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P22413 (ENPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Short name=E-NPP 1
Alternative name(s):
Membrane component chromosome 6 surface marker 1
Phosphodiesterase I/nucleotide pyrophosphatase 1
Plasma-cell membrane glycoprotein PC-1

Including the following 2 domains:

  1. Alkaline phosphodiesterase I
    EC=3.1.4.1
  2. Nucleotide pyrophosphatase
    Short name=NPPase
    EC=3.6.1.9
Gene names
Name:ENPP1
Synonyms:M6S1, NPPS, PC1, PDNP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length925 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7 Ref.10

Catalytic activity

Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides. Ref.7

A dinucleotide + H2O = 2 mononucleotides. Ref.7

Cofactor

Binds 2 zinc ions per subunit By similarity.

Enzyme regulation

At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.

Subunit structure

The secreted form is monomeric By similarity. Homodimer. Interacts with INSR. Ref.10

Subcellular location

Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Secreted By similarity. Note: The proteolytically processed form is secreted By similarity. Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side. Ref.7 Ref.11 Ref.12

Tissue specificity

Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis. Ref.9

Domain

The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells By similarity.

Post-translational modification

Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity.

N-glycosylated. Ref.7

A secreted form is produced through cleavage at Lys-103 by intracellular processing By similarity.

Involvement in disease

Ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]: A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Arterial calcification of infancy, generalized, 1 (GACI1) [MIM:208000]: A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.19 Ref.21 Ref.25

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.20

Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2) [MIM:613312]: A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23

Cole disease (COLED) [MIM:615522]: A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

Sequence similarities

Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

Contains 2 SMB (somatomedin-B) domains.

Caution

It is uncertain whether Met-1 or Met-53 is the initiator.

Sequence caution

The sequence AAA63237.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAH59375.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA02054.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processBiomineralization
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
Disease mutation
Obesity
   DomainRepeat
Signal-anchor
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_process3'-phosphoadenosine 5'-phosphosulfate metabolic process

Inferred from direct assay PubMed 7830796. Source: BHF-UCL

ATP catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

biomineral tissue development

Inferred from electronic annotation. Source: UniProtKB-KW

bone remodeling

Inferred from electronic annotation. Source: Ensembl

cellular phosphate ion homeostasis

Inferred from direct assay PubMed 11159191. Source: BHF-UCL

cellular response to insulin stimulus

Inferred from direct assay PubMed 17849011PubMed 7830796. Source: BHF-UCL

generation of precursor metabolites and energy

Inferred from direct assay PubMed 12746903. Source: BHF-UCL

immune response

Inferred from electronic annotation. Source: InterPro

inorganic diphosphate transport

Inferred from direct assay PubMed 10513816. Source: BHF-UCL

negative regulation of cell growth

Inferred from direct assay PubMed 17849011. Source: BHF-UCL

negative regulation of fat cell differentiation

Inferred from direct assay PubMed 17849011. Source: BHF-UCL

negative regulation of glucose import

Inferred from direct assay PubMed 17849011. Source: BHF-UCL

negative regulation of glycogen biosynthetic process

Inferred from direct assay PubMed 11289049. Source: BHF-UCL

negative regulation of insulin receptor signaling pathway

Inferred from direct assay PubMed 17849011PubMed 7830796. Source: BHF-UCL

negative regulation of ossification

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein autophosphorylation

Inferred from direct assay PubMed 11289049. Source: BHF-UCL

nucleic acid phosphodiester bond hydrolysis

Inferred from sequence or structural similarity. Source: GOC

nucleoside triphosphate catabolic process

Inferred from direct assay PubMed 10513816. Source: BHF-UCL

phosphate-containing compound metabolic process

Inferred from direct assay PubMed 10513816PubMed 11159191. Source: BHF-UCL

regulation of bone mineralization

Inferred by curator PubMed 10513816. Source: BHF-UCL

riboflavin metabolic process

Traceable author statement. Source: Reactome

sequestering of triglyceride

Inferred from direct assay PubMed 17849011. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentbasolateral plasma membrane

Non-traceable author statement PubMed 9553761. Source: BHF-UCL

cell surface

Inferred from direct assay PubMed 10513816. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 11159191. Source: BHF-UCL

integral component of membrane

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 10513816. Source: BHF-UCL

   Molecular_function3'-phosphoadenosine 5'-phosphosulfate binding

Inferred by curator PubMed 7830796. Source: BHF-UCL

ATP binding

Inferred from direct assay PubMed 7830796. Source: BHF-UCL

NADH pyrophosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor binding

Inferred from direct assay PubMed 7830796. Source: BHF-UCL

nucleic acid binding

Inferred from electronic annotation. Source: InterPro

nucleoside-triphosphate diphosphatase activity

Inferred from direct assay PubMed 10513816PubMed 11159191PubMed 7830796. Source: BHF-UCL

nucleotide diphosphatase activity

Inferred from direct assay PubMed 12746903. Source: BHF-UCL

phosphodiesterase I activity

Inferred from sequence or structural similarity. Source: UniProtKB

polysaccharide binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 11289049. Source: IntAct

protein homodimerization activity

Inferred from direct assay PubMed 7830796. Source: BHF-UCL

scavenger receptor activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

INSRP062132EBI-3197846,EBI-475899

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 925925Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
PRO_0000188564

Regions

Topological domain1 – 7676Cytoplasmic Potential
Transmembrane77 – 9721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain98 – 925828Extracellular Potential
Domain104 – 14441SMB 1
Domain145 – 18945SMB 2
Region191 – 591401Phosphodiesterase
Region597 – 64751Linker By similarity
Region654 – 925272Nuclease
Motif45 – 528Di-leucine motif

Sites

Active site2561AMP-threonine intermediate By similarity
Metal binding2181Zinc 1; catalytic By similarity
Metal binding2561Zinc 1; catalytic By similarity
Metal binding3761Zinc 2; catalytic By similarity
Metal binding3801Zinc 2; via tele nitrogen; catalytic By similarity
Metal binding4231Zinc 1; catalytic By similarity
Metal binding4241Zinc 1; via tele nitrogen; catalytic By similarity
Metal binding5351Zinc 2; via tele nitrogen; catalytic By similarity
Metal binding8001Calcium By similarity
Metal binding8021Calcium By similarity
Metal binding8041Calcium By similarity
Metal binding8061Calcium; via carbonyl oxygen By similarity
Metal binding8081Calcium By similarity
Binding site2771Substrate By similarity
Binding site2951Substrate By similarity
Binding site3401Substrate By similarity
Site102 – 1032Cleavage By similarity
Site9151Essential for catalytic activity By similarity

Amino acid modifications

Glycosylation1791N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation3411N-linked (GlcNAc...) Ref.13 Ref.14
Glycosylation4771N-linked (GlcNAc...) Potential
Glycosylation5851N-linked (GlcNAc...) Potential
Glycosylation6431N-linked (GlcNAc...) Ref.14
Glycosylation7001N-linked (GlcNAc...) Potential
Glycosylation7311N-linked (GlcNAc...) Potential
Glycosylation7481N-linked (GlcNAc...) Ref.14
Disulfide bond108 ↔ 122 By similarity
Disulfide bond112 ↔ 140 By similarity
Disulfide bond120 ↔ 133 By similarity
Disulfide bond126 ↔ 132 By similarity
Disulfide bond149 ↔ 166 By similarity
Disulfide bond154 ↔ 184 By similarity
Disulfide bond164 ↔ 177 By similarity
Disulfide bond170 ↔ 176 By similarity
Disulfide bond195 ↔ 241 By similarity
Disulfide bond203 ↔ 415 By similarity
Disulfide bond431 ↔ 530 By similarity
Disulfide bond480 ↔ 868 By similarity
Disulfide bond614 ↔ 672 By similarity
Disulfide bond626 ↔ 726 By similarity
Disulfide bond628 ↔ 711 By similarity
Disulfide bond838 ↔ 848 By similarity

Natural variations

Natural variant911L → P in OPLL. Ref.17
VAR_014141
Natural variant1491C → S in COLED. Ref.26
VAR_070782
Natural variant1641C → S in COLED. Ref.26
VAR_070783
Natural variant1731K → Q Associated with NIDDM. Ref.6 Ref.17 Ref.20 Ref.24
Corresponds to variant rs1044498 [ dbSNP | Ensembl ].
VAR_008873
Natural variant1771C → Y in COLED. Ref.26
VAR_070784
Natural variant1791N → S.
Corresponds to variant rs2273411 [ dbSNP | Ensembl ].
VAR_037432
Natural variant2501P → L in GACI1. Ref.21
VAR_067910
Natural variant2521Missing in GACI1. Ref.21
VAR_067911
Natural variant2661G → V in ARHR2. Ref.22
Corresponds to variant rs121908248 [ dbSNP | Ensembl ].
VAR_063719
Natural variant2681Y → H. Ref.17
Corresponds to variant rs1805139 [ dbSNP | Ensembl ].
VAR_014142
Natural variant2871S → F in OPLL. Ref.17
Corresponds to variant rs190947144 [ dbSNP | Ensembl ].
VAR_014143
Natural variant3051P → T in GACI1. Ref.21
VAR_067912
Natural variant3421G → V in GACI1. Ref.19 Ref.21
VAR_037433
Natural variant3711Y → F in GACI1; unknown pathological significance. Ref.19 Ref.21
VAR_037434
Natural variant5381D → H in GACI1. Ref.25
VAR_067913
Natural variant5791L → F in GACI1. Ref.18
VAR_018514
Natural variant5861G → R in GACI1. Ref.25
VAR_067914
Natural variant7741R → C in GACI1; unknown pathological significance. Ref.18 Ref.21
Corresponds to variant rs28933977 [ dbSNP | Ensembl ].
VAR_018515
Natural variant7791T → P. Ref.17
Corresponds to variant rs1805138 [ dbSNP | Ensembl ].
VAR_014144
Natural variant8861R → T.
Corresponds to variant rs8192683 [ dbSNP | Ensembl ].
VAR_037435
Natural variant9011Y → S in ARHR2; loss of activity. Ref.23
Corresponds to variant rs121908249 [ dbSNP | Ensembl ].
VAR_063720

Secondary structure

......... 925
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22413 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 0ECAA063801CAFEB

FASTA925104,924
        10         20         30         40         50         60 
MERDGCAGGG SRGGEGGRAP REGPAGNGRD RGRSHAAEAP GDPQAAASLL APMDVGEEPL 

        70         80         90        100        110        120 
EKAARARTAK DPNTYKVLSL VLSVCVLTTI LGCIFGLKPS CAKEVKSCKG RCFERTFGNC 

       130        140        150        160        170        180 
RCDAACVELG NCCLDYQETC IEPEHIWTCN KFRCGEKRLT RSLCACSDDC KDKGDCCINY 

       190        200        210        220        230        240 
SSVCQGEKSW VEEPCESINE PQCPAGFETP PTLLFSLDGF RAEYLHTWGG LLPVISKLKK 

       250        260        270        280        290        300 
CGTYTKNMRP VYPTKTFPNH YSIVTGLYPE SHGIIDNKMY DPKMNASFSL KSKEKFNPEW 

       310        320        330        340        350        360 
YKGEPIWVTA KYQGLKSGTF FWPGSDVEIN GIFPDIYKMY NGSVPFEERI LAVLQWLQLP 

       370        380        390        400        410        420 
KDERPHFYTL YLEEPDSSGH SYGPVSSEVI KALQRVDGMV GMLMDGLKEL NLHRCLNLIL 

       430        440        450        460        470        480 
ISDHGMEQGS CKKYIYLNKY LGDVKNIKVI YGPAARLRPS DVPDKYYSFN YEGIARNLSC 

       490        500        510        520        530        540 
REPNQHFKPY LKHFLPKRLH FAKSDRIEPL TFYLDPQWQL ALNPSERKYC GSGFHGSDNV 

       550        560        570        580        590        600 
FSNMQALFVG YGPGFKHGIE ADTFENIEVY NLMCDLLNLT PAPNNGTHGS LNHLLKNPVY 

       610        620        630        640        650        660 
TPKHPKEVHP LVQCPFTRNP RDNLGCSCNP SILPIEDFQT QFNLTVAEEK IIKHETLPYG 

       670        680        690        700        710        720 
RPRVLQKENT ICLLSQHQFM SGYSQDILMP LWTSYTVDRN DSFSTEDFSN CLYQDFRIPL 

       730        740        750        760        770        780 
SPVHKCSFYK NNTKVSYGFL SPPQLNKNSS GIYSEALLTT NIVPMYQSFQ VIWRYFHDTL 

       790        800        810        820        830        840 
LRKYAEERNG VNVVSGPVFD FDYDGRCDSL ENLRQKRRVI RNQEILIPTH FFIVLTSCKD 

       850        860        870        880        890        900 
TSQTPLHCEN LDTLAFILPH RTDNSESCVH GKHDSSWVEE LLMLHRARIT DVEHITGLSF 

       910        920 
YQQRKEPVSD ILKLKTHLPT FSQED 

« Hide

References

« Hide 'large scale' references
[1]"Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location."
Buckley M.F., Loveland K.A., McKinstry W.J., Garson O.M., Goding J.W.
J. Biol. Chem. 265:17506-17511(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skin fibroblast.
[2]"Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase."
Funakoshi I., Kato H., Horie K., Yano T., Hori Y., Kobayashi H., Inoue T., Suzuki H., Fukui S., Tsukahara M., Kajii T., Yamashina I.
Arch. Biochem. Biophys. 295:180-187(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Skin fibroblast.
[3]"Genomic structure of the human PC1 gene."
Bozzali M., Pizzuti A., Trischitta E.
Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[6]"A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance."
Pizzuti A., Frittitta L., Argiolas A., Baratta R., Goldfine I.D., Bozzali M., Ercolino T., Scarlato G., Iacoviello L., Vigneri R., Tassi V., Trischitta V.
Diabetes 48:1881-1884(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 145-185, VARIANT GLN-173.
[7]"Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities."
Belli S.I., Goding J.W.
Eur. J. Biochem. 226:433-443(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TOPOLOGY, CATALYTIC ACTIVITY, FUNCTION, GLYCOSYLATION.
[8]"Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site."
Belli S.I., Mercuri F.A., Sali A., Goding J.W.
Eur. J. Biochem. 228:669-676(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE.
[9]"Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes."
Piao J.-H., Goding J.W., Nakamura H., Sano K.
Genomics 45:412-415(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit."
Maddux B.A., Goldfine I.D.
Diabetes 49:13-19(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INSR, FUNCTION IN INHIBITION OF INSR KINASE ACTIVITY.
[11]"Characterization of a di-leucine-based signal in the cytoplasmic tail of the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not endocytosis."
Bello V., Goding J.W., Greengrass V., Sali A., Dubljevic V., Lenoir C., Trugnan G., Maurice M.
Mol. Biol. Cell 12:3004-3015(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
[12]"Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases."
Yano Y., Hayashi Y., Sano K., Nagano H., Nakaji M., Seo Y., Ninomiya T., Yoon S., Yokozaki H., Kasuga M.
Cancer Lett. 207:139-147(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[13]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341.
Tissue: Liver.
[14]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341; ASN-643 AND ASN-748.
Tissue: Leukemic T-cell.
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Solution structure of the somatomedin B domain of human ectonucleotide pyrophosphatase/phosphodiesterase family member."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2007) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 147-189.
[17]"Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL)."
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.
Hum. Genet. 104:492-497(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OPLL PRO-91 AND PHE-287, VARIANTS GLN-173; HIS-268 AND PRO-779.
[18]"Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification."
Rutsch F., Ruf N., Vaingankar S., Toliat M.R., Suk A., Hohne W., Schauer G., Lehmann M., Roscioli T., Schnabel D., Epplen J.T., Knisely A., Superti-Furga A., McGill J., Filippone M., Sinaiko A.R., Vallance H., Hinrichs B. expand/collapse author list , Smith W., Ferre M., Terkeltaub R., Nuernberg P.
Nat. Genet. 34:379-381(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GACI1 PHE-579 AND CYS-774.
[19]"Generalized arterial calcification of infancy: different clinical courses in two affected siblings."
Cheng K.-S., Chen M.-R., Ruf N., Lin S.-P., Rutsch F.
Am. J. Med. Genet. A 136:210-213(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GACI1 VAL-342 AND PHE-371.
[20]"The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction."
Bacci S., Ludovico O., Prudente S., Zhang Y.Y., Di Paola R., Mangiacotti D., Rauseo A., Nolan D., Duffy J., Fini G., Salvemini L., Amico C., Vigna C., Pellegrini F., Menzaghi C., Doria A., Trischitta V.
Diabetes 54:3021-3025(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-173, ASSOCIATION WITH NIDDM.
[21]"The mutational spectrum oENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI)."
Ruf N., Uhlenberg B., Terkeltaub R., Nurnberg P., Rutsch F.
Hum. Mutat. 25:98-98(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GACI1 LEU-250; TYR-252 DEL; THR-305; VAL-342; PHE-371 AND CYS-774.
[22]"Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets."
Lorenz-Depiereux B., Schnabel D., Tiosano D., Hausler G., Strom T.M.
Am. J. Hum. Genet. 86:267-272(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARHR2 VAL-266.
[23]"Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene."
Levy-Litan V., Hershkovitz E., Avizov L., Leventhal N., Bercovich D., Chalifa-Caspi V., Manor E., Buriakovsky S., Hadad Y., Goding J., Parvari R.
Am. J. Hum. Genet. 86:273-278(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARHR2 SER-901, CHARACTERIZATION OF VARIANT ARHR2 SER-901.
[24]"An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy."
Le Boulanger G., Labreze C., Croue A., Schurgers L.J., Chassaing N., Wittkampf T., Rutsch F., Martin L.
Am. J. Med. Genet. A 152:118-123(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-173.
[25]"Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6."
Nitschke Y., Baujat G., Botschen U., Wittkampf T., du Moulin M., Stella J., Le Merrer M., Guest G., Lambot K., Tazarourte-Pinturier M.F., Chassaing N., Roche O., Feenstra I., Loechner K., Deshpande C., Garber S.J., Chikarmane R., Steinmann B. expand/collapse author list , Shahinyan T., Martorell L., Davies J., Smith W.E., Kahler S.G., McCulloch M., Wraige E., Loidi L., Hohne W., Martin L., Hadj-Rabia S., Terkeltaub R., Rutsch F.
Am. J. Hum. Genet. 90:25-39(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GACI1 HIS-538 AND ARG-586.
[26]"Cole disease results from mutations in ENPP1."
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 S.J., Taieb A., Sprecher E.
Am. J. Hum. Genet. 93:752-757(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS COLED SER-149; SER-164 AND TYR-177.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57736 mRNA. Translation: AAA63237.1. Different initiation.
D12485 mRNA. Translation: BAA02054.1. Different initiation.
AF110304 expand/collapse EMBL AC list , AF110280, AF110281, AF110283, AF110284, AF110285, AF110286, AF110287, AF110288, AF110289, AF110290, AF110291, AF110292, AF110293, AF110294, AF110295, AF110296, AF110297, AF110298, AF110299, AF110300, AF110301, AF110302, AF110303 Genomic DNA. Translation: AAF36094.1.
AJ242020 expand/collapse EMBL AC list , AJ242021, AJ242022, AJ242023, AJ242024, AJ242025, AJ242026, AJ242027, AJ242028, AJ242029, AJ242030, AJ242031, AJ242032, AJ242033, AJ242034, AJ242035, AJ242036, AJ242037, AJ242038, AJ242039, AJ242040, AJ242041, AJ242042, AJ242043, AJ242044 Genomic DNA. Translation: CAC39442.1.
AL117378, AL139805 Genomic DNA. Translation: CAI19514.1.
AL139805, AL117378 Genomic DNA. Translation: CAI20161.1.
BC059375 mRNA. Translation: AAH59375.2. Different initiation.
AF067177 Genomic DNA. Translation: AAD38420.1.
AF067178 Genomic DNA. Translation: AAD38421.1.
CCDSCCDS5150.2.
PIRA39216.
RefSeqNP_006199.2. NM_006208.2.
UniGeneHs.527295.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YS0NMR-A147-189[»]
ProteinModelPortalP22413.
SMRP22413. Positions 106-922.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111193. 3 interactions.
IntActP22413. 3 interactions.
STRING9606.ENSP00000354238.

Chemistry

BindingDBP22413.
ChEMBLCHEMBL5925.
DrugBankDB01143. Amifostine.
DB00811. Ribavirin.

PTM databases

PhosphoSiteP22413.

Polymorphism databases

DMDM23503088.

Proteomic databases

MaxQBP22413.
PaxDbP22413.
PRIDEP22413.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360971; ENSP00000354238; ENSG00000197594.
GeneID5167.
KEGGhsa:5167.
UCSCuc011ecf.2. human.

Organism-specific databases

CTD5167.
GeneCardsGC06P132129.
HGNCHGNC:3356. ENPP1.
HPACAB032904.
MIM125853. phenotype.
173335. gene.
208000. phenotype.
602475. phenotype.
613312. phenotype.
615522. phenotype.
neXtProtNX_P22413.
Orphanet289176. Autosomal recessive hypophosphatemic rickets.
51608. Generalized arterial calcification of infancy.
324561. Hypopigmentation-punctate palmoplantar keratoderma syndrome.
PharmGKBPA27791.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1524.
HOGENOMHOG000037439.
HOVERGENHBG051484.
InParanoidP22413.
KOK01513.
OMAFEERILA.
OrthoDBEOG7XM2X4.
PhylomeDBP22413.
TreeFamTF330032.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP22413.

Gene expression databases

ArrayExpressP22413.
BgeeP22413.
CleanExHS_ENPP1.
GenevestigatorP22413.

Family and domain databases

Gene3D3.40.570.10. 1 hit.
3.40.720.10. 1 hit.
InterProIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR001604. DNA/RNA_non-sp_Endonuclease.
IPR024873. E-NPP.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view]
PANTHERPTHR10151. PTHR10151. 1 hit.
PfamPF01223. Endonuclease_NS. 1 hit.
PF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view]
PRINTSPR00022. SOMATOMEDINB.
SMARTSM00892. Endonuclease_NS. 1 hit.
SM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view]
SUPFAMSSF53649. SSF53649. 1 hit.
PROSITEPS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22413.
GeneWikiEctonucleotide_pyrophosphatase/phosphodiesterase_1.
GenomeRNAi5167.
NextBio19990.
PROP22413.
SOURCESearch...

Entry information

Entry nameENPP1_HUMAN
AccessionPrimary (citable) accession number: P22413
Secondary accession number(s): Q5T9R6 expand/collapse secondary AC list , Q9NPZ3, Q9P1P6, Q9UP61, Q9Y6K3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: September 19, 2002
Last modified: July 9, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries