O14638 (ENPP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	875 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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.
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 component	Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	immune response Inferred from electronic annotation. Source: InterPro nucleoside triphosphate catabolic process Inferred from direct assay PubMed 10513816. Source: BHF-UCL
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc perinuclear region of cytoplasm Inferred from direct assay PubMed 10513816. Source: BHF-UCL
Molecular_function	NADH pyrophosphatase activity Inferred from electronic annotation. Source: 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 875	875	Ectonucleotide pyrophosphatase/phosphodiesterase family member 3		PRO_0000188570
Regions
	Topological domain	1 – 11	11	Cytoplasmic Potential
	Transmembrane	12 – 30	19	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	31 – 875	845	Extracellular Potential
	Domain	50 – 93	44	SMB 1
	Domain	94 – 138	45	SMB 2
	Region	140 – 510	371	Phosphodiesterase
	Region	605 – 875	271	Nuclease
	Motif	78 – 80	3	Cell attachment site Potential
Sites
	Active site	205	1	AMP-threonine intermediate By similarity
	Metal binding	167	1	Divalent metal cation 2 Probable
	Metal binding	325	1	Divalent metal cation 1 Probable
	Metal binding	329	1	Divalent metal cation 1 Probable
	Metal binding	372	1	Divalent metal cation 2 Probable
	Metal binding	373	1	Divalent metal cation 2 Probable
	Metal binding	483	1	Divalent metal cation 1 Probable
Amino acid modifications
	Glycosylation	236	1	N-linked (GlcNAc...) Potential
	Glycosylation	279	1	N-linked (GlcNAc...) Potential
	Glycosylation	290	1	N-linked (GlcNAc...) Potential
	Glycosylation	426	1	N-linked (GlcNAc...) Potential
	Glycosylation	533	1	N-linked (GlcNAc...) Potential
	Glycosylation	582	1	N-linked (GlcNAc...) Potential
	Glycosylation	594	1	N-linked (GlcNAc...) Potential
	Glycosylation	687	1	N-linked (GlcNAc...) Potential
	Glycosylation	699	1	N-linked (GlcNAc...) Potential
	Glycosylation	789	1	N-linked (GlcNAc...) Potential
	Disulfide bond	54 ↔ 71		Alternate By similarity
	Disulfide bond	54 ↔ 58		Alternate By similarity
	Disulfide bond	58 ↔ 89		Alternate By similarity
	Disulfide bond	69 ↔ 82		Alternate By similarity
	Disulfide bond	69 ↔ 71		Alternate By similarity
	Disulfide bond	75 ↔ 81		By similarity
	Disulfide bond	82 ↔ 89		Alternate By similarity
	Disulfide bond	98 ↔ 115		Alternate By similarity
	Disulfide bond	98 ↔ 103		Alternate By similarity
	Disulfide bond	103 ↔ 133		Alternate By similarity
	Disulfide bond	113 ↔ 126		Alternate By similarity
	Disulfide bond	113 ↔ 115		Alternate By similarity
	Disulfide bond	119 ↔ 125		By similarity
	Disulfide bond	126 ↔ 133		Alternate By similarity
Natural variations
	Natural variant	620	1	V → M. Corresponds to variant rs9321309 [ dbSNP | Ensembl ].		VAR_018516
	Natural variant	744	1	N → H. Corresponds to variant rs36094194 [ dbSNP | Ensembl ].		VAR_046538
	Natural variant	786	1	S → N. Corresponds to variant rs17601580 [ dbSNP | Ensembl ].		VAR_031253
Experimental info
	Sequence conflict	122	1	R → K in AAC51813. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O14638 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: 629D2E33B4C45196	FASTA	875	100,124
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00020999.
RefSeq	NP_005012.2. NM_005021.3.
UniGene	Hs.486489.
3D structure databases
ProteinModelPortal	O14638.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-6610326.
STRING	9606.ENSP00000350265.
PTM databases
PhosphoSite	O14638.
Proteomic databases
PaxDb	O14638.
PRIDE	O14638.
Protocols and materials databases
DNASU	5169.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357639; ENSP00000350265; ENSG00000154269. ENST00000414305; ENSP00000406261; ENSG00000154269.
GeneID	5169.
KEGG	hsa:5169.
UCSC	uc003qcu.4. human.
Organism-specific databases
CTD	5169.
GeneCards	GC06P132000.
HGNC	HGNC:3358. ENPP3.
HPA	HPA043772.
MIM	602182. gene.
neXtProt	NX_O14638.
PharmGKB	PA27793.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1524.
HOGENOM	HOG000037439.
HOVERGEN	HBG051484.
InParanoid	O14638.
KO	K01513.
OMA	DSQYDAL.
OrthoDB	EOG43FGW7.
PhylomeDB	O14638.
Gene expression databases
ArrayExpress	O14638.
Bgee	O14638.
CleanEx	HS_ENPP3.
Genevestigator	O14638.
GermOnline	ENSG00000154269. Homo sapiens.
Family and domain databases
Gene3D	3.40.570.10. 1 hit. 3.40.720.10. 1 hit.
InterPro	IPR017849. 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]
PANTHER	PTHR10151. PTHR10151. 1 hit.
Pfam	PF01223. Endonuclease_NS. 1 hit. PF01663. Phosphodiest. 1 hit. PF01033. Somatomedin_B. 2 hits. [Graphical view]
SMART	SM00892. Endonuclease_NS. 1 hit. SM00477. NUC. 1 hit. SM00201. SO. 2 hits. [Graphical view]
SUPFAM	SSF53649. Alkaline_phosphatase_core. 1 hit.
PROSITE	PS00524. SMB_1. 2 hits. PS50958. SMB_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5580.
GenomeRNAi	5169.
NextBio	20000.
SOURCE	Search...

Entry information

Entry name

ENPP3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.