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Database: UniProt
Entry: P34913
LinkDB: P34913
Original site: P34913 
ID   HYES_HUMAN              Reviewed;         555 AA.
AC   P34913; B2Z3B1; B3KTU8; B3KUA0; G3V134; J3KPH7; Q16764; Q9HBJ1;
AC   Q9HBJ2;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2005, sequence version 2.
DT   26-NOV-2014, entry version 152.
DE   RecName: Full=Bifunctional epoxide hydrolase 2;
DE   Includes:
DE     RecName: Full=Cytosolic epoxide hydrolase 2;
DE              Short=CEH;
DE              EC=3.3.2.10;
DE     AltName: Full=Epoxide hydratase;
DE     AltName: Full=Soluble epoxide hydrolase;
DE              Short=SEH;
DE   Includes:
DE     RecName: Full=Lipid-phosphate phosphatase;
DE              EC=3.1.3.76;
GN   Name=EPHX2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   gene (EPHX2).";
RL   Biochem. Biophys. Res. Commun. 221:333-339(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS GLN-287 AND
RP   ARG-403 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
RT   epoxide 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
RT   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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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;
RP   ARG-55; 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.,
RA   Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA   Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA   Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA   DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA   Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA   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.,
RA   O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA   Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA   Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA   Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA   Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA   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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [10]
RP   CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS ARG-55; CYS-103;
RP   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
RP   PHOSPHATASE, AND MUTAGENESIS OF ASP-9.
RX   PubMed=12574508; DOI=10.1073/pnas.0437829100;
RA   Cronin A., Mowbray S., Durk H., Homburg S., Fleming I.,
RA   Fisslthaler B., 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   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
RT   enzyme 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
RP   CHARACTERIZATION OF VARIANTS ARG-55; CYS-103; TYR-154; GLN-287 AND
RP   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
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., 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.,
RA   Buerckstuemmer T., 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   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH PHOSPHATE;
RP   MAGNESIUM AND EPOXIDE HYDROLASE INHIBITOR.
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
RT   on bifunctional catalysis in epoxide and phosphate ester hydrolysis.";
RL   Biochemistry 43:4716-4723(2004).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH DIALKYLUREA
RP   INHIBITORS AND MAGNESIUM.
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-
RT   (3-cyclohexylureido)-carboxylic acids.";
RL   Protein Sci. 15:58-64(2006).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEXES WITH ARYLAMIDE
RP   INHIBITORS.
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   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) IN COMPLEX WITH SYNTHETIC
RP   INHIBITOR.
RX   PubMed=19969453; DOI=10.1016/j.bmcl.2009.11.091;
RA   Eldrup A.B., Soleymanzadeh F., Farrow N.A., Kukulka A.,
RA   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   [21]
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH SYNTHETIC
RP   INHIBITOR.
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. The C-terminal domain has epoxide
CC       hydrolase activity and acts on epoxides (alkene oxides, oxiranes)
CC       and arene oxides. Plays a role in xenobiotic metabolism by
CC       degrading potentially toxic epoxides. Also determines steady-state
CC       levels of physiological mediators. The N-terminal domain has lipid
CC       phosphatase activity, with the highest activity towards threo-
CC       9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-
CC       9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-
CC       octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and
CC       p-nitrophenyl phospate. {ECO:0000269|PubMed:12574508,
CC       ECO:0000269|PubMed:12574510}.
CC   -!- CATALYTIC ACTIVITY: An epoxide + H(2)O = a glycol.
CC   -!- CATALYTIC ACTIVITY: (9S,10S)-10-hydroxy-9-
CC       (phosphonooxy)octadecanoate + H(2)O = (9S,10S)-9,10-
CC       dihydroxyoctadecanoate + phosphate.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:12574510};
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=1.1 mM for p-nitrophenyl phosphate
CC         {ECO:0000269|PubMed:12574508, ECO:0000269|PubMed:12574510,
CC         ECO:0000269|PubMed:15196990};
CC         Vmax=338 nmol/min/mg enzyme with threo-9,10-phosphonooxy-
CC         hydroxy-octadecanoic acid {ECO:0000269|PubMed:12574508,
CC         ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:15196990};
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   -!- 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         Note=No experimental confirmation available.;
CC       Name=3;
CC         IsoId=P34913-3; Sequence=VSP_045597;
CC         Note=No experimental confirmation available.;
CC   -!- INDUCTION: By compounds that cause peroxisome proliferation such
CC       as clofibrate, tiadenol and fenofibrate.
CC   -!- DOMAIN: The N-terminal domain has phosphatase activity. The C-
CC       terminal 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
CC       an alternative to other cysteine modifications, such as S-
CC       nitrosylation and S-palmitoylation (Probable). {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide
CC       hydrolase 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   UniGene; Hs.212088; -.
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   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   ProteinModelPortal; P34913; -.
DR   SMR; P34913; 4-548.
DR   BioGrid; 108367; 5.
DR   IntAct; P34913; 3.
DR   MINT; MINT-1385532; -.
DR   STRING; 9606.ENSP00000369843; -.
DR   BindingDB; P34913; -.
DR   ChEMBL; CHEMBL2409; -.
DR   MEROPS; S33.973; -.
DR   PhosphoSite; P34913; -.
DR   DMDM; 67476665; -.
DR   MaxQB; P34913; -.
DR   PaxDb; P34913; -.
DR   PeptideAtlas; P34913; -.
DR   PRIDE; P34913; -.
DR   DNASU; 2053; -.
DR   Ensembl; ENST00000380476; ENSP00000369843; ENSG00000120915. [P34913-2]
DR   Ensembl; ENST00000521400; ENSP00000430269; ENSG00000120915. [P34913-1]
DR   Ensembl; ENST00000521780; ENSP00000430302; ENSG00000120915. [P34913-3]
DR   GeneID; 2053; -.
DR   KEGG; hsa:2053; -.
DR   UCSC; uc003xfu.4; human. [P34913-1]
DR   CTD; 2053; -.
DR   GeneCards; GC08P027348; -.
DR   HGNC; HGNC:3402; EPHX2.
DR   HPA; CAB009808; -.
DR   HPA; HPA023094; -.
DR   HPA; HPA023660; -.
DR   HPA; HPA023779; -.
DR   MIM; 132811; gene.
DR   neXtProt; NX_P34913; -.
DR   PharmGKB; PA27830; -.
DR   eggNOG; COG0596; -.
DR   GeneTree; ENSGT00530000063213; -.
DR   HOGENOM; HOG000028073; -.
DR   HOVERGEN; HBG006095; -.
DR   InParanoid; P34913; -.
DR   KO; K08726; -.
DR   OMA; GHWTQMD; -.
DR   OrthoDB; EOG72VH5T; -.
DR   PhylomeDB; P34913; -.
DR   TreeFam; TF315395; -.
DR   Reactome; REACT_150417; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR   SABIO-RK; P34913; -.
DR   EvolutionaryTrace; P34913; -.
DR   GeneWiki; Epoxide_hydrolase_2; -.
DR   GenomeRNAi; 2053; -.
DR   NextBio; 35535129; -.
DR   PRO; PR:P34913; -.
DR   Bgee; P34913; -.
DR   CleanEx; HS_EPHX2; -.
DR   ExpressionAtlas; P34913; baseline and differential.
DR   Genevestigator; P34913; -.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
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:0042577; F:lipid 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:0005102; F:receptor binding; IPI:UniProtKB.
DR   GO; GO:0015643; F:toxic substance binding; IDA:UniProtKB.
DR   GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR   GO; GO:0006874; P:cellular calcium ion homeostasis; NAS:UniProtKB.
DR   GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR   GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR   GO; GO:0017144; P:drug metabolic process; NAS:UniProtKB.
DR   GO; GO:0019373; P:epoxygenase P450 pathway; TAS:Reactome.
DR   GO; GO:0006954; P:inflammatory response; NAS: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:0045909; P:positive regulation of vasodilation; NAS:UniProtKB.
DR   GO; GO:0072593; P:reactive oxygen species metabolic process; NAS:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; NAS:UniProtKB.
DR   GO; GO:0090181; P:regulation of cholesterol metabolic process; IMP:UniProtKB.
DR   GO; GO:0009636; P:response to toxic substance; NAS:UniProtKB.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0046272; P:stilbene catabolic process; IDA:UniProtKB.
DR   GO; GO:0006805; P:xenobiotic metabolic process; NAS: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; IPR023214; HAD-like_dom.
DR   InterPro; IPR006439; HAD-SF_hydro_IA.
DR   InterPro; IPR011945; HAD-SF_ppase_IA/epoxid_hydro_N.
DR   InterPro; IPR023198; PGP_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; Complete proteome; Cytoplasm;
KW   Detoxification; Direct protein sequencing; Hydrolase;
KW   Lipid metabolism; Lipoprotein; Magnesium; Metal-binding;
KW   Multifunctional enzyme; Peroxisome; Phosphoprotein; Polymorphism;
KW   Reference proteome.
FT   CHAIN         1    555       Bifunctional epoxide hydrolase 2.
FT                                /FTId=PRO_0000084111.
FT   REGION        1    224       Phosphatase.
FT   REGION      123    124       Phosphate binding.
FT   REGION      235    555       Epoxide hydrolase.
FT   MOTIF       553    555       Microbody targeting signal.
FT                                {ECO:0000255}.
FT   ACT_SITE    335    335       Nucleophile.
FT   ACT_SITE    466    466       Proton donor.
FT   ACT_SITE    524    524       Proton acceptor.
FT   METAL         9      9       Magnesium. {ECO:0000269|PubMed:15096040}.
FT   METAL        11     11       Magnesium. {ECO:0000269|PubMed:15096040}.
FT   METAL       185    185       Magnesium. {ECO:0000269|PubMed:15096040}.
FT   BINDING     383    383       Substrate.
FT   MOD_RES      43     43       N6-acetyllysine.
FT                                {ECO:0000269|PubMed:19608861}.
FT   MOD_RES      55     55       N6-succinyllysine. {ECO:0000250}.
FT   MOD_RES     191    191       N6-acetyllysine. {ECO:0000250}.
FT   MOD_RES     215    215       N6-acetyllysine. {ECO:0000250}.
FT   MOD_RES     370    370       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     421    421       N6-succinyllysine. {ECO:0000250}.
FT   MOD_RES     455    455       N6-succinyllysine. {ECO:0000250}.
FT   MOD_RES     554    554       N6-succinyllysine. {ECO:0000250}.
FT   LIPID       522    522       S-(15-deoxy-Delta12,14-prostaglandin J2-
FT                                9-yl)cysteine.
FT                                {ECO:0000305|PubMed:21164107}.
FT   VAR_SEQ       1     66       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_045597.
FT   VAR_SEQ       1     53       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_045598.
FT   VARIANT      21     21       G -> A. {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_055392.
FT   VARIANT      52     52       R -> Q (in dbSNP:rs72475803).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_055393.
FT   VARIANT      55     55       K -> R (decreased phosphatase activity;
FT                                no effect on epoxyde hydrolase activity;
FT                                dbSNP:rs41507953). {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_051059.
FT   VARIANT     103    103       R -> C (decreased phosphatase activity;
FT                                no effect on epoxyde hydrolase activity;
FT                                dbSNP:rs17057255). {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_033991.
FT   VARIANT     154    154       C -> Y (decreased phosphatase activity;
FT                                no effect on epoxyde hydrolase activity;
FT                                dbSNP:rs57699806). {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_055394.
FT   VARIANT     225    225       P -> L. {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_055395.
FT   VARIANT     287    287       R -> Q (no effect on phosphatase
FT                                activity; decreased epoxyde hydrolase
FT                                activity; dbSNP:rs751141).
FT                                {ECO:0000269|PubMed:10862610,
FT                                ECO:0000269|PubMed:8342951,
FT                                ECO:0000269|Ref.6}.
FT                                /FTId=VAR_014852.
FT   VARIANT     369    369       M -> V (in dbSNP:rs72475894).
FT                                {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_055396.
FT   VARIANT     403    403       R -> RR. {ECO:0000269|PubMed:10862610,
FT                                ECO:0000269|PubMed:14702039}.
FT                                /FTId=VAR_022613.
FT   VARIANT     470    470       E -> G (no effect on phosphatase activity
FT                                and epoxyde hydrolase activity;
FT                                dbSNP:rs68053459). {ECO:0000269|Ref.6}.
FT                                /FTId=VAR_055397.
FT   MUTAGEN       9      9       D->A: Loss of phosphatase activity.
FT                                {ECO:0000269|PubMed:12574508}.
FT   MUTAGEN     522    522       C->S: Loss of S-(15-deoxy-Delta12,14-
FT                                prostaglandin J2-9-yl)cysteine-induced
FT                                inhibition of epoxide hydrolase activity.
FT                                {ECO:0000269|PubMed:21164107}.
FT   CONFLICT      5      5       A -> G (in Ref. 1; AAA02756).
FT                                {ECO:0000305}.
FT   CONFLICT    257    258       SG -> W (in Ref. 1; AAA02756).
FT                                {ECO:0000305}.
FT   CONFLICT    409    409       F -> L (in Ref. 5; BAG53362).
FT                                {ECO:0000305}.
FT   CONFLICT    473    473       W -> R (in Ref. 5; BAG53362).
FT                                {ECO:0000305}.
FT   CONFLICT    494    494       E -> G (in Ref. 5; BAG53362).
FT                                {ECO:0000305}.
FT   STRAND        5      8       {ECO:0000244|PDB:3I28}.
FT   TURN         12     14       {ECO:0000244|PDB:3I28}.
FT   STRAND       15     17       {ECO:0000244|PDB:3I28}.
FT   HELIX        20     29       {ECO:0000244|PDB:3I28}.
FT   HELIX        36     42       {ECO:0000244|PDB:3I28}.
FT   HELIX        45     47       {ECO:0000244|PDB:3I28}.
FT   HELIX        49     54       {ECO:0000244|PDB:3I28}.
FT   STRAND       57     59       {ECO:0000244|PDB:3WK9}.
FT   HELIX        60     77       {ECO:0000244|PDB:3I28}.
FT   HELIX        88     98       {ECO:0000244|PDB:3I28}.
FT   HELIX       103    114       {ECO:0000244|PDB:3I28}.
FT   STRAND      118    123       {ECO:0000244|PDB:3I28}.
FT   TURN        131    133       {ECO:0000244|PDB:3I28}.
FT   HELIX       134    144       {ECO:0000244|PDB:3I28}.
FT   STRAND      147    152       {ECO:0000244|PDB:3I28}.
FT   HELIX       153    156       {ECO:0000244|PDB:3I28}.
FT   HELIX       163    173       {ECO:0000244|PDB:3I28}.
FT   HELIX       177    179       {ECO:0000244|PDB:3I28}.
FT   STRAND      180    185       {ECO:0000244|PDB:3I28}.
FT   HELIX       187    196       {ECO:0000244|PDB:3I28}.
FT   STRAND      199    202       {ECO:0000244|PDB:3I28}.
FT   HELIX       206    217       {ECO:0000244|PDB:3I28}.
FT   HELIX       234    236       {ECO:0000244|PDB:3I28}.
FT   STRAND      237    245       {ECO:0000244|PDB:3I28}.
FT   STRAND      248    255       {ECO:0000244|PDB:3I28}.
FT   STRAND      257    264       {ECO:0000244|PDB:3I28}.
FT   HELIX       271    274       {ECO:0000244|PDB:3I28}.
FT   HELIX       277    283       {ECO:0000244|PDB:3I28}.
FT   STRAND      287    291       {ECO:0000244|PDB:3I28}.
FT   HELIX       305    308       {ECO:0000244|PDB:3I28}.
FT   HELIX       310    324       {ECO:0000244|PDB:3I28}.
FT   STRAND      329    334       {ECO:0000244|PDB:3I28}.
FT   HELIX       336    347       {ECO:0000244|PDB:3I28}.
FT   HELIX       349    351       {ECO:0000244|PDB:3I28}.
FT   STRAND      352    359       {ECO:0000244|PDB:3I28}.
FT   STRAND      367    369       {ECO:0000244|PDB:1ZD3}.
FT   HELIX       371    376       {ECO:0000244|PDB:3I28}.
FT   HELIX       379    381       {ECO:0000244|PDB:3I28}.
FT   HELIX       382    388       {ECO:0000244|PDB:3I28}.
FT   HELIX       392    399       {ECO:0000244|PDB:3I28}.
FT   HELIX       401    408       {ECO:0000244|PDB:3I28}.
FT   HELIX       412    414       {ECO:0000244|PDB:4JNC}.
FT   HELIX       419    421       {ECO:0000244|PDB:4JNC}.
FT   HELIX       422    425       {ECO:0000244|PDB:3I28}.
FT   STRAND      427    429       {ECO:0000244|PDB:3I28}.
FT   STRAND      440    442       {ECO:0000244|PDB:3OTQ}.
FT   HELIX       444    454       {ECO:0000244|PDB:3I28}.
FT   TURN        455    459       {ECO:0000244|PDB:3I28}.
FT   HELIX       460    464       {ECO:0000244|PDB:3I28}.
FT   HELIX       465    467       {ECO:0000244|PDB:3I1Y}.
FT   HELIX       469    477       {ECO:0000244|PDB:3I28}.
FT   TURN        478    481       {ECO:0000244|PDB:3I28}.
FT   STRAND      488    493       {ECO:0000244|PDB:3I28}.
FT   STRAND      497    499       {ECO:0000244|PDB:3I28}.
FT   HELIX       501    504       {ECO:0000244|PDB:3I28}.
FT   HELIX       507    509       {ECO:0000244|PDB:3I28}.
FT   STRAND      515    519       {ECO:0000244|PDB:3I28}.
FT   HELIX       526    529       {ECO:0000244|PDB:3I28}.
FT   HELIX       531    545       {ECO:0000244|PDB:3I28}.
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
//
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