLP
KDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLIL
ISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSC
REPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNV
FSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVY
TPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYG
RPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPL
SPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTL
LRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKD
TSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSF
YQQRKEPVSDILKLKTHLPTFSQED
Number of residues
925
Molecular Weight
104923.58
Theoretical pI
7.14
GO Classification
Functions
3'-phosphoadenosine 5'-phosphosulfate binding / ATP binding / calcium ion binding / insulin receptor binding / NADH pyrophosphatase activity / nucleic acid binding / nucleoside-triphosphate diphosphatase activity / nucleotide diphosphatase activity / phosphodiesterase I activity / polysaccharide binding / protein homodimerization activity / scavenger receptor activity / zinc ion binding
Processes
3'-phosphoadenosine 5'-phosphosulfate metabolic process / biomineral tissue development / bone remodeling / cellular phosphate ion homeostasis / cellular response to insulin stimulus / generation of precursor metabolites and energy / immune response / inorganic diphosphate transport / negative regulation of cell growth / negative regulation of fat cell differentiation / negative regulation of glucose import / negative regulation of glycogen biosynthetic process / negative regulation of insulin receptor signaling pathway / negative regulation of ossification / negative regulation of protein autophosphorylation / nucleic acid phosphodiester bond hydrolysis / nucleoside triphosphate catabolic process / phosphate-containing compound metabolic process / regulation of bone mineralization / riboflavin metabolic process / sequestering of triglyceride / small molecule metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process
Components
basolateral plasma membrane / cell surface / extracellular space / integral component of membrane / integral component of plasma membrane / lysosomal membrane / plasma membrane
General Function
Zinc ion binding
Specific Function
By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Appears to modulate insulin sensitivity and function.
Pfam Domain Function
Transmembrane Regions
77-97
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0016097|Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1)
ATGGAGCGCGACGGCTGCGCGGGGGGCGGGAGCCGCGGCGGCGAGGGCGGGCGCGCTCCC
CGGGAGGGCCCGGCGGGGAACGGCCGCGATCGGGGCCGCAGCCACGCTGCCGAGGCGCCC
GGGGACCCGCAGGCGGCCGCGTCCTTGCTGGCCCCTATGGACGTGGGGGAGGAGCCGCTG
GAGAAGGCGGCGCGCGCCCGCACTGCCAAGGACCCCAACACCTATAAAGTACTCTCGCTG
GTATTGTCAGTATGTGTGTTAACAACAATACTTGGTTGTATATTTGGGTTGAAACCAAGC
TGTGCCAAAGAAGTTAAAAGTTGCAAAGGTCGCTGTTTCGAGAGAACATTTGGGAACTGT
CGCTGTGATGCTGCCTGTGTTGAGCTTGGAAACTGCTGTTTAGATTACCAGGAGACGTGC
ATAGAACCAGAACATATATGGACTTGCAACAAATTCAGGTGTGGTGAGAAAAGGTTGACC
AGAAGCCTCTGTGCCTGTTCAGATGACTGCAAGGACAAGGGCGACTGCTGCATCAACTAC
AGTTCTGTGTGTCAAGGTGAGAAAAGTTGGGTAGAAGAACCATGTGAGAGCATTAATGAG
CCACAGTGCCCAGCAGGGTTTGAAACGCCTCCTACCCTCTTATTTTCTTTGGATGGATTC
AGGGCAGAATATTTACACACTTGGGGTGGACTTCTTCCTGTTATTAGCAAACTAAAAAAA
TGTGGAACATATACTAAAAACATGAGACCGGTATATCCAACAAAAACTTTCCCCAATCAC
TACAGCATTGTCACCGGATTGTATCCAGAATCTCATGGCATAATCGACAATAAAATGTAT
GATCCCAAAATGAATGCTTCCTTTTCACTTAAAAGTAAAGAGAAATTTAATCCTGAGTGG
TACAAAGGAGAACCAATTTGGGTCACAGCTAAGTATCAAGGCCTCAAGTCTGGCACATTT
TTCTGGCCAGGATCAGATGTGGAAATTAACGGAATTTTCCCAGACATCTATAAAATGTAT
AATGGTTCAGTACCATTTGAAGAAAGGATTTTAGCTGTTCTTCAGTGGCTACAGCTTCCT
AAAGATGAAAGACCACACTTTTACACTCTGTATTTAGAAGAACCAGATTCTTCAGGTCAT
TCATATGGACCAGTCAGCAGTGAAGTCATCAAAGCCTTGCAGAGGGTTGATGGTATGGTT
GGTATGCTGATGGATGGTCTGAAAGAGCTGAACTTGCACAGATGCCTGAACCTCATCCTT
ATTTCAGATCATGGCATGGAACAAGGCAGTTGTAAGAAATACATATATCTGAATAAATAT
TTGGGGGATGTTAAAAATATTAAAGTTATCTATGGACCTGCAGCTCGATTGAGACCCTCT
GATGTCCCAGATAAATACTATTCATTTAACTATGAAGGCATTGCCCGAAATCTTTCTTGC
CGGGAACCAAACCAGCACTTCAAACCTTACCTGAAACATTTCTTACCTAAGCGTTTGCAC
TTTGCTAAGAGTGATAGAATTGAGCCCTTGACATTCTATTTGGACCCTCAGTGGCAACTT
GCATTGAATCCCTCAGAAAGGAAATATTGTGGAAGTGGATTTCATGGCTCTGACAATGTA
TTTTCAAATATGCAAGCCCTCTTTGTTGGCTATGGACCTGGATTCAAGCATGGCATTGAG
GCTGACACCTTTGAAAACATTGAAGTCTATAACTTAATGTGTGATTTACTGAATTTGACA
CCGGCTCCTAATAACGGAACTCATGGAAGTCTTAACCACCTTCTAAAGAATCCTGTTTAT
ACGCCAAAGCATCCCAAAGAAGTGCACCCCCTGGTACAGTGCCCCTTCACAAGAAACCCC
AGAGATAACCTTGGCTGCTCATGTAACCCTTCGATTTTGCCGATTGAGGATTTTCAAACA
CAGTTCAATCTGACTGTGGCAGAAGAGAAGATTATTAAGCATGAAACTTTACCCTATGGA
AGACCTAGAGTTCTCCAGAAGGAAAACACCATCTGTCTTCTTTCCCAGCACCAGTTTATG
AGTGGATACAGCCAAGACATCTTAATGCCCCTTTGGACATCCTATACCGTGGACAGAAAT
GACAGTTTCTCTACGGAAGACTTCTCCAACTGTCTGTACCAGGACTTTAGAATTCCTCTT
AGTCCTGTCCATAAATGTTCATTTTATAAAAATAACACCAAAGTGAGTTACGGGTTCCTC
TCCCCACCACAACTAAATAAAAATTCAAGTGGAATATATTCTGAAGCTTTGCTTACTACA
AATATAGTGCCAATGTACCAGAGTTTTCAAGTTATATGGCGCTACTTTCATGACACCCTA
CTGCGAAAGTATGCTGAAGAAAGAAATGGTGTCAATGTCGTCAGTGGTCCTGTGTTTGAC
TTTGATTATGATGGACGTTGTGATTCCTTAGAGAATCTGAGGCAAAAAAGAAGAGTCATC
CGTAACCAAGAAATTTTGATTCCAACTCACTTCTTTATTGTGCTAACAAGCTGTAAAGAT
ACATCTCAGACGCCTTTGCACTGTGAAAACCTAGACACCTTAGCTTTCATTTTGCCTCAC
AGGACTGATAACAGCGAGAGCTGTGTGCATGGGAAGCATGACTCCTCATGGGTTGAAGAA
TTGTTAATGTTACACAGAGCACGGATCACAGATGTTGAGCACATCACTGGACTCAGCTTC
TATCAACAAAGAAAAGAGCCAGTTTCAGACATTTTAAAGTTGAAAACACATTTGCCAACC
TTTAGCCAAGAAGACTGA
Chromosome Location
6
Locus
6q22-q23
External Identifiers
ResourceLink
UniProtKB IDP22413
UniProtKB Entry NameENPP1_HUMAN
GenBank Protein ID189650
GenBank Gene IDM57736
GenAtlas IDENPP1
HGNC IDHGNC:3356
General References
  1. Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW: Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location. J Biol Chem. 1990 Oct 15;265(29):17506-11. [Article]
  2. Funakoshi I, Kato H, Horie K, Yano T, Hori Y, Kobayashi H, Inoue T, Suzuki H, Fukui S, Tsukahara M, et al.: Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase. Arch Biochem Biophys. 1992 May 15;295(1):180-7. [Article]
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  5. Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine ID, Bozzali M, Ercolino T, Scarlato G, Iacoviello L, Vigneri R, Tassi V, Trischitta V: A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes. 1999 Sep;48(9):1881-4. [Article]
  6. Belli SI, Goding JW: Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities. Eur J Biochem. 1994 Dec 1;226(2):433-43. [Article]
  7. Belli SI, Mercuri FA, Sali A, Goding JW: Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site. Eur J Biochem. 1995 Mar 15;228(3):669-76. [Article]
  8. Jin-Hua P, Goding JW, Nakamura H, Sano K: Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes. Genomics. 1997 Oct 15;45(2):412-5. [Article]
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  16. Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Hohne W, Schauer G, Lehmann M, Roscioli T, Schnabel D, Epplen JT, Knisely A, Superti-Furga A, McGill J, Filippone M, Sinaiko AR, Vallance H, Hinrichs B, Smith W, Ferre M, Terkeltaub R, Nurnberg P: Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. Nat Genet. 2003 Aug;34(4):379-81. [Article]
  17. Cheng KS, Chen MR, Ruf N, Lin SP, Rutsch F: Generalized arterial calcification of infancy: different clinical courses in two affected siblings. Am J Med Genet A. 2005 Jul 15;136(2):210-3. [Article]
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  19. Ruf N, Uhlenberg B, Terkeltaub R, Nurnberg P, Rutsch F: The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI). Hum Mutat. 2005 Jan;25(1):98. [Article]
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  23. Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, Le Merrer M, Guest G, Lambot K, Tazarourte-Pinturier MF, Chassaing N, Roche O, Feenstra I, Loechner K, Deshpande C, Garber SJ, Chikarmane R, Steinmann B, Shahinyan T, Martorell L, Davies J, Smith WE, Kahler SG, McCulloch M, Wraige E, Loidi L, Hohne W, Martin L, Hadj-Rabia S, Terkeltaub R, Rutsch F: Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012 Jan 13;90(1):25-39. doi: 10.1016/j.ajhg.2011.11.020. Epub 2011 Dec 29. [Article]
  24. Eytan O, Morice-Picard F, Sarig O, Ezzedine K, Isakov O, Li Q, Ishida-Yamamoto A, Shomron N, Goldsmith T, Fuchs-Telem D, Adir N, Uitto J, Orlow SJ, Taieb A, Sprecher E: Cole Disease Results from Mutations in ENPP1. Am J Hum Genet. 2013 Oct 3;93(4):752-7. doi: 10.1016/j.ajhg.2013.08.007. Epub 2013 Sep 26. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06408TaribavirininvestigationalunknownDetails
DB11077Polyethylene glycol 400approvedunknownotherDetails