ENPP1_RAT
ID ENPP1_RAT Reviewed; 906 AA.
AC Q924C3; Q91XQ3; Q920C8;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 1;
DE Short=E-NPP 1;
DE AltName: Full=Phosphodiesterase I/nucleotide pyrophosphatase 1;
DE AltName: Full=Plasma-cell membrane glycoprotein PC-1;
DE Includes:
DE RecName: Full=Alkaline phosphodiesterase I;
DE EC=3.1.4.1 {ECO:0000250|UniProtKB:P06802};
DE Includes:
DE RecName: Full=Nucleotide pyrophosphatase;
DE Short=NPPase;
DE EC=3.6.1.9 {ECO:0000250|UniProtKB:P06802};
DE AltName: Full=Nucleotide diphosphatase {ECO:0000305};
DE Contains:
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form {ECO:0000305};
GN Name=Enpp1 {ECO:0000312|RGD:628825}; Synonyms=Npps, Pc1, Pdnp1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS.
RC STRAIN=Lewis, Louvain, and Wistar;
RX PubMed=12121276; DOI=10.1046/j.1365-2370.2002.00330.x;
RA Banakh I., Sali A., Dubljevic V., Grobben B., Slegers H., Goding J.W.;
RT "Structural basis of allotypes of ecto-nucleotide
RT pyrophosphatase/phosphodiesterase (plasma cell membrane glycoprotein PC-1)
RT in the mouse and rat, and analysis of allele-specific xenogeneic
RT antibodies.";
RL Eur. J. Immunogenet. 29:307-313(2002).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND THR-238, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Nucleotide pyrophosphatase that generates diphosphate (PPi)
CC and functions in bone mineralization and soft tissue calcification by
CC regulating pyrophosphate levels. PPi inhibits bone mineralization and
CC soft tissue calcification by binding to nascent hydroxyapatite
CC crystals, thereby preventing further growth of these crystals.
CC Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside
CC 5' triphosphates such as GTP, CTP and UTP to their corresponding
CC monophosphates with release of pyrophosphate, as well as diadenosine
CC polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the
CC regulation of the availability of nucleotide sugars in the endoplasmic
CC reticulum and Golgi, and the regulation of purinergic signaling.
CC Inhibits ectopic joint calcification and maintains articular
CC chondrocytes by repressing hedgehog signaling; it is however unclear
CC whether hedgehog inhibition is direct or indirect (By similarity).
CC Appears to modulate insulin sensitivity. Also involved in melanogenesis
CC (By similarity). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a
CC second messenger that activates TMEM173/STING and triggers type-I
CC interferon production (By similarity). 2',3'-cGAMP degradation takes
CC place in the lumen or extracellular space, and not in the cytosol where
CC it is produced; the role of 2',3'-cGAMP hydrolysis is therefore
CC unclear. Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-
CC cGAMP (By similarity). {ECO:0000250|UniProtKB:P06802,
CC ECO:0000250|UniProtKB:P22413}.
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:P06802};
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:P22413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = AMP + diphosphate + H(+); Xref=Rhea:RHEA:14245,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:456215; EC=3.6.1.9;
CC Evidence={ECO:0000250|UniProtKB:P22413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + UTP = diphosphate + H(+) + UMP; Xref=Rhea:RHEA:29395,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:46398, ChEBI:CHEBI:57865; EC=3.6.1.9;
CC Evidence={ECO:0000250|UniProtKB:P22413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = diphosphate + GMP + H(+); Xref=Rhea:RHEA:29391,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58115; EC=3.6.1.9;
CC Evidence={ECO:0000250|UniProtKB:P06802};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + H2O = CMP + diphosphate + H(+); Xref=Rhea:RHEA:27762,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37563, ChEBI:CHEBI:60377; EC=3.6.1.9;
CC Evidence={ECO:0000250|UniProtKB:P06802};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cGAMP + 2 H2O = AMP + GMP + 2 H(+);
CC Xref=Rhea:RHEA:58808, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58115, ChEBI:CHEBI:143093, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:P22413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + P(1),P(4)-bis(5'-adenosyl) tetraphosphate = AMP + ATP +
CC 2 H(+); Xref=Rhea:RHEA:32039, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58141, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:P22413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P22413};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P06802};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P06802};
CC -!- ACTIVITY REGULATION: At low concentrations of ATP, a phosphorylated
CC intermediate is formed which inhibits further hydrolysis.
CC {ECO:0000250|UniProtKB:P06802}.
CC -!- SUBUNIT: Ectonucleotide pyrophosphatase/phosphodiesterase family member
CC 1: Homodimer (By similarity). Ectonucleotide
CC pyrophosphatase/phosphodiesterase family member 1: Interacts with INSR;
CC leading to inhibit INSR autophosphorylation and subsequent activation
CC of INSR kinase activity (By similarity). Ectonucleotide
CC pyrophosphatase/phosphodiesterase family member 1, secreted form:
CC Monomeric (By similarity). {ECO:0000250|UniProtKB:P06802,
CC ECO:0000250|UniProtKB:P22413}.
CC -!- SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase
CC family member 1]: Cell membrane {ECO:0000250|UniProtKB:P06802}; Single-
CC pass type II membrane protein {ECO:0000250|UniProtKB:P06802}.
CC Basolateral cell membrane {ECO:0000250|UniProtKB:P06802}; Single-pass
CC type II membrane protein {ECO:0000250|UniProtKB:P06802}. Note=Targeted
CC to the basolateral membrane in polarized epithelial cells and in
CC hepatocytes, and to matrix vesicles in osteoblasts.
CC {ECO:0000250|UniProtKB:P06802}.
CC -!- SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase
CC family member 1, secreted form]: Secreted
CC {ECO:0000250|UniProtKB:P06802}. Note=Secreted following proteolytic
CC cleavage. {ECO:0000250|UniProtKB:P06802}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=Q924C3-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q924C3-2; Sequence=VSP_006749;
CC -!- DOMAIN: The di-leucine motif is required for basolateral targeting in
CC polarized epithelial cells, and for targeting to matrix vesicles
CC derived from mineralizing cells. {ECO:0000250|UniProtKB:P06802}.
CC -!- PTM: The secreted form is produced through cleavage at Lys-85 by
CC intracellular processing. {ECO:0000250|UniProtKB:P06802}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-35 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AF340185; AAK69653.1; -; mRNA.
DR EMBL; AF340186; AAK69654.1; -; mRNA.
DR EMBL; AF320054; AAL26912.1; -; mRNA.
DR RefSeq; NP_445987.1; NM_053535.1. [Q924C3-1]
DR AlphaFoldDB; Q924C3; -.
DR SMR; Q924C3; -.
DR IntAct; Q924C3; 6.
DR STRING; 10116.ENSRNOP00000019519; -.
DR ChEMBL; CHEMBL4295913; -.
DR GlyGen; Q924C3; 6 sites.
DR iPTMnet; Q924C3; -.
DR PhosphoSitePlus; Q924C3; -.
DR PaxDb; Q924C3; -.
DR PRIDE; Q924C3; -.
DR GeneID; 85496; -.
DR KEGG; rno:85496; -.
DR CTD; 5167; -.
DR RGD; 628825; Enpp1.
DR eggNOG; KOG2645; Eukaryota.
DR InParanoid; Q924C3; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q924C3; -.
DR BRENDA; 3.1.4.1; 5301.
DR BRENDA; 3.6.1.9; 5301.
DR Reactome; R-RNO-196843; Vitamin B2 (riboflavin) metabolism.
DR SABIO-RK; Q924C3; -.
DR PRO; PR:Q924C3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR GO; GO:0097441; C:basal dendrite; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0042995; C:cell projection; IDA:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:RHEA.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0047693; F:ATP diphosphatase activity; IEA:RHEA.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0106177; F:cyclic-GMP-AMP hydrolase activity; ISS:UniProtKB.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004527; F:exonuclease activity; ISO:RGD.
DR GO; GO:0036219; F:GTP diphosphatase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005158; F:insulin receptor binding; ISO:RGD.
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:0004551; F:nucleotide diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; ISO:RGD.
DR GO; GO:0004528; F:phosphodiesterase I activity; IDA:RGD.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISO:RGD.
DR GO; GO:0030247; F:polysaccharide binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0036221; F:UTP diphosphatase activity; IEA:RHEA.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0050427; P:3'-phosphoadenosine 5'-phosphosulfate metabolic process; ISO:RGD.
DR GO; GO:0060612; P:adipose tissue development; ISO:RGD.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR GO; GO:0007568; P:aging; ISO:RGD.
DR GO; GO:0035904; P:aorta development; ISO:RGD.
DR GO; GO:1902742; P:apoptotic process involved in development; ISO:RGD.
DR GO; GO:0060840; P:artery development; ISO:RGD.
DR GO; GO:0061975; P:articular cartilage development; ISO:RGD.
DR GO; GO:0046034; P:ATP metabolic process; ISS:UniProtKB.
DR GO; GO:0031103; P:axon regeneration; ISO:RGD.
DR GO; GO:0001922; P:B-1 B cell homeostasis; ISO:RGD.
DR GO; GO:0031214; P:biomineral tissue development; ISO:RGD.
DR GO; GO:0110148; P:biomineralization; ISO:RGD.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0098868; P:bone growth; ISO:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; ISO:RGD.
DR GO; GO:0046849; P:bone remodeling; ISO:RGD.
DR GO; GO:0045453; P:bone resorption; ISO:RGD.
DR GO; GO:0060346; P:bone trabecula formation; ISO:RGD.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
DR GO; GO:0000904; P:cell morphogenesis involved in differentiation; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0019725; P:cellular homeostasis; ISO:RGD.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0071468; P:cellular response to acidic pH; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:1904384; P:cellular response to sodium phosphate; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0071529; P:cementum mineralization; ISO:RGD.
DR GO; GO:0022010; P:central nervous system myelination; ISO:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0038065; P:collagen-activated signaling pathway; ISO:RGD.
DR GO; GO:0042832; P:defense response to protozoan; ISO:RGD.
DR GO; GO:0008340; P:determination of adult lifespan; ISO:RGD.
DR GO; GO:0071344; P:diphosphate metabolic process; ISO:RGD.
DR GO; GO:0060350; P:endochondral bone morphogenesis; ISO:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR GO; GO:0051649; P:establishment of localization in cell; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0060613; P:fat pad development; ISO:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:RGD.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0046323; P:glucose import; ISO:RGD.
DR GO; GO:0006096; P:glycolytic process; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0097241; P:hematopoietic stem cell migration to bone marrow; ISO:RGD.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0042445; P:hormone metabolic process; ISO:RGD.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; ISO:RGD.
DR GO; GO:0030505; P:inorganic diphosphate transport; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0002269; P:leukocyte activation involved in inflammatory response; ISO:RGD.
DR GO; GO:0036076; P:ligamentous ossification; ISO:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
DR GO; GO:0010960; P:magnesium ion homeostasis; ISO:RGD.
DR GO; GO:0030318; P:melanocyte differentiation; ISS:UniProtKB.
DR GO; GO:0014004; P:microglia differentiation; ISO:RGD.
DR GO; GO:1904124; P:microglial cell migration; ISO:RGD.
DR GO; GO:0042474; P:middle ear morphogenesis; ISO:RGD.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0002009; P:morphogenesis of an epithelium; ISO:RGD.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0070254; P:mucus secretion; ISO:RGD.
DR GO; GO:0010259; P:multicellular organism aging; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0046325; P:negative regulation of glucose import; ISO:RGD.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; ISO:RGD.
DR GO; GO:1990787; P:negative regulation of hh target transcription factor activity; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:RGD.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0006807; P:nitrogen compound metabolic process; ISO:RGD.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISO:RGD.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; ISO:RGD.
DR GO; GO:0042476; P:odontogenesis; ISO:RGD.
DR GO; GO:0021772; P:olfactory bulb development; IEP:RGD.
DR GO; GO:0097252; P:oligodendrocyte apoptotic process; ISO:RGD.
DR GO; GO:0019634; P:organic phosphonate metabolic process; ISO:RGD.
DR GO; GO:0001503; P:ossification; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; ISO:RGD.
DR GO; GO:0002317; P:plasma cell differentiation; ISO:RGD.
DR GO; GO:0035128; P:post-embryonic forelimb morphogenesis; ISO:RGD.
DR GO; GO:0006471; P:protein ADP-ribosylation; ISO:RGD.
DR GO; GO:0140289; P:protein mono-ADP-ribosylation; ISO:RGD.
DR GO; GO:0070212; P:protein poly-ADP-ribosylation; ISO:RGD.
DR GO; GO:0030500; P:regulation of bone mineralization; IBA:GO_Central.
DR GO; GO:0033198; P:response to ATP; ISO:RGD.
DR GO; GO:0002021; P:response to dietary excess; ISO:RGD.
DR GO; GO:0140459; P:response to Gram-positive bacterium; ISO:RGD.
DR GO; GO:0010035; P:response to inorganic substance; ISO:RGD.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:0033591; P:response to L-ascorbic acid; ISO:RGD.
DR GO; GO:0032026; P:response to magnesium ion; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0036119; P:response to platelet-derived growth factor; ISO:RGD.
DR GO; GO:1904383; P:response to sodium phosphate; ISO:RGD.
DR GO; GO:0034516; P:response to vitamin B6; ISO:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0050954; P:sensory perception of mechanical stimulus; ISO:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0050951; P:sensory perception of temperature stimulus; ISO:RGD.
DR GO; GO:0030730; P:sequestering of triglyceride; ISO:RGD.
DR GO; GO:0043588; P:skin development; ISO:RGD.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD.
DR GO; GO:0021510; P:spinal cord development; ISO:RGD.
DR GO; GO:0021756; P:striatum development; IEP:RGD.
DR GO; GO:0030217; P:T cell differentiation; ISO:RGD.
DR GO; GO:0034505; P:tooth mineralization; ISO:RGD.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; ISO:RGD.
DR GO; GO:1990874; P:vascular associated smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR GO; GO:0070640; P:vitamin D3 metabolic process; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
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; IPR029890; ENPP1.
DR InterPro; IPR020821; Extracellular_endonuc_su_A.
DR InterPro; IPR044925; His-Me_finger_sf.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR InterPro; IPR020436; SMB_chordata.
DR InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR InterPro; IPR001212; Somatomedin_B_dom.
DR PANTHER; PTHR10151:SF77; PTHR10151:SF77; 1.
DR Pfam; PF01223; Endonuclease_NS; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR Pfam; PF01033; Somatomedin_B; 2.
DR PRINTS; PR00022; SOMATOMEDINB.
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 1: Evidence at protein level;
KW Alternative splicing; Biomineralization; Calcium; Cell membrane;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..906
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 1"
FT /id="PRO_0000188566"
FT CHAIN 85..906
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 1, secreted form"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT /id="PRO_0000447135"
FT TOPO_DOM 1..58
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..79
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..906
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 86..126
FT /note="SMB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DOMAIN 127..170
FT /note="SMB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..573
FT /note="Phosphodiesterase"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT REGION 579..628
FT /note="Linker"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT REGION 635..906
FT /note="Nuclease"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT MOTIF 27..34
FT /note="Di-leucine motif"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT ACT_SITE 238
FT /note="AMP-threonine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 200
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 238
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 238
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 238
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 238
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 259
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 259
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 259
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 259
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 272
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 277
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 277
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 277
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 322
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 322
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 322
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 322
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 358
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 358
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 358
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 358
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 362
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /ligand_note="substrate"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 405
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 406
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 406
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 406
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 406
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 514
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /ligand_note="substrate"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 517
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 517
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 517
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 517
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 517
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 781
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 783
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 785
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 787
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT BINDING 789
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT SITE 84..85
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P06802"
FT SITE 896
FT /note="Essential for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E6"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 238
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 90..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 94..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 102..115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 108..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 131..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 136..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 146..159
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 152..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 177..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 185..397
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 413..512
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 462..849
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 596..653
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 607..707
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 609..692
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 819..829
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT VAR_SEQ 630
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:12121276"
FT /id="VSP_006749"
FT VARIANT 440..442
FT /note="RPT -> NPP (in strain: Wistar)"
FT VARIANT 457
FT /note="A -> T (in strain: Lewis)"
FT VARIANT 555
FT /note="M -> I (in strain: Lewis)"
FT VARIANT 568
FT /note="E -> G (in strain: Wistar)"
FT VARIANT 583
FT /note="T -> I (in strain: Lewis)"
FT VARIANT 592
FT /note="F -> V (in strain: Lewis)"
FT VARIANT 624
FT /note="N -> K (in strain: Lewis)"
FT VARIANT 640
FT /note="N -> H (in strain: Lewis)"
FT VARIANT 774
FT /note="V -> I (in strain: Lewis)"
FT VARIANT 806
FT /note="N -> I (in strain: Lewis)"
FT VARIANT 850
FT /note="T -> I (in strain: Lewis)"
FT VARIANT 898
FT /note="H -> Q (in strain: Lewis)"
SQ SEQUENCE 906 AA; 102942 MW; 71F56780B279A919 CRC64;
MERDGEQAGQ GPRHGPAGNG RELESPAAAS LLAPMDLGEE PLEKAERART AKDPNTYKVL
SLVLSVCVLT TILGCIFGLK PSCAKEVKSC KGRCFERTFS NCRCDAACVS LGNCCLDFQE
TCVEPTHIWT CNKFRCGEKR LSRFVCSCAD DCKAHNDCCI NYSSVCQEKK SWVEEACETI
DAPQCPAEFE SPPTLLFSLD GFRAEYLHTW GGLLPVISKL KNCGTYTKNM RPVYPTKTFP
NHYSIVTGLY PESHGIIDNK MYDPKMNASF SLKSKEKFNP LWYKGQPIWV TANHQEVRSG
TYFWPGSDVE IDGILPDIYK VYNGSVPFEE RILAVLEWLQ LPSYERPHFY TLYLEEPDSS
GHSHGPVSSE VIKALQKVDH IVGMLMDGLK DLGLDKCLNL ILISDHGMEQ GSCKKYVYLN
KYLGDVNNVK VVYGPAARLR PTEVPETYYS FNYEALAKNL SCRETNQHFR PYLKHFLPKR
LHFAKNDRIE PLTFYLDPQW QLALNPSERK YCGSGFHGSD NLFSNMQALF IGYGPAFKHG
AEVDSFENIE VYNLMCDLLG LIPAPNNESH GSLNHLLKKP IYTPSHPKEE SFLSQCPIKS
VSSDLGCTCD PSIVPIMDFE KQFNLTTDAV EDVYSMTVPN GRPRNLQKQH RVCLLHQQQF
LTGYSLDLLM PLWTSYTFLS NDQFSTDDFS NCLYQDLRIP LSPMHKCSYY KSTSKLSYGF
LTPPRLNRVS RQIYSEALLT SNIVPMYQSF QVIWQYLHDT VLRRYAQERN GVNVVSGPVF
DFDYDGRYDS SEILKQNTRV IRSQENLIPT HFFIVLTSCK QLSESPLKCT ALESSAFLLP
HRPDNIESCT HGKQESAWVE ELLALHRARV TDVELITGLS FYQDRQESVS ELLRLKTHLP
IFSQED