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
//