HYES_HUMAN
ID HYES_HUMAN Reviewed; 555 AA.
AC P34913; B2Z3B1; B3KTU8; B3KUA0; G3V134; J3KPH7; Q16764; Q9HBJ1; Q9HBJ2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Bifunctional epoxide hydrolase 2 {ECO:0000305};
DE Includes:
DE RecName: Full=Cytosolic epoxide hydrolase 2;
DE Short=CEH;
DE EC=3.3.2.10 {ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:12869654, ECO:0000269|PubMed:15196990, ECO:0000269|PubMed:22798687};
DE AltName: Full=Epoxide hydratase;
DE AltName: Full=Soluble epoxide hydrolase {ECO:0000303|PubMed:21217101, ECO:0000303|PubMed:22217705};
DE Short=SEH {ECO:0000303|PubMed:21217101, ECO:0000303|PubMed:22217705};
DE Includes:
DE RecName: Full=Lipid-phosphate phosphatase;
DE EC=3.1.3.76 {ECO:0000269|PubMed:12574508, ECO:0000269|PubMed:12574510};
GN Name=EPHX2 {ECO:0000312|HGNC:HGNC:3402};
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 [GENOMIC DNA / MRNA] (ISOFORM 1), PARTIAL PROTEIN
RP SEQUENCE, AND VARIANT GLN-287.
RC TISSUE=Liver;
RX PubMed=8342951; DOI=10.1006/abbi.1993.1411;
RA Beetham J.K., Tian T., Hammock B.D.;
RT "cDNA cloning and expression of a soluble epoxide hydrolase from human
RT liver.";
RL Arch. Biochem. Biophys. 305:197-201(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=8619856; DOI=10.1006/bbrc.1996.0596;
RA Sandberg M., Meijer J.;
RT "Structural characterization of the human soluble epoxide hydrolase gene
RT (EPHX2).";
RL Biochem. Biophys. Res. Commun. 221:333-339(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS GLN-287 AND ARG-403
RP INS.
RC TISSUE=Liver;
RX PubMed=10862610; DOI=10.1074/jbc.m001153200;
RA Sandberg M., Hassett C., Adman E.T., Meijer J., Omiecinski C.J.;
RT "Identification and functional characterization of human soluble epoxide
RT hydrolase genetic polymorphisms.";
RL J. Biol. Chem. 275:28873-28881(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ARG-403 INS.
RC TISSUE=Kidney, and Prostate;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-21; GLN-52; ARG-55;
RP CYS-103; TYR-154; LEU-225; GLN-287; VAL-369 AND GLY-470.
RG NIEHS SNPs program;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=B-cell, and Lung;
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 [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS ARG-55;
RP CYS-103; TYR-154; GLN-287 AND GLY-470.
RX PubMed=12869654; DOI=10.1124/mol.64.2.482;
RA Przybyla-Zawislak B.D., Srivastava P.K., Vazquez-Matias J.,
RA Mohrenweiser H.W., Maxwell J.E., Hammock B.D., Bradbury J.A.,
RA Enayetallah A.E., Zeldin D.C., Grant D.F.;
RT "Polymorphisms in human soluble epoxide hydrolase.";
RL Mol. Pharmacol. 64:482-490(2003).
RN [11]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION AS PHOSPHATASE,
RP AND MUTAGENESIS OF ASP-9.
RX PubMed=12574508; DOI=10.1073/pnas.0437829100;
RA Cronin A., Mowbray S., Durk H., Homburg S., Fleming I., Fisslthaler B.,
RA Oesch F., Arand M.;
RT "The N-terminal domain of mammalian soluble epoxide hydrolase is a
RT phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1552-1557(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, FUNCTION AS LIPID PHOSPHATASE, COFACTOR, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12574510; DOI=10.1073/pnas.0437724100;
RA Newman J.W., Morisseau C., Harris T.R., Hammock B.D.;
RT "The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme
RT with novel lipid phosphate phosphatase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1558-1563(2003).
RN [13]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF
RP VARIANTS ARG-55; CYS-103; TYR-154; GLN-287 AND GLY-470.
RX PubMed=15196990; DOI=10.1016/j.abb.2004.05.003;
RA Srivastava P.K., Sharma V.K., Kalonia D.S., Grant D.F.;
RT "Polymorphisms in human soluble epoxide hydrolase: effects on enzyme
RT activity, enzyme stability, and quaternary structure.";
RL Arch. Biochem. Biophys. 427:164-169(2004).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-43, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP LIPIDATION AT CYS-522, AND MUTAGENESIS OF CYS-522.
RX PubMed=21164107; DOI=10.1161/circresaha.110.235879;
RA Charles R.L., Burgoyne J.R., Mayr M., Weldon S.M., Hubner N., Dong H.,
RA Morisseau C., Hammock B.D., Landar A., Eaton P.;
RT "Redox regulation of soluble epoxide hydrolase by 15-deoxy-delta-
RT prostaglandin J2 controls coronary hypoxic vasodilation.";
RL Circ. Res. 108:324-334(2011).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=21217101; DOI=10.1194/jlr.m009639;
RA Cronin A., Decker M., Arand M.;
RT "Mammalian soluble epoxide hydrolase is identical to liver hepoxilin
RT hydrolase.";
RL J. Lipid Res. 52:712-719(2011).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=22387545; DOI=10.1016/j.bbrc.2012.02.108;
RA Morisseau C., Schebb N.H., Dong H., Ulu A., Aronov P.A., Hammock B.D.;
RT "Role of soluble epoxide hydrolase phosphatase activity in the metabolism
RT of lysophosphatidic acids.";
RL Biochem. Biophys. Res. Commun. 419:796-800(2012).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF ASP-9.
RX PubMed=22217705; DOI=10.1194/jlr.m022319;
RA Oguro A., Imaoka S.;
RT "Lysophosphatidic acids are new substrates for the phosphatase domain of
RT soluble epoxide hydrolase.";
RL J. Lipid Res. 53:505-512(2012).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=22798687; DOI=10.1194/jlr.m024448;
RA Decker M., Adamska M., Cronin A., Di Giallonardo F., Burgener J.,
RA Marowsky A., Falck J.R., Morisseau C., Hammock B.D., Gruzdev A.,
RA Zeldin D.C., Arand M.;
RT "EH3 (ABHD9): the first member of a new epoxide hydrolase family with high
RT activity for fatty acid epoxides.";
RL J. Lipid Res. 53:2038-2045(2012).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH PHOSPHATE; MAGNESIUM
RP AND EPOXIDE HYDROLASE INHIBITOR, AND ACTIVE SITE.
RX PubMed=15096040; DOI=10.1021/bi036189j;
RA Gomez G.A., Morisseau C., Hammock B.D., Christianson D.W.;
RT "Structure of human epoxide hydrolase reveals mechanistic inferences on
RT bifunctional catalysis in epoxide and phosphate ester hydrolysis.";
RL Biochemistry 43:4716-4723(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH DIALKYLUREA
RP INHIBITORS AND MAGNESIUM, AND ACTIVE SITE.
RX PubMed=16322563; DOI=10.1110/ps.051720206;
RA Gomez G.A., Morisseau C., Hammock B.D., Christianson D.W.;
RT "Human soluble epoxide hydrolase: structural basis of inhibition by 4-(3-
RT cyclohexylureido)-carboxylic acids.";
RL Protein Sci. 15:58-64(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEXES WITH ARYLAMIDE
RP INHIBITORS, AND ACTIVE SITE.
RX PubMed=19746975; DOI=10.1021/jm9005302;
RA Eldrup A.B., Soleymanzadeh F., Taylor S.J., Muegge I., Farrow N.A.,
RA Joseph D., McKellop K., Man C.C., Kukulka A., De Lombaert S.;
RT "Structure-based optimization of arylamides as inhibitors of soluble
RT epoxide hydrolase.";
RL J. Med. Chem. 52:5880-5895(2009).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR,
RP AND ACTIVE SITE.
RX PubMed=19969453; DOI=10.1016/j.bmcl.2009.11.091;
RA Eldrup A.B., Soleymanzadeh F., Farrow N.A., Kukulka A., De Lombaert S.;
RT "Optimization of piperidyl-ureas as inhibitors of soluble epoxide
RT hydrolase.";
RL Bioorg. Med. Chem. Lett. 20:571-575(2010).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR,
RP AND ACTIVE SITE.
RX PubMed=20934334; DOI=10.1016/j.bmcl.2010.09.095;
RA Lo H.Y., Man C.C., Fleck R.W., Farrow N.A., Ingraham R.H., Kukulka A.,
RA Proudfoot J.R., Betageri R., Kirrane T., Patel U., Sharma R.,
RA Hoermann M.A., Kabcenell A., Lombaert S.D.;
RT "Substituted pyrazoles as novel sEH antagonist: investigation of key
RT binding interactions within the catalytic domain.";
RL Bioorg. Med. Chem. Lett. 20:6379-6383(2010).
CC -!- FUNCTION: Bifunctional enzyme (PubMed:12574510). The C-terminal domain
CC has epoxide hydrolase activity and acts on epoxides (alkene oxides,
CC oxiranes) and arene oxides (PubMed:12869654, PubMed:12574510,
CC PubMed:22798687). Plays a role in xenobiotic metabolism by degrading
CC potentially toxic epoxides (By similarity). Also determines steady-
CC state levels of physiological mediators (PubMed:12869654,
CC PubMed:12574510, PubMed:22798687, PubMed:21217101).
CC {ECO:0000250|UniProtKB:P80299, ECO:0000269|PubMed:12574508,
CC ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:12869654,
CC ECO:0000269|PubMed:21217101, ECO:0000269|PubMed:22798687}.
CC -!- FUNCTION: Bifunctional enzyme (PubMed:12574510). The N-terminal domain
CC has lipid phosphatase activity, with the highest activity towards
CC threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-
CC 9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-
CC 9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic acid
CC (PubMed:12574510). Has phosphatase activity toward lyso-
CC glycerophospholipids with also some lower activity toward lysolipids of
CC sphingolipid and isoprenoid phosphates (PubMed:22217705,
CC PubMed:22387545). {ECO:0000269|PubMed:12574510,
CC ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an epoxide + H2O = an ethanediol; Xref=Rhea:RHEA:19037,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32955, ChEBI:CHEBI:140594;
CC EC=3.3.2.10; Evidence={ECO:0000269|PubMed:12574510,
CC ECO:0000269|PubMed:12869654, ECO:0000269|PubMed:22798687};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9S,10S)-10-hydroxy-9-(phosphooxy)octadecanoate + H2O =
CC (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate;
CC Xref=Rhea:RHEA:16537, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58796, ChEBI:CHEBI:58797; EC=3.1.3.76;
CC Evidence={ECO:0000269|PubMed:12574508, ECO:0000269|PubMed:12574510,
CC ECO:0000269|PubMed:15196990};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-phosphooxy-(9Z)-octadecenoate + H2O = 12-hydroxy-(9Z)-
CC octadecenoate + phosphate; Xref=Rhea:RHEA:45272, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:85141, ChEBI:CHEBI:85150;
CC Evidence={ECO:0000269|PubMed:12574510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45273;
CC Evidence={ECO:0000269|PubMed:12574510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-phosphooxy-(9E)-octadecenoate + H2O = 12-hydroxy-(9E)-
CC octadecenoate + phosphate; Xref=Rhea:RHEA:45276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:85137, ChEBI:CHEBI:85152;
CC Evidence={ECO:0000269|PubMed:12574510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45277;
CC Evidence={ECO:0000269|PubMed:12574510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-(phosphooxy)octadecanoate + H2O = 12-hydroxyoctadecanoate +
CC phosphate; Xref=Rhea:RHEA:45280, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84201, ChEBI:CHEBI:85134;
CC Evidence={ECO:0000269|PubMed:12574510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45281;
CC Evidence={ECO:0000269|PubMed:12574510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = 8,9-dihydroxy-
CC (5Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:44048,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:84025, ChEBI:CHEBI:84032;
CC Evidence={ECO:0000269|PubMed:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049;
CC Evidence={ECO:0000305|PubMed:22798687};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = 11,12-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:44044,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:76625, ChEBI:CHEBI:84031;
CC Evidence={ECO:0000269|PubMed:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045;
CC Evidence={ECO:0000305|PubMed:22798687};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = 14,15-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:44040,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:84024, ChEBI:CHEBI:84029;
CC Evidence={ECO:0000269|PubMed:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44041;
CC Evidence={ECO:0000305|PubMed:22798687};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9,10-epoxy-(12Z)-octadecenoate + H2O = 9,10-dihydroxy-(12Z)-
CC octadecenoate; Xref=Rhea:RHEA:44032, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:84023, ChEBI:CHEBI:84027;
CC Evidence={ECO:0000269|PubMed:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44033;
CC Evidence={ECO:0000305|PubMed:22798687};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate + H2O =
CC (8,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50896, ChEBI:CHEBI:15377, ChEBI:CHEBI:78100,
CC ChEBI:CHEBI:132127; Evidence={ECO:0000269|PubMed:21217101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50897;
CC Evidence={ECO:0000269|PubMed:21217101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate + H2O
CC = (10,11S,12R)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50900, ChEBI:CHEBI:15377, ChEBI:CHEBI:78084,
CC ChEBI:CHEBI:78099; Evidence={ECO:0000269|PubMed:21217101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50901;
CC Evidence={ECO:0000269|PubMed:21217101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycerol 3-phosphate + H2O = 1-
CC tetradecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:53592,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72683,
CC ChEBI:CHEBI:75536; Evidence={ECO:0000269|PubMed:22387545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53593;
CC Evidence={ECO:0000269|PubMed:22387545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-sn-glycero-3-phosphate + H2O = 1-octadecanoyl-
CC sn-glycerol + phosphate; Xref=Rhea:RHEA:53596, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:74565, ChEBI:CHEBI:75550;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53597;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:53600, ChEBI:CHEBI:15377, ChEBI:CHEBI:34071,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:74938;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53601;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-
CC sn-glycerol + phosphate; Xref=Rhea:RHEA:53604, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57518, ChEBI:CHEBI:75542;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53605;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544,
CC ChEBI:CHEBI:75757; Evidence={ECO:0000269|PubMed:22217705,
CC ECO:0000269|PubMed:22387545};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836;
CC Evidence={ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8S,9S)-
CC dihydroxy-(5Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53972,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131974, ChEBI:CHEBI:138002;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53973;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53980,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131969, ChEBI:CHEBI:138004;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53981;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53984,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131969, ChEBI:CHEBI:138005;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53985;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53992,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131964, ChEBI:CHEBI:138003;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53993;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14S,15S)-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53996,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131964, ChEBI:CHEBI:138006;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53997;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:54004,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131970, ChEBI:CHEBI:138005;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54005;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:54000,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131970, ChEBI:CHEBI:138004;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54001;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8R,9R)-
CC dihydroxy-(5Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:54016,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131974, ChEBI:CHEBI:138008;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54017;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53976,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131965, ChEBI:CHEBI:138003;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53977;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:15096040,
CC ECO:0000269|PubMed:16322563};
CC -!- ACTIVITY REGULATION: Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-
CC (trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea
CC (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S,
CC 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU),
CC N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S,
CC 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-
CC (((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-
CC yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-
CC (4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB)
CC and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)
CC octanoic acid (AUOA). Phosphatase activity is inhibited by dodecyl-
CC phosphate, phospholipids such as phospho-lysophosphatidic acids and
CC fatty acids such as palmitic acid and lauric acid (PubMed:22217705,
CC PubMed:22387545). {ECO:0000269|PubMed:21217101,
CC ECO:0000269|PubMed:22217705, ECO:0000269|PubMed:22387545,
CC ECO:0000269|PubMed:22798687}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21 uM for threo-9,10-phosphonooxy-hydroxy-octadecanoic acid
CC {ECO:0000269|PubMed:12574508, ECO:0000269|PubMed:12574510,
CC ECO:0000269|PubMed:15196990};
CC KM=1.7 uM for 8,9-EET {ECO:0000269|PubMed:22798687};
CC KM=3.4 uM for 11,12-EET {ECO:0000269|PubMed:22798687};
CC KM=15 uM for 14,15-EET {ECO:0000269|PubMed:22798687};
CC KM=1.5 uM for leukotoxin {ECO:0000269|PubMed:22798687};
CC KM=1.1 mM for p-nitrophenyl phosphate {ECO:0000269|PubMed:12574508,
CC ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:15196990};
CC KM=7.3 uM for 8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate
CC {ECO:0000269|PubMed:21217101};
CC KM=10.8 uM for 10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-
CC eicosatrienoate {ECO:0000269|PubMed:21217101};
CC KM=3 uM for palmitoyl-lysophosphatidic acid
CC {ECO:0000269|PubMed:22217705};
CC KM=6.4 uM for stearoyl-lysophosphatidic acid
CC {ECO:0000269|PubMed:22217705};
CC KM=6.2 uM for oleoyl-lysophosphatidic acid
CC {ECO:0000269|PubMed:22217705};
CC KM=5.9 uM for arachidonoyl-lysophosphatidic acid
CC {ECO:0000269|PubMed:22217705};
CC KM=5.3 uM for arachidoyl-lysophosphatidic acid
CC {ECO:0000269|PubMed:22217705};
CC KM=23.5 uM for 1-alkyl lysophosphatidic acid (C18:0)
CC {ECO:0000269|PubMed:22217705};
CC KM=14.8 uM for sphingosine-1-phosphate {ECO:0000269|PubMed:22217705};
CC KM=20.9 uM for geranylgeranyl pyrophosphate
CC {ECO:0000269|PubMed:22217705};
CC KM=10 uM for farnesyl pyro-phosphate {ECO:0000269|PubMed:22387545};
CC KM=5.1 uM for 1-myristoyl-2-hydroxy-3-glycerophosphate
CC {ECO:0000269|PubMed:22387545};
CC KM=23 uM for 1-palmityl-2-hydroxy-3-glycerophosphate
CC {ECO:0000269|PubMed:22387545};
CC KM=4.2 uM for 1-stearyl-2-hydroxy-3-glycerophosphate
CC {ECO:0000269|PubMed:22387545};
CC KM=6.9 uM for 1-oleoyl-2-hydroxy-3-glycerophosphate
CC {ECO:0000269|PubMed:22387545};
CC KM=13 uM for 1-arachidonoyl-2-hydroxy-3-glycerophosphate
CC {ECO:0000269|PubMed:22387545};
CC KM=31 uM for shingosine-1-phosphate {ECO:0000269|PubMed:22387545};
CC KM=67 uM for N-acetyl-ceramide-phosphate
CC {ECO:0000269|PubMed:22387545};
CC Vmax=338 nmol/min/mg enzyme with threo-9,10-phosphonooxy-hydroxy-
CC octadecanoic acid {ECO:0000269|PubMed:12574508,
CC ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:15196990};
CC Vmax=0.9 umol/min/mg enzyme with 8,9-EET as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=4.5 umol/min/mg enzyme with 11,12-EET as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=7 umol/min/mg enzyme with 14,15-EET as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=0.55 umol/min/mg enzyme with leukotoxin as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=5.8 nmol/min/mg enzyme with p-nitrophenyl phosphate
CC {ECO:0000269|PubMed:12574508, ECO:0000269|PubMed:12574510,
CC ECO:0000269|PubMed:15196990};
CC Vmax=385 nmol/min/mg enzyme with 8-hydroxy-(11S,12S)-epoxy-
CC (5Z,9E,14Z)-eicosatrienoate as substrate
CC {ECO:0000269|PubMed:21217101};
CC Vmax=95 nmol/min/mg enzyme with 10-hydroxy-(11S,12S)-
CC epoxy- (5Z,8Z,14Z)-eicosatrienoate as substrate
CC {ECO:0000269|PubMed:21217101};
CC Vmax=150.4 nmol/min/mg enzyme with palmitoyl-lysophosphatidic acid as
CC substrate {ECO:0000269|PubMed:22217705};
CC Vmax=193.5 nmol/min/mg enzyme with stearoyl-lysophosphatidic acid as
CC substrate {ECO:0000269|PubMed:22217705};
CC Vmax=191.6 nmol/min/mg enzyme with oleoyl-lysophosphatidic acid as
CC substrate {ECO:0000269|PubMed:22217705};
CC Vmax=157.9 nmol/min/mg enzyme with arachidonoyl-lysophosphatidic acid
CC as substrate {ECO:0000269|PubMed:22217705};
CC Vmax=26.8 nmol/min/mg enzyme with arachidoyl-lysophosphatidic acid as
CC substrate {ECO:0000269|PubMed:22217705};
CC Vmax=171.1 nmol/min/mg enzyme with 1-alkyl lysophosphatidic acid
CC (C18:0) as substrate {ECO:0000269|PubMed:22217705};
CC Vmax=60.6 nmol/min/mg enzyme with sphingosine-1-phosphate as
CC substrate {ECO:0000269|PubMed:22217705};
CC Vmax=101.3 nmol/min/mg enzyme with geranylgeranyl pyrophosphate as
CC substrate {ECO:0000269|PubMed:22217705};
CC Note=kcat are 14 sec(-1), 354 sec(-1), 167 sec(-1), 125 sec(-1), 177
CC sec(-1), 250 sec(-1), 18 sec(-1) and 136 sec(-1) for farnesyl pyro-
CC phosphate, 1-myristoyl-2-hydroxy-3-glycerophosphate, 1-palmityl-2-
CC hydroxy-3-glycerophosphate, 1-stearyl-2-hydroxy-3-glycerophosphate,
CC 1-oleoyl-2-hydroxy-3-glycerophosphate, 1-arachidonoyl-2-hydroxy-3-
CC glycerophosphate, shingosine-1-phosphate and N-acetyl-ceramide-
CC phosphate, respectively. {ECO:0000269|PubMed:22387545};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15096040,
CC ECO:0000269|PubMed:19969453, ECO:0000269|PubMed:20934334}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Peroxisome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P34913-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P34913-2; Sequence=VSP_045598;
CC Name=3;
CC IsoId=P34913-3; Sequence=VSP_045597;
CC -!- INDUCTION: By compounds that cause peroxisome proliferation such as
CC clofibrate, tiadenol and fenofibrate.
CC -!- DOMAIN: The N-terminal domain has phosphatase activity. The C-terminal
CC domain has epoxide hydrolase activity.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14-
CC prostaglandin-J2 is autocatalytic and reversible. It may occur as an
CC alternative to other cysteine modifications, such as S-nitrosylation
CC and S-palmitoylation (Probable). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide hydrolase
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ephx2/";
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DR EMBL; L05779; AAA02756.1; -; mRNA.
DR EMBL; X97024; CAA65751.1; -; Genomic_DNA.
DR EMBL; X97025; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97026; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97027; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97028; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97029; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97030; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97031; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97032; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97033; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97034; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97035; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97036; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97037; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; X97038; CAA65751.1; JOINED; Genomic_DNA.
DR EMBL; AF233334; AAG14966.1; -; mRNA.
DR EMBL; AF233335; AAG14967.1; -; mRNA.
DR EMBL; AF233336; AAG14968.1; -; mRNA.
DR EMBL; BT006885; AAP35531.1; -; mRNA.
DR EMBL; AK096089; BAG53210.1; -; mRNA.
DR EMBL; AK096770; BAG53362.1; -; mRNA.
DR EMBL; EU584434; ACD11487.1; -; Genomic_DNA.
DR EMBL; AF311103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63548.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63549.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63551.1; -; Genomic_DNA.
DR EMBL; BC007708; AAH07708.1; -; mRNA.
DR EMBL; BC011628; AAH11628.1; -; mRNA.
DR EMBL; BC013874; AAH13874.1; -; mRNA.
DR CCDS; CCDS59097.1; -. [P34913-2]
DR CCDS; CCDS59098.1; -. [P34913-3]
DR CCDS; CCDS6060.1; -. [P34913-1]
DR PIR; JC4711; JC4711.
DR RefSeq; NP_001243411.1; NM_001256482.1. [P34913-2]
DR RefSeq; NP_001243412.1; NM_001256483.1. [P34913-3]
DR RefSeq; NP_001243413.1; NM_001256484.1. [P34913-2]
DR RefSeq; NP_001970.2; NM_001979.5. [P34913-1]
DR PDB; 1S8O; X-ray; 2.60 A; A=1-555.
DR PDB; 1VJ5; X-ray; 2.35 A; A=1-555.
DR PDB; 1ZD2; X-ray; 3.00 A; P=1-555.
DR PDB; 1ZD3; X-ray; 2.30 A; A=1-555.
DR PDB; 1ZD4; X-ray; 2.70 A; A=1-555.
DR PDB; 1ZD5; X-ray; 2.60 A; A=1-555.
DR PDB; 3ANS; X-ray; 1.98 A; A/B=230-555.
DR PDB; 3ANT; X-ray; 2.40 A; A/B=230-555.
DR PDB; 3I1Y; X-ray; 2.47 A; A=1-555.
DR PDB; 3I28; X-ray; 1.95 A; A=1-555.
DR PDB; 3KOO; X-ray; 2.79 A; A=1-555.
DR PDB; 3OTQ; X-ray; 3.00 A; A=1-555.
DR PDB; 3PDC; X-ray; 2.60 A; A/B=226-548.
DR PDB; 3WK4; X-ray; 2.11 A; A=1-555.
DR PDB; 3WK5; X-ray; 2.77 A; A=1-555.
DR PDB; 3WK6; X-ray; 2.10 A; A=1-555.
DR PDB; 3WK7; X-ray; 2.20 A; A=1-555.
DR PDB; 3WK8; X-ray; 2.20 A; A=1-555.
DR PDB; 3WK9; X-ray; 2.20 A; A=1-555.
DR PDB; 3WKA; X-ray; 2.01 A; A=1-555.
DR PDB; 3WKB; X-ray; 2.20 A; A=1-555.
DR PDB; 3WKC; X-ray; 2.20 A; A=1-555.
DR PDB; 3WKD; X-ray; 2.48 A; A=1-555.
DR PDB; 3WKE; X-ray; 2.75 A; A=1-555.
DR PDB; 4C4X; X-ray; 2.17 A; A/B=230-555.
DR PDB; 4C4Y; X-ray; 2.41 A; A=230-555.
DR PDB; 4C4Z; X-ray; 2.06 A; A/B=230-555.
DR PDB; 4HAI; X-ray; 2.55 A; A=1-555.
DR PDB; 4J03; X-ray; 2.92 A; A=1-555.
DR PDB; 4JNC; X-ray; 1.96 A; A=238-549.
DR PDB; 4OCZ; X-ray; 2.94 A; A=1-555.
DR PDB; 4OD0; X-ray; 2.92 A; A=1-555.
DR PDB; 4X6X; X-ray; 1.80 A; A/B=230-555.
DR PDB; 4X6Y; X-ray; 2.10 A; A/B=230-555.
DR PDB; 4Y2J; X-ray; 2.15 A; A=1-555.
DR PDB; 4Y2P; X-ray; 2.05 A; A=1-555.
DR PDB; 4Y2Q; X-ray; 2.40 A; A=1-555.
DR PDB; 4Y2R; X-ray; 2.45 A; A=1-555.
DR PDB; 4Y2S; X-ray; 2.30 A; A=1-555.
DR PDB; 4Y2T; X-ray; 2.40 A; A=1-555.
DR PDB; 4Y2U; X-ray; 2.75 A; A=1-555.
DR PDB; 4Y2V; X-ray; 2.40 A; A=1-555.
DR PDB; 4Y2X; X-ray; 2.50 A; A=1-555.
DR PDB; 4Y2Y; X-ray; 2.30 A; A=1-555.
DR PDB; 5AHX; X-ray; 2.00 A; A=1-548.
DR PDB; 5AI0; X-ray; 1.75 A; A=1-548.
DR PDB; 5AI4; X-ray; 1.93 A; A=1-548.
DR PDB; 5AI5; X-ray; 2.28 A; A=1-548.
DR PDB; 5AI6; X-ray; 2.30 A; A=1-548.
DR PDB; 5AI8; X-ray; 1.85 A; A=1-548.
DR PDB; 5AI9; X-ray; 1.80 A; A=1-548.
DR PDB; 5AIA; X-ray; 2.26 A; A=1-548.
DR PDB; 5AIB; X-ray; 1.95 A; A=1-548.
DR PDB; 5AIC; X-ray; 1.89 A; A=1-548.
DR PDB; 5AK3; X-ray; 2.28 A; A=1-548.
DR PDB; 5AK4; X-ray; 1.79 A; A=1-548.
DR PDB; 5AK5; X-ray; 2.22 A; A=1-548.
DR PDB; 5AK6; X-ray; 2.15 A; A=1-548.
DR PDB; 5AKE; X-ray; 2.26 A; A=1-548.
DR PDB; 5AKG; X-ray; 2.51 A; A=1-548.
DR PDB; 5AKH; X-ray; 2.10 A; A=1-548.
DR PDB; 5AKI; X-ray; 1.81 A; A=1-548.
DR PDB; 5AKJ; X-ray; 2.03 A; A=1-548.
DR PDB; 5AKK; X-ray; 1.90 A; A=1-548.
DR PDB; 5AKL; X-ray; 2.00 A; A=1-548.
DR PDB; 5AKX; X-ray; 2.09 A; A=1-548.
DR PDB; 5AKY; X-ray; 2.18 A; A=1-548.
DR PDB; 5AKZ; X-ray; 2.18 A; A=1-548.
DR PDB; 5ALD; X-ray; 2.26 A; A=1-548.
DR PDB; 5ALE; X-ray; 1.95 A; A=1-548.
DR PDB; 5ALF; X-ray; 2.32 A; A=1-548.
DR PDB; 5ALG; X-ray; 2.40 A; A=1-548.
DR PDB; 5ALH; X-ray; 1.90 A; A=1-548.
DR PDB; 5ALI; X-ray; 1.85 A; A=1-548.
DR PDB; 5ALJ; X-ray; 2.10 A; A=1-548.
DR PDB; 5ALK; X-ray; 2.33 A; A=1-548.
DR PDB; 5ALL; X-ray; 2.20 A; A=1-548.
DR PDB; 5ALM; X-ray; 2.00 A; A=1-548.
DR PDB; 5ALN; X-ray; 2.00 A; A=1-548.
DR PDB; 5ALO; X-ray; 2.00 A; A=1-548.
DR PDB; 5ALP; X-ray; 2.06 A; A=1-548.
DR PDB; 5ALQ; X-ray; 2.78 A; A=1-548.
DR PDB; 5ALR; X-ray; 2.60 A; A=1-548.
DR PDB; 5ALS; X-ray; 2.57 A; A=1-548.
DR PDB; 5ALT; X-ray; 2.15 A; A=1-548.
DR PDB; 5ALU; X-ray; 1.87 A; A=1-548.
DR PDB; 5ALV; X-ray; 1.80 A; A=1-548.
DR PDB; 5ALW; X-ray; 2.20 A; A=1-548.
DR PDB; 5ALX; X-ray; 2.23 A; A=1-548.
DR PDB; 5ALY; X-ray; 1.90 A; A=1-548.
DR PDB; 5ALZ; X-ray; 2.30 A; A=1-548.
DR PDB; 5AM0; X-ray; 1.88 A; A=1-548.
DR PDB; 5AM1; X-ray; 2.15 A; A=1-548.
DR PDB; 5AM2; X-ray; 1.70 A; A=1-548.
DR PDB; 5AM3; X-ray; 2.20 A; A=1-548.
DR PDB; 5AM4; X-ray; 1.87 A; A=1-548.
DR PDB; 5AM5; X-ray; 2.26 A; A=1-548.
DR PDB; 5FP0; X-ray; 2.35 A; A=1-548.
DR PDB; 5MWA; X-ray; 1.55 A; A=2-224.
DR PDB; 6AUM; X-ray; 2.95 A; A=1-555.
DR PDB; 6I5E; X-ray; 2.60 A; A/B=230-555.
DR PDB; 6I5G; X-ray; 2.00 A; A/B=230-555.
DR PDB; 7EBA; X-ray; 2.30 A; A/B=230-555.
DR PDBsum; 1S8O; -.
DR PDBsum; 1VJ5; -.
DR PDBsum; 1ZD2; -.
DR PDBsum; 1ZD3; -.
DR PDBsum; 1ZD4; -.
DR PDBsum; 1ZD5; -.
DR PDBsum; 3ANS; -.
DR PDBsum; 3ANT; -.
DR PDBsum; 3I1Y; -.
DR PDBsum; 3I28; -.
DR PDBsum; 3KOO; -.
DR PDBsum; 3OTQ; -.
DR PDBsum; 3PDC; -.
DR PDBsum; 3WK4; -.
DR PDBsum; 3WK5; -.
DR PDBsum; 3WK6; -.
DR PDBsum; 3WK7; -.
DR PDBsum; 3WK8; -.
DR PDBsum; 3WK9; -.
DR PDBsum; 3WKA; -.
DR PDBsum; 3WKB; -.
DR PDBsum; 3WKC; -.
DR PDBsum; 3WKD; -.
DR PDBsum; 3WKE; -.
DR PDBsum; 4C4X; -.
DR PDBsum; 4C4Y; -.
DR PDBsum; 4C4Z; -.
DR PDBsum; 4HAI; -.
DR PDBsum; 4J03; -.
DR PDBsum; 4JNC; -.
DR PDBsum; 4OCZ; -.
DR PDBsum; 4OD0; -.
DR PDBsum; 4X6X; -.
DR PDBsum; 4X6Y; -.
DR PDBsum; 4Y2J; -.
DR PDBsum; 4Y2P; -.
DR PDBsum; 4Y2Q; -.
DR PDBsum; 4Y2R; -.
DR PDBsum; 4Y2S; -.
DR PDBsum; 4Y2T; -.
DR PDBsum; 4Y2U; -.
DR PDBsum; 4Y2V; -.
DR PDBsum; 4Y2X; -.
DR PDBsum; 4Y2Y; -.
DR PDBsum; 5AHX; -.
DR PDBsum; 5AI0; -.
DR PDBsum; 5AI4; -.
DR PDBsum; 5AI5; -.
DR PDBsum; 5AI6; -.
DR PDBsum; 5AI8; -.
DR PDBsum; 5AI9; -.
DR PDBsum; 5AIA; -.
DR PDBsum; 5AIB; -.
DR PDBsum; 5AIC; -.
DR PDBsum; 5AK3; -.
DR PDBsum; 5AK4; -.
DR PDBsum; 5AK5; -.
DR PDBsum; 5AK6; -.
DR PDBsum; 5AKE; -.
DR PDBsum; 5AKG; -.
DR PDBsum; 5AKH; -.
DR PDBsum; 5AKI; -.
DR PDBsum; 5AKJ; -.
DR PDBsum; 5AKK; -.
DR PDBsum; 5AKL; -.
DR PDBsum; 5AKX; -.
DR PDBsum; 5AKY; -.
DR PDBsum; 5AKZ; -.
DR PDBsum; 5ALD; -.
DR PDBsum; 5ALE; -.
DR PDBsum; 5ALF; -.
DR PDBsum; 5ALG; -.
DR PDBsum; 5ALH; -.
DR PDBsum; 5ALI; -.
DR PDBsum; 5ALJ; -.
DR PDBsum; 5ALK; -.
DR PDBsum; 5ALL; -.
DR PDBsum; 5ALM; -.
DR PDBsum; 5ALN; -.
DR PDBsum; 5ALO; -.
DR PDBsum; 5ALP; -.
DR PDBsum; 5ALQ; -.
DR PDBsum; 5ALR; -.
DR PDBsum; 5ALS; -.
DR PDBsum; 5ALT; -.
DR PDBsum; 5ALU; -.
DR PDBsum; 5ALV; -.
DR PDBsum; 5ALW; -.
DR PDBsum; 5ALX; -.
DR PDBsum; 5ALY; -.
DR PDBsum; 5ALZ; -.
DR PDBsum; 5AM0; -.
DR PDBsum; 5AM1; -.
DR PDBsum; 5AM2; -.
DR PDBsum; 5AM3; -.
DR PDBsum; 5AM4; -.
DR PDBsum; 5AM5; -.
DR PDBsum; 5FP0; -.
DR PDBsum; 5MWA; -.
DR PDBsum; 6AUM; -.
DR PDBsum; 6I5E; -.
DR PDBsum; 6I5G; -.
DR PDBsum; 7EBA; -.
DR AlphaFoldDB; P34913; -.
DR SMR; P34913; -.
DR BioGRID; 108367; 16.
DR IntAct; P34913; 5.
DR STRING; 9606.ENSP00000430269; -.
DR BindingDB; P34913; -.
DR ChEMBL; CHEMBL2409; -.
DR DrugBank; DB08257; 4-{[(CYCLOHEXYLAMINO)CARBONYL]AMINO}BUTANOIC ACID.
DR DrugBank; DB08258; 6-{[(CYCLOHEXYLAMINO)CARBONYL]AMINO}HEXANOIC ACID.
DR DrugBank; DB08259; 7-{[(CYCLOHEXYLAMINO)CARBONYL]AMINO}HEPTANOIC ACID.
DR DrugBank; DB06345; AR-9281.
DR DrugBank; DB12610; Ebselen.
DR DrugBank; DB08256; N-[(CYCLOHEXYLAMINO)CARBONYL]GLYCINE.
DR DrugBank; DB02029; N-Cyclohexyl-N'-(4-Iodophenyl)Urea.
DR DrugBank; DB04213; N-Cyclohexyl-N'-(Propyl)Phenyl Urea.
DR DrugBank; DB03677; N-Cyclohexyl-N'-Decylurea.
DR DrugCentral; P34913; -.
DR GuidetoPHARMACOLOGY; 2970; -.
DR SwissLipids; SLP:000001105; -.
DR ESTHER; human-EPHX2; Epoxide_hydrolase.
DR MEROPS; S33.973; -.
DR DEPOD; EPHX2; -.
DR iPTMnet; P34913; -.
DR PhosphoSitePlus; P34913; -.
DR BioMuta; EPHX2; -.
DR DMDM; 67476665; -.
DR EPD; P34913; -.
DR jPOST; P34913; -.
DR MassIVE; P34913; -.
DR MaxQB; P34913; -.
DR PaxDb; P34913; -.
DR PeptideAtlas; P34913; -.
DR PRIDE; P34913; -.
DR ProteomicsDB; 32244; -.
DR ProteomicsDB; 54953; -. [P34913-1]
DR ABCD; P34913; 10 sequenced antibodies.
DR Antibodypedia; 4070; 433 antibodies from 34 providers.
DR DNASU; 2053; -.
DR Ensembl; ENST00000380476.7; ENSP00000369843.3; ENSG00000120915.14. [P34913-2]
DR Ensembl; ENST00000521400.6; ENSP00000430269.1; ENSG00000120915.14. [P34913-1]
DR Ensembl; ENST00000521780.5; ENSP00000430302.1; ENSG00000120915.14. [P34913-3]
DR GeneID; 2053; -.
DR KEGG; hsa:2053; -.
DR MANE-Select; ENST00000521400.6; ENSP00000430269.1; NM_001979.6; NP_001970.2.
DR UCSC; uc003xfu.5; human. [P34913-1]
DR CTD; 2053; -.
DR DisGeNET; 2053; -.
DR GeneCards; EPHX2; -.
DR HGNC; HGNC:3402; EPHX2.
DR HPA; ENSG00000120915; Tissue enhanced (liver).
DR MalaCards; EPHX2; -.
DR MIM; 132811; gene.
DR neXtProt; NX_P34913; -.
DR OpenTargets; ENSG00000120915; -.
DR PharmGKB; PA27830; -.
DR VEuPathDB; HostDB:ENSG00000120915; -.
DR eggNOG; KOG3085; Eukaryota.
DR eggNOG; KOG4178; Eukaryota.
DR GeneTree; ENSGT00940000158614; -.
DR HOGENOM; CLU_036085_1_1_1; -.
DR InParanoid; P34913; -.
DR OMA; YAMEVLC; -.
DR OrthoDB; 616687at2759; -.
DR PhylomeDB; P34913; -.
DR TreeFam; TF315395; -.
DR BRENDA; 3.1.3.106; 2681.
DR BRENDA; 3.3.2.10; 2681.
DR PathwayCommons; P34913; -.
DR Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-HSA-9018682; Biosynthesis of maresins.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SABIO-RK; P34913; -.
DR SignaLink; P34913; -.
DR BioGRID-ORCS; 2053; 12 hits in 1085 CRISPR screens.
DR ChiTaRS; EPHX2; human.
DR EvolutionaryTrace; P34913; -.
DR GeneWiki; Epoxide_hydrolase_2; -.
DR GenomeRNAi; 2053; -.
DR Pharos; P34913; Tchem.
DR PRO; PR:P34913; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P34913; protein.
DR Bgee; ENSG00000120915; Expressed in right lobe of liver and 127 other tissues.
DR ExpressionAtlas; P34913; baseline and differential.
DR Genevisible; P34913; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0033885; F:10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004301; F:epoxide hydrolase activity; IDA:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IBA:GO_Central.
DR GO; GO:0042577; F:lipid phosphatase activity; IDA:UniProtKB.
DR GO; GO:0052642; F:lysophosphatidic acid phosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0015643; F:toxic substance binding; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0097176; P:epoxide metabolic process; IDA:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR GO; GO:0046272; P:stilbene catabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.150.240; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR000639; Epox_hydrolase-like.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR006439; HAD-SF_hydro_IA.
DR InterPro; IPR011945; HAD-SF_ppase_IA/epoxid_hydro_N.
DR InterPro; IPR041492; HAD_2.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR023198; PGP-like_dom2.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR Pfam; PF13419; HAD_2; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR02247; HAD-1A3-hyp; 1.
DR TIGRFAMs; TIGR01509; HAD-SF-IA-v3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Aromatic hydrocarbons catabolism; Cytoplasm; Detoxification;
KW Direct protein sequencing; Hydrolase; Lipid metabolism; Lipoprotein;
KW Magnesium; Metal-binding; Multifunctional enzyme; Peroxisome;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..555
FT /note="Bifunctional epoxide hydrolase 2"
FT /id="PRO_0000084111"
FT DOMAIN 259..531
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT REGION 1..224
FT /note="Phosphatase"
FT REGION 235..555
FT /note="Epoxide hydrolase"
FT MOTIF 553..555
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 335
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:15096040,
FT ECO:0000269|PubMed:16322563, ECO:0000269|PubMed:19746975,
FT ECO:0000269|PubMed:19969453, ECO:0000269|PubMed:20934334"
FT ACT_SITE 466
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:15096040,
FT ECO:0000269|PubMed:16322563, ECO:0000269|PubMed:19746975,
FT ECO:0000269|PubMed:19969453, ECO:0000269|PubMed:20934334"
FT ACT_SITE 524
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:15096040,
FT ECO:0000269|PubMed:16322563, ECO:0000269|PubMed:19746975,
FT ECO:0000269|PubMed:19969453, ECO:0000269|PubMed:20934334"
FT BINDING 9
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15096040"
FT BINDING 11
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15096040"
FT BINDING 123..124
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:15096040"
FT BINDING 185
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15096040"
FT BINDING 383
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15096040,
FT ECO:0000269|PubMed:16322563, ECO:0000269|PubMed:19746975,
FT ECO:0000269|PubMed:19969453, ECO:0000269|PubMed:20934334"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 55
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 191
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 215
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 421
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 455
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 554
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT LIPID 522
FT /note="S-(15-deoxy-Delta12,14-prostaglandin J2-9-
FT yl)cysteine"
FT /evidence="ECO:0000305|PubMed:21164107"
FT VAR_SEQ 1..66
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045597"
FT VAR_SEQ 1..53
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045598"
FT VARIANT 21
FT /note="G -> A (in dbSNP:rs72473930)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_055392"
FT VARIANT 52
FT /note="R -> Q (in dbSNP:rs72475803)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_055393"
FT VARIANT 55
FT /note="K -> R (decreased phosphatase activity; no effect on
FT epoxyde hydrolase activity; dbSNP:rs41507953)"
FT /evidence="ECO:0000269|PubMed:12869654,
FT ECO:0000269|PubMed:15196990, ECO:0000269|Ref.6"
FT /id="VAR_051059"
FT VARIANT 103
FT /note="R -> C (decreased phosphatase activity; no effect on
FT epoxyde hydrolase activity; dbSNP:rs17057255)"
FT /evidence="ECO:0000269|PubMed:12869654,
FT ECO:0000269|PubMed:15196990, ECO:0000269|Ref.6"
FT /id="VAR_033991"
FT VARIANT 154
FT /note="C -> Y (decreased phosphatase activity; no effect on
FT epoxyde hydrolase activity; dbSNP:rs57699806)"
FT /evidence="ECO:0000269|PubMed:12869654,
FT ECO:0000269|PubMed:15196990, ECO:0000269|Ref.6"
FT /id="VAR_055394"
FT VARIANT 225
FT /note="P -> L (in dbSNP:rs72475821)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_055395"
FT VARIANT 287
FT /note="R -> Q (no effect on phosphatase activity; decreased
FT epoxyde hydrolase activity; dbSNP:rs751141)"
FT /evidence="ECO:0000269|PubMed:10862610,
FT ECO:0000269|PubMed:12869654, ECO:0000269|PubMed:15196990,
FT ECO:0000269|PubMed:8342951, ECO:0000269|Ref.6"
FT /id="VAR_014852"
FT VARIANT 369
FT /note="M -> V (in dbSNP:rs72475894)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_055396"
FT VARIANT 403
FT /note="R -> RR"
FT /evidence="ECO:0000269|PubMed:10862610,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_022613"
FT VARIANT 470
FT /note="E -> G (no effect on phosphatase activity and
FT epoxyde hydrolase activity; dbSNP:rs68053459)"
FT /evidence="ECO:0000269|PubMed:12869654,
FT ECO:0000269|PubMed:15196990, ECO:0000269|Ref.6"
FT /id="VAR_055397"
FT MUTAGEN 9
FT /note="D->A: Loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12574508,
FT ECO:0000269|PubMed:22217705"
FT MUTAGEN 522
FT /note="C->S: Loss of S-(15-deoxy-Delta12,14-prostaglandin
FT J2-9-yl)cysteine-induced inhibition of epoxide hydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:21164107"
FT CONFLICT 5
FT /note="A -> G (in Ref. 1; AAA02756)"
FT /evidence="ECO:0000305"
FT CONFLICT 257..258
FT /note="SG -> W (in Ref. 1; AAA02756)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="F -> L (in Ref. 5; BAG53362)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="W -> R (in Ref. 5; BAG53362)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="E -> G (in Ref. 5; BAG53362)"
FT /evidence="ECO:0000305"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:5MWA"
FT TURN 12..14
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 36..42
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 49..54
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:5ALI"
FT HELIX 60..72
FT /evidence="ECO:0007829|PDB:5MWA"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:5ALG"
FT HELIX 88..97
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:5MWA"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 140..145
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:5ALQ"
FT HELIX 163..173
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 187..195
FT /evidence="ECO:0007829|PDB:5MWA"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 206..217
FT /evidence="ECO:0007829|PDB:5MWA"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 237..245
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:5AM2"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 310..324
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 336..347
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 352..359
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:4X6X"
FT HELIX 371..376
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 379..382
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 383..386
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 392..398
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 401..408
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:4X6X"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:4JNC"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:5AM2"
FT TURN 428..431
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:5AIA"
FT HELIX 444..455
FT /evidence="ECO:0007829|PDB:5AM2"
FT TURN 456..459
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:5AM2"
FT TURN 465..468
FT /evidence="ECO:0007829|PDB:5ALV"
FT HELIX 469..477
FT /evidence="ECO:0007829|PDB:5AM2"
FT TURN 478..481
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 488..493
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 497..499
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:5AM2"
FT STRAND 515..519
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 526..529
FT /evidence="ECO:0007829|PDB:5AM2"
FT HELIX 531..545
FT /evidence="ECO:0007829|PDB:5AM2"
SQ SEQUENCE 555 AA; 62616 MW; 1B5ACE7F80F9A26C CRC64;
MTLRAAVFDL DGVLALPAVF GVLGRTEEAL ALPRGLLNDA FQKGGPEGAT TRLMKGEITL
SQWIPLMEEN CRKCSETAKV CLPKNFSIKE IFDKAISARK INRPMLQAAL MLRKKGFTTA
ILTNTWLDDR AERDGLAQLM CELKMHFDFL IESCQVGMVK PEPQIYKFLL DTLKASPSEV
VFLDDIGANL KPARDLGMVT ILVQDTDTAL KELEKVTGIQ LLNTPAPLPT SCNPSDMSHG
YVTVKPRVRL HFVELGSGPA VCLCHGFPES WYSWRYQIPA LAQAGYRVLA MDMKGYGESS
APPEIEEYCM EVLCKEMVTF LDKLGLSQAV FIGHDWGGML VWYMALFYPE RVRAVASLNT
PFIPANPNMS PLESIKANPV FDYQLYFQEP GVAEAELEQN LSRTFKSLFR ASDESVLSMH
KVCEAGGLFV NSPEEPSLSR MVTEEEIQFY VQQFKKSGFR GPLNWYRNME RNWKWACKSL
GRKILIPALM VTAEKDFVLV PQMSQHMEDW IPHLKRGHIE DCGHWTQMDK PTEVNQILIK
WLDSDARNPP VVSKM
