Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O14638 (ENPP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 3

Short name=E-NPP 3
Alternative name(s):
Phosphodiesterase I beta
Short name=PD-Ibeta
Phosphodiesterase I/nucleotide pyrophosphatase 3
CD_antigen=CD203c

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:ENPP3
Synonyms:PDNP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length875 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cleaves a variety of phosphodiester and phosphosulfate bonds including deoxynucleotides, nucleotide sugars, and NAD By similarity.

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 active site intermediate is formed which inhibits further ATP hydrolysis.

Subcellular location

Membrane; Single-pass type II membrane protein Potential. Secreted. Note: Located to the apical surface in intestinal and kidney epithelial cells. Located to the cell surface of basophils, and to the apical plasma membrane of bile duct cells. Secreted in serum, and in lumen of epithelial cells. Ref.5 Ref.6

Tissue specificity

Expressed in bile ducts, prostate, uterus and colon. Exclusively expressed on basophils, mast cells and their progenitors. Ref.1 Ref.6

Induction

Up-regulated by stimulation by allergen or by cross-linking with IgE. The IgE-mediated activation is enhanced by tetradecanoyl phorbol acetate (TPA), a stimulator of the PKC pathway, and inhibited by the P13 kinase inhibitors, LY294002 and wortmannin. Up-regulated in invasive bile duct cancers. Ref.7

Post-translational modification

N-glycosylation is necessary for correct trafficking to the apical surface, but is not the apical targeting signal By similarity.

Sequence similarities

Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

Contains 2 SMB (somatomedin-B) domains.

Sequence caution

The sequence AAD05192.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentMembrane
Secreted
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal-anchor
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processimmune response

Inferred from electronic annotation. Source: InterPro

nucleic acid phosphodiester bond hydrolysis

Traceable author statement Ref.1. 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 10513816. Source: BHF-UCL

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708. Source: UniProt

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

perinuclear region of cytoplasm

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

   Molecular_functionNADH pyrophosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

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 PubMed 10513816. Source: BHF-UCL

nucleotide diphosphatase activity

Traceable author statement Ref.1. Source: ProtInc

phosphodiesterase I activity

Traceable author statement Ref.1. Source: ProtInc

polysaccharide binding

Inferred from electronic annotation. Source: InterPro

scavenger receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 875875Ectonucleotide pyrophosphatase/phosphodiesterase family member 3
PRO_0000188570

Regions

Topological domain1 – 1111Cytoplasmic Potential
Transmembrane12 – 3019Helical; Signal-anchor for type II membrane protein; Potential
Topological domain31 – 875845Extracellular Potential
Domain50 – 9344SMB 1
Domain94 – 13845SMB 2
Region140 – 510371Phosphodiesterase
Region605 – 875271Nuclease
Motif78 – 803Cell attachment site Potential

Sites

Active site2051AMP-threonine intermediate By similarity
Metal binding1671Zinc 1; catalytic By similarity
Metal binding2051Zinc 1; catalytic By similarity
Metal binding3251Zinc 2; catalytic By similarity
Metal binding3291Zinc 2; via tele nitrogen; catalytic By similarity
Metal binding3721Zinc 1; catalytic By similarity
Metal binding3731Zinc 1; via tele nitrogen; catalytic By similarity
Metal binding4831Zinc 2; via tele nitrogen; catalytic By similarity
Binding site2261Substrate By similarity
Binding site3201Substrate By similarity

Amino acid modifications

Glycosylation2361N-linked (GlcNAc...) Potential
Glycosylation2791N-linked (GlcNAc...) Potential
Glycosylation2901N-linked (GlcNAc...) Potential
Glycosylation4261N-linked (GlcNAc...) Potential
Glycosylation5331N-linked (GlcNAc...) Potential
Glycosylation5821N-linked (GlcNAc...) Potential
Glycosylation5941N-linked (GlcNAc...) Potential
Glycosylation6871N-linked (GlcNAc...) Potential
Glycosylation6991N-linked (GlcNAc...) Potential
Glycosylation7891N-linked (GlcNAc...) Potential
Disulfide bond54 ↔ 71 By similarity
Disulfide bond58 ↔ 89 By similarity
Disulfide bond69 ↔ 82 By similarity
Disulfide bond75 ↔ 81 By similarity
Disulfide bond98 ↔ 115 By similarity
Disulfide bond103 ↔ 133 By similarity
Disulfide bond113 ↔ 126 By similarity
Disulfide bond119 ↔ 125 By similarity
Disulfide bond144 ↔ 190 By similarity
Disulfide bond152 ↔ 364 By similarity
Disulfide bond380 ↔ 478 By similarity
Disulfide bond429 ↔ 818 By similarity
Disulfide bond575 ↔ 679 By similarity
Disulfide bond577 ↔ 664 By similarity
Disulfide bond787 ↔ 797 By similarity

Natural variations

Natural variant6201V → M.
Corresponds to variant rs9321309 [ dbSNP | Ensembl ].
VAR_018516
Natural variant7441N → H.
Corresponds to variant rs36094194 [ dbSNP | Ensembl ].
VAR_046538
Natural variant7861S → N.
Corresponds to variant rs17601580 [ dbSNP | Ensembl ].
VAR_031253

Experimental info

Sequence conflict1221R → K in AAC51813. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O14638 [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: 629D2E33B4C45196

FASTA875100,124
        10         20         30         40         50         60 
MESTLTLATE QPVKKNTLKK YKIACIVLLA LLVIMSLGLG LGLGLRKLEK QGSCRKKCFD 

        70         80         90        100        110        120 
ASFRGLENCR CDVACKDRGD CCWDFEDTCV ESTRIWMCNK FRCGETRLEA SLCSCSDDCL 

       130        140        150        160        170        180 
QRKDCCADYK SVCQGETSWL EENCDTAQQS QCPEGFDLPP VILFSMDGFR AEYLYTWDTL 

       190        200        210        220        230        240 
MPNINKLKTC GIHSKYMRAM YPTKTFPNHY TIVTGLYPES HGIIDNNMYD VNLNKNFSLS 

       250        260        270        280        290        300 
SKEQNNPAWW HGQPMWLTAM YQGLKAATYF WPGSEVAING SFPSIYMPYN GSVPFEERIS 

       310        320        330        340        350        360 
TLLKWLDLPK AERPRFYTMY FEEPDSSGHA GGPVSARVIK ALQVVDHAFG MLMEGLKQRN 

       370        380        390        400        410        420 
LHNCVNIILL ADHGMDQTYC NKMEYMTDYF PRINFFYMYE GPAPRIRAHN IPHDFFSFNS 

       430        440        450        460        470        480 
EEIVRNLSCR KPDQHFKPYL TPDLPKRLHY AKNVRIDKVH LFVDQQWLAV RSKSNTNCGG 

       490        500        510        520        530        540 
GNHGYNNEFR SMEAIFLAHG PSFKEKTEVE PFENIEVYNL MCDLLRIQPA PNNGTHGSLN 

       550        560        570        580        590        600 
HLLKVPFYEP SHAEEVSKFS VCGFANPLPT ESLDCFCPHL QNSTQLEQVN QMLNLTQEEI 

       610        620        630        640        650        660 
TATVKVNLPF GRPRVLQKNV DHCLLYHREY VSGFGKAMRM PMWSSYTVPQ LGDTSPLPPT 

       670        680        690        700        710        720 
VPDCLRADVR VPPSESQKCS FYLADKNITH GFLYPPASNR TSDSQYDALI TSNLVPMYEE 

       730        740        750        760        770        780 
FRKMWDYFHS VLLIKHATER NGVNVVSGPI FDYNYDGHFD APDEITKHLA NTDVPIPTHY 

       790        800        810        820        830        840 
FVVLTSCKNK SHTPENCPGW LDVLPFIIPH RPTNVESCPE GKPEALWVEE RFTAHIARVR 

       850        860        870 
DVELLTGLDF YQDKVQPVSE ILQLKTYLPT FETTI 

« Hide

References

« Hide 'large scale' references
[1]"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: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Prostate.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Endometrium.
[3]"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].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The basophil activation marker defined by antibody 97A6 is identical to the ectonucleotide pyrophosphatase/phosphodiesterase 3."
Buehring H.J., Seiffert M., Giesert C., Marxer A., Kanz L., Valent P., Sano K.
Blood 97:3303-3305(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 393-405, IDENTIFICATION AS CD203C, SUBCELLULAR LOCATION.
[6]"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, TISSUE SPECIFICITY.
[7]"The basophil-specific ectoenzyme E-NPP3 (CD203c) as a marker for cell activation and allergy diagnosis."
Buehring H.J., Streble A., Valent P.
Int. Arch. Allergy Immunol. 133:317-329(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, POSSIBLE APPLICATION IN ALLERGY DIAGNOSIS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF005632 mRNA. Translation: AAC51813.1.
EF560735 mRNA. Translation: ABQ59045.1.
AC005587 Genomic DNA. Translation: AAD05192.1. Sequence problems.
AL121575, AC005587, AL355150 Genomic DNA. Translation: CAI23322.1.
AL355150, AC005587, AL121575 Genomic DNA. Translation: CAI40481.1.
CH471051 Genomic DNA. Translation: EAW48045.1.
RefSeqNP_005012.2. NM_005021.3.
UniGeneHs.486489.

3D structure databases

ProteinModelPortalO14638.
SMRO14638. Positions 52-872.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111195. 2 interactions.
IntActO14638. 1 interaction.
MINTMINT-6610326.
STRING9606.ENSP00000350265.

Chemistry

ChEMBLCHEMBL5580.

PTM databases

PhosphoSiteO14638.

Proteomic databases

PaxDbO14638.
PRIDEO14638.

Protocols and materials databases

DNASU5169.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357639; ENSP00000350265; ENSG00000154269.
ENST00000414305; ENSP00000406261; ENSG00000154269.
GeneID5169.
KEGGhsa:5169.
UCSCuc003qcu.4. human.

Organism-specific databases

CTD5169.
GeneCardsGC06P132000.
HGNCHGNC:3358. ENPP3.
HPAHPA043772.
MIM602182. gene.
neXtProtNX_O14638.
PharmGKBPA27793.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1524.
HOGENOMHOG000037439.
HOVERGENHBG051484.
InParanoidO14638.
KOK01513.
OMATSDSQYD.
OrthoDBEOG7XM2X4.
PhylomeDBO14638.
TreeFamTF330032.

Gene expression databases

ArrayExpressO14638.
BgeeO14638.
CleanExHS_ENPP3.
GenevestigatorO14638.

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.
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]
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

GeneWikiENPP3.
GenomeRNAi5169.
NextBio20000.
PROO14638.
SOURCESearch...

Entry information

Entry nameENPP3_HUMAN
AccessionPrimary (citable) accession number: O14638
Secondary accession number(s): Q5JTL3
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: September 23, 2008
Last modified: April 16, 2014
This is version 127 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

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