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Protein

Bifunctional epoxide hydrolase 2

Gene

Ephx2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 and 12-phosphonooxy-octadec-9E-enoic acid.By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi9MagnesiumBy similarity1
Metal bindingi11MagnesiumBy similarity1
Metal bindingi185MagnesiumBy similarity1
Active sitei333Nucleophile2 Publications1
Binding sitei381SubstrateBy similarity1
Active sitei465Proton donor2 Publications1
Active sitei523Proton acceptor2 Publications1

GO - Molecular functioni

GO - Biological processi

  • cholesterol homeostasis Source: UniProtKB
  • dephosphorylation Source: MGI
  • epoxide metabolic process Source: MGI
  • phospholipid dephosphorylation Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • regulation of cholesterol metabolic process Source: UniProtKB
  • response to toxic substance Source: UniProtKB-KW
  • stilbene catabolic process Source: MGI

Keywordsi

Molecular functionHydrolase, Multifunctional enzyme
Biological processAromatic hydrocarbons catabolism, Detoxification, Lipid metabolism
LigandMagnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.3.2.10 3474
ReactomeiR-MMU-2142670 Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)

Protein family/group databases

ESTHERimouse-hyes Epoxide_hydrolase
MEROPSiS33.973

Chemistry databases

SwissLipidsiSLP:000001106

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional epoxide hydrolase 2
Including the following 2 domains:
Cytosolic epoxide hydrolase 2 (EC:3.3.2.10By similarity)
Short name:
CEH
Alternative name(s):
Epoxide hydratase
Soluble epoxide hydrolase
Short name:
SEH
Lipid-phosphate phosphatase (EC:3.1.3.76By similarity)
Gene namesi
Name:Ephx2
Synonyms:Eph2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:99500 Ephx2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Peroxisome

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4140

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000841121 – 554Bifunctional epoxide hydrolase 2Add BLAST554

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei55N6-succinyllysineCombined sources1
Modified residuei176N6-acetyllysine; alternateCombined sources1
Modified residuei176N6-succinyllysine; alternateCombined sources1
Modified residuei191N6-acetyllysineCombined sources1
Modified residuei215N6-acetyllysineCombined sources1
Modified residuei368PhosphoserineCombined sources1
Modified residuei371N6-succinyllysineCombined sources1
Modified residuei420N6-succinyllysineCombined sources1
Modified residuei454N6-succinyllysineCombined sources1
Modified residuei504N6-succinyllysineCombined sources1
Modified residuei508N6-acetyllysine; alternateCombined sources1
Modified residuei508N6-succinyllysine; alternateCombined sources1
Lipidationi521S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteineBy similarity1
Modified residuei553N6-succinyllysineCombined sources1

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
PeptideAtlasiP34914
PRIDEiP34914

2D gel databases

SWISS-2DPAGEiP34914

PTM databases

iPTMnetiP34914
PhosphoSitePlusiP34914
SwissPalmiP34914

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

BgeeiENSMUSG00000022040
CleanExiMM_EPHX2
ExpressionAtlasiP34914 baseline and differential
GenevisibleiP34914 MM

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiP34914, 5 interactors
MINTiP34914
STRINGi10090.ENSMUSP00000069209

Chemistry databases

BindingDBiP34914

Structurei

Secondary structure

1554
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 8Combined sources4
Helixi10 – 12Combined sources3
Beta strandi13 – 17Combined sources5
Helixi20 – 28Combined sources9
Turni29 – 31Combined sources3
Turni34 – 37Combined sources4
Helixi38 – 41Combined sources4
Turni51 – 56Combined sources6
Beta strandi57 – 62Combined sources6
Helixi64 – 74Combined sources11
Turni75 – 78Combined sources4
Helixi94 – 97Combined sources4
Helixi103 – 114Combined sources12
Beta strandi118 – 123Combined sources6
Beta strandi130 – 132Combined sources3
Helixi134 – 143Combined sources10
Helixi144 – 146Combined sources3
Beta strandi148 – 152Combined sources5
Helixi153 – 156Combined sources4
Helixi163 – 173Combined sources11
Beta strandi177 – 187Combined sources11
Turni188 – 190Combined sources3
Helixi191 – 195Combined sources5
Beta strandi199 – 202Combined sources4
Beta strandi205 – 207Combined sources3
Helixi208 – 215Combined sources8
Beta strandi216 – 218Combined sources3
Beta strandi232 – 241Combined sources10
Beta strandi243 – 245Combined sources3
Beta strandi247 – 254Combined sources8
Beta strandi256 – 262Combined sources7
Helixi269 – 274Combined sources6
Helixi275 – 281Combined sources7
Beta strandi285 – 290Combined sources6
Helixi304 – 306Combined sources3
Helixi308 – 322Combined sources15
Beta strandi327 – 332Combined sources6
Helixi334 – 345Combined sources12
Turni347 – 349Combined sources3
Beta strandi350 – 357Combined sources8
Helixi369 – 375Combined sources7
Helixi377 – 379Combined sources3
Helixi380 – 385Combined sources6
Helixi390 – 397Combined sources8
Helixi399 – 406Combined sources8
Turni418 – 420Combined sources3
Helixi421 – 424Combined sources4
Turni427 – 430Combined sources4
Beta strandi439 – 441Combined sources3
Helixi443 – 456Combined sources14
Helixi459 – 462Combined sources4
Helixi463 – 467Combined sources5
Helixi468 – 475Combined sources8
Helixi476 – 478Combined sources3
Beta strandi487 – 492Combined sources6
Beta strandi496 – 498Combined sources3
Helixi500 – 503Combined sources4
Helixi506 – 508Combined sources3
Beta strandi514 – 518Combined sources5
Helixi525 – 528Combined sources4
Helixi530 – 543Combined sources14

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP34914

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini257 – 530AB hydrolase-1Sequence analysisAdd BLAST274

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 224PhosphataseAdd BLAST224
Regioni123 – 124Phosphate bindingBy similarity2
Regioni233 – 554Epoxide hydrolaseAdd BLAST322

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi552 – 554Microbody targeting signalSequence analysis3

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3085 Eukaryota
KOG4178 Eukaryota
COG1011 LUCA
GeneTreeiENSGT00530000063213
HOGENOMiHOG000028073
HOVERGENiHBG006095
InParanoidiP34914
KOiK08726
OMAiGHWTQMD
OrthoDBiEOG091G078G
PhylomeDBiP34914
TreeFamiTF315395

Family and domain databases

Gene3Di1.10.150.240, 1 hit
3.40.50.1000, 2 hits
3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR000073 AB_hydrolase_1
IPR000639 Epox_hydrolase-like
IPR036412 HAD-like_sf
IPR006439 HAD-SF_hydro_IA
IPR023214 HAD_sf
IPR023198 PGP-like_dom2
PfamiView protein in Pfam
PF00561 Abhydrolase_1, 1 hit
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti77A → T in CAA85471 (PubMed:8750907).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0139041 – 62MALRV…ITFSQ → MRFAAMAAFSVFFVSKGLLM NSNIWCVGQEGPSQEDTDTI HTSE in isoform 2. 1 PublicationAdd BLAST62

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]
ENSMUST00000224698; ENSMUSP00000153161; ENSMUSG00000022040 [P34914-2]
GeneIDi13850
KEGGimmu:13850
UCSCiuc007ujv.2 mouse [P34914-1]
uc033grp.1 mouse [P34914-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHYES_MOUSE
AccessioniPrimary (citable) accession number: P34914
Secondary accession number(s): Q8CGV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: October 1, 1996
Last modified: March 28, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health