ENPP2_MOUSE
ID ENPP2_MOUSE Reviewed; 862 AA.
AC Q9R1E6; A8UH85; A8UH93; B2ZP54; Q6PDE0; Q99LG9;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 3.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 2;
DE Short=E-NPP 2;
DE EC=3.1.4.39 {ECO:0000269|PubMed:17208043, ECO:0000269|PubMed:18175805, ECO:0000269|PubMed:21240269, ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639};
DE AltName: Full=Autotaxin {ECO:0000303|PubMed:18175805};
DE AltName: Full=Extracellular lysophospholipase D;
DE Short=LysoPLD;
DE Flags: Precursor;
GN Name=Enpp2; Synonyms=Npps2, Pdnp2 {ECO:0000303|PubMed:10702660};
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).
RC STRAIN=C57BL/6J;
RX PubMed=10702660; DOI=10.1159/000015459;
RA Piao J.-H., Matsuda Y., Nakamura H., Sano K.;
RT "Assignment of Pdnp2, the gene encoding phosphodiesterase I/nucleotide
RT pyrophosphatase 2, to mouse chromosome 15D2.";
RL Cytogenet. Cell Genet. 87:172-174(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), CATALYTIC ACTIVITY,
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Adipocyte, and Skeletal muscle;
RX PubMed=18175805; DOI=10.1074/jbc.m708705200;
RA Giganti A., Rodriguez M., Fould B., Moulharat N., Coge F., Chomarat P.,
RA Galizzi J.-P., Valet P., Saulnier-Blache J.-S., Boutin J.A., Ferry G.;
RT "Murine and human autotaxin alpha, beta, and gamma isoforms: gene
RT organization, tissue distribution, and biochemical characterization.";
RL J. Biol. Chem. 283:7776-7789(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MRL/MpJ;
RA Burgess-Herbert S.L., Shockley K., Sheehan S., Bickerstaff L.,
RA Harwood B.I.V., Shen Y., Li R., Churchill G.A., Paigen B.;
RT "Comparative genomics, experimental biology, and bioinformatics merge to
RT narrow a QTL for HDL cholesterol on mouse chromosome 15 and human
RT chromosome 8.";
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary gland, and Retina;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INDUCTION, AND POSSIBLE FUNCTION IN OBESITY.
RX PubMed=15700135; DOI=10.1007/s00125-004-1660-8;
RA Boucher J., Quilliot D., Pradere J.P., Simon M.F., Gres S., Guigne C.,
RA Prevot D., Ferry G., Boutin J.A., Carpene C., Valet P.,
RA Saulnier-Blache J.S.;
RT "Potential involvement of adipocyte insulin resistance in obesity-
RT associated up-regulation of adipocyte lysophospholipase D/autotaxin
RT expression.";
RL Diabetologia 48:569-577(2005).
RN [8]
RP PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY,
RP GLYCOSYLATION, AND MUTAGENESIS OF 12-VAL--VAL-22; 12-VAL--GLY-27;
RP 23-ASN--GLY-27; CYS-25; GLY-27; 27-GLY--ALA-30; 27-GLY--ARG-35;
RP 30-ALA--ILE-33; 30-ALA--GLY-41; 32-ARG--ARG-35; 36-ALA--GLU-40; ASN-53 AND
RP ASN-410.
RX PubMed=17208043; DOI=10.1016/j.bbalip.2006.11.010;
RA Pradere J.P., Tarnus E., Gres S., Valet P., Saulnier-Blache J.S.;
RT "Secretion and lysophospholipase D activity of autotaxin by adipocytes are
RT controlled by N-glycosylation and signal peptidase.";
RL Biochim. Biophys. Acta 1771:93-102(2007).
RN [9]
RP SUBCELLULAR LOCATION, INTERDOMAIN DISULFIDE BOND, AND MUTAGENESIS OF
RP 851-LEU--THR-853; LEU-851; LYS-852 AND THR-853.
RX PubMed=19329427; DOI=10.1074/jbc.m900790200;
RA Jansen S., Andries M., Derua R., Waelkens E., Bollen M.;
RT "Domain interplay mediated by an essential disulfide linkage is critical
RT for the activity and secretion of the metastasis-promoting enzyme
RT autotaxin.";
RL J. Biol. Chem. 284:14296-14302(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 [11]
RP FUNCTION.
RX PubMed=28414242; DOI=10.1021/acs.jmedchem.7b00032;
RA Desroy N., Housseman C., Bock X., Joncour A., Bienvenu N., Cherel L.,
RA Labeguere V., Rondet E., Peixoto C., Grassot J.M., Picolet O., Annoot D.,
RA Triballeau N., Monjardet A., Wakselman E., Roncoroni V., Le Tallec S.,
RA Blanque R., Cottereaux C., Vandervoort N., Christophe T., Mollat P.,
RA Lamers M., Auberval M., Hrvacic B., Ralic J., Oste L., van der Aar E.,
RA Brys R., Heckmann B.;
RT "Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-
RT oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-
RT (4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class
RT Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of
RT Idiopathic Pulmonary Fibrosis.";
RL J. Med. Chem. 60:3580-3590(2017).
RN [12] {ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 36-862 IN COMPLEXES WITH
RP LYSOPHOSPHATIDIC ACID; ZINC AND CALCIUM IONS, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, DISULFIDE BONDS, GLYCOSYLATION AT ASN-53; ASN-410 AND ASN-524,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-210; LEU-213; ASN-230;
RP LEU-243; GLU-247 AND PHE-249.
RX PubMed=21240269; DOI=10.1038/nsmb.1998;
RA Nishimasu H., Okudaira S., Hama K., Mihara E., Dohmae N., Inoue A.,
RA Ishitani R., Takagi J., Aoki J., Nureki O.;
RT "Crystal structure of autotaxin and insight into GPCR activation by lipid
RT mediators.";
RL Nat. Struct. Mol. Biol. 18:205-212(2011).
RN [13] {ECO:0007744|PDB:4GTW, ECO:0007744|PDB:4GTX, ECO:0007744|PDB:4GTY, ECO:0007744|PDB:4GTZ}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 51-58.
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 [14] {ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 36-862 IN COMPLEXES WITH
RP INHIBITORS; CALCIUM AND ZINC, GLYCOSYLATION AT ASN-53; ASN-410 AND ASN-524,
RP CATALYTIC ACTIVITY, COFACTOR, AND DISULFIDE BOND.
RX PubMed=23688339; DOI=10.1021/cb400150c;
RA Kawaguchi M., Okabe T., Okudaira S., Nishimasu H., Ishitani R., Kojima H.,
RA Nureki O., Aoki J., Nagano T.;
RT "Screening and X-ray crystal structure-based optimization of autotaxin
RT (ENPP2) inhibitors, using a newly developed fluorescence probe.";
RL ACS Chem. Biol. 8:1713-1721(2013).
RN [15] {ECO:0007744|PDB:5LIA}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 36-862 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR; CALCIUM AND ZINC, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP GLYCOSYLATION AT ASN-410 AND ASN-524, AND DISULFIDE BONDS.
RX PubMed=27780639; DOI=10.1016/j.bmcl.2016.10.036;
RA Shah P., Cheasty A., Foxton C., Raynham T., Farooq M., Gutierrez I.F.,
RA Lejeune A., Pritchard M., Turnbull A., Pang L., Owen P., Boyd S.,
RA Stowell A., Jordan A., Hamilton N.M., Hitchin J.R., Stockley M.,
RA MacDonald E., Quesada M.J., Trivier E., Skeete J., Ovaa H., Moolenaar W.H.,
RA Ryder H.;
RT "Discovery of potent inhibitors of the lysophospholipase autotaxin.";
RL Bioorg. Med. Chem. Lett. 26:5403-5410(2016).
RN [16] {ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB}
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 36-862 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR; CALCIUM AND ZINC, GLYCOSYLATION AT ASN-53; ASN-410 AND ASN-524,
RP AND DISULFIDE BONDS.
RX PubMed=29259743; DOI=10.1021/acsmedchemlett.7b00312;
RA Kuttruff C.A., Ferrara M., Bretschneider T., Hoerer S., Handschuh S.,
RA Nosse B., Romig H., Nicklin P., Roth G.J.;
RT "Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly
RT Reduces LPA Levels in Vivo.";
RL ACS Med. Chem. Lett. 8:1252-1257(2017).
CC -!- FUNCTION: Hydrolyzes lysophospholipids to produce the signaling
CC molecule lysophosphatidic acid (LPA) in extracellular fluids
CC (PubMed:17208043, PubMed:28414242, PubMed:27780639). Major substrate is
CC lysophosphatidylcholine (PubMed:17208043, PubMed:27780639). Can also
CC act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a
CC modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some
CC extent pNP-TMP, and barely ATP (PubMed:18175805). Involved in several
CC motility-related processes such as angiogenesis and neurite outgrowth.
CC Acts as an angiogenic factor by stimulating migration of smooth muscle
CC cells and microtubule formation. Stimulates migration of melanoma
CC cells, probably via a pertussis toxin-sensitive G protein. May have a
CC role in induction of parturition (By similarity). Possible involvement
CC in cell proliferation and adipose tissue development (Probable). Tumor
CC cell motility-stimulating factor. Required for LPA production in
CC activated platelets, cleaves the sn-1 lysophospholipids to generate sn-
CC 1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty
CC acids (By similarity). Shows a preference for the sn-1 to the sn-2
CC isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (By
CC similarity). {ECO:0000250|UniProtKB:Q13822,
CC ECO:0000269|PubMed:17208043, ECO:0000269|PubMed:18175805,
CC ECO:0000269|PubMed:21240269, ECO:0000269|PubMed:27780639,
CC ECO:0000269|PubMed:28414242, ECO:0000305|PubMed:15700135}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-O-alkyl-
CC sn-glycero-3-phosphate + ethanolamine + H(+); Xref=Rhea:RHEA:15965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57603,
CC ChEBI:CHEBI:58014, ChEBI:CHEBI:76168; EC=3.1.4.39;
CC Evidence={ECO:0000269|PubMed:17208043, ECO:0000269|PubMed:18175805,
CC ECO:0000269|PubMed:21240269, ECO:0000269|PubMed:23688339,
CC ECO:0000269|PubMed:27780639};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(9Z-octadecenyl)-sn-glycero-3-phosphocholine + H2O = 1-O-
CC (9Z-octadecenyl)-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41684, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64396, ChEBI:CHEBI:78402;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41685;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2-acyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-
CC glycerol 3-phosphate + choline + H(+); Xref=Rhea:RHEA:41712,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57875, ChEBI:CHEBI:64982;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41713;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2-acyl-sn-glycero-3-phospho-L-serine + H2O = a 2-acyl-sn-
CC glycerol 3-phosphate + H(+) + L-serine; Xref=Rhea:RHEA:41716,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:64982, ChEBI:CHEBI:65214;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41717;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-dodecanoyl-sn-glycero-3-phosphocholine + H2O = 1-dodecanoyl-
CC sn-glycerol 3-phosphate + choline + H(+); Xref=Rhea:RHEA:38991,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72682, ChEBI:CHEBI:74966;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38992;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sphing-4-enine-phosphocholine = choline + H(+) + sphing-
CC 4-enine 1-phosphate; Xref=Rhea:RHEA:38919, ChEBI:CHEBI:15354,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58906,
CC ChEBI:CHEBI:60119; Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38920;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:38915, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28610, ChEBI:CHEBI:74544;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38916;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC tetradecanoyl-sn-glycerol 3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:38983, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64489, ChEBI:CHEBI:72683;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38984;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-decanoyl-sn-glycero-3-phosphocholine + H2O = 1-decanoyl-sn-
CC glycero-3-phosphate + choline + H(+); Xref=Rhea:RHEA:41131,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:77724, ChEBI:CHEBI:77726;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41132;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:38975, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57518, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38976;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC octadecanoyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:38979, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:73858, ChEBI:CHEBI:74565;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38980;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphocholine + H2O =
CC 1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41135, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28733, ChEBI:CHEBI:74547;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41136;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine
CC + H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate +
CC choline + H(+); Xref=Rhea:RHEA:41139, ChEBI:CHEBI:15354,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:74344,
CC ChEBI:CHEBI:74938; Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41140;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-
CC hexadecyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41143, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64496, ChEBI:CHEBI:77580;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41144;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexanoyl-sn-
CC glycero-3-phosphate + choline + H(+); Xref=Rhea:RHEA:41400,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:78215, ChEBI:CHEBI:78223;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41401;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-
CC dioctanoyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41416, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:78228, ChEBI:CHEBI:78229;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41417;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-didecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-
CC didecanoyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41412, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:78226, ChEBI:CHEBI:78227;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41413;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z-alkenyl)-sn-glycero-3-phosphocholine + H2O = 1-O-(1Z-
CC alkenyl)-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41588, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:77283, ChEBI:CHEBI:77287;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41589;
CC Evidence={ECO:0000250|UniProtKB:Q13822};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O =
CC 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ethanolamine + H(+);
CC Xref=Rhea:RHEA:38927, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:74544, ChEBI:CHEBI:74971;
CC Evidence={ECO:0000250|UniProtKB:Q64610};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38928;
CC Evidence={ECO:0000250|UniProtKB:Q64610};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-
CC (9Z-octadecenoyl)-sn-glycero-3-phosphate + H(+) + L-serine;
CC Xref=Rhea:RHEA:38931, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33384, ChEBI:CHEBI:74544, ChEBI:CHEBI:74617;
CC Evidence={ECO:0000250|UniProtKB:Q64610};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38932;
CC Evidence={ECO:0000250|UniProtKB:Q64610};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:21240269, ECO:0000269|PubMed:23688339,
CC ECO:0000269|PubMed:27780639};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:21240269,
CC ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:21240269, ECO:0000269|PubMed:23688339,
CC ECO:0000269|PubMed:27780639};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:21240269,
CC ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and EGTA.
CC {ECO:0000269|PubMed:18175805}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.9 mM for pNppp (isoform 1) {ECO:0000269|PubMed:18175805};
CC KM=4.4 mM for pNppp (isoform 2) {ECO:0000269|PubMed:18175805};
CC KM=11.8 mM for pNppp (isoform 3) {ECO:0000269|PubMed:18175805};
CC Vmax=1.9 nmol/min/ug enzyme with pNppp as substrate (isoform 1)
CC {ECO:0000269|PubMed:18175805};
CC Vmax=0.35 nmol/min/ug enzyme with pNppp as substrate (isoform 2)
CC {ECO:0000269|PubMed:18175805};
CC Vmax=1.8 nmol/min/ug enzyme with pNppp as substrate (isoform 3)
CC {ECO:0000269|PubMed:18175805};
CC pH dependence:
CC Optimum pH is 8.0 for isoforms 1, 2 and 3.
CC {ECO:0000269|PubMed:18175805};
CC Temperature dependence:
CC Isoforms 1 and 3 have maximum activity from 45 to 55 degrees Celsius.
CC {ECO:0000269|PubMed:18175805};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17208043,
CC ECO:0000269|PubMed:19329427, ECO:0000269|PubMed:21240269}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Beta;
CC IsoId=Q9R1E6-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=Q9R1E6-2; Sequence=VSP_036396;
CC Name=3; Synonyms=Gamma;
CC IsoId=Q9R1E6-3; Sequence=VSP_036397;
CC -!- TISSUE SPECIFICITY: Expressed in brain and adipose tissue.
CC {ECO:0000269|PubMed:18175805}.
CC -!- INDUCTION: Up-regulated in adipocytes of obese-diabetic db/db mice.
CC {ECO:0000269|PubMed:15700135}.
CC -!- PTM: N-glycosylation, but not furin-cleavage, plays a critical role on
CC secretion and on lysoPLD activity. Secretion requires simultaneous
CC glycosylation on Asn-53 and Asn-410, while probable glycosylation of
CC Asn-410 has a preferential role on lysoPLD activity. Not O-
CC glycosylated. {ECO:0000269|PubMed:17208043,
CC ECO:0000269|PubMed:21240269, ECO:0000269|PubMed:23688339}.
CC -!- PTM: The interdomain disulfide bond between Cys-413 and Cys-805 is
CC essential for catalytic activity. {ECO:0000269|PubMed:19329427}.
CC -!- DISEASE: Note=May contribute to obesity (PubMed:15700135).
CC {ECO:0000269|PubMed:15700135}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; AF123542; AAD46480.1; -; mRNA.
DR EMBL; EU131009; ABW38314.1; -; mRNA.
DR EMBL; EU131010; ABW38315.1; -; mRNA.
DR EMBL; EU677474; ACD12865.1; -; Genomic_DNA.
DR EMBL; EU677475; ACD12866.1; -; Genomic_DNA.
DR EMBL; AK161144; BAE36214.1; -; mRNA.
DR EMBL; CH466545; EDL29265.1; -; Genomic_DNA.
DR EMBL; BC003264; AAH03264.1; -; mRNA.
DR EMBL; BC058759; AAH58759.1; -; mRNA.
DR CCDS; CCDS27472.1; -. [Q9R1E6-1]
DR CCDS; CCDS49607.1; -. [Q9R1E6-2]
DR CCDS; CCDS70628.1; -. [Q9R1E6-3]
DR RefSeq; NP_001129549.1; NM_001136077.3. [Q9R1E6-2]
DR RefSeq; NP_001272923.1; NM_001285994.2. [Q9R1E6-3]
DR RefSeq; NP_001272924.1; NM_001285995.2.
DR RefSeq; NP_056559.2; NM_015744.4. [Q9R1E6-1]
DR PDB; 3NKM; X-ray; 2.00 A; A=36-862.
DR PDB; 3NKN; X-ray; 1.80 A; A=36-862.
DR PDB; 3NKO; X-ray; 1.75 A; A=36-862.
DR PDB; 3NKP; X-ray; 1.75 A; A=36-862.
DR PDB; 3NKQ; X-ray; 1.70 A; A=36-862.
DR PDB; 3NKR; X-ray; 1.70 A; A=36-862.
DR PDB; 3WAV; X-ray; 1.80 A; A=36-862.
DR PDB; 3WAW; X-ray; 1.95 A; A=36-862.
DR PDB; 3WAX; X-ray; 1.90 A; A=36-862.
DR PDB; 3WAY; X-ray; 1.75 A; A=36-862.
DR PDB; 4GTW; X-ray; 2.70 A; A/B=51-58.
DR PDB; 4GTX; X-ray; 3.20 A; A/B=51-58.
DR PDB; 4GTY; X-ray; 3.19 A; A/B=51-58.
DR PDB; 4GTZ; X-ray; 3.19 A; A/B=51-58.
DR PDB; 5HRT; X-ray; 2.00 A; A=36-862.
DR PDB; 5INH; X-ray; 1.84 A; A=36-862.
DR PDB; 5JVG; X-ray; 3.43 A; U=1-81.
DR PDB; 5LIA; X-ray; 1.92 A; A=36-862.
DR PDB; 5OHI; X-ray; 1.66 A; A=36-862.
DR PDB; 5OLB; X-ray; 1.82 A; A=36-862.
DR PDB; 6LEH; X-ray; 2.00 A; A=36-862.
DR PDB; 6Y5M; X-ray; 2.01 A; A=36-862.
DR PDB; 7MFH; X-ray; 2.30 A; A=36-862.
DR PDBsum; 3NKM; -.
DR PDBsum; 3NKN; -.
DR PDBsum; 3NKO; -.
DR PDBsum; 3NKP; -.
DR PDBsum; 3NKQ; -.
DR PDBsum; 3NKR; -.
DR PDBsum; 3WAV; -.
DR PDBsum; 3WAW; -.
DR PDBsum; 3WAX; -.
DR PDBsum; 3WAY; -.
DR PDBsum; 4GTW; -.
DR PDBsum; 4GTX; -.
DR PDBsum; 4GTY; -.
DR PDBsum; 4GTZ; -.
DR PDBsum; 5HRT; -.
DR PDBsum; 5INH; -.
DR PDBsum; 5JVG; -.
DR PDBsum; 5LIA; -.
DR PDBsum; 5OHI; -.
DR PDBsum; 5OLB; -.
DR PDBsum; 6LEH; -.
DR PDBsum; 6Y5M; -.
DR PDBsum; 7MFH; -.
DR AlphaFoldDB; Q9R1E6; -.
DR SMR; Q9R1E6; -.
DR STRING; 10090.ENSMUSP00000132640; -.
DR BindingDB; Q9R1E6; -.
DR ChEMBL; CHEMBL3826871; -.
DR GuidetoPHARMACOLOGY; 2901; -.
DR GlyConnect; 2275; 5 N-Linked glycans (2 sites).
DR GlyGen; Q9R1E6; 4 sites, 5 N-linked glycans (2 sites).
DR iPTMnet; Q9R1E6; -.
DR PhosphoSitePlus; Q9R1E6; -.
DR MaxQB; Q9R1E6; -.
DR PeptideAtlas; Q9R1E6; -.
DR PRIDE; Q9R1E6; -.
DR ProteomicsDB; 275871; -. [Q9R1E6-1]
DR ProteomicsDB; 275872; -. [Q9R1E6-2]
DR ProteomicsDB; 275873; -. [Q9R1E6-3]
DR Antibodypedia; 13653; 418 antibodies from 39 providers.
DR DNASU; 18606; -.
DR Ensembl; ENSMUST00000041591; ENSMUSP00000036180; ENSMUSG00000022425. [Q9R1E6-1]
DR Ensembl; ENSMUST00000167541; ENSMUSP00000132640; ENSMUSG00000022425. [Q9R1E6-3]
DR Ensembl; ENSMUST00000171545; ENSMUSP00000128941; ENSMUSG00000022425. [Q9R1E6-2]
DR GeneID; 18606; -.
DR KEGG; mmu:18606; -.
DR UCSC; uc007vro.3; mouse. [Q9R1E6-1]
DR UCSC; uc007vrq.3; mouse. [Q9R1E6-3]
DR UCSC; uc011zsx.2; mouse. [Q9R1E6-2]
DR CTD; 5168; -.
DR MGI; MGI:1321390; Enpp2.
DR VEuPathDB; HostDB:ENSMUSG00000022425; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000155778; -.
DR HOGENOM; CLU_012256_0_0_1; -.
DR InParanoid; Q9R1E6; -.
DR OMA; TNYHVVC; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q9R1E6; -.
DR TreeFam; TF330032; -.
DR BRENDA; 3.1.4.39; 3474.
DR SABIO-RK; Q9R1E6; -.
DR BioGRID-ORCS; 18606; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Enpp2; mouse.
DR EvolutionaryTrace; Q9R1E6; -.
DR PRO; PR:Q9R1E6; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9R1E6; protein.
DR Bgee; ENSMUSG00000022425; Expressed in choroid plexus epithelium and 358 other tissues.
DR ExpressionAtlas; Q9R1E6; baseline and differential.
DR Genevisible; Q9R1E6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:MGI.
DR GO; GO:0047391; F:alkylglycerophosphoethanolamine phosphodiesterase activity; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004622; F:lysophospholipase activity; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0004551; F:nucleotide diphosphatase activity; ISS:MGI.
DR GO; GO:0004528; F:phosphodiesterase I activity; ISS:MGI.
DR GO; GO:0030247; F:polysaccharide binding; IEA:InterPro.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; ISO:MGI.
DR GO; GO:0044849; P:estrous cycle; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; ISO:MGI.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; IDA:UniProtKB.
DR GO; GO:0009395; P:phospholipid catabolic process; ISO:MGI.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISO:MGI.
DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; ISO:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0045765; P:regulation of angiogenesis; IEA:InterPro.
DR GO; GO:0030334; P:regulation of cell migration; ISO:MGI.
DR GO; GO:0030149; P:sphingolipid catabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.570.10; -; 1.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR InterPro; IPR029881; ENPP2.
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:SF21; PTHR10151:SF21; 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; Calcium; Chemotaxis;
KW Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW Hydrolase; Lipid degradation; Lipid metabolism; Metal-binding; Obesity;
KW Reference proteome; Repeat; Secreted; Signal; Zinc.
FT SIGNAL 1..27
FT /evidence="ECO:0000250|UniProtKB:Q64610"
FT PROPEP 28..35
FT /note="Removed by furin"
FT /evidence="ECO:0000250|UniProtKB:Q64610"
FT /id="PRO_0000281650"
FT CHAIN 36..862
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 2"
FT /id="PRO_0000188568"
FT DOMAIN 54..97
FT /note="SMB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DOMAIN 98..142
FT /note="SMB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT REGION 144..501
FT /note="Phosphodiesterase"
FT REGION 597..862
FT /note="Nuclease"
FT REGION 829..850
FT /note="Required for secretion"
FT MOTIF 126..128
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 209
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:21240269"
FT BINDING 171
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH"
FT BINDING 209
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH"
FT BINDING 210..213
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0007744|PDB:3NKR"
FT BINDING 230
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0007744|PDB:3NKR"
FT BINDING 243..254
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:21240269"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0007744|PDB:3NKR"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA"
FT BINDING 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH"
FT BINDING 474
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA"
FT BINDING 739
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5LIA"
FT BINDING 741
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA"
FT BINDING 743
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5LIA"
FT BINDING 745
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5LIA"
FT BINDING 747
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA"
FT SITE 852
FT /note="Essential for catalytic activity"
FT /evidence="ECO:0000269|PubMed:19329427"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5INH"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5LIA"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5LIA"
FT CARBOHYD 806
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 58..75
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 62..93
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 73..86
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 79..85
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 102..119
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 107..137
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 117..130
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 123..129
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 148..194
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 156..350
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:29259743,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5LIA, ECO:0007744|PDB:5OHI,
FT ECO:0007744|PDB:5OLB"
FT DISULFID 366..468
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:29259743,
FT ECO:0007744|PDB:3NKM, ECO:0007744|PDB:3NKN,
FT ECO:0007744|PDB:3NKO, ECO:0007744|PDB:3NKP,
FT ECO:0007744|PDB:3NKQ, ECO:0007744|PDB:3NKR,
FT ECO:0007744|PDB:3WAV, ECO:0007744|PDB:3WAW,
FT ECO:0007744|PDB:3WAX, ECO:0007744|PDB:3WAY,
FT ECO:0007744|PDB:5HRT, ECO:0007744|PDB:5INH,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 413..805
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 566..666
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 568..651
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT DISULFID 774..784
FT /evidence="ECO:0000269|PubMed:21240269,
FT ECO:0000269|PubMed:23688339, ECO:0000269|PubMed:27780639,
FT ECO:0000269|PubMed:29259743, ECO:0007744|PDB:3NKM,
FT ECO:0007744|PDB:3NKN, ECO:0007744|PDB:3NKO,
FT ECO:0007744|PDB:3NKP, ECO:0007744|PDB:3NKQ,
FT ECO:0007744|PDB:3NKR, ECO:0007744|PDB:3WAV,
FT ECO:0007744|PDB:3WAW, ECO:0007744|PDB:3WAX,
FT ECO:0007744|PDB:3WAY, ECO:0007744|PDB:5HRT,
FT ECO:0007744|PDB:5INH, ECO:0007744|PDB:5LIA,
FT ECO:0007744|PDB:5OHI, ECO:0007744|PDB:5OLB"
FT VAR_SEQ 323
FT /note="E -> EESSYGSPLTPAKRPKRKVAPKRRQERPVAPPKKRRRKLHRMDHYTA
FT ETRQDK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18175805"
FT /id="VSP_036396"
FT VAR_SEQ 592
FT /note="E -> EAETGKFRGSKHENKKSLNGNVEPRK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:18175805"
FT /id="VSP_036397"
FT MUTAGEN 12..27
FT /note="Missing: Complete inhibition of secretion."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 12..22
FT /note="Missing: Complete inhibition of secretion."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 23..27
FT /note="Missing: No effect on secretion."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 23
FT /note="Missing: No effect on secretion."
FT MUTAGEN 25
FT /note="Missing: No effect on secretion."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 27..35
FT /note="Missing: No effect on secretion nor
FT lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 27..30
FT /note="Missing: No effect on secretion."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 27
FT /note="Missing: No effect on secretion."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 30..41
FT /note="Missing: No effect on secretion nor
FT lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 30..33
FT /note="Missing: No effect on secretion nor
FT lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 32..35
FT /note="Missing: No effect on secretion nor
FT lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 36..40
FT /note="Missing: No effect on secretion nor
FT lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 53
FT /note="Missing: No effect on secretion; slightly decreases
FT lysophospholipase activity. Almost complete loss of
FT lysophospholipase activity; when associated with N-410
FT del."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 210
FT /note="F->A: Reduced lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:21240269"
FT MUTAGEN 213
FT /note="L->A: Reduced lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:21240269"
FT MUTAGEN 230
FT /note="N->A: Reduced lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:21240269"
FT MUTAGEN 243
FT /note="L->A: Reduced lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:21240269"
FT MUTAGEN 247
FT /note="E->A: Reduced lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:21240269"
FT MUTAGEN 249
FT /note="F->A: Reduced lysophospholipase activity."
FT /evidence="ECO:0000269|PubMed:21240269"
FT MUTAGEN 410
FT /note="Missing: No effect on secretion; greatly inhibits
FT lysoPLD activity. Inhibits secretion. Almost complete loss
FT of lysoPLD activity; when associated with N-53 del."
FT /evidence="ECO:0000269|PubMed:17208043"
FT MUTAGEN 512
FT /note="M->A: Reduced lysophospholipase activity."
FT MUTAGEN 851..853
FT /note="LKT->AAA,RRR,SSS: No catalytic activity."
FT /evidence="ECO:0000269|PubMed:19329427"
FT MUTAGEN 851
FT /note="L->A: No effect."
FT /evidence="ECO:0000269|PubMed:19329427"
FT MUTAGEN 852
FT /note="K->A,R: Strongly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:19329427"
FT MUTAGEN 853
FT /note="T->A: No effect."
FT /evidence="ECO:0000269|PubMed:19329427"
FT CONFLICT 103
FT /note="T -> I (in Ref. 3; ACD12866)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="G -> S (in Ref. 1; AAD46480)"
FT /evidence="ECO:0000305"
FT CONFLICT 550
FT /note="P -> T (in Ref. 1; AAD46480)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="E -> K (in Ref. 1; AAD46480)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="N -> D (in Ref. 3; ACD12866 and 6; AAH03264)"
FT /evidence="ECO:0000305"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:6LEH"
FT TURN 59..63
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 89..93
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:5HRT"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 165..171
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 175..183
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 186..194
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 209..218
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 235..238
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:3NKQ"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 259..265
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 281..292
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 301..310
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 311..317
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 325..344
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 352..358
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:3NKQ"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 387..396
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 404..411
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 419..424
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 425..427
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 430..432
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 442..447
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 452..456
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 457..459
FT /evidence="ECO:0007829|PDB:3WAV"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:3WAY"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 487..494
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 496..499
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 508..515
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 527..530
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 531..533
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 559..561
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 579..581
FT /evidence="ECO:0007829|PDB:5LIA"
FT TURN 583..586
FT /evidence="ECO:0007829|PDB:3WAV"
FT TURN 593..595
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 609..613
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 618..622
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 623..626
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 627..635
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 646..648
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 666..671
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 676..681
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 683..685
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 689..695
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 698..700
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 701..704
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 706..717
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 719..727
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 729..737
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 743..745
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 749..751
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 765..776
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 781..783
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 788..796
FT /evidence="ECO:0007829|PDB:5OHI"
FT TURN 805..808
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 811..813
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 815..821
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 826..833
FT /evidence="ECO:0007829|PDB:5OHI"
FT STRAND 834..836
FT /evidence="ECO:0007829|PDB:5OHI"
FT HELIX 845..853
FT /evidence="ECO:0007829|PDB:5OHI"
SQ SEQUENCE 862 AA; 98885 MW; 343D44DEAA8FA352 CRC64;
MARQGCFGSY QVISLFTFAI GVNLCLGFTA SRIKRAEWDE GPPTVLSDSP WTNTSGSCKG
RCFELQEVGP PDCRCDNLCK SYSSCCHDFD ELCLKTARGW ECTKDRCGEV RNEENACHCS
EDCLSRGDCC TNYQVVCKGE SHWVDDDCEE IRVPECPAGF VRPPLIIFSV DGFRASYMKK
GSKVMPNIEK LRSCGTHAPY MRPVYPTKTF PNLYTLATGL YPESHGIVGN SMYDPVFDAT
FHLRGREKFN HRWWGGQPLW ITATKQGVRA GTFFWSVSIP HERRILTILQ WLSLPDNERP
SVYAFYSEQP DFSGHKYGPF GPEMTNPLRE IDKTVGQLMD GLKQLKLHRC VNVIFVGDHG
MEDVTCDRTE FLSNYLTNVD DITLVPGTLG RIRPKIPNNL KYDPKAIIAN LTCKKPDQHF
KPYMKQHLPK RLHYANNRRI EDLHLLVERR WHVARKPLDV YKKPSGKCFF QGDHGFDNKV
NSMQTVFVGY GPTFKYRTKV PPFENIELYN VMCDLLGLKP APNNGTHGSL NHLLRTNTFR
PTLPEEVSRP NYPGIMYLQS DFDLGCTCDD KVEPKNKLEE LNKRLHTKGS TEERHLLYGR
PAVLYRTSYD ILYHTDFESG YSEIFLMPLW TSYTISKQAE VSSIPEHLTN CVRPDVRVSP
GFSQNCLAYK NDKQMSYGFL FPPYLSSSPE AKYDAFLVTN MVPMYPAFKR VWTYFQRVLV
KKYASERNGV NVISGPIFDY NYNGLRDIED EIKQYVEGSS IPVPTHYYSI ITSCLDFTQP
ADKCDGPLSV SSFILPHRPD NDESCNSSED ESKWVEELMK MHTARVRDIE HLTGLDFYRK
TSRSYSEILT LKTYLHTYES EI
