ID ENPP2_HUMAN Reviewed; 863 AA. AC Q13822; A8UHA1; E9PHP7; Q13827; Q14555; Q15117; Q9UCQ8; Q9UCR0; Q9UCR1; AC Q9UCR2; Q9UCR3; Q9UCR4; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 02-MAR-2010, sequence version 3. DT 27-MAR-2024, entry version 202. DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 2; DE Short=E-NPP 2; DE EC=3.1.4.39 {ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:18175805, ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:26371182}; DE AltName: Full=Autotaxin {ECO:0000303|PubMed:12176993, ECO:0000303|PubMed:7982964}; DE AltName: Full=Extracellular lysophospholipase D; DE Short=LysoPLD {ECO:0000303|PubMed:12176993}; DE Flags: Precursor; GN Name=ENPP2; GN Synonyms=ATX {ECO:0000303|PubMed:18175805, GN ECO:0000303|PubMed:26371182}, PDNP2 {ECO:0000303|PubMed:8586446}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE, RP CHARACTERIZATION, AND VARIANT PRO-493. RC TISSUE=Melanoma; RX PubMed=7982964; DOI=10.1016/s0021-9258(18)43838-0; RA Murata J., Lee H.Y., Clair T., Krutzsch H.C., Arestad A.A., Sobel M.E., RA Liotta L.A., Stracke M.L.; RT "cDNA cloning of the human tumor motility-stimulating protein, autotaxin, RT reveals a homology with phosphodiesterases."; RL J. Biol. Chem. 269:30479-30484(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] RP OF 1-45, TISSUE SPECIFICITY, AND VARIANT PRO-493. RX PubMed=8586446; DOI=10.1006/geno.1995.0036; RA Kawagoe H., Soma O., Goji J., Nishimura N., Narita M., Inazawa J., RA Nakamura H., Sano K.; RT "Molecular cloning and chromosomal assignment of the human brain-type RT phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)."; RL Genomics 30:380-384(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT RP PRO-493. RC TISSUE=Teratocarcinoma; RX PubMed=8579579; DOI=10.1006/bbrc.1996.0127; RA Lee H.Y., Murata J., Clair T., Polymeropoulos M.H., Torres R., Manrow R.E., RA Liotta L.A., Stracke M.L.; RT "Cloning, chromosomal localization, and tissue expression of autotaxin from RT human teratocarcinoma cells."; RL Biochem. Biophys. Res. Commun. 218:714-719(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, ACTIVITY REGULATION, AND VARIANT PRO-493. RX PubMed=15769751; DOI=10.1074/jbc.m413183200; RA van Meeteren L.A., Ruurs P., Christodoulou E., Goding J.W., Takakusa H., RA Kikuchi K., Perrakis A., Nagano T., Moolenaar W.H.; RT "Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1- RT phosphate."; RL J. Biol. Chem. 280:21155-21161(2005). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), PROTEIN SEQUENCE OF 36-42 RP AND 49-54, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, TISSUE SPECIFICITY, AND VARIANT PRO-493. RC TISSUE=Brain, and Melanoma; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-493. RC TISSUE=Testis; 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 [8] RP PROTEIN SEQUENCE OF 36-49; 318-330; 335-344; 440-450 AND 854-863, FUNCTION, RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=12176993; DOI=10.1074/jbc.m205623200; RA Tokumura A., Majima E., Kariya Y., Tominaga K., Kogure K., Yasuda K., RA Fukuzawa K.; RT "Identification of human plasma lysophospholipase D, a lysophosphatidic RT acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase."; RL J. Biol. Chem. 277:39436-39442(2002). RN [9] RP PROTEIN SEQUENCE OF 256-266; 370-392; 457-463; 481-496; 501-510; 545-554; RP 639-643; 706-710 AND 829-840, FUNCTION, SUBCELLULAR LOCATION, AND VARIANT RP PRO-493. RC TISSUE=Melanoma; RX PubMed=1733949; DOI=10.1016/s0021-9258(18)45911-x; RA Stracke M.L., Krutzsch H.C., Unsworth E.J., Aarestad A., Cioce V., RA Schiffmann E., Liotta L.A.; RT "Identification, purification, and partial sequence analysis of autotaxin, RT a novel motility-stimulating protein."; RL J. Biol. Chem. 267:2524-2529(1992). RN [10] RP FUNCTION IN ANGIOGENESIS. RX PubMed=11559573; RA Nam S.W., Clair T., Kim Y.S., McMarlin A., Schiffmann E., Liotta L.A., RA Stracke M.L.; RT "Autotaxin (NPP-2), a metastasis-enhancing mitogen, is an angiogenic RT factor."; RL Cancer Res. 61:6938-6944(2001). RN [11] RP FUNCTION. RX PubMed=12354767; DOI=10.1074/jbc.m206812200; RA Aoki J., Taira A., Takanezawa Y., Kishi Y., Hama K., Kishimoto T., RA Mizuno K., Saku K., Taguchi R., Arai H.; RT "Serum lysophosphatidic acid is produced through diverse phospholipase RT pathways."; RL J. Biol. Chem. 277:48737-48744(2002). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF THR-210; HIS-316 AND HIS-360. RX PubMed=14500380; RA Clair T., Aoki J., Koh E., Bandle R.W., Nam S.W., Ptaszynska M.M., RA Mills G.B., Schiffmann E., Liotta L.A., Stracke M.L.; RT "Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator RT of migration, sphingosine-1-phosphate."; RL Cancer Res. 63:5446-5453(2003). RN [13] 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 [14] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=21393252; DOI=10.1194/jlr.m013326; RA Bolen A.L., Naren A.P., Yarlagadda S., Beranova-Giorgianni S., Chen L., RA Norman D., Baker D.L., Rowland M.M., Best M.D., Sano T., Tsukahara T., RA Liliom K., Igarashi Y., Tigyi G.; RT "The phospholipase A1 activity of lysophospholipase A-I links platelet RT activation to LPA production during blood coagulation."; RL J. Lipid Res. 52:958-970(2011). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF RP THR-210; PHE-211; ALA-218; ASN-231 AND TYR-307. RX PubMed=21240271; DOI=10.1038/nsmb.1980; RA Hausmann J., Kamtekar S., Christodoulou E., Day J.E., Wu T., Fulkerson Z., RA Albers H.M., van Meeteren L.A., Houben A.J., van Zeijl L., Jansen S., RA Andries M., Hall T., Pegg L.E., Benson T.E., Kasiem M., Harlos K., RA Kooi C.W., Smyth S.S., Ovaa H., Bollen M., Morris A.J., Moolenaar W.H., RA Perrakis A.; RT "Structural basis of substrate discrimination and integrin binding by RT autotaxin."; RL Nat. Struct. Mol. Biol. 18:198-204(2011). RN [16] {ECO:0007744|PDB:4ZG6, ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:4ZGA} RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 55-860 IN COMPLEX WITH SYNTHETIC RP INHIBITOR; CALCIUM AND ZINC, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION AT ASN-525, AND RP DISULFIDE BONDS. RX PubMed=26371182; DOI=10.1124/mol.115.100404; RA Stein A.J., Bain G., Prodanovich P., Santini A.M., Darlington J., RA Stelzer N.M., Sidhu R.S., Schaub J., Goulet L., Lonergan D., Calderon I., RA Evans J.F., Hutchinson J.H.; RT "Structural Basis for Inhibition of Human Autotaxin by Four Potent RT Compounds with Distinct Modes of Binding."; RL Mol. Pharmacol. 88:982-992(2015). RN [17] {ECO:0007744|PDB:5MHP} RP X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR; RP CALCIUM AND ZINC, COFACTOR, AND DISULFIDE BONDS. 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 [18] {ECO:0007744|PDB:5KXA} RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR; RP CALCIUM AND ZINC, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, SUBCELLULAR RP LOCATION, AND DISULFIDE BONDS. RX PubMed=27754931; DOI=10.1124/jpet.116.237156; RA Bain G., Shannon K.E., Huang F., Darlington J., Goulet L., Prodanovich P., RA Ma G.L., Santini A.M., Stein A.J., Lonergan D., King C.D., Calderon I., RA Lai A., Hutchinson J.H., Evans J.F.; RT "Selective Inhibition of Autotaxin Is Efficacious in Mouse Models of Liver RT Fibrosis."; RL J. Pharmacol. Exp. Ther. 360:1-13(2017). CC -!- FUNCTION: Hydrolyzes lysophospholipids to produce the signaling CC molecule lysophosphatidic acid (LPA) in extracellular fluids CC (PubMed:15769751, PubMed:26371182, PubMed:27754931, PubMed:14500380, CC PubMed:12354767). Major substrate is lysophosphatidylcholine CC (PubMed:12176993, PubMed:27754931, PubMed:14500380). Can also act on CC sphingosylphosphorylcholine producing sphingosine-1-phosphate, a CC modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, CC bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, CC PubMed:12176993). Involved in several motility-related processes such CC as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by CC stimulating migration of smooth muscle cells and microtubule formation CC (PubMed:11559573). Stimulates migration of melanoma cells, probably via CC a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role CC in induction of parturition (PubMed:12176993). Possible involvement in CC cell proliferation and adipose tissue development (Probable). Tumor CC cell motility-stimulating factor (PubMed:1733949, PubMed:11559573). CC Required for LPA production in activated platelets, cleaves the sn-1 CC lysophospholipids to generate sn-1 lysophosphatidic acids containing CC predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a CC preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3- CC phosphocholine (lyso-PAF) (PubMed:21393252). CC {ECO:0000269|PubMed:11559573, ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:12354767, ECO:0000269|PubMed:14500380, CC ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, CC ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:21393252, CC ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, CC 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:12176993, ECO:0000269|PubMed:15769751, CC ECO:0000269|PubMed:18175805, ECO:0000269|PubMed:21240271, CC ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931}; 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:0000269|PubMed:21393252}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41685; CC Evidence={ECO:0000305|PubMed:21393252}; 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:0000269|PubMed:21393252}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41713; CC Evidence={ECO:0000305|PubMed:21393252}; 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:0000269|PubMed:21393252}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41717; CC Evidence={ECO:0000305|PubMed:21393252}; 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:0000269|PubMed:12176993, ECO:0000269|PubMed:21240271}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38992; CC Evidence={ECO:0000305|PubMed:12176993, ECO:0000305|PubMed:21240271}; 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:0000269|PubMed:14500380}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38920; CC Evidence={ECO:0000305|PubMed:14500380}; 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:0000269|PubMed:12176993, ECO:0000269|PubMed:14500380}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38916; CC Evidence={ECO:0000305|PubMed:12176993, ECO:0000305|PubMed:14500380}; 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:0000269|PubMed:12176993, ECO:0000269|PubMed:21240271}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38984; CC Evidence={ECO:0000305|PubMed:12176993, ECO:0000305|PubMed:21240271}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41132; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993, ECO:0000269|PubMed:21240271}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38976; CC Evidence={ECO:0000305|PubMed:12176993, ECO:0000305|PubMed:21240271}; 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:0000269|PubMed:12176993, ECO:0000269|PubMed:21240271}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38980; CC Evidence={ECO:0000305|PubMed:12176993, ECO:0000305|PubMed:21240271}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41136; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41140; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41144; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41401; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41417; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41413; CC Evidence={ECO:0000305|PubMed:12176993}; 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:0000269|PubMed:12176993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41589; CC Evidence={ECO:0000305|PubMed:12176993}; 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:26371182, ECO:0000269|PubMed:27754931, CC ECO:0000269|PubMed:28414242}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:26371182, CC ECO:0000269|PubMed:27754931, ECO:0000269|PubMed:28414242}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, CC ECO:0000269|PubMed:28414242}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:26371182, CC ECO:0000269|PubMed:27754931, ECO:0000269|PubMed:28414242}; CC -!- ACTIVITY REGULATION: Inhibited by lysophosphatidic acid (LPA) and CC sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA (Probable). CC {ECO:0000305|PubMed:15769751, ECO:0000305|PubMed:18175805, CC ECO:0000305|PubMed:21240271}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.5 mM for 16:0-LPC (at pH 8.5) {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805}; CC KM=5.5 mM for pNP-TMP (at pH 8.5) {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805}; CC KM=11.3 mM for pNppp (isoform 1) {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805}; CC KM=5.7 mM for pNppp (isoform 2) {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805}; CC KM=19.8 mM for pNppp (isoform 3) {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805}; CC KM=96 uM for sn-1 lyso-PAF {ECO:0000269|PubMed:21393252}; CC KM=51 uM for sn-2 lyso-PAF {ECO:0000269|PubMed:21393252}; CC KM=0.1 mM for lysophosphatidylcholine {ECO:0000269|PubMed:14500380}; CC KM=0.23 mM for sphingosylphosphorylcholine CC {ECO:0000269|PubMed:14500380}; CC Vmax=1.9 nmol/min/ug enzyme with pNppp as substrate (isoform 1) CC {ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:18175805}; CC Vmax=0.67 nmol/min/ug enzyme with pNppp as substrate (isoform 2) CC {ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:18175805}; CC Vmax=1.6 nmol/min/ug enzyme with pNppp as substrate (isoform 3) CC {ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:18175805}; CC Vmax=0.11 umol/min/mg enzyme with sn-1 lyso-PAF as substrate CC {ECO:0000269|PubMed:21393252}; CC Vmax=0.025 umol/min/mg enzyme with sn-2 lyso-PAF as substrate CC {ECO:0000269|PubMed:21393252}; CC Vmax=11.8 nmol/min/ug enzyme with lysophosphatidylcholine as CC substrate {ECO:0000269|PubMed:14500380}; CC Vmax=6.1 nmol/min/ug enzyme with sphingosylphosphorylcholine as CC substrate {ECO:0000269|PubMed:14500380}; CC pH dependence: CC Optimum pH is 9.0 (isoform 1), 8.0 (isoform 3). Isoform 1 is less CC sensitive to pH. Isoform 1, isoform 2 and isoform 3 all retain some CC activity at pH 9.5. {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805}; CC Temperature dependence: CC Isoform 1 and isoform 3 are active from 45 to 60 degrees Celsius. CC {ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:18175805}; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, CC ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=ATXter, Beta; CC IsoId=Q13822-1; Sequence=Displayed; CC Name=2; Synonyms=ATXmel, Alpha; CC IsoId=Q13822-2; Sequence=VSP_006750; CC Name=3; Synonyms=Gamma; CC IsoId=Q13822-3; Sequence=VSP_036398; CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level) CC (PubMed:12176993, PubMed:26371182). Predominantly expressed in brain, CC placenta, ovary, and small intestine. Expressed in a number of CC carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma CC and non-small-cell lung cancer. Expressed in body fluids such as CC plasma, cerebral spinal fluid (CSF), saliva, follicular and amniotic CC fluids. Not detected in leukocytes. Isoform 1 is more highly expressed CC in peripheral tissues than in the central nervous system (CNS). CC Adipocytes only express isoform 1. Isoform 3 is more highly expressed CC in the brain than in peripheral tissues. {ECO:0000269|PubMed:12176993, CC ECO:0000269|PubMed:18175805, ECO:0000269|PubMed:26371182, CC ECO:0000269|PubMed:8579579, ECO:0000269|PubMed:8586446}. CC -!- INDUCTION: Up-regulated in massively obese subjects with glucose CC intolerance, and during adipogenesis. {ECO:0000269|PubMed:15700135}. CC -!- PTM: N-glycosylation, but not furin-cleavage, plays a critical role on CC secretion and on lysoPLD activity. {ECO:0000250|UniProtKB:Q9R1E6}. CC -!- PTM: The interdomain disulfide bond between Cys-414 and Cys-806 is CC essential for catalytic activity. {ECO:0000250|UniProtKB:Q9R1E6}. CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40455/ENPP2"; 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; L35594; AAA64785.1; -; mRNA. DR EMBL; D45421; BAA08260.1; -; mRNA. DR EMBL; D45914; BAA08342.1; -; Genomic_DNA. DR EMBL; L46720; AAB00855.1; -; mRNA. DR EMBL; EU131011; ABW38316.2; -; mRNA. DR EMBL; AC099818; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC107960; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034961; AAH34961.1; -; mRNA. DR CCDS; CCDS34936.1; -. [Q13822-1] DR CCDS; CCDS47914.1; -. [Q13822-3] DR CCDS; CCDS6329.1; -. [Q13822-2] DR PIR; A55144; A55144. DR RefSeq; NP_001035181.1; NM_001040092.2. [Q13822-1] DR RefSeq; NP_001124335.1; NM_001130863.2. [Q13822-3] DR RefSeq; NP_006200.3; NM_006209.4. [Q13822-2] DR PDB; 4ZG6; X-ray; 1.80 A; A/B=17-863. DR PDB; 4ZG7; X-ray; 1.75 A; A=55-860. DR PDB; 4ZG9; X-ray; 2.95 A; A/B=1-863. DR PDB; 4ZGA; X-ray; 2.60 A; A=1-863. DR PDB; 5KXA; X-ray; 2.59 A; A=1-863. DR PDB; 5M7M; X-ray; 2.70 A; A=1-863. DR PDB; 5MHP; X-ray; 2.43 A; A=1-863. DR PDB; 8C3O; X-ray; 2.47 A; A/B=1-863. DR PDB; 8C3P; X-ray; 2.38 A; A/B=1-863. DR PDBsum; 4ZG6; -. DR PDBsum; 4ZG7; -. DR PDBsum; 4ZG9; -. DR PDBsum; 4ZGA; -. DR PDBsum; 5KXA; -. DR PDBsum; 5M7M; -. DR PDBsum; 5MHP; -. DR PDBsum; 8C3O; -. DR PDBsum; 8C3P; -. DR AlphaFoldDB; Q13822; -. DR SMR; Q13822; -. DR BioGRID; 111194; 4. DR IntAct; Q13822; 5. DR MINT; Q13822; -. DR STRING; 9606.ENSP00000259486; -. DR BindingDB; Q13822; -. DR ChEMBL; CHEMBL3691; -. DR DrugCentral; Q13822; -. DR GuidetoPHARMACOLOGY; 2901; -. DR SwissLipids; SLP:000000393; -. DR SwissLipids; SLP:000000641; -. [Q13822-1] DR GlyConnect; 1197; 4 N-Linked glycans (1 site). DR GlyCosmos; Q13822; 4 sites, 4 glycans. DR GlyGen; Q13822; 5 sites, 4 N-linked glycans (1 site). DR iPTMnet; Q13822; -. DR PhosphoSitePlus; Q13822; -. DR BioMuta; ENPP2; -. DR DMDM; 290457674; -. DR jPOST; Q13822; -. DR MassIVE; Q13822; -. DR PaxDb; 9606-ENSP00000259486; -. DR PeptideAtlas; Q13822; -. DR ProteomicsDB; 20576; -. DR ProteomicsDB; 59692; -. [Q13822-1] DR ProteomicsDB; 59693; -. [Q13822-2] DR ProteomicsDB; 59694; -. [Q13822-3] DR Antibodypedia; 13653; 564 antibodies from 39 providers. DR DNASU; 5168; -. DR Ensembl; ENST00000075322.11; ENSP00000075322.6; ENSG00000136960.13. [Q13822-1] DR Ensembl; ENST00000259486.10; ENSP00000259486.6; ENSG00000136960.13. [Q13822-2] DR Ensembl; ENST00000522826.5; ENSP00000428291.1; ENSG00000136960.13. [Q13822-3] DR GeneID; 5168; -. DR KEGG; hsa:5168; -. DR MANE-Select; ENST00000075322.11; ENSP00000075322.6; NM_001040092.3; NP_001035181.1. DR UCSC; uc003yos.3; human. [Q13822-1] DR AGR; HGNC:3357; -. DR CTD; 5168; -. DR DisGeNET; 5168; -. DR GeneCards; ENPP2; -. DR HGNC; HGNC:3357; ENPP2. DR HPA; ENSG00000136960; Tissue enriched (choroid). DR MIM; 601060; gene. DR neXtProt; NX_Q13822; -. DR OpenTargets; ENSG00000136960; -. DR PharmGKB; PA27792; -. DR VEuPathDB; HostDB:ENSG00000136960; -. DR eggNOG; KOG2645; Eukaryota. DR GeneTree; ENSGT00940000155778; -. DR HOGENOM; CLU_012256_0_0_1; -. DR InParanoid; Q13822; -. DR OMA; EEIHLMV; -. DR OrthoDB; 1366859at2759; -. DR PhylomeDB; Q13822; -. DR TreeFam; TF330032; -. DR BioCyc; MetaCyc:HS06258-MONOMER; -. DR BRENDA; 3.1.4.39; 2681. DR PathwayCommons; Q13822; -. DR Reactome; R-HSA-199220; Vitamin B5 (pantothenate) metabolism. DR SABIO-RK; Q13822; -. DR SignaLink; Q13822; -. DR BioGRID-ORCS; 5168; 17 hits in 1154 CRISPR screens. DR ChiTaRS; ENPP2; human. DR GeneWiki; Autotaxin; -. DR GenomeRNAi; 5168; -. DR Pharos; Q13822; Tchem. DR PRO; PR:Q13822; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q13822; Protein. DR Bgee; ENSG00000136960; Expressed in pigmented layer of retina and 208 other cell types or tissues. DR ExpressionAtlas; Q13822; baseline and differential. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0047391; F:alkylglycerophosphoethanolamine phosphodiesterase activity; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0016787; F:hydrolase activity; TAS:UniProtKB. DR GO; GO:0004622; F:lysophospholipase activity; IDA:UniProtKB. DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro. DR GO; GO:0004528; F:phosphodiesterase I activity; IBA:GO_Central. 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:0048870; P:cell motility; TAS:UniProtKB. DR GO; GO:0006935; P:chemotaxis; NAS:UniProtKB. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0034638; P:phosphatidylcholine catabolic process; IDA:UniProtKB. DR GO; GO:0009395; P:phospholipid catabolic process; IDA:UniProtKB. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:UniProtKB. DR GO; GO:2000394; P:positive regulation of lamellipodium morphogenesis; IGI:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; IDA:UniProtKB. DR GO; GO:0030149; P:sphingolipid catabolic process; IDA:UniProtKB. 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:SF21; ECTONUCLEOTIDE PYROPHOSPHATASE_PHOSPHODIESTERASE FAMILY MEMBER 2; 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. DR Genevisible; Q13822; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Chemotaxis; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Hydrolase; Lipid degradation; KW Lipid metabolism; Metal-binding; Obesity; Reference proteome; Repeat; KW 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:0000269|PubMed:12176993, FT ECO:0000269|PubMed:18175805" FT /id="PRO_0000281649" FT CHAIN 36..863 FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase FT family member 2" FT /id="PRO_0000188567" FT DOMAIN 55..98 FT /note="SMB 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350" FT DOMAIN 99..143 FT /note="SMB 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350" FT REGION 830..851 FT /note="Required for secretion" FT /evidence="ECO:0000250" FT MOTIF 127..129 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT ACT_SITE 210 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:Q9R1E6" FT BINDING 172 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:5KXA" FT BINDING 210 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:5KXA" FT BINDING 211..214 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9R1E6" FT BINDING 231 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:26371182, FT ECO:0007744|PDB:4ZG7" FT BINDING 244..255 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9R1E6" FT BINDING 307 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9R1E6" FT BINDING 312 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0007744|PDB:4ZG6, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:4ZGA" FT BINDING 316 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0007744|PDB:4ZG6, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:4ZGA" 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:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:5KXA" FT BINDING 360 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:5KXA" FT BINDING 475 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0007744|PDB:4ZG6, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:4ZGA" FT BINDING 740 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA" FT BINDING 742 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA" FT BINDING 744 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0007744|PDB:4ZG6, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:4ZGA" FT BINDING 746 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA" FT BINDING 748 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0000269|PubMed:27754931, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA" FT SITE 853 FT /note="Essential for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:Q9R1E6" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 411 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 525 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:26371182, FT ECO:0007744|PDB:4ZG6, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:4ZGA" FT CARBOHYD 807 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 59..76 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 63..94 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 74..87 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 80..86 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 103..120 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 108..138 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 118..131 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 124..130 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 149..195 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 157..351 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 367..469 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:4ZG9, ECO:0007744|PDB:5M7M" FT DISULFID 414..806 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 567..667 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 569..652 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG7, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT DISULFID 775..785 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:26371182, ECO:0007744|PDB:4ZG6, FT ECO:0007744|PDB:4ZG7, ECO:0007744|PDB:4ZG9, FT ECO:0007744|PDB:4ZGA, ECO:0007744|PDB:5KXA, FT ECO:0007744|PDB:5M7M, ECO:0007744|PDB:5MHP" FT VAR_SEQ 324 FT /note="E -> EESSYGSPFTPAKRPKRKVAPKRRQERPVAPPKKRRRKIHRMDHYAA FT ETRQDK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18175805, FT ECO:0000303|PubMed:7982964" FT /id="VSP_006750" FT VAR_SEQ 593 FT /note="E -> EAETRKFRGSRNENKENINGNFEPRK (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18175805" FT /id="VSP_036398" FT VARIANT 493 FT /note="S -> P (in dbSNP:rs10283100)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, FT ECO:0000269|PubMed:18175805, ECO:0000269|PubMed:7982964, FT ECO:0000269|PubMed:8579579, ECO:0000269|PubMed:8586446" FT /id="VAR_060469" FT VARIANT 577 FT /note="N -> S (in dbSNP:rs2289886)" FT /id="VAR_057472" FT VARIANT 726 FT /note="S -> L (in dbSNP:rs16892767)" FT /id="VAR_057473" FT MUTAGEN 170 FT /note="S->E: Reduces lysophospholipase activity by about FT 70%." FT MUTAGEN 210 FT /note="T->A: Loss of lysophospholipase activity and ability FT to hydrolyze sphingosylphosphorylcholine." FT /evidence="ECO:0000269|PubMed:14500380, FT ECO:0000269|PubMed:21240271" FT MUTAGEN 211 FT /note="F->Y: Reduces lysophospholipase activity by about FT 70%." FT /evidence="ECO:0000269|PubMed:21240271" FT MUTAGEN 218 FT /note="A->V: Reduces lysophospholipase activity by about FT 50%." FT /evidence="ECO:0000269|PubMed:21240271" FT MUTAGEN 231 FT /note="N->A: Strongly reduced lysophospholipase activity." FT /evidence="ECO:0000269|PubMed:21240271" FT MUTAGEN 307 FT /note="Y->Q: Reduces lysophospholipase activity by about FT 70%." FT /evidence="ECO:0000269|PubMed:21240271" FT MUTAGEN 316 FT /note="H->Q: Loss of ability to hydrolyze FT sphingosylphosphorylcholine." FT /evidence="ECO:0000269|PubMed:14500380" FT MUTAGEN 360 FT /note="H->Q: Loss of ability to hydrolyze FT sphingosylphosphorylcholine." FT /evidence="ECO:0000269|PubMed:14500380" FT CONFLICT 23 FT /note="N -> S (in Ref. 1; AAA64785 and 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT 73 FT /note="D -> H (in Ref. 2; BAA08260)" FT /evidence="ECO:0000305" FT CONFLICT 100 FT /note="G -> A (in Ref. 3; AAB00855)" FT /evidence="ECO:0000305" FT CONFLICT 291 FT /note="Q -> R (in Ref. 1; AAA64785 and 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT 349 FT /note="H -> R (in Ref. 1; AAA64785 and 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT 457 FT /note="K -> P (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 501 FT /note="V -> S (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 508 FT /note="E -> N (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 554 FT /note="P -> L (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 629 FT /note="P -> L (in Ref. 1; AAA64785 and 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT 644 FT /note="S -> R (in Ref. 2; BAA08260)" FT /evidence="ECO:0000305" FT CONFLICT 703 FT /note="V -> A (in Ref. 2; BAA08260)" FT /evidence="ECO:0000305" FT CONFLICT 769 FT /note="Y -> H (in Ref. 2; BAA08260)" FT /evidence="ECO:0000305" FT TURN 60..64 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 80..83 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 90..94 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 99..101 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 105..107 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 116..119 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 121..123 FT /evidence="ECO:0007829|PDB:4ZG9" FT HELIX 124..127 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 134..138 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 144..146 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 166..172 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 176..181 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 182..185 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 187..195 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 210..219 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 223..226 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 230..235 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 236..239 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 244..247 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 252..254 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:4ZG9" FT HELIX 260..266 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:4ZGA" FT HELIX 282..292 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 297..299 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 302..311 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 312..318 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 326..345 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 349..351 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 353..359 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 369..372 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 373..375 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 380..382 FT /evidence="ECO:0007829|PDB:4ZG6" FT STRAND 383..386 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 388..399 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 405..412 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 413..416 FT /evidence="ECO:0007829|PDB:5M7M" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 426..428 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 431..433 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 443..448 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 453..457 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 472..474 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 482..484 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 488..492 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 497..500 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 506..508 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 509..516 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 528..531 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 532..534 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 535..537 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 560..562 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 593..596 FT /evidence="ECO:0007829|PDB:4ZG6" FT STRAND 610..614 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 619..623 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 624..627 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 628..636 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 647..649 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 661..663 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 667..672 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 677..682 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 684..686 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 690..692 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 693..696 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 699..701 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 702..705 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 707..718 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 720..728 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 730..738 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 744..746 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 750..752 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 766..777 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 782..784 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 789..797 FT /evidence="ECO:0007829|PDB:4ZG7" FT TURN 806..809 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 812..814 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 816..822 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 827..834 FT /evidence="ECO:0007829|PDB:4ZG7" FT STRAND 841..844 FT /evidence="ECO:0007829|PDB:4ZG7" FT HELIX 846..854 FT /evidence="ECO:0007829|PDB:4ZG7" FT CONFLICT Q13822-3:23 FT /note="N -> S (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT Q13822-3:291 FT /note="Q -> R (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT Q13822-3:349 FT /note="H -> R (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT Q13822-3:493 FT /note="S -> P (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT Q13822-3:599 FT /note="F -> Y (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT Q13822-3:602 FT /note="S -> T (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" FT CONFLICT Q13822-3:654 FT /note="P -> L (in Ref. 5; ABW38316)" FT /evidence="ECO:0000305" SQ SEQUENCE 863 AA; 98994 MW; 94A7A2B3701F0993 CRC64; MARRSSFQSC QIISLFTFAV GVNICLGFTA HRIKRAEGWE EGPPTVLSDS PWTNISGSCK GRCFELQEAG PPDCRCDNLC KSYTSCCHDF DELCLKTARG WECTKDRCGE VRNEENACHC SEDCLARGDC CTNYQVVCKG ESHWVDDDCE EIKAAECPAG FVRPPLIIFS VDGFRASYMK KGSKVMPNIE KLRSCGTHSP YMRPVYPTKT FPNLYTLATG LYPESHGIVG NSMYDPVFDA TFHLRGREKF NHRWWGGQPL WITATKQGVK AGTFFWSVVI PHERRILTIL QWLTLPDHER PSVYAFYSEQ PDFSGHKYGP FGPEMTNPLR EIDKIVGQLM DGLKQLKLHR CVNVIFVGDH GMEDVTCDRT EFLSNYLTNV DDITLVPGTL GRIRSKFSNN AKYDPKAIIA NLTCKKPDQH FKPYLKQHLP KRLHYANNRR IEDIHLLVER RWHVARKPLD VYKKPSGKCF FQGDHGFDNK VNSMQTVFVG YGSTFKYKTK VPPFENIELY NVMCDLLGLK PAPNNGTHGS LNHLLRTNTF RPTMPEEVTR PNYPGIMYLQ SDFDLGCTCD DKVEPKNKLD ELNKRLHTKG STEERHLLYG RPAVLYRTRY DILYHTDFES GYSEIFLMPL WTSYTVSKQA EVSSVPDHLT SCVRPDVRVS PSFSQNCLAY KNDKQMSYGF LFPPYLSSSP EAKYDAFLVT NMVPMYPAFK RVWNYFQRVL VKKYASERNG VNVISGPIFD YDYDGLHDTE DKIKQYVEGS SIPVPTHYYS IITSCLDFTQ PADKCDGPLS VSSFILPHRP DNEESCNSSE DESKWVEELM KMHTARVRDI EHLTSLDFFR KTSRSYPEIL TLKTYLHTYE SEI //