P34914 · HYES_MOUSE

  • Protein
    Bifunctional epoxide hydrolase 2
  • Gene
    Ephx2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides (PubMed:21217101, PubMed:7840649).
Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity).
Also determines steady-state levels of physiological mediators (By similarity).
Bifunctional enzyme. 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 and 12-phosphonooxy-octadec-9E-enoic acid (By similarity).
Has phosphatase activity toward lyso-glycerophospholipids with also some lower activity toward lysolipids of sphingolipid and isoprenoid phosphates (By similarity).

Catalytic activity

  • an epoxide + H2O = an ethanediol
    EC:3.3.2.10 (UniProtKB | ENZYME | Rhea)
  • (9S,10S)-10-hydroxy-9-(phosphooxy)octadecanoate + H2O = (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate
    EC:3.1.3.76 (UniProtKB | ENZYME | Rhea)
  • 8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate + H2O = (8,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • 10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate + H2O = (10,11S,12R)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8S,9S)-dihydroxy-(5Z,11Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-dihydroxy-(5Z,8Z,11Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14S,15S)-dihydroxy-(5Z,8Z,11Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • (8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8R,9R)-dihydroxy-(5Z,11Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • 12-phosphooxy-(9Z)-octadecenoate + H2O = 12-hydroxy-(9Z)-octadecenoate + phosphate
    This reaction proceeds in the forward direction.
  • 12-phosphooxy-(9E)-octadecenoate + H2O = 12-hydroxy-(9E)-octadecenoate + phosphate
    This reaction proceeds in the forward direction.
  • 12-(phosphooxy)octadecanoate + H2O = 12-hydroxyoctadecanoate + phosphate
    This reaction proceeds in the forward direction.
  • 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = 8,9-dihydroxy-(5Z,11Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = 11,12-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = 14,15-dihydroxy-(5Z,8Z,11Z)-eicosatrienoate
    This reaction proceeds in the forward direction.
  • 9,10-epoxy-(12Z)-octadecenoate + H2O = 9,10-dihydroxy-(12Z)-octadecenoate
    This reaction proceeds in the forward direction.
  • 1-tetradecanoyl-sn-glycerol 3-phosphate + H2O = 1-tetradecanoyl-sn-glycerol + phosphate
    This reaction proceeds in the forward direction.
  • 1-octadecanoyl-sn-glycero-3-phosphate + H2O = 1-octadecanoyl-sn-glycerol + phosphate
    This reaction proceeds in the forward direction.
  • 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + phosphate
    This reaction proceeds in the forward direction.
  • 1-hexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-sn-glycerol + phosphate
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphate
    This reaction proceeds in the forward direction.
  • (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-dihydroxy-(5Z,8Z,11Z)-eicosatrienoate
    This reaction proceeds in the forward direction.

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Activity regulation

Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA) (By similarity).
Phosphatase activity is inhibited by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic acids and fatty acids such as palmitic acid and lauric acid (PubMed:21217101).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
4 μM14(R),15(S)-EET
5 μM14(S),15(R)-EET
3 μM11(R),12(R)-EET
4 μM11(S),12(R)-EET
41 μM8(R),9(S)-EET
5 μM8(S),9(R)-EET
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
9.03 μmol/min/mgwith 14(R),15(S)-EET as substrate
1.36 μmol/min/mgwith 14(S),15(R)-EET as substrate
0.82 μmol/min/mgwith 11(R),12(R)-EET as substrate
3.02 μmol/min/mgwith 11(S),12(R)-EET as substrate
0.83 μmol/min/mgwith 8(R),9(S)-EET as substrate
3.1 μmol/min/mgwith 8(S),9(R)-EET as substrate

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site9Mg2+ (UniProtKB | ChEBI)
Binding site11Mg2+ (UniProtKB | ChEBI)
Binding site123-124phosphate (UniProtKB | ChEBI)
Binding site185Mg2+ (UniProtKB | ChEBI)
Active site333Nucleophile
Binding site381substrate
Active site465Proton donor
Active site523Proton acceptor

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentperoxisome
Molecular Function10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity
Molecular Functionepoxide hydrolase activity
Molecular Functionlipid phosphatase activity
Molecular Functionlysophosphatidic acid phosphatase activity
Molecular Functionmagnesium ion binding
Molecular Functionphosphatase activity
Molecular Functionprotein homodimerization activity
Molecular Functiontoxic substance binding
Biological Processcholesterol homeostasis
Biological Processdephosphorylation
Biological Processepoxide metabolic process
Biological Processlinoleic acid metabolic process
Biological Processphospholipid dephosphorylation
Biological Processpositive regulation of blood pressure
Biological Processpositive regulation of gene expression
Biological Processprostaglandin production involved in inflammatory response
Biological Processregulation of cholesterol metabolic process
Biological Processresponse to toxic substance
Biological Processstilbene catabolic process

Keywords

Enzyme and pathway databases

Protein family/group databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Bifunctional epoxide hydrolase 2

Including 2 domains:

  • Recommended name
    Cytosolic epoxide hydrolase 2
  • EC number
  • Short names
    CEH
  • Alternative names
    • Epoxide hydratase
    • Soluble epoxide hydrolase
      (SEH
      )
  • Recommended name
    Lipid-phosphate phosphatase
  • EC number

Gene names

    • Name
      Ephx2
    • Synonyms
      Eph2

Organism names

  • Taxonomic identifier
  • Strains
    • NMRI
    • C57BL/6J
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P34914
  • Secondary accessions
    • Q8CGV0

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

In knockout mice, hepoxilin turnover to trioxilins is greatly abolished (PubMed:21217101).
In livers, the activity toward HxA3 (8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate) and HxB3 (10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate) is greatly reduced compared with the WT mice (PubMed:21217101).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 42 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue, lipidation.

TypeIDPosition(s)Description
ChainPRO_00000841121-554Bifunctional epoxide hydrolase 2
Modified residue55N6-succinyllysine
Modified residue176N6-acetyllysine; alternate
Modified residue176N6-succinyllysine; alternate
Modified residue191N6-acetyllysine
Modified residue215N6-acetyllysine
Modified residue368Phosphoserine
Modified residue371N6-succinyllysine
Modified residue420N6-succinyllysine
Modified residue454N6-succinyllysine
Modified residue504N6-succinyllysine
Modified residue508N6-acetyllysine; alternate
Modified residue508N6-succinyllysine; alternate
Lipidation521S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine
Modified residue553N6-succinyllysine

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 (By similarity).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in liver, intestine, ovary and kidney. Detected at low levels in heart and muscle.

Induction

Up-regulated during the luteal phase of the stimulated estrus cycle and by compounds that cause peroxisome proliferation, such as clofibrate, tiadenol and fenofibrate.

Gene expression databases

Interaction

Subunit

Homodimer.

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, domain, motif.

TypeIDPosition(s)Description
Region1-224Phosphatase
Region233-554Epoxide hydrolase
Domain257-530AB hydrolase-1
Motif552-554Microbody targeting signal

Domain

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

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

P34914-1

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.

  • Name
    1
  • Synonyms
    Ephx2A
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    554
  • Mass (Da)
    62,515
  • Last updated
    1996-10-01 v2
  • Checksum
    2F3A3F7DACE47C93
MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQLMKGKITFSQWVPLMDESYRKSSKACGANLPENFSISQIFSQAMAARSINRPMLQAAIALKKKGFTTCIVTNNWLDDGDKRDSLAQMMCELSQHFDFLIESCQVGMIKPEPQIYNFLLDTLKAKPNEVVFLDDFGSNLKPARDMGMVTILVHNTASALRELEKVTGTQFPEAPLPVPCNPNDVSHGYVTVKPGIRLHFVEMGSGPALCLCHGFPESWFSWRYQIPALAQAGFRVLAIDMKGYGDSSSPPEIEEYAMELLCKEMVTFLDKLGIPQAVFIGHDWAGVMVWNMALFYPERVRAVASLNTPFMPPDPDVSPMKVIRSIPVFNYQLYFQEPGVAEAELEKNMSRTFKSFFRASDETGFIAVHKATEIGGILVNTPEDPNLSKITTEEEIEFYIQQFKKTGFRGPLNWYRNTERNWKWSCKGLGRKILVPALMVTAEKDIVLRPEMSKNMEKWIPFLKRGHIEDCGHWTQIEKPTEVNQILIKWLQTEVQNPSVTSKI

P34914-2

  • Name
    2
  • Synonyms
    Ephx2B
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-62: MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQLMKGKITFSQ → MRFAAMAAFSVFFVSKGLLMNSNIWCVGQEGPSQEDTDTIHTSE

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A8JYK8A8JYK8_MOUSEEphx2488

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0139041-62in isoform 2
Sequence conflict77in Ref. 2; CAA85471

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
L05781
EMBL· GenBank· DDBJ
AAA37555.1
EMBL· GenBank· DDBJ
mRNA
Z37107
EMBL· GenBank· DDBJ
CAA85471.1
EMBL· GenBank· DDBJ
mRNA
AY098585
EMBL· GenBank· DDBJ
AAM28238.1
EMBL· GenBank· DDBJ
mRNA
BC015087
EMBL· GenBank· DDBJ
AAH15087.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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