P34914 · HYES_MOUSE
- ProteinBifunctional epoxide hydrolase 2
- GeneEphx2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids554 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
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
- 8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate + H2O = (8,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- 10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate + H2O = (10,11S,12R)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8S,9S)-dihydroxy-(5Z,11Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-dihydroxy-(5Z,8Z,11Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14S,15S)-dihydroxy-(5Z,8Z,11Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-dihydroxy-(5Z,8Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- (8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8R,9R)-dihydroxy-(5Z,11Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- 12-phosphooxy-(9Z)-octadecenoate + H2O = 12-hydroxy-(9Z)-octadecenoate + phosphateThis reaction proceeds in the forward direction.
- 12-phosphooxy-(9E)-octadecenoate + H2O = 12-hydroxy-(9E)-octadecenoate + phosphateThis reaction proceeds in the forward direction.
- 12-(phosphooxy)octadecanoate + H2O = 12-hydroxyoctadecanoate + phosphateThis reaction proceeds in the forward direction.
- 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = 8,9-dihydroxy-(5Z,11Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = 11,12-dihydroxy-(5Z,8Z,14Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = 14,15-dihydroxy-(5Z,8Z,11Z)-eicosatrienoateThis reaction proceeds in the forward direction.
- 9,10-epoxy-(12Z)-octadecenoate + H2O = 9,10-dihydroxy-(12Z)-octadecenoateThis reaction proceeds in the forward direction.
- 1-tetradecanoyl-sn-glycerol 3-phosphate + H2O = 1-tetradecanoyl-sn-glycerol + phosphateThis reaction proceeds in the forward direction.
- 1-octadecanoyl-sn-glycero-3-phosphate + H2O = 1-octadecanoyl-sn-glycerol + phosphateThis 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 + phosphateThis reaction proceeds in the forward direction.
- 1-hexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-sn-glycerol + phosphateThis reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphateThis reaction proceeds in the forward direction.
- (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-dihydroxy-(5Z,8Z,11Z)-eicosatrienoateThis reaction proceeds in the forward direction.
Cofactor
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).
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 μM | 14(R),15(S)-EET | |||||
5 μM | 14(S),15(R)-EET | |||||
3 μM | 11(R),12(R)-EET | |||||
4 μM | 11(S),12(R)-EET | |||||
41 μM | 8(R),9(S)-EET | |||||
5 μM | 8(S),9(R)-EET |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
9.03 μmol/min/mg | with 14(R),15(S)-EET as substrate | ||||
1.36 μmol/min/mg | with 14(S),15(R)-EET as substrate | ||||
0.82 μmol/min/mg | with 11(R),12(R)-EET as substrate | ||||
3.02 μmol/min/mg | with 11(S),12(R)-EET as substrate | ||||
0.83 μmol/min/mg | with 8(R),9(S)-EET as substrate | ||||
3.1 μmol/min/mg | with 8(S),9(R)-EET as substrate |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 9 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 11 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 123-124 | phosphate (UniProtKB | ChEBI) | ||||
Sequence: TN | ||||||
Binding site | 185 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 333 | Nucleophile | ||||
Sequence: D | ||||||
Binding site | 381 | substrate | ||||
Sequence: Y | ||||||
Active site | 465 | Proton donor | ||||
Sequence: Y | ||||||
Active site | 523 | Proton acceptor | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameBifunctional epoxide hydrolase 2
Including 2 domains:
- Recommended nameCytosolic epoxide hydrolase 2
- EC number
- Short namesCEH
- Alternative names
- Recommended nameLipid-phosphate phosphatase
- EC number
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP34914
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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).
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.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000084112 | 1-554 | Bifunctional epoxide hydrolase 2 | |||
Sequence: MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQLMKGKITFSQWVPLMDESYRKSSKACGANLPENFSISQIFSQAMAARSINRPMLQAAIALKKKGFTTCIVTNNWLDDGDKRDSLAQMMCELSQHFDFLIESCQVGMIKPEPQIYNFLLDTLKAKPNEVVFLDDFGSNLKPARDMGMVTILVHNTASALRELEKVTGTQFPEAPLPVPCNPNDVSHGYVTVKPGIRLHFVEMGSGPALCLCHGFPESWFSWRYQIPALAQAGFRVLAIDMKGYGDSSSPPEIEEYAMELLCKEMVTFLDKLGIPQAVFIGHDWAGVMVWNMALFYPERVRAVASLNTPFMPPDPDVSPMKVIRSIPVFNYQLYFQEPGVAEAELEKNMSRTFKSFFRASDETGFIAVHKATEIGGILVNTPEDPNLSKITTEEEIEFYIQQFKKTGFRGPLNWYRNTERNWKWSCKGLGRKILVPALMVTAEKDIVLRPEMSKNMEKWIPFLKRGHIEDCGHWTQIEKPTEVNQILIKWLQTEVQNPSVTSKI | ||||||
Modified residue | 55 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 176 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 176 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 191 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 215 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 368 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 371 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 420 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 454 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 504 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 508 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 508 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Lipidation | 521 | S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine | ||||
Sequence: C | ||||||
Modified residue | 553 | N6-succinyllysine | ||||
Sequence: K |
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
- PTM
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
Structure
Family & Domains
Features
Showing features for region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-224 | Phosphatase | ||||
Sequence: MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQLMKGKITFSQWVPLMDESYRKSSKACGANLPENFSISQIFSQAMAARSINRPMLQAAIALKKKGFTTCIVTNNWLDDGDKRDSLAQMMCELSQHFDFLIESCQVGMIKPEPQIYNFLLDTLKAKPNEVVFLDDFGSNLKPARDMGMVTILVHNTASALRELEKVTGTQFPEA | ||||||
Region | 233-554 | Epoxide hydrolase | ||||
Sequence: NDVSHGYVTVKPGIRLHFVEMGSGPALCLCHGFPESWFSWRYQIPALAQAGFRVLAIDMKGYGDSSSPPEIEEYAMELLCKEMVTFLDKLGIPQAVFIGHDWAGVMVWNMALFYPERVRAVASLNTPFMPPDPDVSPMKVIRSIPVFNYQLYFQEPGVAEAELEKNMSRTFKSFFRASDETGFIAVHKATEIGGILVNTPEDPNLSKITTEEEIEFYIQQFKKTGFRGPLNWYRNTERNWKWSCKGLGRKILVPALMVTAEKDIVLRPEMSKNMEKWIPFLKRGHIEDCGHWTQIEKPTEVNQILIKWLQTEVQNPSVTSKI | ||||||
Domain | 257-530 | AB hydrolase-1 | ||||
Sequence: PALCLCHGFPESWFSWRYQIPALAQAGFRVLAIDMKGYGDSSSPPEIEEYAMELLCKEMVTFLDKLGIPQAVFIGHDWAGVMVWNMALFYPERVRAVASLNTPFMPPDPDVSPMKVIRSIPVFNYQLYFQEPGVAEAELEKNMSRTFKSFFRASDETGFIAVHKATEIGGILVNTPEDPNLSKITTEEEIEFYIQQFKKTGFRGPLNWYRNTERNWKWSCKGLGRKILVPALMVTAEKDIVLRPEMSKNMEKWIPFLKRGHIEDCGHWTQIEKP | ||||||
Motif | 552-554 | Microbody targeting signal | ||||
Sequence: SKI |
Domain
The N-terminal domain has phosphatase activity. The C-terminal domain has epoxide hydrolase activity.
Sequence similarities
Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- Name1
- SynonymsEphx2A
- Length554
- Mass (Da)62,515
- Last updated1996-10-01 v2
- Checksum2F3A3F7DACE47C93
P34914-2
- Name2
- SynonymsEphx2B
- Differences from canonical
- 1-62: MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQLMKGKITFSQ → MRFAAMAAFSVFFVSKGLLMNSNIWCVGQEGPSQEDTDTIHTSE
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A8JYK8 | A8JYK8_MOUSE | Ephx2 | 488 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_013904 | 1-62 | in isoform 2 | |||
Sequence: MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQLMKGKITFSQ → MRFAAMAAFSVFFVSKGLLMNSNIWCVGQEGPSQEDTDTIHTSE | ||||||
Sequence conflict | 77 | in Ref. 2; CAA85471 | ||||
Sequence: A → T |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |