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P34913

- HYES_HUMAN

UniProt

P34913 - HYES_HUMAN

Protein

Bifunctional epoxide hydrolase 2

Gene

EPHX2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 2 (07 Jun 2005)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Catalytic activityi

    An epoxide + H2O = a glycol.
    (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate.

    Cofactori

    Magnesium.1 Publication

    Kineticsi

    1. KM=21 µM for threo-9,10-phosphonooxy-hydroxy-octadecanoic acid3 Publications
    2. KM=1.1 mM for p-nitrophenyl phosphate3 Publications

    Vmax=338 nmol/min/mg enzyme with threo-9,10-phosphonooxy-hydroxy-octadecanoic acid3 Publications

    Vmax=5.8 nmol/min/mg enzyme with p-nitrophenyl phosphate3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi9 – 91Magnesium1 Publication
    Metal bindingi11 – 111Magnesium1 Publication
    Metal bindingi185 – 1851Magnesium1 Publication
    Active sitei335 – 3351Nucleophile
    Binding sitei383 – 3831Substrate
    Active sitei466 – 4661Proton donor
    Active sitei524 – 5241Proton acceptor

    GO - Molecular functioni

    1. 10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity Source: UniProtKB-EC
    2. epoxide hydrolase activity Source: UniProtKB
    3. lipid phosphatase activity Source: UniProtKB
    4. magnesium ion binding Source: UniProtKB
    5. phosphatase activity Source: UniProtKB
    6. protein homodimerization activity Source: UniProtKB
    7. receptor binding Source: UniProtKB
    8. toxic substance binding Source: UniProtKB

    GO - Biological processi

    1. arachidonic acid metabolic process Source: Reactome
    2. cellular calcium ion homeostasis Source: UniProtKB
    3. cholesterol homeostasis Source: UniProtKB
    4. dephosphorylation Source: UniProtKB
    5. drug metabolic process Source: UniProtKB
    6. epoxygenase P450 pathway Source: Reactome
    7. inflammatory response Source: UniProtKB
    8. phospholipid dephosphorylation Source: UniProtKB
    9. positive regulation of gene expression Source: UniProtKB
    10. positive regulation of vasodilation Source: UniProtKB
    11. reactive oxygen species metabolic process Source: UniProtKB
    12. regulation of blood pressure Source: UniProtKB
    13. regulation of cholesterol metabolic process Source: UniProtKB
    14. response to toxic substance Source: UniProtKB
    15. small molecule metabolic process Source: Reactome
    16. stilbene catabolic process Source: UniProtKB
    17. xenobiotic metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Aromatic hydrocarbons catabolism, Detoxification, Lipid metabolism

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_150417. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    SABIO-RKP34913.

    Protein family/group databases

    MEROPSiS33.973.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional epoxide hydrolase 2
    Including the following 2 domains:
    Cytosolic epoxide hydrolase 2 (EC:3.3.2.10)
    Short name:
    CEH
    Alternative name(s):
    Epoxide hydratase
    Soluble epoxide hydrolase
    Short name:
    SEH
    Lipid-phosphate phosphatase (EC:3.1.3.76)
    Gene namesi
    Name:EPHX2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:3402. EPHX2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. extracellular vesicular exosome Source: UniProt
    3. peroxisome Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Peroxisome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi9 – 91D → A: Loss of phosphatase activity. 1 Publication
    Mutagenesisi522 – 5221C → S: Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine-induced inhibition of epoxide hydrolase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA27830.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 555555Bifunctional epoxide hydrolase 2PRO_0000084111Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei43 – 431N6-acetyllysine1 Publication
    Modified residuei55 – 551N6-succinyllysineBy similarity
    Modified residuei191 – 1911N6-acetyllysineBy similarity
    Modified residuei215 – 2151N6-acetyllysineBy similarity
    Modified residuei370 – 3701PhosphoserineBy similarity
    Modified residuei421 – 4211N6-succinyllysineBy similarity
    Modified residuei455 – 4551N6-succinyllysineBy similarity
    Lipidationi522 – 5221S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine1 Publication
    Modified residuei554 – 5541N6-succinyllysineBy similarity

    Post-translational modificationi

    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.Curated

    Keywords - PTMi

    Acetylation, Lipoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiP34913.
    PaxDbiP34913.
    PeptideAtlasiP34913.
    PRIDEiP34913.

    PTM databases

    PhosphoSiteiP34913.

    Expressioni

    Inductioni

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

    Gene expression databases

    ArrayExpressiP34913.
    BgeeiP34913.
    CleanExiHS_EPHX2.
    GenevestigatoriP34913.

    Organism-specific databases

    HPAiCAB009808.
    HPA023094.
    HPA023660.
    HPA023779.

    Interactioni

    Subunit structurei

    Homodimer.3 Publications

    Protein-protein interaction databases

    BioGridi108367. 5 interactions.
    IntActiP34913. 3 interactions.
    MINTiMINT-1385532.
    STRINGi9606.ENSP00000369843.

    Structurei

    Secondary structure

    1
    555
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 84
    Turni12 – 143
    Beta strandi15 – 173
    Helixi20 – 2910
    Helixi36 – 427
    Helixi45 – 473
    Helixi49 – 546
    Beta strandi57 – 593
    Helixi60 – 7718
    Helixi88 – 9811
    Helixi103 – 11412
    Beta strandi118 – 1236
    Turni131 – 1333
    Helixi134 – 14411
    Beta strandi147 – 1526
    Helixi153 – 1564
    Helixi163 – 17311
    Helixi177 – 1793
    Beta strandi180 – 1856
    Helixi187 – 19610
    Beta strandi199 – 2024
    Helixi206 – 21712
    Helixi234 – 2363
    Beta strandi237 – 2459
    Beta strandi248 – 2558
    Beta strandi257 – 2648
    Helixi271 – 2744
    Helixi277 – 2837
    Beta strandi287 – 2915
    Helixi305 – 3084
    Helixi310 – 32415
    Beta strandi329 – 3346
    Helixi336 – 34712
    Helixi349 – 3513
    Beta strandi352 – 3598
    Beta strandi367 – 3693
    Helixi371 – 3766
    Helixi379 – 3813
    Helixi382 – 3887
    Helixi392 – 3998
    Helixi401 – 4088
    Helixi412 – 4143
    Helixi419 – 4213
    Helixi422 – 4254
    Beta strandi427 – 4293
    Beta strandi440 – 4423
    Helixi444 – 45411
    Turni455 – 4595
    Helixi460 – 4645
    Helixi465 – 4673
    Helixi469 – 4779
    Turni478 – 4814
    Beta strandi488 – 4936
    Beta strandi497 – 4993
    Helixi501 – 5044
    Helixi507 – 5093
    Beta strandi515 – 5195
    Helixi526 – 5294
    Helixi531 – 54515

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP34913.
    SMRiP34913. Positions 2-548.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP34913.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 224224PhosphataseAdd
    BLAST
    Regioni123 – 1242Phosphate binding
    Regioni235 – 555321Epoxide hydrolaseAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi553 – 5553Microbody targeting signalSequence Analysis

    Domaini

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

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0596.
    HOGENOMiHOG000028073.
    HOVERGENiHBG006095.
    InParanoidiP34913.
    KOiK08726.
    OMAiGHWTQMD.
    OrthoDBiEOG72VH5T.
    PhylomeDBiP34913.
    TreeFamiTF315395.

    Family and domain databases

    Gene3Di1.10.150.240. 1 hit.
    3.40.50.1000. 1 hit.
    3.40.50.1820. 1 hit.
    InterProiIPR029058. 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]
    PfamiPF00561. Abhydrolase_1. 1 hit.
    PF13419. HAD_2. 1 hit.
    [Graphical view]
    PRINTSiPR00111. ABHYDROLASE.
    PR00412. EPOXHYDRLASE.
    SUPFAMiSSF53474. SSF53474. 1 hit.
    SSF56784. SSF56784. 1 hit.
    TIGRFAMsiTIGR02247. HAD-1A3-hyp. 1 hit.
    TIGR01509. HAD-SF-IA-v3. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P34913-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MTLRAAVFDL DGVLALPAVF GVLGRTEEAL ALPRGLLNDA FQKGGPEGAT    50
    TRLMKGEITL SQWIPLMEEN CRKCSETAKV CLPKNFSIKE IFDKAISARK 100
    INRPMLQAAL MLRKKGFTTA ILTNTWLDDR AERDGLAQLM CELKMHFDFL 150
    IESCQVGMVK PEPQIYKFLL DTLKASPSEV VFLDDIGANL KPARDLGMVT 200
    ILVQDTDTAL KELEKVTGIQ LLNTPAPLPT SCNPSDMSHG YVTVKPRVRL 250
    HFVELGSGPA VCLCHGFPES WYSWRYQIPA LAQAGYRVLA MDMKGYGESS 300
    APPEIEEYCM EVLCKEMVTF LDKLGLSQAV FIGHDWGGML VWYMALFYPE 350
    RVRAVASLNT PFIPANPNMS PLESIKANPV FDYQLYFQEP GVAEAELEQN 400
    LSRTFKSLFR ASDESVLSMH KVCEAGGLFV NSPEEPSLSR MVTEEEIQFY 450
    VQQFKKSGFR GPLNWYRNME RNWKWACKSL GRKILIPALM VTAEKDFVLV 500
    PQMSQHMEDW IPHLKRGHIE DCGHWTQMDK PTEVNQILIK WLDSDARNPP 550
    VVSKM 555
    Length:555
    Mass (Da):62,616
    Last modified:June 7, 2005 - v2
    Checksum:i1B5ACE7F80F9A26C
    GO
    Isoform 2 (identifier: P34913-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-53: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:502
    Mass (Da):57,123
    Checksum:iCB56A36CDF4F2FFF
    GO
    Isoform 3 (identifier: P34913-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-66: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:489
    Mass (Da):55,626
    Checksum:i7188F0A08408CD29
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti5 – 51A → G in AAA02756. (PubMed:8342951)Curated
    Sequence conflicti257 – 2582SG → W in AAA02756. (PubMed:8342951)Curated
    Sequence conflicti409 – 4091F → L in BAG53362. (PubMed:14702039)Curated
    Sequence conflicti473 – 4731W → R in BAG53362. (PubMed:14702039)Curated
    Sequence conflicti494 – 4941E → G in BAG53362. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti21 – 211G → A.1 Publication
    VAR_055392
    Natural varianti52 – 521R → Q.1 Publication
    Corresponds to variant rs72475803 [ dbSNP | Ensembl ].
    VAR_055393
    Natural varianti55 – 551K → R Decreased phosphatase activity; no effect on epoxyde hydrolase activity. 1 Publication
    Corresponds to variant rs41507953 [ dbSNP | Ensembl ].
    VAR_051059
    Natural varianti103 – 1031R → C Decreased phosphatase activity; no effect on epoxyde hydrolase activity. 1 Publication
    Corresponds to variant rs17057255 [ dbSNP | Ensembl ].
    VAR_033991
    Natural varianti154 – 1541C → Y Decreased phosphatase activity; no effect on epoxyde hydrolase activity. 1 Publication
    Corresponds to variant rs57699806 [ dbSNP | Ensembl ].
    VAR_055394
    Natural varianti225 – 2251P → L.1 Publication
    VAR_055395
    Natural varianti287 – 2871R → Q No effect on phosphatase activity; decreased epoxyde hydrolase activity. 3 Publications
    Corresponds to variant rs751141 [ dbSNP | Ensembl ].
    VAR_014852
    Natural varianti369 – 3691M → V.1 Publication
    Corresponds to variant rs72475894 [ dbSNP | Ensembl ].
    VAR_055396
    Natural varianti403 – 4031R → RR.2 Publications
    VAR_022613
    Natural varianti470 – 4701E → G No effect on phosphatase activity and epoxyde hydrolase activity. 1 Publication
    Corresponds to variant rs68053459 [ dbSNP | Ensembl ].
    VAR_055397

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6666Missing in isoform 3. 1 PublicationVSP_045597Add
    BLAST
    Alternative sequencei1 – 5353Missing in isoform 2. 1 PublicationVSP_045598Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L05779 mRNA. Translation: AAA02756.1.
    X97024
    , 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.
    CCDSiCCDS59097.1. [P34913-2]
    CCDS59098.1. [P34913-3]
    CCDS6060.1. [P34913-1]
    PIRiJC4711.
    RefSeqiNP_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]
    UniGeneiHs.212088.

    Genome annotation databases

    EnsembliENST00000380476; ENSP00000369843; ENSG00000120915. [P34913-2]
    ENST00000521400; ENSP00000430269; ENSG00000120915. [P34913-1]
    ENST00000521780; ENSP00000430302; ENSG00000120915. [P34913-3]
    GeneIDi2053.
    KEGGihsa:2053.
    UCSCiuc003xfu.4. human. [P34913-1]

    Polymorphism databases

    DMDMi67476665.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L05779 mRNA. Translation: AAA02756.1 .
    X97024
    , 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 .
    CCDSi CCDS59097.1. [P34913-2 ]
    CCDS59098.1. [P34913-3 ]
    CCDS6060.1. [P34913-1 ]
    PIRi JC4711.
    RefSeqi NP_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 ]
    UniGenei Hs.212088.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1S8O X-ray 2.60 A 1-555 [» ]
    1VJ5 X-ray 2.35 A 1-555 [» ]
    1ZD2 X-ray 3.00 P 1-555 [» ]
    1ZD3 X-ray 2.30 A 1-555 [» ]
    1ZD4 X-ray 2.70 A 1-555 [» ]
    1ZD5 X-ray 2.60 A 1-555 [» ]
    3ANS X-ray 1.98 A/B 230-555 [» ]
    3ANT X-ray 2.40 A/B 230-555 [» ]
    3I1Y X-ray 2.47 A 1-555 [» ]
    3I28 X-ray 1.95 A 1-555 [» ]
    3KOO X-ray 2.79 A 1-555 [» ]
    3OTQ X-ray 3.00 A 1-555 [» ]
    3PDC X-ray 2.60 A/B 226-548 [» ]
    3WK4 X-ray 2.11 A 1-555 [» ]
    3WK5 X-ray 2.77 A 1-555 [» ]
    3WK6 X-ray 2.10 A 1-555 [» ]
    3WK7 X-ray 2.20 A 1-555 [» ]
    3WK8 X-ray 2.20 A 1-555 [» ]
    3WK9 X-ray 2.20 A 1-555 [» ]
    3WKA X-ray 2.01 A 1-555 [» ]
    3WKB X-ray 2.20 A 1-555 [» ]
    3WKC X-ray 2.20 A 1-555 [» ]
    3WKD X-ray 2.48 A 1-555 [» ]
    3WKE X-ray 2.75 A 1-555 [» ]
    4HAI X-ray 2.55 A 1-555 [» ]
    4J03 X-ray 2.92 A 1-555 [» ]
    4JNC X-ray 1.96 A 238-549 [» ]
    ProteinModelPortali P34913.
    SMRi P34913. Positions 2-548.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108367. 5 interactions.
    IntActi P34913. 3 interactions.
    MINTi MINT-1385532.
    STRINGi 9606.ENSP00000369843.

    Chemistry

    BindingDBi P34913.
    ChEMBLi CHEMBL2409.
    DrugBanki DB00675. Tamoxifen.

    Protein family/group databases

    MEROPSi S33.973.

    PTM databases

    PhosphoSitei P34913.

    Polymorphism databases

    DMDMi 67476665.

    Proteomic databases

    MaxQBi P34913.
    PaxDbi P34913.
    PeptideAtlasi P34913.
    PRIDEi P34913.

    Protocols and materials databases

    DNASUi 2053.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000380476 ; ENSP00000369843 ; ENSG00000120915 . [P34913-2 ]
    ENST00000521400 ; ENSP00000430269 ; ENSG00000120915 . [P34913-1 ]
    ENST00000521780 ; ENSP00000430302 ; ENSG00000120915 . [P34913-3 ]
    GeneIDi 2053.
    KEGGi hsa:2053.
    UCSCi uc003xfu.4. human. [P34913-1 ]

    Organism-specific databases

    CTDi 2053.
    GeneCardsi GC08P027348.
    HGNCi HGNC:3402. EPHX2.
    HPAi CAB009808.
    HPA023094.
    HPA023660.
    HPA023779.
    MIMi 132811. gene.
    neXtProti NX_P34913.
    PharmGKBi PA27830.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0596.
    HOGENOMi HOG000028073.
    HOVERGENi HBG006095.
    InParanoidi P34913.
    KOi K08726.
    OMAi GHWTQMD.
    OrthoDBi EOG72VH5T.
    PhylomeDBi P34913.
    TreeFami TF315395.

    Enzyme and pathway databases

    Reactomei REACT_150417. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    SABIO-RK P34913.

    Miscellaneous databases

    EvolutionaryTracei P34913.
    GeneWikii Epoxide_hydrolase_2.
    GenomeRNAii 2053.
    NextBioi 35535129.
    PROi P34913.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P34913.
    Bgeei P34913.
    CleanExi HS_EPHX2.
    Genevestigatori P34913.

    Family and domain databases

    Gene3Di 1.10.150.240. 1 hit.
    3.40.50.1000. 1 hit.
    3.40.50.1820. 1 hit.
    InterProi IPR029058. 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 ]
    Pfami PF00561. Abhydrolase_1. 1 hit.
    PF13419. HAD_2. 1 hit.
    [Graphical view ]
    PRINTSi PR00111. ABHYDROLASE.
    PR00412. EPOXHYDRLASE.
    SUPFAMi SSF53474. SSF53474. 1 hit.
    SSF56784. SSF56784. 1 hit.
    TIGRFAMsi TIGR02247. HAD-1A3-hyp. 1 hit.
    TIGR01509. HAD-SF-IA-v3. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.
      , 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. 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. 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. 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.

    Entry informationi

    Entry nameiHYES_HUMAN
    AccessioniPrimary (citable) accession number: P34913
    Secondary accession number(s): B2Z3B1
    , B3KTU8, B3KUA0, G3V134, J3KPH7, Q16764, Q9HBJ1, Q9HBJ2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: June 7, 2005
    Last modified: October 1, 2014
    This is version 150 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3