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P34914 (HYES_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·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
Synonyms:Eph2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length554 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 By similarity.

Catalytic activity

An epoxide + H2O = a glycol.

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

Cofactor

Magnesium By similarity.

Subunit structure

Homodimer.

Subcellular location

Cytoplasm. Peroxisome.

Tissue specificity

Detected in liver, intestine, ovary and kidney. Detected at low levels in heart and muscle. Ref.2 Ref.3

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. Ref.1 Ref.2 Ref.3

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 By similarity.

Sequence similarities

Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.

Ontologies

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

Inferred from direct assay PubMed 18974052. Source: UniProtKB

phospholipid dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 18974052. Source: UniProtKB

regulation of cholesterol metabolic process

Inferred from mutant phenotype PubMed 18974052. Source: UniProtKB

response to toxic substance

Inferred from electronic annotation. Source: UniProtKB-KW

stilbene catabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

focal adhesion

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from electronic annotation. Source: Ensembl

peroxisome

Inferred from electronic annotation. Source: UniProtKB-SubCell

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

Inferred from electronic annotation. Source: UniProtKB-EC

epoxide hydrolase activity

Inferred from electronic annotation. Source: UniProtKB-EC

lipid phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

toxic substance binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P34914-1)

Also known as: Ephx2A;

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: P34914-2)

Also known as: Ephx2B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-62: MALRVAAFDL...LMKGKITFSQ → MRFAAMAAFS...EDTDTIHTSE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 554554Bifunctional epoxide hydrolase 2
PRO_0000084112

Regions

Region1 – 224224Phosphatase
Region123 – 1242Phosphate binding By similarity
Region233 – 554322Epoxide hydrolase
Motif552 – 5543Microbody targeting signal Potential

Sites

Active site3331Nucleophile
Active site4651Proton donor
Active site5231Proton acceptor
Metal binding91Magnesium By similarity
Metal binding111Magnesium By similarity
Metal binding1851Magnesium By similarity
Binding site3811Substrate By similarity

Amino acid modifications

Modified residue551N6-succinyllysine Ref.6
Modified residue1761N6-acetyllysine; alternate Ref.7
Modified residue1761N6-succinyllysine; alternate Ref.6
Modified residue1911N6-acetyllysine Ref.7
Modified residue2151N6-acetyllysine Ref.7
Modified residue3681Phosphoserine Ref.5
Modified residue3711N6-succinyllysine Ref.6
Modified residue4201N6-succinyllysine Ref.6
Modified residue4541N6-succinyllysine Ref.6
Modified residue5041N6-succinyllysine Ref.6
Modified residue5081N6-acetyllysine; alternate Ref.7
Modified residue5081N6-succinyllysine; alternate Ref.6
Modified residue5531N6-succinyllysine Ref.6
Lipidation5211S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine By similarity

Natural variations

Alternative sequence1 – 6262MALRV…ITFSQ → MRFAAMAAFSVFFVSKGLLM NSNIWCVGQEGPSQEDTDTI HTSE in isoform 2.
VSP_013904

Experimental info

Sequence conflict771A → T in CAA85471. Ref.2

Secondary structure

................................................................................................ 554
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Ephx2A) [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 2F3A3F7DACE47C93

FASTA55462,515
        10         20         30         40         50         60 
MALRVAAFDL DGVLALPSIA GAFRRSEEAL ALPRDFLLGA YQTEFPEGPT EQLMKGKITF 

        70         80         90        100        110        120 
SQWVPLMDES YRKSSKACGA NLPENFSISQ IFSQAMAARS INRPMLQAAI ALKKKGFTTC 

       130        140        150        160        170        180 
IVTNNWLDDG DKRDSLAQMM CELSQHFDFL IESCQVGMIK PEPQIYNFLL DTLKAKPNEV 

       190        200        210        220        230        240 
VFLDDFGSNL KPARDMGMVT ILVHNTASAL RELEKVTGTQ FPEAPLPVPC NPNDVSHGYV 

       250        260        270        280        290        300 
TVKPGIRLHF VEMGSGPALC LCHGFPESWF SWRYQIPALA QAGFRVLAID MKGYGDSSSP 

       310        320        330        340        350        360 
PEIEEYAMEL LCKEMVTFLD KLGIPQAVFI GHDWAGVMVW NMALFYPERV RAVASLNTPF 

       370        380        390        400        410        420 
MPPDPDVSPM KVIRSIPVFN YQLYFQEPGV AEAELEKNMS RTFKSFFRAS DETGFIAVHK 

       430        440        450        460        470        480 
ATEIGGILVN TPEDPNLSKI TTEEEIEFYI QQFKKTGFRG PLNWYRNTER NWKWSCKGLG 

       490        500        510        520        530        540 
RKILVPALMV TAEKDIVLRP EMSKNMEKWI PFLKRGHIED CGHWTQIEKP TEVNQILIKW 

       550 
LQTEVQNPSV TSKI 

« Hide

Isoform 2 (Ephx2B) [UniParc].

Checksum: D9BD995CB9347551
Show »

FASTA53660,613

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of murine liver soluble epoxide hydrolase."
Grant D.F., Storms D.H., Hammock B.D.
J. Biol. Chem. 268:17628-17633(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, INDUCTION.
Tissue: Liver.
[2]"Tissue specific basal expression of soluble murine epoxide hydrolase and effects of clofibrate on the mRNA levels in extrahepatic tissues and liver."
Johansson C., Stark A., Sandberg M., Ek B., Rask L., Meijer J.
Arch. Toxicol. 70:61-63(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION.
Strain: NMRI.
[3]"Identification and characterization of an ovary-selective isoform of epoxide hydrolase."
Hennebold J.D., Mah K., Perez W., Vance J.E., Stouffer R.L., Morisseau C., Hammock B.D., Adashi E.Y.
Biol. Reprod. 72:968-975(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INDUCTION.
Strain: C57BL/6.
[4]"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).
Strain: FVB/N.
Tissue: Colon.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-55; LYS-176; LYS-371; LYS-420; LYS-454; LYS-504; LYS-508 AND LYS-553, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-176; LYS-191; LYS-215 AND LYS-508, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase."
Argiriadi M.A., Morisseau C., Hammock B.D., Christianson D.W.
Proc. Natl. Acad. Sci. U.S.A. 96:10637-10642(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Tissue: Liver.
[9]"Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation."
Argiriadi M.A., Morisseau C., Goodrow M.H., Dowdy D.L., Hammock B.D., Christianson D.W.
J. Biol. Chem. 275:15265-15270(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH EPOXIDE HYDROLASE INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L05781 mRNA. Translation: AAA37555.1.
Z37107 mRNA. Translation: CAA85471.1.
AY098585 mRNA. Translation: AAM28238.1.
BC015087 mRNA. Translation: AAH15087.1.
CCDSCCDS27218.1. [P34914-1]
PIRA47504.
RefSeqNP_001258332.1. NM_001271403.1. [P34914-2]
NP_031966.2. NM_007940.4. [P34914-1]
UniGeneMm.15295.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CQZX-ray2.80A/B1-554[»]
1CR6X-ray2.80A/B1-554[»]
1EK1X-ray3.10A/B1-554[»]
1EK2X-ray3.00A/B1-554[»]
ProteinModelPortalP34914.
SMRP34914. Positions 4-544.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP34914. 5 interactions.
MINTMINT-1859181.

Chemistry

BindingDBP34914.
ChEMBLCHEMBL4140.

Protein family/group databases

MEROPSS33.973.

PTM databases

PhosphoSiteP34914.

2D gel databases

SWISS-2DPAGEP34914.

Proteomic databases

MaxQBP34914.
PaxDbP34914.
PRIDEP34914.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000070515; ENSMUSP00000069209; ENSMUSG00000022040. [P34914-1]
GeneID13850.
KEGGmmu:13850.
UCSCuc007ujv.1. mouse. [P34914-1]

Organism-specific databases

CTD2053.
MGIMGI:99500. Ephx2.

Phylogenomic databases

eggNOGCOG0596.
GeneTreeENSGT00530000063213.
HOGENOMHOG000028073.
HOVERGENHBG006095.
InParanoidP34914.
KOK08726.
OMAGHWTQMD.
OrthoDBEOG72VH5T.
PhylomeDBP34914.
TreeFamTF315395.

Enzyme and pathway databases

BRENDA3.3.2.10. 3474.

Gene expression databases

ArrayExpressP34914.
BgeeP34914.
CleanExMM_EPHX2.
GenevestigatorP34914.

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.
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.
TIGRFAMsTIGR01509. HAD-SF-IA-v3. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP34914.
NextBio284704.
PROP34914.
SOURCESearch...

Entry information

Entry nameHYES_MOUSE
AccessionPrimary (citable) accession number: P34914
Secondary accession number(s): Q8CGV0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot