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P34913 (HYES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional epoxide hydrolase 2

Including the following 2 domains:

  1. Cytosolic epoxide hydrolase 2
    Short name=CEH
    EC=3.3.2.10
    Alternative name(s):
    Epoxide hydratase
    Soluble epoxide hydrolase
    Short name=SEH
  2. Lipid-phosphate phosphatase
    EC=3.1.3.76
Gene names
Name:EPHX2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length555 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate. Ref.11 Ref.12

Catalytic activity

An epoxide + H2O = a glycol. Ref.10 Ref.11 Ref.12 Ref.13

(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate. Ref.10 Ref.11 Ref.12 Ref.13

Cofactor

Magnesium. Ref.12

Subunit structure

Homodimer.

Subcellular location

Cytoplasm. Peroxisome.

Induction

By compounds that cause peroxisome proliferation such as clofibrate, tiadenol and fenofibrate.

Domain

The N-terminal domain has phosphatase activity. The C-terminal domain has epoxide hydrolase activity.

Post-translational modification

The N-terminus is blocked.

The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation Probable.

Sequence similarities

Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.

Biophysicochemical properties

Kinetic parameters:

KM=21 µM for threo-9,10-phosphonooxy-hydroxy-octadecanoic acid Ref.11 Ref.12 Ref.13

KM=1.1 mM for p-nitrophenyl phosphate

Vmax=338 nmol/min/mg enzyme with threo-9,10-phosphonooxy-hydroxy-octadecanoic acid

Vmax=5.8 nmol/min/mg enzyme with p-nitrophenyl phosphate

Ontologies

Keywords
   Biological processAromatic hydrocarbons catabolism
Detoxification
Lipid metabolism
   Cellular componentCytoplasm
Peroxisome
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandMagnesium
Metal-binding
   Molecular functionHydrolase
   PTMAcetylation
Lipoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Traceable author statement. Source: Reactome

cellular calcium ion homeostasis

Non-traceable author statement Ref.3. Source: UniProtKB

cholesterol homeostasis

Inferred from direct assay PubMed 18974052. Source: UniProtKB

dephosphorylation

Inferred from direct assay Ref.11. Source: UniProtKB

drug metabolic process

Non-traceable author statement Ref.3. Source: UniProtKB

epoxygenase P450 pathway

Traceable author statement. Source: Reactome

inflammatory response

Non-traceable author statement Ref.3. Source: UniProtKB

phospholipid dephosphorylation

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 18974052. Source: UniProtKB

positive regulation of vasodilation

Non-traceable author statement Ref.3. Source: UniProtKB

reactive oxygen species metabolic process

Non-traceable author statement Ref.3. Source: UniProtKB

regulation of blood pressure

Non-traceable author statement Ref.3. Source: UniProtKB

regulation of cholesterol metabolic process

Inferred from mutant phenotype PubMed 18974052. Source: UniProtKB

response to toxic substance

Non-traceable author statement Ref.3. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

stilbene catabolic process

Inferred from direct assay Ref.1. Source: UniProtKB

xenobiotic metabolic process

Non-traceable author statement Ref.3. Source: UniProtKB

   Cellular_componentcytosol

Inferred from direct assay PubMed 16314446PubMed 18513744Ref.1. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

peroxisome

Inferred from direct assay PubMed 16314446PubMed 18513744. Source: UniProtKB

   Molecular_function10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

epoxide hydrolase activity

Inferred from direct assay Ref.3Ref.1. Source: UniProtKB

lipid phosphatase activity

Inferred from direct assay Ref.12. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.12. Source: UniProtKB

phosphatase activity

Inferred from direct assay Ref.11Ref.13. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.17PubMed 18513744. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 20178365. Source: UniProtKB

toxic substance binding

Inferred from direct assay Ref.17. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P34913-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P34913-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P34913-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 555555Bifunctional epoxide hydrolase 2
PRO_0000084111

Regions

Region1 – 224224Phosphatase
Region123 – 1242Phosphate binding
Region235 – 555321Epoxide hydrolase
Motif553 – 5553Microbody targeting signal Potential

Sites

Active site3351Nucleophile
Active site4661Proton donor
Active site5241Proton acceptor
Metal binding91Magnesium
Metal binding111Magnesium
Metal binding1851Magnesium
Binding site3831Substrate

Amino acid modifications

Modified residue431N6-acetyllysine Ref.14
Modified residue551N6-succinyllysine By similarity
Modified residue1911N6-acetyllysine By similarity
Modified residue2151N6-acetyllysine By similarity
Modified residue3701Phosphoserine By similarity
Modified residue4211N6-succinyllysine By similarity
Modified residue4551N6-succinyllysine By similarity
Modified residue5541N6-succinyllysine By similarity
Lipidation5221S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine Probable

Natural variations

Alternative sequence1 – 6666Missing in isoform 3.
VSP_045597
Alternative sequence1 – 5353Missing in isoform 2.
VSP_045598
Natural variant211G → A. Ref.6
VAR_055392
Natural variant521R → Q. Ref.6
Corresponds to variant rs72475803 [ dbSNP | Ensembl ].
VAR_055393
Natural variant551K → R Decreased phosphatase activity; no effect on epoxyde hydrolase activity. Ref.6 Ref.10 Ref.13
Corresponds to variant rs41507953 [ dbSNP | Ensembl ].
VAR_051059
Natural variant1031R → C Decreased phosphatase activity; no effect on epoxyde hydrolase activity. Ref.6 Ref.10 Ref.13
Corresponds to variant rs17057255 [ dbSNP | Ensembl ].
VAR_033991
Natural variant1541C → Y Decreased phosphatase activity; no effect on epoxyde hydrolase activity. Ref.6 Ref.10 Ref.13
Corresponds to variant rs57699806 [ dbSNP | Ensembl ].
VAR_055394
Natural variant2251P → L. Ref.6
VAR_055395
Natural variant2871R → Q No effect on phosphatase activity; decreased epoxyde hydrolase activity. Ref.1 Ref.3 Ref.6 Ref.10 Ref.13
Corresponds to variant rs751141 [ dbSNP | Ensembl ].
VAR_014852
Natural variant3691M → V. Ref.6
Corresponds to variant rs72475894 [ dbSNP | Ensembl ].
VAR_055396
Natural variant4031R → RR. Ref.3 Ref.5
VAR_022613
Natural variant4701E → G No effect on phosphatase activity and epoxyde hydrolase activity. Ref.6 Ref.10 Ref.13
Corresponds to variant rs68053459 [ dbSNP | Ensembl ].
VAR_055397

Experimental info

Mutagenesis91D → A: Loss of phosphatase activity. Ref.11
Mutagenesis5221C → S: Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine-induced inhibition of epoxide hydrolase activity. Ref.16
Sequence conflict51A → G in AAA02756. Ref.1
Sequence conflict257 – 2582SG → W in AAA02756. Ref.1
Sequence conflict4091F → L in BAG53362. Ref.5
Sequence conflict4731W → R in BAG53362. Ref.5
Sequence conflict4941E → G in BAG53362. Ref.5

Secondary structure

.......................................................................................................... 555
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: 1B5ACE7F80F9A26C

FASTA55562,616
        10         20         30         40         50         60 
MTLRAAVFDL DGVLALPAVF GVLGRTEEAL ALPRGLLNDA FQKGGPEGAT TRLMKGEITL 

        70         80         90        100        110        120 
SQWIPLMEEN CRKCSETAKV CLPKNFSIKE IFDKAISARK INRPMLQAAL MLRKKGFTTA 

       130        140        150        160        170        180 
ILTNTWLDDR AERDGLAQLM CELKMHFDFL IESCQVGMVK PEPQIYKFLL DTLKASPSEV 

       190        200        210        220        230        240 
VFLDDIGANL KPARDLGMVT ILVQDTDTAL KELEKVTGIQ LLNTPAPLPT SCNPSDMSHG 

       250        260        270        280        290        300 
YVTVKPRVRL HFVELGSGPA VCLCHGFPES WYSWRYQIPA LAQAGYRVLA MDMKGYGESS 

       310        320        330        340        350        360 
APPEIEEYCM EVLCKEMVTF LDKLGLSQAV FIGHDWGGML VWYMALFYPE RVRAVASLNT 

       370        380        390        400        410        420 
PFIPANPNMS PLESIKANPV FDYQLYFQEP GVAEAELEQN LSRTFKSLFR ASDESVLSMH 

       430        440        450        460        470        480 
KVCEAGGLFV NSPEEPSLSR MVTEEEIQFY VQQFKKSGFR GPLNWYRNME RNWKWACKSL 

       490        500        510        520        530        540 
GRKILIPALM VTAEKDFVLV PQMSQHMEDW IPHLKRGHIE DCGHWTQMDK PTEVNQILIK 

       550 
WLDSDARNPP VVSKM 

« Hide

Isoform 2 [UniParc].

Checksum: CB56A36CDF4F2FFF
Show »

FASTA50257,123
Isoform 3 [UniParc].

Checksum: 7188F0A08408CD29
Show »

FASTA48955,626

References

« Hide 'large scale' references
[1]"cDNA cloning and expression of a soluble epoxide hydrolase from human liver."
Beetham J.K., Tian T., Hammock B.D.
Arch. Biochem. Biophys. 305:197-201(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT GLN-287.
Tissue: Liver.
[2]"Structural characterization of the human soluble epoxide hydrolase gene (EPHX2)."
Sandberg M., Meijer J.
Biochem. Biophys. Res. Commun. 221:333-339(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms."
Sandberg M., Hassett C., Adman E.T., Meijer J., Omiecinski C.J.
J. Biol. Chem. 275:28873-28881(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLN-287 AND ARG-403 INS.
Tissue: Liver.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANT ARG-403 INS.
Tissue: Kidney and Prostate.
[6]NIEHS SNPs program
Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-21; GLN-52; ARG-55; CYS-103; TYR-154; LEU-225; GLN-287; VAL-369 AND GLY-470.
[7]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: B-cell and Lung.
[10]"Polymorphisms in human soluble epoxide hydrolase."
Przybyla-Zawislak B.D., Srivastava P.K., Vazquez-Matias J., Mohrenweiser H.W., Maxwell J.E., Hammock B.D., Bradbury J.A., Enayetallah A.E., Zeldin D.C., Grant D.F.
Mol. Pharmacol. 64:482-490(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS ARG-55; CYS-103; TYR-154; GLN-287 AND GLY-470.
[11]"The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase."
Cronin A., Mowbray S., Durk H., Homburg S., Fleming I., Fisslthaler B., Oesch F., Arand M.
Proc. Natl. Acad. Sci. U.S.A. 100:1552-1557(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION AS PHOSPHATASE, MUTAGENESIS OF ASP-9.
[12]"The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity."
Newman J.W., Morisseau C., Harris T.R., Hammock B.D.
Proc. Natl. Acad. Sci. U.S.A. 100:1558-1563(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION AS LIPID PHOSPHATASE, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
[13]"Polymorphisms in human soluble epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure."
Srivastava P.K., Sharma V.K., Kalonia D.S., Grant D.F.
Arch. Biochem. Biophys. 427:164-169(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANTS ARG-55; CYS-103; TYR-154; GLN-287 AND GLY-470.
[14]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-43, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Redox regulation of soluble epoxide hydrolase by 15-deoxy-delta-prostaglandin J2 controls coronary hypoxic vasodilation."
Charles R.L., Burgoyne J.R., Mayr M., Weldon S.M., Hubner N., Dong H., Morisseau C., Hammock B.D., Landar A., Eaton P.
Circ. Res. 108:324-334(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: LIPIDATION AT CYS-522, MUTAGENESIS OF CYS-522.
[17]"Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis."
Gomez G.A., Morisseau C., Hammock B.D., Christianson D.W.
Biochemistry 43:4716-4723(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH PHOSPHATE; MAGNESIUM AND EPOXIDE HYDROLASE INHIBITOR.
[18]"Human soluble epoxide hydrolase: structural basis of inhibition by 4-(3-cyclohexylureido)-carboxylic acids."
Gomez G.A., Morisseau C., Hammock B.D., Christianson D.W.
Protein Sci. 15:58-64(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH DIALKYLUREA INHIBITORS AND MAGNESIUM.
[19]"Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase."
Eldrup A.B., Soleymanzadeh F., Taylor S.J., Muegge I., Farrow N.A., Joseph D., McKellop K., Man C.C., Kukulka A., De Lombaert S.
J. Med. Chem. 52:5880-5895(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEXES WITH ARYLAMIDE INHIBITORS.
[20]"Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase."
Eldrup A.B., Soleymanzadeh F., Farrow N.A., Kukulka A., De Lombaert S.
Bioorg. Med. Chem. Lett. 20:571-575(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR.
[21]"Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain."
Lo H.Y., Man C.C., Fleck R.W., Farrow N.A., Ingraham R.H., Kukulka A., Proudfoot J.R., Betageri R., Kirrane T., Patel U., Sharma R., Hoermann M.A., Kabcenell A., Lombaert S.D.
Bioorg. Med. Chem. Lett. 20:6379-6383(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L05779 mRNA. Translation: AAA02756.1.
X97024 expand/collapse EMBL AC list , X97025, X97026, X97027, X97028, X97029, X97030, X97031, X97032, X97033, X97034, X97035, X97036, X97037, X97038 Genomic DNA. Translation: CAA65751.1.
AF233334 mRNA. Translation: AAG14966.1.
AF233335 mRNA. Translation: AAG14967.1.
AF233336 mRNA. Translation: AAG14968.1.
BT006885 mRNA. Translation: AAP35531.1.
AK096089 mRNA. Translation: BAG53210.1.
AK096770 mRNA. Translation: BAG53362.1.
EU584434 Genomic DNA. Translation: ACD11487.1.
AF311103 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63548.1.
CH471080 Genomic DNA. Translation: EAW63549.1.
CH471080 Genomic DNA. Translation: EAW63551.1.
BC007708 mRNA. Translation: AAH07708.1.
BC011628 mRNA. Translation: AAH11628.1.
BC013874 mRNA. Translation: AAH13874.1.
CCDSCCDS59097.1. [P34913-2]
CCDS59098.1. [P34913-3]
CCDS6060.1. [P34913-1]
PIRJC4711.
RefSeqNP_001243411.1. NM_001256482.1. [P34913-2]
NP_001243412.1. NM_001256483.1. [P34913-3]
NP_001243413.1. NM_001256484.1. [P34913-2]
NP_001970.2. NM_001979.5. [P34913-1]
UniGeneHs.212088.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S8OX-ray2.60A1-555[»]
1VJ5X-ray2.35A1-555[»]
1ZD2X-ray3.00P1-555[»]
1ZD3X-ray2.30A1-555[»]
1ZD4X-ray2.70A1-555[»]
1ZD5X-ray2.60A1-555[»]
3ANSX-ray1.98A/B230-555[»]
3ANTX-ray2.40A/B230-555[»]
3I1YX-ray2.47A1-555[»]
3I28X-ray1.95A1-555[»]
3KOOX-ray2.79A1-555[»]
3OTQX-ray3.00A1-555[»]
3PDCX-ray2.60A/B226-548[»]
3WK4X-ray2.11A1-555[»]
3WK5X-ray2.77A1-555[»]
3WK6X-ray2.10A1-555[»]
3WK7X-ray2.20A1-555[»]
3WK8X-ray2.20A1-555[»]
3WK9X-ray2.20A1-555[»]
3WKAX-ray2.01A1-555[»]
3WKBX-ray2.20A1-555[»]
3WKCX-ray2.20A1-555[»]
3WKDX-ray2.48A1-555[»]
3WKEX-ray2.75A1-555[»]
4HAIX-ray2.55A1-555[»]
4J03X-ray2.92A1-555[»]
4JNCX-ray1.96A238-549[»]
ProteinModelPortalP34913.
SMRP34913. Positions 2-548.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108367. 5 interactions.
IntActP34913. 3 interactions.
MINTMINT-1385532.
STRING9606.ENSP00000369843.

Chemistry

BindingDBP34913.
ChEMBLCHEMBL2409.
DrugBankDB00675. Tamoxifen.

Protein family/group databases

MEROPSS33.973.

PTM databases

PhosphoSiteP34913.

Polymorphism databases

DMDM67476665.

Proteomic databases

MaxQBP34913.
PaxDbP34913.
PeptideAtlasP34913.
PRIDEP34913.

Protocols and materials databases

DNASU2053.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380476; ENSP00000369843; ENSG00000120915. [P34913-2]
ENST00000521400; ENSP00000430269; ENSG00000120915. [P34913-1]
ENST00000521780; ENSP00000430302; ENSG00000120915. [P34913-3]
GeneID2053.
KEGGhsa:2053.
UCSCuc003xfu.4. human. [P34913-1]

Organism-specific databases

CTD2053.
GeneCardsGC08P027348.
HGNCHGNC:3402. EPHX2.
HPACAB009808.
HPA023094.
HPA023660.
HPA023779.
MIM132811. gene.
neXtProtNX_P34913.
PharmGKBPA27830.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0596.
HOGENOMHOG000028073.
HOVERGENHBG006095.
InParanoidP34913.
KOK08726.
OMAGHWTQMD.
OrthoDBEOG72VH5T.
PhylomeDBP34913.
TreeFamTF315395.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKP34913.

Gene expression databases

ArrayExpressP34913.
BgeeP34913.
CleanExHS_EPHX2.
GenevestigatorP34913.

Family and domain databases

Gene3D1.10.150.240. 1 hit.
3.40.50.1000. 1 hit.
3.40.50.1820. 1 hit.
InterProIPR029058. AB_hydrolase.
IPR000073. AB_hydrolase_1.
IPR000639. Epox_hydrolase-like.
IPR023214. HAD-like_dom.
IPR006439. HAD-SF_hydro_IA.
IPR011945. HAD-SF_ppase_IA/epoxid_hydro_N.
IPR023198. PGP_dom2.
[Graphical view]
PfamPF00561. Abhydrolase_1. 1 hit.
PF13419. HAD_2. 1 hit.
[Graphical view]
PRINTSPR00111. ABHYDROLASE.
PR00412. EPOXHYDRLASE.
SUPFAMSSF53474. SSF53474. 1 hit.
SSF56784. SSF56784. 1 hit.
TIGRFAMsTIGR02247. HAD-1A3-hyp. 1 hit.
TIGR01509. HAD-SF-IA-v3. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP34913.
GeneWikiEpoxide_hydrolase_2.
GenomeRNAi2053.
NextBio35535129.
PROP34913.
SOURCESearch...

Entry information

Entry nameHYES_HUMAN
AccessionPrimary (citable) accession number: P34913
Secondary accession number(s): B2Z3B1 expand/collapse secondary AC list , B3KTU8, B3KUA0, G3V134, J3KPH7, Q16764, Q9HBJ1, Q9HBJ2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 7, 2005
Last modified: July 9, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM