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 27-MAR-2024, entry version 215. 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}, Pc1 GN {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] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=35147247; DOI=10.1002/jbmr.4528; RA Szeri F., Niaziorimi F., Donnelly S., Fariha N., Tertyshnaia M., Patel D., RA Lundkvist S., van de Wetering K.; RT "The Mineralization Regulator ANKH Mediates Cellular Efflux of ATP, Not RT Pyrophosphate."; RL J. Bone Miner. Res. 37:1024-1031(2022). RN [27] {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 [28] {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 [29] {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 PubMed:35147247). Preferentially hydrolyzes ATP, but can also hydrolyze CC other nucleoside 5' triphosphates such as GTP, CTP and UTP to their CC corresponding monophosphates with release of pyrophosphate, as well as CC diadenosine polyphosphates, and also 3',5'-cAMP to AMP CC (PubMed:11027689, PubMed:1647027, PubMed:23027977, PubMed:8223581). May CC also be involved in the regulation of the availability of nucleotide CC sugars in the endoplasmic reticulum and Golgi, and the regulation of CC purinergic signaling (PubMed:1647027). Inhibits ectopic joint CC calcification and maintains articular chondrocytes by repressing CC hedgehog signaling; it is however unclear whether hedgehog inhibition CC is direct or indirect (PubMed:30111653). Appears to modulate insulin CC sensitivity (By similarity). Also involved in melanogenesis (By CC 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 (PubMed:25344812). 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 unclear CC (By similarity). Not able to hydrolyze the 2',3'-cGAMP linkage isomer CC 3',3'-cGAMP (By 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:35147247, CC ECO:0000269|PubMed:8223581, 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 Bones and plasma of deficient mice are almost devoid of PPi. CC {ECO:0000269|PubMed:12082181, ECO:0000269|PubMed:25260930, CC ECO:0000269|PubMed:35147247}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSMUSP00000114273; -. DR BindingDB; P06802; -. DR GlyConnect; 2414; 1 N-Linked glycan (1 site). [P06802-2] DR GlyCosmos; P06802; 6 sites, 1 glycan. DR GlyGen; P06802; 7 sites, 1 N-linked glycan (1 site), 1 O-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; 10090-ENSMUSP00000101159; -. DR ProteomicsDB; 275869; -. [P06802-1] DR ProteomicsDB; 275870; -. [P06802-2] DR Pumba; P06802; -. DR DNASU; 18605; -. DR GeneID; 18605; -. DR KEGG; mmu:18605; -. DR AGR; MGI:97370; -. DR CTD; 5167; -. DR MGI; MGI:97370; Enpp1. DR eggNOG; KOG2645; Eukaryota. DR InParanoid; P06802; -. DR OrthoDB; 1366859at2759; -. 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 77 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:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. 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:0010945; F:coenzyme A diphosphatase activity; TAS:MGI. DR GO; GO:0106177; F:cyclic-GMP-AMP hydrolase activity; IDA:UniProtKB. DR GO; GO:0004551; F:dinucleotide phosphatase activity; IDA:UniProtKB. 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:0003676; F:nucleic acid binding; IEA:InterPro. DR GO; GO:0047429; F:nucleoside triphosphate 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:0016462; F:pyrophosphatase 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: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: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:0000902; P:cell morphogenesis; IDA:MGI. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0019725; P:cellular homeostasis; IMP:MGI. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI. DR GO; GO:1904384; P:cellular response to sodium phosphate; IMP:MGI. DR GO; GO:0071529; P:cementum mineralization; IDA:MGI. DR GO; GO:0022010; P:central nervous system myelination; IMP:MGI. DR GO; GO:0015938; P:coenzyme A catabolic process; ISO: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:0140928; P:inhibition of non-skeletal tissue mineralization; IDA:MGI. DR GO; GO:0030505; P:inorganic diphosphate transport; IDA:MGI. DR GO; GO:0030643; P:intracellular phosphate ion homeostasis; ISO: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:0035264; P:multicellular organism growth; IMP:MGI. DR GO; GO:0046716; P:muscle cell cellular homeostasis; 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: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: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: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 CDD; cd16018; Enpp; 1. DR CDD; cd00091; NUC; 1. DR Gene3D; 4.10.410.20; -; 2. DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1. DR Gene3D; 3.40.570.10; Extracellular Endonuclease, subunit A; 1. DR InterPro; IPR017850; Alkaline_phosphatase_core_sf. DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease. DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf. DR InterPro; IPR020821; Extracellular_endonuc_su_A. DR InterPro; IPR044925; His-Me_finger_sf. DR InterPro; IPR002591; Phosphodiest/P_Trfase. DR InterPro; IPR020436; SMB_chordata. DR InterPro; IPR036024; Somatomedin_B-like_dom_sf. DR InterPro; IPR001212; Somatomedin_B_dom. DR PANTHER; PTHR10151; ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE; 1. DR PANTHER; PTHR10151:SF77; ECTONUCLEOTIDE PYROPHOSPHATASE_PHOSPHODIESTERASE FAMILY MEMBER 1; 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; Alkaline phosphatase-like; 1. DR SUPFAM; SSF54060; His-Me finger endonucleases; 1. DR SUPFAM; SSF90188; Somatomedin B domain; 2. DR PROSITE; PS00524; SMB_1; 2. DR PROSITE; PS50958; SMB_2; 2. PE 1: Evidence at protein level; KW 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 FT A-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 //