Reviewed, UniProtKB/Swiss-Prot P97675 (ENPP3_RAT)

Names and origin

Protein names

Recommended name:
    Ectonucleotide pyrophosphatase/phosphodiesterase family member 3
      Short name=E-NPP 3
Alternative name(s):
    Phosphodiesterase I/nucleotide pyrophosphatase 3
    Phosphodiesterase I beta
      Short name=PD-Ibeta
    RB13-6 antigen
    B10
    CD_antigen=CD203c
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:	Enpp3
Synonyms:	Pdnp3

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	875 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 can be formed which inhibits further hydrolysis By similarity.
Subcellular location	Membrane; Single-pass type II membrane protein Potential. Secreted By similarity. 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 By similarity.
Tissue specificity	Highly expressed in intestinal epithelium. Also expressed in liver. Ref.2
Post-translational modification	The N-terminal is blocked. N-glycosylation is necessary for correct trafficking to the apical surface, but is not the apical targeting signal. No O-glycosylation. 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.

Ontologies

Keywords
Cellular component	Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal-anchor Transmembrane
Ligand	Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	metabolic process Inferred from electronic annotation. Source: InterPro regulation of smooth muscle cell differentiation Non-traceable author statement. Source: RGD
Cellular component	cell surface Ref.2 Traceable author statement. Source: RGD extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid binding Inferred from electronic annotation. Source: InterPro nucleotide diphosphatase activity Ref.2 Traceable author statement. Source: RGD phosphodiesterase I activity Ref.2 Traceable author statement. Source: RGD
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_0000188571
Regions
	Topological domain	1 – 11	11	Cytoplasmic Potential
	Transmembrane	12 – 30	19	Signal-anchor for type II membrane protein Potential
	Topological domain	31 – 875	845	Extracellular Potential
	Domain	51 – 94	44	SMB 1
	Domain	95 – 139	45	SMB 2
	Region	141 – 510	370	Phosphodiesterase
	Region	605 – 875	271	Nuclease
	Motif	79 – 81	3	Cell attachment site Potential
Sites
	Active site	206	1	AMP-threonine intermediate By similarity
	Metal binding	168	1	Divalent metal cation 2 Probable
	Metal binding	326	1	Divalent metal cation 1 Probable
	Metal binding	330	1	Divalent metal cation 1 Probable
	Metal binding	373	1	Divalent metal cation 2 Probable
	Metal binding	374	1	Divalent metal cation 2 Probable
	Metal binding	483	1	Divalent metal cation 1 Probable
Amino acid modifications
	Glycosylation	237	1	N-linked (GlcNAc...) Potential
	Glycosylation	280	1	N-linked (GlcNAc...) Potential
	Glycosylation	289	1	N-linked (GlcNAc...) Potential
	Glycosylation	533	1	N-linked (GlcNAc...) Potential
	Glycosylation	574	1	N-linked (GlcNAc...) Potential
	Glycosylation	594	1	N-linked (GlcNAc...) Potential
	Glycosylation	702	1	N-linked (GlcNAc...) Potential
	Glycosylation	789	1	N-linked (GlcNAc...) Potential
	Disulfide bond	55 ↔ 72		Alternate By similarity
	Disulfide bond	55 ↔ 59		Alternate By similarity
	Disulfide bond	59 ↔ 90		Alternate By similarity
	Disulfide bond	70 ↔ 83		Alternate By similarity
	Disulfide bond	70 ↔ 72		Alternate By similarity
	Disulfide bond	76 ↔ 82		By similarity
	Disulfide bond	83 ↔ 90		Alternate By similarity
	Disulfide bond	99 ↔ 116		Alternate By similarity
	Disulfide bond	99 ↔ 104		Alternate By similarity
	Disulfide bond	104 ↔ 134		Alternate By similarity
	Disulfide bond	114 ↔ 127		Alternate By similarity
	Disulfide bond	114 ↔ 116		Alternate By similarity
	Disulfide bond	120 ↔ 126		By similarity
	Disulfide bond	127 ↔ 134		Alternate By similarity
Natural variations
	Natural variant	124	1	K → E
	Natural variant	201	1	M → V
	Natural variant	596 – 597	2	SG → NR
Experimental info
	Sequence conflict	111	1	A → T in BAA06333. Ref.3
	Sequence conflict	273	1	P → L in CAA88029. Ref.1
	Sequence conflict	475 – 476	2	SS → VP in BAA06333. Ref.3
	Sequence conflict	814	1	N → KP in BAA06333. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P97675-1 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 4205F263E8A933EA	FASTA	875	99,072
	10 20 30 40 50 60 MDSRLALATE EPIKKDSLKR YKILCAVLLA LLVIVSLGLG LGLGLRKPEE HIGSCRKKCF 70 80 90 100 110 120 DSSHRGLEGC RCDSGCTDRG DCCWDFEDTC VKSTQIWTCN SFRCGETRLE AALCSCADDC 130 140 150 160 170 180 LQRKDCCTDY KAVCQGEVPW VTEACASSQE PQCPEGFDQP PVILFSMDGF RAEYLQTWST 190 200 210 220 230 240 LLPNINKLKT CGLHSKYMRA MYPTKTFPNH YTIVTGLYPE SHGIIDNNMY DVYLNKNFSL 250 260 270 280 290 300 SSVEKSNPAW WSGQPIWLTA MYQGLKAASY YWPGSDVAVN GSFPNIYRNY SNSVPYESRI 310 320 330 340 350 360 ATLLQWLDLP KAERPSFYTI YVEEPDSAGH KSGPVSAGVI KALQLVDDAF GMLMEGLKQR 370 380 390 400 410 420 NLHNCVNIIV LADHGMDQTS CDRVEYMTDY FPEINFYMYQ GPAPRIRTRN IPQDFFTFNS 430 440 450 460 470 480 EEIVRDLSCR KSDQHFKPYL TPDLPKRLHY AKNVRIDKVH LMVDRQWLAY RNKGSSNCEG 490 500 510 520 530 540 GTHGYNNEFK SMEAIFLAHG PSFKEKTVIE PFENIEVYNL LCDLLHIQPA PNNGSHGSLN 550 560 570 580 590 600 HLLKAPFYQP SHAEELSKSA GCGFTTPLPK DSLNCSCLAL QTSGQEEQVN QRLNLSGGEV 610 620 630 640 650 660 SATEKTNLPF GRPRVIQKNK DHCLLYHREY VSGFGKAMKM PMWSSYTVPK PGDTSSLPPT 670 680 690 700 710 720 VPDCLRADVR VDPSESQKCS FYLADQNIDH GFLYPPAIKG NNESQYDALI TSNLVPMYKE 730 740 750 760 770 780 FKKMWDYFHK VLLIKYAIER NGVNVVSGPI FDYNYDGHFD APDEITNYVA GTDVPVPTHY 790 800 810 820 830 840 FVVLTSCKNK THTPDSCPGW LDVLPFVVPH RPTNVESCPE NKAEDLWVEE RFKAHIARVR 850 860 870 DVELLTGLDF YQEKTQPVSE ILQLKTYLPT FETII

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Affinity purification and cDNA cloning of rat neural differentiation and tumor cell surface antigen gp130RB13-6 reveals relationship to human and murine PC-1." Deissler H., Lottspeich F., Rajewsky M.F. J. Biol. Chem. 270:9849-9855(1995) [PubMed: 7730366] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 331-339; 473-504; 544-558 AND 605-618, GLYCOSYLATION. Strain: Sprague-Dawley. Tissue: Fetal brain.
[2]	"Biochemical and molecular identification of distinct forms of alkaline phosphodiesterase I expressed on the apical and basolateral plasma membrane surfaces of rat hepatocytes." Scott L.J., Delautier D., Meerson N.R., Trugnan G., Goding J.W., Maurice M. Hepatology 25:995-1002(1997) [PubMed: 9096610] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 494-503 AND 726-746, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Intestine.
[3]	"Molecular cloning of phosphodiesterase I cDNA from rat small intestine." Sano K. Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Small intestine.
[4]	"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.
[5]	"Intracellular traffic of the ecto-nucleotide pyrophosphatase/phosphodiesterase NPP3 to the apical plasma membrane of MDCK and Caco-2 cells: apical targeting occurs in the absence of N-glycosylation." Meerson N.R., Bello V., Delaunay J.-L., Slimane T.A., Delautier D., Lenoir C., Trugnan G., Maurice M. J. Cell Sci. 113:4193-4202(2000) [PubMed: 11069764] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z47987 mRNA. Translation: CAA88029.1. U78787 mRNA. Translation: AAB61535.1. U78788 mRNA. Translation: AAB61536.1. D30649 mRNA. Translation: BAA06333.1. BC097326 mRNA. Translation: AAH97326.1.
IPI	IPI00326462.
PIR	A57080.
RefSeq	NP_062243.2.
UniGene	Rn.44
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	P97675.
Genome annotation databases
Ensembl	ENSRNOG00000013791. Rattus norvegicus. [Contig view]
GeneID	54410.
KEGG	rno:54410.
Organism-specific databases
RGD	708511. Enpp3.
Phylogenomic databases
HOVERGEN	P97675.
OMA	P97675. CVNIILL.
Enzyme and pathway databases
BRENDA	3.1.4.1. 248. 3.6.1.9. 248.
Gene expression databases
ArrayExpress	P97675.
GermOnline	ENSRNOG00000013791. Rattus norvegicus.
Family and domain databases
InterPro	IPR017849. Alkaline_Pase-like_a/b/a. IPR001604. Endonuclease. IPR002591. Phosphodiest/P_Trfase. IPR001212. Somatomedin_B. [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]
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
NextBio	611055.

Entry information

Entry name

ENPP3_RAT

Accession

Primary (citable) accession number: P97675
Secondary accession number(s): P70641 , P97676, Q4V8L6, Q63490

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	September 19, 2002
Last modified:	June 16, 2009
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)