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P34914

- HYES_MOUSE

UniProt

P34914 - HYES_MOUSE

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Protein
Bifunctional epoxide hydrolase 2
Gene
Ephx2, Eph2
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 By similarity.

Catalytic activityi

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

Cofactori

Magnesium By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi9 – 91Magnesium By similarity
Metal bindingi11 – 111Magnesium By similarity
Metal bindingi185 – 1851Magnesium By similarity
Active sitei333 – 3331Nucleophile
Binding sitei381 – 3811Substrate By similarity
Active sitei465 – 4651Proton donor
Active sitei523 – 5231Proton acceptor

GO - Molecular functioni

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

GO - Biological processi

  1. cholesterol homeostasis Source: UniProtKB
  2. phospholipid dephosphorylation Source: UniProtKB
  3. positive regulation of gene expression Source: UniProtKB
  4. regulation of cholesterol metabolic process Source: UniProtKB
  5. response to toxic substance Source: UniProtKB-KW
  6. stilbene catabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Aromatic hydrocarbons catabolism, Detoxification, Lipid metabolism

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.3.2.10. 3474.
ReactomeiREACT_196570. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).

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
Synonyms:Eph2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 14

Organism-specific databases

MGIiMGI:99500. Ephx2.

Subcellular locationi

GO - Cellular componenti

  1. Golgi apparatus Source: Ensembl
  2. focal adhesion Source: Ensembl
  3. nucleolus Source: Ensembl
  4. peroxisome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Peroxisome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 554554Bifunctional epoxide hydrolase 2
PRO_0000084112Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei55 – 551N6-succinyllysine1 Publication
Modified residuei176 – 1761N6-acetyllysine; alternate1 Publication
Modified residuei176 – 1761N6-succinyllysine; alternate1 Publication
Modified residuei191 – 1911N6-acetyllysine1 Publication
Modified residuei215 – 2151N6-acetyllysine1 Publication
Modified residuei368 – 3681Phosphoserine1 Publication
Modified residuei371 – 3711N6-succinyllysine1 Publication
Modified residuei420 – 4201N6-succinyllysine1 Publication
Modified residuei454 – 4541N6-succinyllysine1 Publication
Modified residuei504 – 5041N6-succinyllysine1 Publication
Modified residuei508 – 5081N6-acetyllysine; alternate1 Publication
Modified residuei508 – 5081N6-succinyllysine; alternate1 Publication
Lipidationi521 – 5211S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine By similarity
Modified residuei553 – 5531N6-succinyllysine1 Publication

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 By similarity.

Keywords - PTMi

Acetylation, Lipoprotein, Phosphoprotein

Proteomic databases

MaxQBiP34914.
PaxDbiP34914.
PRIDEiP34914.

2D gel databases

SWISS-2DPAGEP34914.

PTM databases

PhosphoSiteiP34914.

Expressioni

Tissue specificityi

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

Inductioni

Up-regulated during the luteal phase of the stimulated estrus cycle and by compounds that cause peroxisome proliferation, such as clofibrate, tiadenol and fenofibrate.3 Publications

Gene expression databases

ArrayExpressiP34914.
BgeeiP34914.
CleanExiMM_EPHX2.
GenevestigatoriP34914.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

IntActiP34914. 5 interactions.
MINTiMINT-1859181.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 84
Helixi10 – 123
Beta strandi13 – 175
Turni51 – 566
Beta strandi57 – 626
Helixi94 – 974
Helixi103 – 11412
Beta strandi118 – 1236
Beta strandi130 – 1323
Helixi134 – 14310
Helixi144 – 1463
Beta strandi148 – 1525
Helixi153 – 1564
Helixi163 – 17311
Beta strandi177 – 18711
Turni188 – 1903
Helixi191 – 1955
Beta strandi199 – 2024
Beta strandi205 – 2073
Helixi208 – 2158
Beta strandi216 – 2183
Beta strandi232 – 24110
Beta strandi243 – 2453
Beta strandi247 – 2548
Beta strandi256 – 2627
Helixi269 – 2746
Helixi275 – 2817
Beta strandi285 – 2906
Helixi304 – 3063
Helixi308 – 32215
Beta strandi327 – 3326
Helixi334 – 34512
Turni347 – 3493
Beta strandi350 – 3578
Helixi369 – 3757
Helixi377 – 3793
Helixi380 – 3856
Helixi390 – 3978
Helixi399 – 4068
Turni418 – 4203
Helixi421 – 4244
Turni427 – 4304
Beta strandi439 – 4413
Helixi443 – 45614
Helixi459 – 4624
Helixi463 – 4675
Helixi468 – 4758
Helixi476 – 4783
Beta strandi487 – 4926
Beta strandi496 – 4983
Helixi500 – 5034
Helixi506 – 5083
Beta strandi514 – 5185
Helixi525 – 5284
Helixi530 – 54314

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CQZX-ray2.80A/B1-554[»]
1CR6X-ray2.80A/B1-554[»]
1EK1X-ray3.10A/B1-554[»]
1EK2X-ray3.00A/B1-554[»]
ProteinModelPortaliP34914.
SMRiP34914. Positions 4-544.

Miscellaneous databases

EvolutionaryTraceiP34914.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 224224Phosphatase
Add
BLAST
Regioni123 – 1242Phosphate binding By similarity
Regioni233 – 554322Epoxide hydrolase
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi552 – 5543Microbody targeting signal Reviewed prediction

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0596.
GeneTreeiENSGT00530000063213.
HOGENOMiHOG000028073.
HOVERGENiHBG006095.
InParanoidiP34914.
KOiK08726.
OMAiGHWTQMD.
OrthoDBiEOG72VH5T.
PhylomeDBiP34914.
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.
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.
TIGRFAMsiTIGR01509. HAD-SF-IA-v3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P34914-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MALRVAAFDL DGVLALPSIA GAFRRSEEAL ALPRDFLLGA YQTEFPEGPT    50
EQLMKGKITF SQWVPLMDES YRKSSKACGA NLPENFSISQ IFSQAMAARS 100
INRPMLQAAI ALKKKGFTTC IVTNNWLDDG DKRDSLAQMM CELSQHFDFL 150
IESCQVGMIK PEPQIYNFLL DTLKAKPNEV VFLDDFGSNL KPARDMGMVT 200
ILVHNTASAL RELEKVTGTQ FPEAPLPVPC NPNDVSHGYV TVKPGIRLHF 250
VEMGSGPALC LCHGFPESWF SWRYQIPALA QAGFRVLAID MKGYGDSSSP 300
PEIEEYAMEL LCKEMVTFLD KLGIPQAVFI GHDWAGVMVW NMALFYPERV 350
RAVASLNTPF MPPDPDVSPM KVIRSIPVFN YQLYFQEPGV AEAELEKNMS 400
RTFKSFFRAS DETGFIAVHK ATEIGGILVN TPEDPNLSKI TTEEEIEFYI 450
QQFKKTGFRG PLNWYRNTER NWKWSCKGLG RKILVPALMV TAEKDIVLRP 500
EMSKNMEKWI PFLKRGHIED CGHWTQIEKP TEVNQILIKW LQTEVQNPSV 550
TSKI 554
Length:554
Mass (Da):62,515
Last modified:October 1, 1996 - v2
Checksum:i2F3A3F7DACE47C93
GO
Isoform 2 (identifier: P34914-2) [UniParc]FASTAAdd to Basket

Also known as: Ephx2B

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

Show »
Length:536
Mass (Da):60,613
Checksum:iD9BD995CB9347551
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6262MALRV…ITFSQ → MRFAAMAAFSVFFVSKGLLM NSNIWCVGQEGPSQEDTDTI HTSE in isoform 2.
VSP_013904Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti77 – 771A → T in CAA85471. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L05781 mRNA. Translation: AAA37555.1.
Z37107 mRNA. Translation: CAA85471.1.
AY098585 mRNA. Translation: AAM28238.1.
BC015087 mRNA. Translation: AAH15087.1.
CCDSiCCDS27218.1. [P34914-1]
PIRiA47504.
RefSeqiNP_001258332.1. NM_001271403.1. [P34914-2]
NP_031966.2. NM_007940.4. [P34914-1]
UniGeneiMm.15295.

Genome annotation databases

EnsembliENSMUST00000070515; ENSMUSP00000069209; ENSMUSG00000022040. [P34914-1]
GeneIDi13850.
KEGGimmu:13850.
UCSCiuc007ujv.1. mouse. [P34914-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L05781 mRNA. Translation: AAA37555.1 .
Z37107 mRNA. Translation: CAA85471.1 .
AY098585 mRNA. Translation: AAM28238.1 .
BC015087 mRNA. Translation: AAH15087.1 .
CCDSi CCDS27218.1. [P34914-1 ]
PIRi A47504.
RefSeqi NP_001258332.1. NM_001271403.1. [P34914-2 ]
NP_031966.2. NM_007940.4. [P34914-1 ]
UniGenei Mm.15295.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1CQZ X-ray 2.80 A/B 1-554 [» ]
1CR6 X-ray 2.80 A/B 1-554 [» ]
1EK1 X-ray 3.10 A/B 1-554 [» ]
1EK2 X-ray 3.00 A/B 1-554 [» ]
ProteinModelPortali P34914.
SMRi P34914. Positions 4-544.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P34914. 5 interactions.
MINTi MINT-1859181.

Chemistry

BindingDBi P34914.
ChEMBLi CHEMBL4140.

Protein family/group databases

MEROPSi S33.973.

PTM databases

PhosphoSitei P34914.

2D gel databases

SWISS-2DPAGE P34914.

Proteomic databases

MaxQBi P34914.
PaxDbi P34914.
PRIDEi P34914.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000070515 ; ENSMUSP00000069209 ; ENSMUSG00000022040 . [P34914-1 ]
GeneIDi 13850.
KEGGi mmu:13850.
UCSCi uc007ujv.1. mouse. [P34914-1 ]

Organism-specific databases

CTDi 2053.
MGIi MGI:99500. Ephx2.

Phylogenomic databases

eggNOGi COG0596.
GeneTreei ENSGT00530000063213.
HOGENOMi HOG000028073.
HOVERGENi HBG006095.
InParanoidi P34914.
KOi K08726.
OMAi GHWTQMD.
OrthoDBi EOG72VH5T.
PhylomeDBi P34914.
TreeFami TF315395.

Enzyme and pathway databases

BRENDAi 3.3.2.10. 3474.
Reactomei REACT_196570. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).

Miscellaneous databases

EvolutionaryTracei P34914.
NextBioi 284704.
PROi P34914.
SOURCEi Search...

Gene expression databases

ArrayExpressi P34914.
Bgeei P34914.
CleanExi MM_EPHX2.
Genevestigatori P34914.

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.
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 TIGR01509. HAD-SF-IA-v3. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiHYES_MOUSE
AccessioniPrimary (citable) accession number: P34914
Secondary accession number(s): Q8CGV0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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