ID ENPP3_BOVIN Reviewed; 874 AA.
AC P15396; Q0II99;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 27-MAR-2024, entry version 139.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 3;
DE Short=E-NPP 3;
DE AltName: Full=Phosphodiesterase I beta;
DE Short=PD-Ibeta;
DE AltName: Full=Phosphodiesterase I/nucleotide pyrophosphatase 3;
DE AltName: CD_antigen=CD203c;
DE Includes:
DE RecName: Full=Alkaline phosphodiesterase I;
DE EC=3.1.4.1 {ECO:0000250|UniProtKB:O14638};
DE Includes:
DE RecName: Full=Nucleotide pyrophosphatase;
DE Short=NPPase;
DE EC=3.6.1.9 {ECO:0000250|UniProtKB:O14638};
DE AltName: Full=Nucleotide diphosphatase {ECO:0000305};
GN Name=ENPP3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 167-226, AND ACTIVE SITE THR-205.
RC TISSUE=Intestine;
RX PubMed=2989287; DOI=10.1016/s0021-9258(17)39474-7;
RA Culp J.S., Blytt H.J., Hermodson M., Butler L.G.;
RT "Amino acid sequence of the active site peptide of bovine intestinal 5'-
RT nucleotide phosphodiesterase and identification of the active site residue
RT as threonine.";
RL J. Biol. Chem. 260:8320-8324(1985).
CC -!- FUNCTION: Hydrolase that metabolizes extracellular nucleotides,
CC including ATP, GTP, UTP and CTP (By similarity). Limits mast cell and
CC basophil responses during inflammation and during the chronic phases of
CC allergic responses by eliminating the extracellular ATP that functions
CC as signaling molecule and activates basophils and mast cells and
CC induces the release of inflammatory cytokines. Metabolizes
CC extracellular ATP in the lumen of the small intestine, and thereby
CC prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic
CC cells (By similarity). Has also alkaline phosphodiesterase activity (By
CC similarity). {ECO:0000250|UniProtKB:O14638,
CC ECO:0000250|UniProtKB:Q6DYE8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolytically removes 5'-nucleotides successively from the
CC 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.;
CC EC=3.1.4.1; Evidence={ECO:0000250|UniProtKB:O14638};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9;
CC Evidence={ECO:0000250|UniProtKB:O14638};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-
CC deoxyribonucleoside 5'-phosphate + diphosphate + H(+);
CC Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9;
CC Evidence={ECO:0000250|UniProtKB:O14638};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O14638};
CC Note=Binds 2 zinc ions per subunit. {ECO:0000250|UniProtKB:O14638};
CC -!- SUBUNIT: Monomer and homodimer. {ECO:0000250|UniProtKB:O14638}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O14638};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:O14638}.
CC Apical cell membrane {ECO:0000250|UniProtKB:O14638}; Single-pass type
CC II membrane protein {ECO:0000250|UniProtKB:O14638}. Secreted
CC {ECO:0000250|UniProtKB:O14638}. Note=Detected at the cell surface of
CC basophils. Detected at the apical plasma membrane of bile duct cells.
CC Located to the apical surface in intestinal and kidney epithelial
CC cells. Secreted in serum, and in lumen of epithelial cells.
CC {ECO:0000250|UniProtKB:O14638}.
CC -!- PTM: N-glycosylated. N-glycosylation is necessary for normal transport
CC to the cell membrane, but is not the apical targeting signal.
CC {ECO:0000250|UniProtKB:P97675}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; BC122742; AAI22743.1; -; mRNA.
DR PIR; A25274; A25274.
DR RefSeq; NP_001069391.1; NM_001075923.2.
DR AlphaFoldDB; P15396; -.
DR SMR; P15396; -.
DR STRING; 9913.ENSBTAP00000026900; -.
DR BindingDB; P15396; -.
DR ChEMBL; CHEMBL3593152; -.
DR GlyCosmos; P15396; 11 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000026900; -.
DR Ensembl; ENSBTAT00000026900.6; ENSBTAP00000026900.6; ENSBTAG00000020196.6.
DR GeneID; 529405; -.
DR KEGG; bta:529405; -.
DR CTD; 5169; -.
DR VEuPathDB; HostDB:ENSBTAG00000020196; -.
DR VGNC; VGNC:28506; ENPP3.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000159640; -.
DR InParanoid; P15396; -.
DR OMA; PMYKEFK; -.
DR OrthoDB; 1366859at2759; -.
DR SABIO-RK; P15396; -.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000020196; Expressed in caput epididymis and 61 other cell types or tissues.
DR ExpressionAtlas; P15396; baseline.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0047429; F:nucleoside triphosphate diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0004528; F:phosphodiesterase I activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; ISS:UniProtKB.
DR GO; GO:0002276; P:basophil activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; ISS:UniProtKB.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0055062; P:phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0006220; P:pyrimidine nucleotide metabolic process; ISS:UniProtKB.
DR CDD; cd16018; Enpp; 1.
DR CDD; cd00091; NUC; 1.
DR Gene3D; 4.10.410.20; -; 2.
DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1.
DR Gene3D; 3.40.570.10; Extracellular Endonuclease, subunit A; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR InterPro; IPR020821; Extracellular_endonuc_su_A.
DR InterPro; IPR044925; His-Me_finger_sf.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR InterPro; IPR001212; Somatomedin_B_dom.
DR PANTHER; PTHR10151; ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE; 1.
DR PANTHER; PTHR10151:SF107; ECTONUCLEOTIDE PYROPHOSPHATASE_PHOSPHODIESTERASE FAMILY MEMBER 3; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR Pfam; PF01033; Somatomedin_B; 2.
DR SMART; SM00892; Endonuclease_NS; 1.
DR SMART; SM00477; NUC; 1.
DR SMART; SM00201; SO; 2.
DR SUPFAM; SSF53649; Alkaline phosphatase-like; 1.
DR SUPFAM; SSF54060; His-Me finger endonucleases; 1.
DR SUPFAM; SSF90188; Somatomedin B domain; 2.
DR PROSITE; PS00524; SMB_1; 2.
DR PROSITE; PS50958; SMB_2; 2.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Reference proteome;
KW Repeat; Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..874
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 3"
FT /id="PRO_0000058534"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..874
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 50..93
FT /note="SMB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DOMAIN 94..138
FT /note="SMB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT REGION 140..509
FT /note="Phosphodiesterase"
FT REGION 604..874
FT /note="Nuclease"
FT MOTIF 78..80
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 205
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:2989287"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 289
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 325
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 482
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 751
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 755
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 757
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 759
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 532
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 677
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 698
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 770
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 788
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 820
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 58..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 69..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 75..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 98..115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 103..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 113..126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 119..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 144..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 152..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 380..477
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 428..817
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 561..622
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 574..678
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 576..663
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 786..796
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
SQ SEQUENCE 874 AA; 99523 MW; A901CC5B7E787F40 CRC64;
MQSTLNLSTE EPVKRNTVKK YKIICIVLLI LLVAVSLALG LVAGLRQQEE QGSCRKKCFD
ASHRGLEGCR CDVGCKGRGD CCWDFEDTCV QSTQIWTCNK FRCGETRLES SLCSCSDDCL
QRKDCCADYK SVCQGETSWV DEDCSTAQQP QCPEGFDLPP VILFSMDGFR AEYLQTWSTL
VPNINKLKTC GVHSQYLRPA YPTKTFPNHY TIVTGLYPES HGIIDNNMYD INLNKNFSLS
SKEKDNPAWW QGQPIWLTAM YQGLKVGTYF WPGSDVAING TFPSIYKIYN RSVTYEERIF
TLLKWLDLPK AERPDFYTIY VEEPDSQGHN YGPVSAGVIQ ALQLVDKTFG LLMEGLKQRN
LVNCVNIILL ADHGMDQTYC DKLEYMADYF SSINFYMFEG PAPRIRTRNI PQDFFTFNSE
EIVRNLSCRK PDQHFKPYLS PDLPKRLHFA KNVRIDKVNL LVDRQWQAVR NRAYSYCGGG
NHGYDNEFKS MEAIFLAHGP SFKQKTEVEP FDNIEVYNLL CDLLHIQPAP NNGTHGSLNH
LLKVPFYEPS HAEELSKFSV CGFTVPLPTD TLGCSCSRLQ TNSDLERVNQ MLDLTQDEIT
ATEKLNLPFG RPRLIQKNKE PCLLYHREYV SGFDKTLRMP LWSSYTVPKP GDTSPLPPTV
PDCLRADVRV APSESQNCSF SLADKNITHG FLYPPANNRT SNSQYDALIT SNLVPMYEAF
KTMWNYFHSV LLVKYAMERN GVNVVSGPVF DYDYDGHFDA PDEIADYAVN TSVPIPTHYF
VVLTSCKNQS QTPDACTGWL DVLPFVIPHR PTNVESCPEN KSESLWVEER FNVHTARVRD
VELLTGLDFY QEKAQPVSEI LQLKTYLPVF ETVI
//
