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P34914

- HYES_MOUSE

UniProt

P34914 - HYES_MOUSE

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Protein

Bifunctional epoxide hydrolase 2

Gene

Ephx2

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).By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi9 – 91MagnesiumBy similarity
Metal bindingi11 – 111MagnesiumBy similarity
Metal bindingi185 – 1851MagnesiumBy similarity
Active sitei333 – 3331Nucleophile
Binding sitei381 – 3811SubstrateBy 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. extracellular vesicular exosome Source: Ensembl
  2. peroxisome Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Peroxisome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 554554Bifunctional epoxide hydrolase 2PRO_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)cysteineBy 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).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

BgeeiP34914.
CleanExiMM_EPHX2.
ExpressionAtlasiP34914. baseline and differential.
GenevestigatoriP34914.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

IntActiP34914. 5 interactions.
MINTiMINT-1859181.

Structurei

Secondary structure

1
554
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 84Combined sources
Helixi10 – 123Combined sources
Beta strandi13 – 175Combined sources
Turni51 – 566Combined sources
Beta strandi57 – 626Combined sources
Helixi94 – 974Combined sources
Helixi103 – 11412Combined sources
Beta strandi118 – 1236Combined sources
Beta strandi130 – 1323Combined sources
Helixi134 – 14310Combined sources
Helixi144 – 1463Combined sources
Beta strandi148 – 1525Combined sources
Helixi153 – 1564Combined sources
Helixi163 – 17311Combined sources
Beta strandi177 – 18711Combined sources
Turni188 – 1903Combined sources
Helixi191 – 1955Combined sources
Beta strandi199 – 2024Combined sources
Beta strandi205 – 2073Combined sources
Helixi208 – 2158Combined sources
Beta strandi216 – 2183Combined sources
Beta strandi232 – 24110Combined sources
Beta strandi243 – 2453Combined sources
Beta strandi247 – 2548Combined sources
Beta strandi256 – 2627Combined sources
Helixi269 – 2746Combined sources
Helixi275 – 2817Combined sources
Beta strandi285 – 2906Combined sources
Helixi304 – 3063Combined sources
Helixi308 – 32215Combined sources
Beta strandi327 – 3326Combined sources
Helixi334 – 34512Combined sources
Turni347 – 3493Combined sources
Beta strandi350 – 3578Combined sources
Helixi369 – 3757Combined sources
Helixi377 – 3793Combined sources
Helixi380 – 3856Combined sources
Helixi390 – 3978Combined sources
Helixi399 – 4068Combined sources
Turni418 – 4203Combined sources
Helixi421 – 4244Combined sources
Turni427 – 4304Combined sources
Beta strandi439 – 4413Combined sources
Helixi443 – 45614Combined sources
Helixi459 – 4624Combined sources
Helixi463 – 4675Combined sources
Helixi468 – 4758Combined sources
Helixi476 – 4783Combined sources
Beta strandi487 – 4926Combined sources
Beta strandi496 – 4983Combined sources
Helixi500 – 5034Combined sources
Helixi506 – 5083Combined sources
Beta strandi514 – 5185Combined sources
Helixi525 – 5284Combined sources
Helixi530 – 54314Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP34914.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 224224PhosphataseAdd
BLAST
Regioni123 – 1242Phosphate bindingBy similarity
Regioni233 – 554322Epoxide hydrolaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi552 – 5543Microbody targeting signalSequence Analysis

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

        10         20         30         40         50
MALRVAAFDL DGVLALPSIA GAFRRSEEAL ALPRDFLLGA YQTEFPEGPT
60 70 80 90 100
EQLMKGKITF SQWVPLMDES YRKSSKACGA NLPENFSISQ IFSQAMAARS
110 120 130 140 150
INRPMLQAAI ALKKKGFTTC IVTNNWLDDG DKRDSLAQMM CELSQHFDFL
160 170 180 190 200
IESCQVGMIK PEPQIYNFLL DTLKAKPNEV VFLDDFGSNL KPARDMGMVT
210 220 230 240 250
ILVHNTASAL RELEKVTGTQ FPEAPLPVPC NPNDVSHGYV TVKPGIRLHF
260 270 280 290 300
VEMGSGPALC LCHGFPESWF SWRYQIPALA QAGFRVLAID MKGYGDSSSP
310 320 330 340 350
PEIEEYAMEL LCKEMVTFLD KLGIPQAVFI GHDWAGVMVW NMALFYPERV
360 370 380 390 400
RAVASLNTPF MPPDPDVSPM KVIRSIPVFN YQLYFQEPGV AEAELEKNMS
410 420 430 440 450
RTFKSFFRAS DETGFIAVHK ATEIGGILVN TPEDPNLSKI TTEEEIEFYI
460 470 480 490 500
QQFKKTGFRG PLNWYRNTER NWKWSCKGLG RKILVPALMV TAEKDIVLRP
510 520 530 540 550
EMSKNMEKWI PFLKRGHIED CGHWTQIEKP TEVNQILIKW LQTEVQNPSV

TSKI
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti77 – 771A → T in CAA85471. (PubMed:8750907)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6262MALRV…ITFSQ → MRFAAMAAFSVFFVSKGLLM NSNIWCVGQEGPSQEDTDTI HTSE in isoform 2. 1 PublicationVSP_013904Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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

ChiTaRSi Ephx2. mouse.
EvolutionaryTracei P34914.
NextBioi 284704.
PROi P34914.
SOURCEi Search...

Gene expression databases

Bgeei P34914.
CleanExi MM_EPHX2.
ExpressionAtlasi P34914. baseline and differential.
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: November 26, 2014
This is version 139 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