Reviewed, UniProtKB/Swiss-Prot P22413 (ENPP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
      Short name=E-NPP 1
Alternative name(s):
    Phosphodiesterase I/nucleotide pyrophosphatase 1
    Plasma-cell membrane glycoprotein PC-1
Including the following 2 domains:
    1- Recommended name:
            Alkaline phosphodiesterase I
              EC=3.1.4.1
    2- Recommended name:
            Nucleotide pyrophosphatase
                Short name=NPPase
              EC=3.6.1.9

Gene names

Name:	ENPP1
Synonyms:	M6S1, NPPS, PC1, PDNP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	925 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved primarily in ATP hydrolysis at the plasma membrane. Plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. In vitro, has a broad specificity, hydrolyzing 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.
Catalytic activity	Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides. A dinucleotide + H2O = 2 mononucleotides.
Cofactor	Binds 2 divalent metal cations per subunit Probable.
Enzyme regulation	At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.
Subunit structure	Homodimer; disulfide-linked.
Subcellular location	Membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Note: 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.10 Ref.11
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.12 Ref.13 It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.
Involvement in disease	Defects in ENPP1 are a cause of increased susceptibility for ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]. OPLL is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups. Ref.15 Defects in ENPP1 are a cause of idiopathic infantile arterial calcification (IIAC) [MIM:208000]; also known as generalized arterial calcification of infancy. IIAC is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. Ref.16 Ref.17 Defects in ENPP1 are associated with obesity, glucose intolerance, and type II diabetes non-insulin dependent (NIDDM) [MIM:125853]. Ref.18
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.

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation Obesity
Domain	Repeat Signal-anchor Transmembrane
Ligand	Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	3'-phosphoadenosine 5'-phosphosulfate metabolic process Inferred from direct assay. Source: UniProtKB biomineral formation Inferred from electronic annotation. Source: UniProtKB-KW cellular phosphate ion homeostasis Inferred from direct assay. Source: UniProtKB cellular response to insulin stimulus Inferred from direct assay. Source: UniProtKB generation of precursor metabolites and energy Inferred from direct assay. Source: UniProtKB inorganic diphosphate transport Inferred from direct assay. Source: UniProtKB negative regulation of cell growth Inferred from direct assay. Source: UniProtKB negative regulation of fat cell differentiation Inferred from direct assay. Source: UniProtKB negative regulation of glucose import Inferred from direct assay. Source: UniProtKB negative regulation of glycogen biosynthetic process Inferred from direct assay. Source: UniProtKB negative regulation of insulin receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of protein amino acid autophosphorylation Inferred from direct assay. Source: UniProtKB nucleoside triphosphate catabolic process Inferred from direct assay. Source: UniProtKB phosphate metabolic process Inferred from direct assay. Source: UniProtKB regulation of bone mineralization Inferred by curator. Source: UniProtKB sequestering of triglyceride Inferred from direct assay. Source: UniProtKB
Cellular component	basolateral plasma membrane Non-traceable author statement. Source: UniProtKB cell surface Inferred from direct assay. Source: UniProtKB extracellular space Inferred from direct assay. Source: UniProtKB integral to membrane Ref.2 Traceable author statement. Source: ProtInc
Molecular function	3'-phosphoadenosine 5'-phosphosulfate binding Inferred by curator. Source: UniProtKB ATP binding Inferred from direct assay. Source: UniProtKB insulin receptor binding Inferred from direct assay. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid binding Inferred from electronic annotation. Source: InterPro nucleoside-triphosphate diphosphatase activity Inferred from direct assay. Source: UniProtKB nucleotide diphosphatase activity Ref.7 Inferred from direct assay. Source: UniProtKB phosphodiesterase I activity Inferred from electronic annotation. Source: EC protein homodimerization activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 925

925

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

PRO_0000188564

Regions

Topological domain

1 – 76

76

Cytoplasmic Potential

Transmembrane

77 – 97

21

Signal-anchor for type II membrane protein Potential

Topological domain

98 – 925

828

Extracellular Potential

Domain

104 – 144

41

SMB 1

Domain

145 – 189

45

SMB 2

Region

191 – 591

401

Phosphodiesterase

Region

654 – 925

272

Nuclease

Motif

45 – 52

8

Di-leucine motif

Sites

Active site

256

1

AMP-threonine intermediate By similarity

Metal binding

218

1

Divalent metal cation 2 Probable

Metal binding

376

1

Divalent metal cation 1 Probable

Metal binding

380

1

Divalent metal cation 1 Probable

Metal binding

423

1

Divalent metal cation 2 Probable

Metal binding

424

1

Divalent metal cation 2 Probable

Metal binding

535

1

Divalent metal cation 1 Probable

Site

915

1

Essential for catalytic activity By similarity

Amino acid modifications

Glycosylation

179

1

N-linked (GlcNAc...) Potential

Glycosylation

285

1

N-linked (GlcNAc...) Potential

Glycosylation

341

1

N-linked (GlcNAc...) Ref.12 Ref.13

Glycosylation

477

1

N-linked (GlcNAc...) Potential

Glycosylation

585

1

N-linked (GlcNAc...) Potential

Glycosylation

643

1

N-linked (GlcNAc...) Ref.13

Glycosylation

700

1

N-linked (GlcNAc...) Potential

Glycosylation

731

1

N-linked (GlcNAc...) Potential

Glycosylation

748

1

N-linked (GlcNAc...) Ref.13

Disulfide bond

108 ↔ 122

Alternate By similarity

Disulfide bond

108 ↔ 112

Alternate By similarity

Disulfide bond

112 ↔ 140

Alternate By similarity

Disulfide bond

120 ↔ 133

Alternate By similarity

Disulfide bond

120 ↔ 122

Alternate By similarity

Disulfide bond

126 ↔ 132

By similarity

Disulfide bond

133 ↔ 140

Alternate By similarity

Disulfide bond

149 ↔ 166

Alternate By similarity

Disulfide bond

149 ↔ 154

Alternate By similarity

Disulfide bond

154 ↔ 184

Alternate By similarity

Disulfide bond

164 ↔ 177

Alternate By similarity

Disulfide bond

164 ↔ 166

Alternate By similarity

Disulfide bond

170 ↔ 176

By similarity

Disulfide bond

177 ↔ 184

Alternate By similarity

Disulfide bond

480 ↔ 868

By similarity

Natural variations

Natural variant

91

1

L → P in OPLL. Ref.15

VAR_014141

Natural variant

173

1

K → Q Associated with NIDDM. dbSNP rs1044498. Ref.15 Ref.18 Ref.6

VAR_008873

Natural variant

179

1

N → S: dbSNP rs2273411.

VAR_037432

Natural variant

268

1

Y → H: dbSNP rs1805139. Ref.15

VAR_014142

Natural variant

287

1

S → F in OPLL. Ref.15

VAR_014143

Natural variant

342

1

G → V in IIAC. Ref.17

VAR_037433

Natural variant

371

1

Y → F in IIAC. Ref.17

VAR_037434

Natural variant

579

1

L → F in IIAC. Ref.16

VAR_018514

Natural variant

774

1

R → C in IIAC. dbSNP rs28933977. Ref.16

VAR_018515

Natural variant

779

1

T → P: dbSNP rs1805138. Ref.15

VAR_014144

Natural variant

886

1

R → T: dbSNP rs8192683.

VAR_037435

Secondary structure

1

.

.

.

.

.

.

.

.

.

925

Helix Strand Turn

Details...

Turn

151 – 155

5

Beta strand

163 – 165

3

Helix

168 – 173

6

Helix

180 – 183

4

Sequences

	Sequence		Length	Mass (Da)
	P22413-1 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 0ECAA063801CAFEB	FASTA	925	104,924
	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

References

	« Hide 'large scale' referencesShow '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: 2211644] [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: 1315502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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. , 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: 14574404] [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: 15489334] [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: 10480624] [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: 8001561] [Abstract] Cited for: CHARACTERIZATION.
[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: 7737162] [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: 9344668] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"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: 11598187] [Abstract] Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
[11]	"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: 15072822] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341, MASS SPECTROMETRY. Tissue: Liver.
[13]	"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: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341; ASN-643 AND ASN-748, MASS SPECTROMETRY.
[14]	"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.
[15]	"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: 10453738] [Abstract] Cited for: VARIANTS OPLL PRO-91 AND PHE-287, VARIANTS GLN-173; HIS-268 AND PRO-779.
[16]	"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. , Smith W., Ferre M., Terkeltaub R., Nuernberg P. Nat. Genet. 34:379-381(2003) [PubMed: 12881724] [Abstract] Cited for: VARIANTS IIAC PHE-579 AND CYS-774.
[17]	"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: 15940697] [Abstract] Cited for: VARIANTS IIAC VAL-342 AND PHE-371.
[18]	"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: 16186408] [Abstract] Cited for: VARIANT GLN-173, ASSOCIATION WITH OBESITY, GLUCOSE INTOLERANCE AND NIDDM.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M57736 mRNA. Translation: AAA63237.1. Different initiation.
D12485 mRNA. Translation: BAA02054.1. Different initiation.
AF110304 , 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 , 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.

IPI

IPI00184311.

PIR

A39216.

RefSeq

NP_006199.2.

UniGene

Hs.527295

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YS0	NMR	-	A	147-189	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P22413.

PTM databases

PhosphoSite

P22413.

Proteomic databases

PRIDE

P22413.

Genome annotation databases

Ensembl

ENST00000358229; ENSP00000350964; ENSG00000197594; Homo sapiens. [Genome view]
ENST00000360971; ENSP00000354238; ENSG00000197594; Homo sapiens. [Genome view]

GeneID

5167.

KEGG

hsa:5167.

UCSC

uc003qcx.2. human.

Organism-specific databases

CTD

5167.

GeneCards

GC06P132170.

H-InvDB

HIX0025075.

HGNC

HGNC:3356. ENPP1.

MIM

125853. phenotype.
173335. gene.
208000. phenotype.
602475. phenotype.

Orphanet

51608. Arterial calcification, generalized, of infancy.

PharmGKB

PA27791.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P22413.

OMA

ERPHFYT.

Enzyme and pathway databases

BRENDA

3.1.4.1. 247.
3.6.1.9. 247.

Reactome

REACT_11193. Metabolism of vitamins and cofactors.

Gene expression databases

ArrayExpress

P22413.

Bgee

P22413.

CleanEx

HS_ENPP1.

Genevestigator

P22413.

GermOnline

ENSG00000197594. Homo sapiens.

Family and domain databases

InterPro

IPR017849. Alkaline_Pase-like_a/b/a.
IPR001604. Endonuclease.
IPR002591. Phosphodiest/P_Trfase.
IPR001212. Somatomedin_B.
IPR020436. Somatomedin_B_chordata.
[Graphical view]

Gene3D

G3DSA:3.40.720.10. Alk_phosphtse. 1 hit.
G3DSA:3.40.570.10. Endonuclease. 1 hit.

Pfam

PF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view]

PRINTS

PR00022. SOMATOMEDINB.

SMART

SM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view]

PROSITE

PS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01143. Amifostine.
DB00811. Ribavirin.

NextBio

19990.

SOURCE

Search...

Entry information

Entry name

ENPP1_HUMAN

Accession

Primary (citable) accession number: P22413
Secondary accession number(s): Q5T9R6 , Q9NPZ3, Q9P1P6, Q9UP61, Q9Y6K3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	September 19, 2002
Last modified:	November 3, 2009
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.