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 01-MAY-2013, entry version 134.
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).
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 MASS SPECTROMETRY.
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 PROBABLE LIPID MODIFICATION 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.
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: Magnesium.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21 uM for threo-9,10-phosphonooxy-hydroxy-octadecanoic acid;
CC KM=1.1 mM for p-nitrophenyl phosphate;
CC Vmax=338 nmol/min/mg enzyme with threo-9,10-phosphonooxy-
CC hydroxy-octadecanoic acid;
CC Vmax=5.8 nmol/min/mg enzyme with p-nitrophenyl phosphate;
CC -!- SUBUNIT: Homodimer.
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, VSP_045599;
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).
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide
CC hydrolase family.
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 IPI; IPI00104341; -.
DR IPI; IPI00984813; -.
DR PIR; JC4711; JC4711.
DR RefSeq; NP_001243411.1; NM_001256482.1.
DR RefSeq; NP_001243412.1; NM_001256483.1.
DR RefSeq; NP_001243413.1; NM_001256484.1.
DR RefSeq; NP_001970.2; NM_001979.5.
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; 4HAI; X-ray; 2.55 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; 4HAI; -.
DR ProteinModelPortal; P34913; -.
DR IntAct; P34913; 3.
DR MINT; MINT-1385532; -.
DR STRING; 9606.ENSP00000369843; -.
DR MEROPS; S33.973; -.
DR PhosphoSite; P34913; -.
DR DMDM; 67476665; -.
DR PaxDb; P34913; -.
DR PeptideAtlas; P34913; -.
DR PRIDE; P34913; -.
DR DNASU; 2053; -.
DR Ensembl; ENST00000380476; ENSP00000369843; ENSG00000120915.
DR Ensembl; ENST00000521400; ENSP00000430269; ENSG00000120915.
DR Ensembl; ENST00000521780; ENSP00000430302; ENSG00000120915.
DR GeneID; 2053; -.
DR KEGG; hsa:2053; -.
DR UCSC; uc003xfu.3; human.
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 HOGENOM; HOG000028073; -.
DR HOVERGEN; HBG006095; -.
DR InParanoid; P34913; -.
DR KO; K08726; -.
DR OMA; GHWTQMD; -.
DR OrthoDB; EOG45QHCT; -.
DR PhylomeDB; P34913; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P34913; -.
DR BindingDB; P34913; -.
DR ChEMBL; CHEMBL2409; -.
DR DrugBank; DB00675; Tamoxifen.
DR EvolutionaryTrace; P34913; -.
DR GenomeRNAi; 2053; -.
DR NextBio; 35535129; -.
DR ArrayExpress; P34913; -.
DR Bgee; P34913; -.
DR CleanEx; HS_EPHX2; -.
DR Genevestigator; P34913; -.
DR GermOnline; ENSG00000120915; Homo sapiens.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0033885; F:10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity; IEA:EC.
DR GO; GO:0003869; F:4-nitrophenylphosphatase activity; IDA:UniProtKB.
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:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0015643; F:toxin binding; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; NAS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR GO; GO:0017144; P:drug metabolic process; NAS:UniProtKB.
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 toxin; NAS:UniProtKB.
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 InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR000639; Epox_hydrolase-like.
DR InterPro; IPR023214; HAD-like_dom.
DR InterPro; IPR006402; HAD-SF_hydro_IA_v3.
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; SSF56784; HAD-like_dom; 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; Polymorphism; 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 (Potential).
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.
FT METAL 11 11 Magnesium.
FT METAL 185 185 Magnesium.
FT BINDING 383 383 Substrate.
FT MOD_RES 43 43 N6-acetyllysine.
FT LIPID 522 522 S-(15-deoxy-Delta12,14-prostaglandin J2-
FT 9-yl)cysteine (Probable).
FT VAR_SEQ 1 66 Missing (in isoform 3).
FT /FTId=VSP_045597.
FT VAR_SEQ 1 53 Missing (in isoform 2).
FT /FTId=VSP_045598.
FT VAR_SEQ 402 402 S -> SR (in isoform 3).
FT /FTId=VSP_045599.
FT VARIANT 21 21 G -> A.
FT /FTId=VAR_055392.
FT VARIANT 52 52 R -> Q.
FT /FTId=VAR_055393.
FT VARIANT 55 55 K -> R (decreased phosphatase activity;
FT no effect on epoxyde hydrolase activity;
FT dbSNP:rs41507953).
FT /FTId=VAR_051059.
FT VARIANT 103 103 R -> C (decreased phosphatase activity;
FT no effect on epoxyde hydrolase activity;
FT dbSNP:rs17057255).
FT /FTId=VAR_033991.
FT VARIANT 154 154 C -> Y (decreased phosphatase activity;
FT no effect on epoxyde hydrolase activity;
FT dbSNP:rs57699806).
FT /FTId=VAR_055394.
FT VARIANT 225 225 P -> L.
FT /FTId=VAR_055395.
FT VARIANT 287 287 R -> Q (no effect on phosphatase
FT activity; decreased epoxyde hydrolase
FT activity; dbSNP:rs751141).
FT /FTId=VAR_014852.
FT VARIANT 369 369 M -> V.
FT /FTId=VAR_055396.
FT VARIANT 403 403 R -> RR.
FT /FTId=VAR_022613.
FT VARIANT 470 470 E -> G (no effect on phosphatase activity
FT and epoxyde hydrolase activity).
FT /FTId=VAR_055397.
FT MUTAGEN 9 9 D->A: Loss of phosphatase activity.
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 CONFLICT 5 5 A -> G (in Ref. 1; AAA02756).
FT CONFLICT 257 258 SG -> W (in Ref. 1; AAA02756).
FT CONFLICT 409 409 F -> L (in Ref. 5; BAG53362).
FT CONFLICT 473 473 W -> R (in Ref. 5; BAG53362).
FT CONFLICT 494 494 E -> G (in Ref. 5; BAG53362).
FT STRAND 5 8
FT TURN 12 14
FT STRAND 15 17
FT HELIX 20 29
FT HELIX 36 42
FT HELIX 45 47
FT HELIX 49 54
FT STRAND 57 59
FT HELIX 60 77
FT HELIX 88 98
FT HELIX 103 114
FT STRAND 118 123
FT TURN 131 133
FT HELIX 134 144
FT STRAND 147 152
FT HELIX 153 156
FT HELIX 163 173
FT HELIX 177 179
FT STRAND 180 185
FT HELIX 187 196
FT STRAND 199 202
FT HELIX 206 217
FT HELIX 234 236
FT STRAND 237 245
FT STRAND 248 255
FT STRAND 257 264
FT HELIX 271 274
FT HELIX 277 283
FT STRAND 287 291
FT HELIX 305 308
FT HELIX 310 324
FT STRAND 329 334
FT HELIX 336 347
FT HELIX 349 351
FT STRAND 352 359
FT STRAND 367 369
FT HELIX 371 376
FT HELIX 379 381
FT HELIX 382 388
FT HELIX 392 399
FT HELIX 401 408
FT HELIX 412 414
FT STRAND 419 421
FT HELIX 422 425
FT STRAND 427 429
FT STRAND 440 442
FT HELIX 444 454
FT TURN 455 459
FT HELIX 460 464
FT HELIX 465 467
FT HELIX 469 477
FT TURN 478 481
FT STRAND 488 493
FT STRAND 497 499
FT HELIX 501 504
FT HELIX 507 509
FT STRAND 515 519
FT HELIX 526 529
FT HELIX 531 545
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
//
