ENPP1_MOUSE
ID ENPP1_MOUSE Reviewed; 906 AA.
AC P06802; Q542E9; Q924C4;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 4.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 1;
DE Short=E-NPP 1;
DE AltName: Full=Lymphocyte antigen 41;
DE Short=Ly-41;
DE AltName: Full=Phosphodiesterase I/nucleotide pyrophosphatase 1;
DE AltName: Full=Plasma-cell membrane glycoprotein PC-1 {ECO:0000303|PubMed:3104326};
DE Includes:
DE RecName: Full=Alkaline phosphodiesterase I;
DE EC=3.1.4.1 {ECO:0000269|PubMed:11027689, ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:8223581};
DE Includes:
DE RecName: Full=Nucleotide pyrophosphatase;
DE Short=NPPase;
DE EC=3.6.1.9 {ECO:0000269|PubMed:11027689, ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:8223581};
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:0000303|PubMed:23027977, ECO:0000312|MGI:MGI:97370};
GN Synonyms=Npps {ECO:0000303|PubMed:9662402},
GN Pc1 {ECO:0000303|PubMed:3104326}, Pdnp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TOPOLOGY, AND
RP SUBUNIT.
RC STRAIN=BALB/cJ;
RX PubMed=3104326; DOI=10.1016/s0021-9258(18)61278-5;
RA van Driel I.R., Goding J.W.;
RT "Plasma cell membrane glycoprotein PC-1. Primary structure deduced from
RT cDNA clones.";
RL J. Biol. Chem. 262:4882-4887(1987).
RN [2]
RP SEQUENCE REVISION TO 24; 46-47; 642 AND 693.
RA Goding J.W.;
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Plasmacytoma;
RX PubMed=1647027; DOI=10.1073/pnas.88.12.5192;
RA Rebbe N.F., Tong B.D., Finley E.M., Hickman S.;
RT "Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I
RT activity associated with the mouse plasma cell differentiation antigen PC-
RT 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5192-5196(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-651 AND SER-680, AND
RP ALTERNATIVE SPLICING.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 168-188, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=8223581; DOI=10.1111/j.1432-1033.1993.tb18261.x;
RA Belli S.I., van Driel I.R., Goding J.W.;
RT "Identification and characterization of a soluble form of the plasma cell
RT membrane glycoprotein PC-1 (5'-nucleotide phosphodiesterase).";
RL Eur. J. Biochem. 217:421-428(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 203-219.
RX PubMed=3001713; DOI=10.1073/pnas.82.24.8619;
RA van Driel I.R., Wilks A.F., Pietersz G.A., Goding J.W.;
RT "Murine plasma cell membrane antigen PC-1: molecular cloning of cDNA and
RT analysis of expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:8619-8623(1985).
RN [8]
RP PROTEIN SEQUENCE OF 204-219; 332-351; 486-509; 716-725; 803-818 AND
RP 855-867, AND SUBCELLULAR LOCATION.
RX PubMed=3917281;
RA Stearne P.A., van Driel I.R., Grego B., Simpson R.J., Goding J.W.;
RT "The murine plasma cell antigen PC-1: purification and partial amino acid
RT sequence.";
RL J. Immunol. 134:443-448(1985).
RN [9]
RP IDENTIFICATION OF POSSIBLE INITIATION SITE.
RX PubMed=2211644; DOI=10.1016/s0021-9258(18)38193-6;
RA Buckley M.F., Loveland K.A., McKinstry W.J., Garson O.M., Goding J.W.;
RT "Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human
RT molecule, amino acid sequence, and chromosomal location.";
RL J. Biol. Chem. 265:17506-17511(1990).
RN [10]
RP DISEASE, FUNCTION, AND VARIANT 568-GLY--ASP-906 DEL.
RX PubMed=9662402; DOI=10.1038/956;
RA Okawa A., Nakamura I., Goto S., Moriya H., Nakamura Y., Ikegawa S.;
RT "Mutation in Npps in a mouse model of ossification of the posterior
RT longitudinal ligament of the spine.";
RL Nat. Genet. 19:271-273(1998).
RN [11]
RP FUNCTION.
RX PubMed=10352096; DOI=10.1359/jbmr.1999.14.6.883;
RA Johnson K., Moffa A., Chen Y., Pritzker K., Goding J., Terkeltaub R.;
RT "Matrix vesicle plasma cell membrane glycoprotein-1 regulates
RT mineralization by murine osteoblastic MC3T3 cells.";
RL J. Bone Miner. Res. 14:883-892(1999).
RN [12]
RP FUNCTION.
RX PubMed=11004006; DOI=10.1152/ajpregu.2000.279.4.r1365;
RA Johnson K.A., Hessle L., Vaingankar S., Wennberg C., Mauro S., Narisawa S.,
RA Goding J.W., Sano K., Millan J.L., Terkeltaub R.;
RT "Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and
RT regulates PC-1.";
RL Am. J. Physiol. 279:R1365-R1377(2000).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12082181; DOI=10.1073/pnas.142063399;
RA Hessle L., Johnson K.A., Anderson H.C., Narisawa S., Sali A., Goding J.W.,
RA Terkeltaub R., Millan J.L.;
RT "Tissue-nonspecific alkaline phosphatase and plasma cell membrane
RT glycoprotein-1 are central antagonistic regulators of bone
RT mineralization.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:9445-9449(2002).
RN [14]
RP FUNCTION, ACTIVE SITE, METAL-BINDING, MUTAGENESIS OF ASP-200; LYS-237;
RP THR-238; PHE-239; ASP-358; HIS-362; ASP-405; HIS-406 AND HIS-517, AND
RP CATALYTIC ACTIVITY.
RX PubMed=11027689; DOI=10.1074/jbc.m007552200;
RA Gijsbers R., Ceulemans H., Stalmans W., Bollen M.;
RT "Structural and catalytic similarities between nucleotide
RT pyrophosphatases/phosphodiesterases and alkaline phosphatases.";
RL J. Biol. Chem. 276:1361-1368(2001).
RN [15]
RP DI-LEUCINE MOTIF, MUTAGENESIS OF ALA-28; SER-30; LEU-31 AND LEU-32, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11598187; DOI=10.1091/mbc.12.10.3004;
RA Bello V., Goding J.W., Greengrass V., Sali A., Dubljevic V., Lenoir C.,
RA Trugnan G., Maurice M.;
RT "Characterization of a di-leucine-based signal in the cytoplasmic tail of
RT the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but
RT not endocytosis.";
RL Mol. Biol. Cell 12:3004-3015(2001).
RN [16]
RP DI-LEUCINE MOTIF, MUTAGENESIS OF LEU-31; LEU-32; LEU-42 AND TYR-57, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15075217; DOI=10.1152/ajpcell.00320.2003;
RA Vaingankar S.M., Fitzpatrick T.A., Johnson K., Goding J.W., Maurice M.,
RA Terkeltaub R.;
RT "Subcellular targeting and function of osteoblast nucleotide
RT pyrophosphatase phosphodiesterase 1.";
RL Am. J. Physiol. 286:C1177-C1187(2004).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF CYS-397.
RX PubMed=19419305; DOI=10.1359/jbmr.090417;
RA Babij P., Roudier M., Graves T., Han C.Y., Chhoa M., Li C.M., Juan T.,
RA Morony S., Grisanti M., Li X., Yu L., Dwyer D., Lloyd D.J., Bass M.B.,
RA Richards W.G., Ebeling C., Amato J., Carlson G.;
RT "New variants in the Enpp1 and Ptpn6 genes cause low BMD, crystal-related
RT arthropathy, and vascular calcification.";
RL J. Bone Miner. Res. 24:1552-1564(2009).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-267; ASN-323 AND ASN-624.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP FUNCTION, AND DISEASE.
RX PubMed=22510396; DOI=10.1136/annrheumdis-2011-200892;
RA Bertrand J., Nitschke Y., Fuerst M., Hermann S., Schaefers M., Sherwood J.,
RA Nalesso G., Ruether W., Rutsch F., Dell'Accio F., Pap T.;
RT "Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are
RT associated with cartilage calcification in osteoarthritis and trigger
RT osteoarthritic changes in mice.";
RL Ann. Rheum. Dis. 71:1249-1253(2012).
RN [21]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25260930; DOI=10.1016/j.bone.2014.09.016;
RA Hajjawi M.O., MacRae V.E., Huesa C., Boyde A., Millan J.L., Arnett T.R.,
RA Orriss I.R.;
RT "Mineralisation of collagen rich soft tissues and osteocyte lacunae in
RT Enpp1(-/-) mice.";
RL Bone 69:139-147(2014).
RN [22]
RP FUNCTION.
RX PubMed=25344812; DOI=10.1038/nchembio.1661;
RA Li L., Yin Q., Kuss P., Maliga Z., Millan J.L., Wu H., Mitchison T.J.;
RT "Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs.";
RL Nat. Chem. Biol. 10:1043-1048(2014).
RN [23]
RP DISEASE, AND FUNCTION.
RX PubMed=25479107; DOI=10.1371/journal.pone.0113542;
RA Li Q., Pratt C.H., Dionne L.A., Fairfield H., Karst S.Y., Sundberg J.P.,
RA Uitto J.;
RT "Spontaneous asj-2J mutant mouse as a model for generalized arterial
RT calcification of infancy: a large deletion/insertion mutation in the Enpp1
RT gene.";
RL PLoS ONE 9:E113542-E113542(2014).
RN [24]
RP DISEASE, AND FUNCTION.
RX PubMed=26910915; DOI=10.18632/oncotarget.7455;
RA Zhang J., Dyment N.A., Rowe D.W., Siu S.Y., Sundberg J.P., Uitto J., Li Q.;
RT "Ectopic mineralization of cartilage and collagen-rich tendons and
RT ligaments in Enpp1asj-2J mice.";
RL Oncotarget 7:12000-12009(2016).
RN [25]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30111653; DOI=10.1242/dev.164830;
RA Jin Y., Cong Q., Gvozdenovic-Jeremic J., Hu J., Zhang Y., Terkeltaub R.,
RA Yang Y.;
RT "Enpp1 inhibits ectopic joint calcification and maintains articular
RT chondrocytes by repressing hedgehog signaling.";
RL Development 145:0-0(2018).
RN [26] {ECO:0007744|PDB:4GTW, ECO:0007744|PDB:4GTX, ECO:0007744|PDB:4GTY, ECO:0007744|PDB:4GTZ}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 92-906 IN COMPLEXES WITH AMP;
RP CMP; GMP; TMP; CALCIUM AND ZINC, GLYCOSYLATION AT ASN-267; ASN-323 AND
RP ASN-567, DISULFIDE BOND, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE
RP SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF PHE-239;
RP HIS-242; 304-TRP--ASN-323; ASP-308 AND TYR-322, AND COFACTOR.
RX PubMed=23027977; DOI=10.1073/pnas.1208017109;
RA Kato K., Nishimasu H., Okudaira S., Mihara E., Ishitani R., Takagi J.,
RA Aoki J., Nureki O.;
RT "Crystal structure of Enpp1, an extracellular glycoprotein involved in bone
RT mineralization and insulin signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:16876-16881(2012).
RN [27] {ECO:0007744|PDB:4B56}
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 87-906 IN COMPLEX WITH CALCIUM;
RP PHOSPHATE AND ZINC, DISULFIDE BONDS, METAL-BINDING SITES, SUBUNIT,
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-323; ASN-459; ASN-567 AND
RP ASN-624, COFACTOR, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=23041369; DOI=10.1016/j.str.2012.09.001;
RA Jansen S., Perrakis A., Ulens C., Winkler C., Andries M., Joosten R.P.,
RA Van Acker M., Luyten F.P., Moolenaar W.H., Bollen M.;
RT "Structure of NPP1, an ectonucleotide pyrophosphatase/ phosphodiesterase
RT involved in tissue calcification.";
RL Structure 20:1948-1959(2012).
RN [28] {ECO:0007744|PDB:6AEK, ECO:0007744|PDB:6AEL}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 190-578 AND 629-902 IN COMPLEX
RP WITH 3'3'-CGAMP AND ZINC, CATALYTIC ACTIVITY, AND MUTAGENESIS OF THR-238
RP AND SER-514.
RX PubMed=30356045; DOI=10.1038/s41467-018-06922-7;
RA Kato K., Nishimasu H., Oikawa D., Hirano S., Hirano H., Kasuya G.,
RA Ishitani R., Tokunaga F., Nureki O.;
RT "Structural insights into cGAMP degradation by Ecto-nucleotide
RT pyrophosphatase phosphodiesterase 1.";
RL Nat. Commun. 9:4424-4424(2018).
CC -!- FUNCTION: Nucleotide pyrophosphatase that generates diphosphate (PPi)
CC and functions in bone mineralization and soft tissue calcification by
CC regulating pyrophosphate levels (PubMed:9662402, PubMed:10352096,
CC PubMed:11004006, PubMed:12082181, PubMed:22510396, PubMed:25260930).
CC PPi inhibits bone mineralization and soft tissue calcification by
CC binding to nascent hydroxyapatite crystals, thereby preventing further
CC growth of these crystals (PubMed:9662402, PubMed:10352096,
CC PubMed:11004006, PubMed:12082181, PubMed:19419305, PubMed:22510396,
CC PubMed:25260930, PubMed:25479107, PubMed:26910915, PubMed:30111653).
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 (PubMed:11027689,
CC PubMed:1647027, PubMed:23027977, PubMed:8223581). May also be involved
CC in the regulation of the availability of nucleotide sugars in the
CC endoplasmic reticulum and Golgi, and the regulation of purinergic
CC signaling (PubMed:1647027). Inhibits ectopic joint calcification and
CC maintains articular chondrocytes by repressing hedgehog signaling; it
CC is however unclear whether hedgehog inhibition is direct or indirect
CC (PubMed:30111653). Appears to modulate insulin sensitivity (By
CC similarity). Also involved in melanogenesis (By similarity). Also able
CC to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that
CC activates TMEM173/STING and triggers type-I interferon production
CC (PubMed:25344812). 2',3'-cGAMP degradation takes place in the lumen or
CC extracellular space, and not in the cytosol where it is produced; the
CC role of 2',3'-cGAMP hydrolysis is therefore unclear (By similarity).
CC Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3',3'-cGAMP (By
CC similarity). {ECO:0000250|UniProtKB:P22413,
CC ECO:0000269|PubMed:10352096, ECO:0000269|PubMed:11004006,
CC ECO:0000269|PubMed:11027689, ECO:0000269|PubMed:12082181,
CC ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:19419305,
CC ECO:0000269|PubMed:22510396, ECO:0000269|PubMed:23027977,
CC ECO:0000269|PubMed:25260930, ECO:0000269|PubMed:25344812,
CC ECO:0000269|PubMed:25479107, ECO:0000269|PubMed:26910915,
CC ECO:0000269|PubMed:30111653, ECO:0000269|PubMed:8223581,
CC ECO:0000269|PubMed:9662402}.
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:0000269|PubMed:11027689,
CC ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:8223581};
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:0000269|PubMed:11027689, ECO:0000269|PubMed:1647027,
CC ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:30356045,
CC ECO:0000269|PubMed:8223581};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23997;
CC Evidence={ECO:0000269|PubMed:30356045};
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:0000269|PubMed:23027977};
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:0000269|PubMed:23027977};
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:0000269|PubMed:23027977};
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:0000269|PubMed:23027977};
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:0000269|PubMed:30356045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58809;
CC Evidence={ECO:0000269|PubMed:30356045};
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:0000269|PubMed:23027977, ECO:0000269|PubMed:23041369,
CC ECO:0000269|PubMed:30356045};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:23027977,
CC ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045};
CC -!- ACTIVITY REGULATION: At low concentrations of ATP, a phosphorylated
CC intermediate is formed which inhibits further hydrolysis.
CC {ECO:0000269|PubMed:11027689}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=46 uM for ATP {ECO:0000269|PubMed:23027977};
CC KM=4.3 mM for UTP {ECO:0000269|PubMed:23027977};
CC KM=4.2 mM for GTP {ECO:0000269|PubMed:23027977};
CC KM=1.2 mM for CTP {ECO:0000269|PubMed:23027977};
CC Note=kcat is 16 sec(-1) with ATP as substrate. kcat is 200 sec(-1)
CC with UTP as substrate. kcat is 820 sec(-1) with GTP as substrate.
CC kcat is 8.7 sec(-1) with CTP as substrate.
CC {ECO:0000269|PubMed:23027977};
CC -!- SUBUNIT: Ectonucleotide pyrophosphatase/phosphodiesterase family member
CC 1: Homodimer (PubMed:23027977, PubMed:23041369). 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 (PubMed:23041369). {ECO:0000250|UniProtKB:P22413,
CC ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:23041369}.
CC -!- INTERACTION:
CC P06802; P06802: Enpp1; NbExp=2; IntAct=EBI-16016057, EBI-16016057;
CC -!- SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase
CC family member 1]: Cell membrane {ECO:0000269|PubMed:1647027,
CC ECO:0000269|PubMed:3104326, ECO:0000269|PubMed:3917281}; Single-pass
CC type II membrane protein. Basolateral cell membrane
CC {ECO:0000269|PubMed:11598187, ECO:0000269|PubMed:15075217}; Single-pass
CC type II membrane protein. Note=Targeted to the basolateral membrane in
CC polarized epithelial cells and in hepatocytes, and to matrix vesicles
CC in osteoblasts. {ECO:0000269|PubMed:11598187,
CC ECO:0000269|PubMed:15075217}.
CC -!- SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase
CC family member 1, secreted form]: Secreted {ECO:0000269|PubMed:23041369,
CC ECO:0000269|PubMed:8223581}. Note=Secreted following proteolytic
CC cleavage. {ECO:0000269|PubMed:23041369}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=P06802-1; Sequence=Displayed;
CC Name=1;
CC IsoId=P06802-2; Sequence=VSP_006748;
CC -!- TISSUE SPECIFICITY: Selectively expressed on the surface of antibody-
CC secreting cells (PubMed:3104326). Expressed in osteocytes and
CC osteoclasts (PubMed:25260930). {ECO:0000269|PubMed:25260930,
CC ECO:0000269|PubMed:3104326}.
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:0000269|PubMed:11598187,
CC ECO:0000269|PubMed:15075217}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1647027,
CC ECO:0000269|PubMed:19656770, ECO:0000269|PubMed:23027977,
CC ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:8223581}.
CC -!- PTM: The secreted form is produced through cleavage at Lys-85 by
CC intracellular processing. {ECO:0000269|PubMed:23041369}.
CC -!- DISEASE: Note=Defects in Enpp1 are the cause of the tiptoe walking
CC (ttw) phenotype. Ttw mice exhibit ossification of the spinal ligaments
CC (PubMed:9662402). Mice display increased bone formation process in
CC joints and develop spontaneous osteoarthritis-like changes
CC (PubMed:22510396). {ECO:0000269|PubMed:22510396,
CC ECO:0000269|PubMed:9662402}.
CC -!- DISEASE: Note=Defects in Enpp1 are the cause of spontaneous asj-2J
CC mutant characterized by gait due to stiffening of the joints
CC (PubMed:25479107). Defects are caused by a significant reduction in the
CC plasma diphosphate (PPi) concentration, leading to extensive aberrant
CC mineralization affecting the arterial vasculature, a number of internal
CC organs and the dermal sheath of vibrissae (PubMed:25479107). Asj-2J
CC mice are used as a model for arterial calcification of infancy disorder
CC (GACI1) (PubMed:25479107). Mice also show ectopic mineralization of
CC cartilage and collagen-rich tendons and ligaments (PubMed:26910915).
CC {ECO:0000269|PubMed:25479107, ECO:0000269|PubMed:26910915}.
CC -!- DISRUPTION PHENOTYPE: Mice show ectopic calcification of articular
CC cartilage, the joint capsule and certain tendons (PubMed:25260930).
CC Mice also display calcification of the joints and vertebrae as well as
CC soft tissues including the whisker follicles, ear pinna and trachea
CC (PubMed:25260930). This calcification worsened as the animals aged
CC (PubMed:25260930). Bone mineralization in mice lacking both Enpp1 and
CC Alpl is essentially normal, demonstrating that Enpp1 and Alpl are
CC antagonist key regulators of bone mineralization by determining the
CC normal steady-state levels of diphosphate (PPi) (PubMed:12082181).
CC {ECO:0000269|PubMed:12082181, ECO:0000269|PubMed:25260930}.
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; J02700; AAA39893.2; -; mRNA.
DR EMBL; AF339910; AAK84174.1; -; mRNA.
DR EMBL; AK088857; BAC40616.1; -; mRNA.
DR EMBL; L04516; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR EMBL; M12552; AAA39892.1; -; mRNA.
DR CCDS; CCDS35870.1; -. [P06802-2]
DR CCDS; CCDS78802.1; -. [P06802-1]
DR PIR; A27410; A27410.
DR RefSeq; NP_001295256.1; NM_001308327.1.
DR PDB; 4B56; X-ray; 3.00 A; A/B=87-906.
DR PDB; 4GTW; X-ray; 2.70 A; A/B=92-906.
DR PDB; 4GTX; X-ray; 3.20 A; A/B=92-906.
DR PDB; 4GTY; X-ray; 3.19 A; A/B=92-906.
DR PDB; 4GTZ; X-ray; 3.19 A; A/B=92-906.
DR PDB; 6AEK; X-ray; 1.80 A; A=170-906.
DR PDB; 6AEL; X-ray; 1.90 A; A=170-906.
DR PDB; 6XKD; X-ray; 3.20 A; A/B=92-906.
DR PDBsum; 4B56; -.
DR PDBsum; 4GTW; -.
DR PDBsum; 4GTX; -.
DR PDBsum; 4GTY; -.
DR PDBsum; 4GTZ; -.
DR PDBsum; 6AEK; -.
DR PDBsum; 6AEL; -.
DR PDBsum; 6XKD; -.
DR AlphaFoldDB; P06802; -.
DR SMR; P06802; -.
DR BioGRID; 202097; 4.
DR DIP; DIP-59981N; -.
DR STRING; 10090.ENSMUSP00000101159; -.
DR GlyConnect; 2414; 1 N-Linked glycan (1 site). [P06802-2]
DR GlyGen; P06802; 6 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P06802; -.
DR PhosphoSitePlus; P06802; -.
DR SwissPalm; P06802; -.
DR CPTAC; non-CPTAC-4032; -.
DR jPOST; P06802; -.
DR MaxQB; P06802; -.
DR PaxDb; P06802; -.
DR PRIDE; P06802; -.
DR ProteomicsDB; 275869; -. [P06802-1]
DR ProteomicsDB; 275870; -. [P06802-2]
DR DNASU; 18605; -.
DR GeneID; 18605; -.
DR KEGG; mmu:18605; -.
DR CTD; 5167; -.
DR MGI; MGI:97370; Enpp1.
DR eggNOG; KOG2645; Eukaryota.
DR InParanoid; P06802; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; P06802; -.
DR BRENDA; 3.1.4.1; 3474.
DR BRENDA; 3.6.1.9; 3474.
DR Reactome; R-MMU-196843; Vitamin B2 (riboflavin) metabolism.
DR SABIO-RK; P06802; -.
DR BioGRID-ORCS; 18605; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Enpp1; mouse.
DR PRO; PR:P06802; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P06802; protein.
DR GO; GO:0097440; C:apical dendrite; ISO:MGI.
DR GO; GO:0097441; C:basal dendrite; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IMP:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:RHEA.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0047693; F:ATP diphosphatase activity; IEA:RHEA.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0106177; F:cyclic-GMP-AMP hydrolase activity; IDA:UniProtKB.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004527; F:exonuclease activity; ISO:MGI.
DR GO; GO:0036219; F:GTP diphosphatase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0004551; F:nucleotide diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; IDA:MGI.
DR GO; GO:0004528; F:phosphodiesterase I activity; IDA:UniProtKB.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:MGI.
DR GO; GO:0030247; F:polysaccharide binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
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; IDA:UniProtKB.
DR GO; GO:0050427; P:3'-phosphoadenosine 5'-phosphosulfate metabolic process; ISO:MGI.
DR GO; GO:0060612; P:adipose tissue development; IMP:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0007568; P:aging; IMP:MGI.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:MGI.
DR GO; GO:0060840; P:artery development; IMP:MGI.
DR GO; GO:0061975; P:articular cartilage development; IMP:MGI.
DR GO; GO:0046034; P:ATP metabolic process; IDA:UniProtKB.
DR GO; GO:0031103; P:axon regeneration; IMP:MGI.
DR GO; GO:0001922; P:B-1 B cell homeostasis; IMP:MGI.
DR GO; GO:0031214; P:biomineral tissue development; IMP:MGI.
DR GO; GO:0110148; P:biomineralization; IDA:MGI.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0098868; P:bone growth; IMP:MGI.
DR GO; GO:0030282; P:bone mineralization; IDA:MGI.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; IMP:MGI.
DR GO; GO:0046849; P:bone remodeling; IMP:MGI.
DR GO; GO:0045453; P:bone resorption; IMP:MGI.
DR GO; GO:0060346; P:bone trabecula formation; IMP:MGI.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0000904; P:cell morphogenesis involved in differentiation; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0019725; P:cellular homeostasis; IMP:MGI.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; ISO:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
DR GO; GO:1904384; P:cellular response to sodium phosphate; IDA:MGI.
DR GO; GO:0071529; P:cementum mineralization; IDA:MGI.
DR GO; GO:0022010; P:central nervous system myelination; IMP:MGI.
DR GO; GO:0038065; P:collagen-activated signaling pathway; IMP:MGI.
DR GO; GO:0042832; P:defense response to protozoan; IMP:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR GO; GO:0071344; P:diphosphate metabolic process; IDA:MGI.
DR GO; GO:0060350; P:endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0060613; P:fat pad development; IMP:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; IMP:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0046323; P:glucose import; IMP:MGI.
DR GO; GO:0006096; P:glycolytic process; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0097241; P:hematopoietic stem cell migration to bone marrow; IMP:MGI.
DR GO; GO:0042445; P:hormone metabolic process; IMP:MGI.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IMP:MGI.
DR GO; GO:0030505; P:inorganic diphosphate transport; IDA:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0002269; P:leukocyte activation involved in inflammatory response; IMP:MGI.
DR GO; GO:0036076; P:ligamentous ossification; IMP:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:MGI.
DR GO; GO:0030225; P:macrophage differentiation; IMP:MGI.
DR GO; GO:0010960; P:magnesium ion homeostasis; IMP:MGI.
DR GO; GO:0030318; P:melanocyte differentiation; ISO:MGI.
DR GO; GO:0014004; P:microglia differentiation; IMP:MGI.
DR GO; GO:1904124; P:microglial cell migration; IMP:MGI.
DR GO; GO:0042474; P:middle ear morphogenesis; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IMP:MGI.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0070254; P:mucus secretion; IMP:MGI.
DR GO; GO:0010259; P:multicellular organism aging; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:BHF-UCL.
DR GO; GO:0046325; P:negative regulation of glucose import; ISO:MGI.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; ISO:MGI.
DR GO; GO:1990787; P:negative regulation of hh target transcription factor activity; IMP:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:MGI.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISO:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IMP:MGI.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISO:MGI.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; ISO:MGI.
DR GO; GO:0042476; P:odontogenesis; IMP:MGI.
DR GO; GO:0097252; P:oligodendrocyte apoptotic process; IMP:MGI.
DR GO; GO:0019634; P:organic phosphonate metabolic process; IMP:MGI.
DR GO; GO:0001503; P:ossification; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:MGI.
DR GO; GO:0055062; P:phosphate ion homeostasis; IDA:MGI.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; ISO:MGI.
DR GO; GO:0002317; P:plasma cell differentiation; IMP:MGI.
DR GO; GO:0035128; P:post-embryonic forelimb morphogenesis; IMP:MGI.
DR GO; GO:0006471; P:protein ADP-ribosylation; IDA:MGI.
DR GO; GO:0140289; P:protein mono-ADP-ribosylation; IDA:MGI.
DR GO; GO:0070212; P:protein poly-ADP-ribosylation; IDA:MGI.
DR GO; GO:0030500; P:regulation of bone mineralization; IBA:GO_Central.
DR GO; GO:0033198; P:response to ATP; ISO:MGI.
DR GO; GO:0002021; P:response to dietary excess; IMP:MGI.
DR GO; GO:0140459; P:response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0010035; P:response to inorganic substance; ISO:MGI.
DR GO; GO:0032868; P:response to insulin; IMP:MGI.
DR GO; GO:0033591; P:response to L-ascorbic acid; IMP:MGI.
DR GO; GO:0032026; P:response to magnesium ion; IMP:MGI.
DR GO; GO:0036119; P:response to platelet-derived growth factor; IMP:MGI.
DR GO; GO:1904383; P:response to sodium phosphate; IMP:MGI.
DR GO; GO:0034516; P:response to vitamin B6; IGI:MGI.
DR GO; GO:0009611; P:response to wounding; IMP:MGI.
DR GO; GO:0050954; P:sensory perception of mechanical stimulus; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR GO; GO:0050951; P:sensory perception of temperature stimulus; IMP:MGI.
DR GO; GO:0030730; P:sequestering of triglyceride; ISO:MGI.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR GO; GO:0021510; P:spinal cord development; IMP:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:MGI.
DR GO; GO:0034505; P:tooth mineralization; IMP:MGI.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; IMP:MGI.
DR GO; GO:1990874; P:vascular associated smooth muscle cell proliferation; IMP:MGI.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR GO; GO:0070640; P:vitamin D3 metabolic process; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IMP:MGI.
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 3D-structure; Alternative splicing; Biomineralization; Calcium;
KW Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..906
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 1"
FT /id="PRO_0000188565"
FT CHAIN 85..906
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 1, secreted form"
FT /evidence="ECO:0000305|PubMed:23041369"
FT /id="PRO_0000447134"
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..171
FT /note="SMB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..573
FT /note="Phosphodiesterase"
FT /evidence="ECO:0000305|PubMed:23027977,
FT ECO:0000305|PubMed:23041369"
FT REGION 579..628
FT /note="Linker"
FT /evidence="ECO:0000305|PubMed:23027977,
FT ECO:0000305|PubMed:23041369"
FT REGION 635..906
FT /note="Nuclease"
FT /evidence="ECO:0000305|PubMed:23027977,
FT ECO:0000305|PubMed:23041369"
FT MOTIF 27..34
FT /note="Di-leucine motif"
FT /evidence="ECO:0000269|PubMed:11598187,
FT ECO:0000269|PubMed:15075217"
FT ACT_SITE 238
FT /note="AMP-threonine intermediate"
FT /evidence="ECO:0000269|PubMed:11027689"
FT BINDING 200
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045"
FT BINDING 238
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 238
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 238
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTX"
FT BINDING 238
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT BINDING 259
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 259
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 259
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTX"
FT BINDING 259
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 272
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 277
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 277
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 277
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 322
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 322
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 322
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTX"
FT BINDING 322
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 358
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 358
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 358
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTX"
FT BINDING 358
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045"
FT BINDING 362
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /ligand_note="substrate"
FT /evidence="ECO:0000269|PubMed:30356045"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045"
FT BINDING 405
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045"
FT BINDING 406
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 406
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 406
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTX"
FT BINDING 406
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045"
FT BINDING 514
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /ligand_note="substrate"
FT /evidence="ECO:0000269|PubMed:30356045"
FT BINDING 517
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTW"
FT BINDING 517
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000312|PDB:4GTZ"
FT BINDING 517
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTX"
FT BINDING 517
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0007744|PDB:4GTY"
FT BINDING 517
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:30356045"
FT BINDING 781
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT BINDING 783
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT BINDING 785
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT BINDING 787
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT BINDING 789
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT SITE 84..85
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:23041369"
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:0000250|UniProtKB:Q924C3"
FT MOD_RES 238
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q924C3"
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:0000269|PubMed:19656770,
FT ECO:0000269|PubMed:23027977"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770,
FT ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:23041369"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23041369"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770,
FT ECO:0000269|PubMed:23041369"
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:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 185..397
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 413..512
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 462..849
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 596..653
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 607..707
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 609..692
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT DISULFID 819..829
FT /evidence="ECO:0000269|PubMed:23027977,
FT ECO:0000269|PubMed:23041369"
FT VAR_SEQ 630
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:3104326"
FT /id="VSP_006748"
FT VARIANT 568..906
FT /note="Missing (in ttw)"
FT /evidence="ECO:0000269|PubMed:9662402"
FT VARIANT 651
FT /note="H -> R (in allele ENPP1b)"
FT /evidence="ECO:0000269|PubMed:12121276"
FT VARIANT 680
FT /note="R -> S (in allele ENPP1b)"
FT /evidence="ECO:0000269|PubMed:12121276"
FT MUTAGEN 28
FT /note="A->G: No effect on basolateral sorting in epithelial
FT cells."
FT /evidence="ECO:0000269|PubMed:11598187"
FT MUTAGEN 30
FT /note="S->A,D: Little change in baolateral sorting in
FT epithelial cells."
FT /evidence="ECO:0000269|PubMed:11598187"
FT MUTAGEN 31
FT /note="L->A: 60% of ENPP1 redirected to apical surface in
FT epithelial cells. 75% of ENPP1 redirected to apical surface
FT in epithelial cells; abrogation of increased NPP activity
FT in oestoblastic matrix vesicles; when associated with A-
FT 32."
FT /evidence="ECO:0000269|PubMed:11598187,
FT ECO:0000269|PubMed:15075217"
FT MUTAGEN 32
FT /note="L->A: 70% of ENPP1 redirected to apical surface in
FT epithelial cells; abrogation of increased NPP activity in
FT oestoblastic matrix vesicles. 75% of ENPP1 redirected to
FT apical surface in epithelial cells; abrogation of increased
FT NPP activity in oestoblastic matrix vesicles; when
FT associated with A-31."
FT /evidence="ECO:0000269|PubMed:11598187,
FT ECO:0000269|PubMed:15075217"
FT MUTAGEN 42
FT /note="L->A: No change in increased NPP activity in
FT oestoblastic matrix vesicles."
FT /evidence="ECO:0000269|PubMed:15075217"
FT MUTAGEN 57
FT /note="Y->G: No change in increased NPP activity in
FT oestoblastic matrix vesicles."
FT /evidence="ECO:0000269|PubMed:15075217"
FT MUTAGEN 200
FT /note="D->N: Decreases phosphodiesterase activity by 95%.
FT Abolishes formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 237
FT /note="K->A: Decreases phosphodiesterase activity by 40%.
FT Decreased formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 238
FT /note="T->A: Abolishes all phosphodiesterase activity.
FT Abolishes formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689,
FT ECO:0000269|PubMed:30356045"
FT MUTAGEN 238
FT /note="T->S: Decreases phosphodiesterase activity by 95%.
FT Accumulates nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 239
FT /note="F->A: Decreases phosphodiesterase activity by 50%.
FT Decreased formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689,
FT ECO:0000269|PubMed:23027977"
FT MUTAGEN 242
FT /note="H->L: Strongly decreased phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:23027977"
FT MUTAGEN 304..323
FT /note="Missing: Nearly abolishes activity with nucleotide
FT phosphates. Confers very low activity with
FT lysophospholipids."
FT /evidence="ECO:0000269|PubMed:23027977"
FT MUTAGEN 308
FT /note="D->A: Decreased phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:23027977"
FT MUTAGEN 322
FT /note="Y->A: Strongly decreased phosphodiesterase
FT activity."
FT /evidence="ECO:0000269|PubMed:23027977"
FT MUTAGEN 358
FT /note="D->Q: Decreases phosphodiesterase activity by 90%.
FT Accumulates nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 362
FT /note="H->Q: Decreases phosphodiesterase activity by 95%.
FT 65% activity can be restored by addition of Zn(2+) ions.
FT Accumulates nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 397
FT /note="C->S: Mice display a low bone mass density and show
FT a striking joint disease and calcification of blood
FT vessels. Probably affects protein stability."
FT /evidence="ECO:0000269|PubMed:19419305"
FT MUTAGEN 405
FT /note="D->N: Abolishes all phosphodiesterase activity. 10%
FT activity can be restored by addition of Zn(2+) ions.
FT Abolishes formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 406
FT /note="H->Q: Abolishes all phosphodiesterase activity. 15%
FT activity can be restored by addition of Zn(2+) ions.
FT Abolishes formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT MUTAGEN 514
FT /note="S->L: Abolished ability to hydrolyze 2',3'-cGAMP
FT without affecting ability to hydrolyze ATP."
FT /evidence="ECO:0000269|PubMed:30356045"
FT MUTAGEN 517
FT /note="H->Q: Abolishes all phosphodiesterase activity. 60%
FT activity can be restored by addition of Zn(2+) ions.
FT Abolishes formation of nucleotidylated intermediate."
FT /evidence="ECO:0000269|PubMed:11027689"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:4B56"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 108..111
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 118..122
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:4B56"
FT TURN 133..137
FT /evidence="ECO:0007829|PDB:4B56"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 162..167
FT /evidence="ECO:0007829|PDB:4B56"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 204..210
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 215..222
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 264..267
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:4GTW"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 288..294
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 299..303
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 305..308
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:4B56"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:6AEL"
FT HELIX 328..338
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 343..345
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 348..354
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 358..364
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 369..391
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:6XKD"
FT STRAND 399..403
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 415..418
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 420..423
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 428..432
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:4GTW"
FT STRAND 438..443
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 444..450
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 453..459
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:4GTX"
FT STRAND 468..473
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 474..476
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:6XKD"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:4GTW"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 501..505
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 530..534
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 539..543
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 548..550
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 551..559
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 570..573
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 577..579
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 591..594
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 611..613
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 617..624
FT /evidence="ECO:0007829|PDB:4B56"
FT HELIX 631..637
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 651..656
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 661..665
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 666..669
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 670..678
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 703..705
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 707..710
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 717..722
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 728..732
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 735..738
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 740..742
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 743..746
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 748..759
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 761..769
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 772..779
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 785..787
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 791..796
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 799..801
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 804..806
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 810..821
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 826..828
FT /evidence="ECO:0007829|PDB:4B56"
FT STRAND 830..840
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 846..848
FT /evidence="ECO:0007829|PDB:6AEK"
FT TURN 851..853
FT /evidence="ECO:0007829|PDB:4GTZ"
FT HELIX 855..865
FT /evidence="ECO:0007829|PDB:6AEK"
FT HELIX 870..877
FT /evidence="ECO:0007829|PDB:6AEK"
FT STRAND 885..887
FT /evidence="ECO:0007829|PDB:6AEL"
FT HELIX 889..897
FT /evidence="ECO:0007829|PDB:6AEK"
SQ SEQUENCE 906 AA; 103176 MW; 068D45B0ED0F224D CRC64;
MERDGDQAGH GPRHGSAGNG RELESPAAAS LLAPMDLGEE PLEKAERARP AKDPNTYKVL
SLVLSVCVLT TILGCIFGLK PSCAKEVKSC KGRCFERTFS NCRCDAACVS LGNCCLDFQE
TCVEPTHIWT CNKFRCGEKR LSRFVCSCAD DCKTHNDCCI NYSSVCQDKK SWVEETCESI
DTPECPAEFE SPPTLLFSLD GFRAEYLHTW GGLLPVISKL KNCGTYTKNM RPMYPTKTFP
NHYSIVTGLY PESHGIIDNK MYDPKMNASF SLKSKEKFNP LWYKGQPIWV TANHQEVKSG
TYFWPGSDVE IDGILPDIYK VYNGSVPFEE RILAVLEWLQ LPSHERPHFY TLYLEEPDSS
GHSHGPVSSE VIKALQKVDR LVGMLMDGLK DLGLDKCLNL ILISDHGMEQ GSCKKYVYLN
KYLGDVNNVK VVYGPAARLR PTDVPETYYS FNYEALAKNL SCREPNQHFR PYLKPFLPKR
LHFAKSDRIE PLTFYLDPQW QLALNPSERK YCGSGFHGSD NLFSNMQALF IGYGPAFKHG
AEVDSFENIE VYNLMCDLLG LIPAPNNGSH GSLNHLLKKP IYNPSHPKEE GFLSQCPIKS
TSNDLGCTCD PWIVPIKDFE KQLNLTTEDV DDIYHMTVPY GRPRILLKQH HVCLLQQQQF
LTGYSLDLLM PLWASYTFLR NDQFSRDDFS NCLYQDLRIP LSPVHKCSYY KSNSKLSYGF
LTPPRLNRVS NHIYSEALLT SNIVPMYQSF QVIWHYLHDT LLQRYAHERN GINVVSGPVF
DFDYDGRYDS LEILKQNSRV IRSQEILIPT HFFIVLTSCK QLSETPLECS ALESSAYILP
HRPDNIESCT HGKRESSWVE ELLTLHRARV TDVELITGLS FYQDRQESVS ELLRLKTHLP
IFSQED
