ENPP3_PONAB
ID ENPP3_PONAB Reviewed; 873 AA.
AC Q5R5M5;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 85.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
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DR EMBL; CR860832; CAH92941.1; -; mRNA.
DR RefSeq; NP_001126732.1; NM_001133260.1.
DR AlphaFoldDB; Q5R5M5; -.
DR SMR; Q5R5M5; -.
DR STRING; 9601.ENSPPYP00000019047; -.
DR GeneID; 100173734; -.
DR KEGG; pon:100173734; -.
DR CTD; 5169; -.
DR InParanoid; Q5R5M5; -.
DR OrthoDB; 999163at2759; -.
DR Proteomes; UP000001595; Unplaced.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0035529; F:NADH pyrophosphatase activity; IEA:UniProtKB-EC.
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:0006220; P:pyrimidine nucleotide metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.570.10; -; 1.
DR Gene3D; 3.40.720.10; -; 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 Pfam; PF01223; Endonuclease_NS; 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; SSF53649; 1.
DR SUPFAM; SSF54060; SSF54060; 1.
DR SUPFAM; SSF90188; SSF90188; 2.
DR PROSITE; PS00524; SMB_1; 2.
DR PROSITE; PS50958; SMB_2; 2.
PE 2: Evidence at transcript level;
KW Calcium; Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Multifunctional enzyme; Reference proteome; Repeat;
KW Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..873
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 3"
FT /id="PRO_0000282961"
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..873
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 51..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 603..873
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:0000250|UniProtKB:P15396"
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 275
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 750
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 752
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 754
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 756
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT BINDING 758
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 592
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 685
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 697
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 787
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..71
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 58..89
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 69..82
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 75..81
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 98..115
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 103..133
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 113..126
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 119..125
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 144..190
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 152..364
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 380..477
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 428..816
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 561..621
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 573..677
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 575..662
FT /evidence="ECO:0000250|UniProtKB:O14638"
FT DISULFID 785..795
FT /evidence="ECO:0000250|UniProtKB:O14638"
SQ SEQUENCE 873 AA; 99908 MW; 823149DFF08875BD CRC64;
MESMLTLAME QPVKRNTLKK YKIACIVLLA LLVIVSLGLG LGLGLRKPEK QGSCRKKCFD
ASFRGLENCR CDVACKDRGD CCWDFEDTCV ESTRIWMCNQ FRCGETRLEA SLCSCSDDCL
QRKDCCADYK SVCQGETSWL EENCDTAQQS QCPEGFDLPP VILFSMDGFR AEYLHTWDTL
MPNINKLKTC GIHSKYMRAM YPTKTFPNHY TIVMGLYPES HGIIDNNMYD VNLNKNFSLS
SKEQNNPAWW HGQPMWLTAM YQGLKAATYF WPGSEAAING SFPSIYMPYN GSVPFEERIS
TLLKWLDLPK AERPRFYTMY FEEPDFSGHA GGPVSARVIK ALQIVDHAFG MLMEGLKQRN
LHNCVNIILL ADHGMEQTYC NKMEYMTDYF PRINFYMYEG PAPRIRAHSI PHDFFSFNSE
EIVRNLSCRK PDQHFKPYLT PDLPKRLHYA KNVRIDKVHL FVDRQWLAVR SKSNTNCGGG
NHGYNNEFRS MEAIFLAHGP SFKEKTEVEP FENIEVYNLM CDLLRIQPAP NNGTHGSLNH
LLKVPFYEPS HAEEVSKFSV CGFANPLPAE SDCLCPHLQN SIQLEQVNQM LNLTQEEITA
TVKVNLPFGR PRVLQKNVDH CLLYHREYVS GFGKAMRMPM WSSYTVPQLG DTSPLPPTVP
DCLRADVRVP PSESQKCSFY LADKNITHGF LYPPASNRTS DSQYDALITS NLVPMYEEFT
KMWDYFHSVL LIKHATERNG VNVVSGPIFD YNYDGHFDAP DEITKHLANT DVPIPTHYFV
VLTSCKNKSH TPENCPGWLD VLPFIIPHRP TNMESCPEGK PEALWVEERF TAHIARVRDV
ELLTGLDFYQ EKVQPVSEIL QLKTYLPTFE TTI
