Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bifunctional epoxide hydrolase 2

Gene

Ephx2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Bifunctional enzyme (PubMed:8626766, PubMed:12574508). The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides (PubMed:8626766). Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (PubMed:8626766). Also determines steady-state levels of physiological mediators (By similarity). 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).By similarity2 Publications

Catalytic activityi

An epoxide + H2O = a glycol.1 Publication
(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate.1 Publication

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

Kineticsi

  1. KM=0.235 mM for p-nitrophenyl phosphate1 Publication
  1. Vmax=1450 nmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi9MagnesiumBy similarity1
Metal bindingi11MagnesiumBy similarity1
Metal bindingi185MagnesiumBy similarity1
Active sitei333Nucleophile1 Publication1
Binding sitei381SubstrateBy similarity1
Active sitei465Proton donorBy similarity1
Active sitei523Proton acceptor1 Publication1

GO - Molecular functioni

  • 10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity Source: UniProtKB-EC
  • epoxide hydrolase activity Source: RGD
  • lipid phosphatase activity Source: UniProtKB
  • magnesium ion binding Source: RGD
  • phosphatase activity Source: RGD

GO - Biological processi

  • aromatic compound catabolic process Source: UniProtKB-KW
  • inflammatory response Source: RGD
  • linoleic acid metabolic process Source: RGD
  • phospholipid dephosphorylation Source: UniProtKB
  • positive regulation of blood pressure Source: RGD
  • prostaglandin production involved in inflammatory response Source: RGD
  • response to toxic substance Source: UniProtKB-KW
  • sensory perception of pain Source: RGD

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.3.2.10 5301
SABIO-RKiP80299

Protein family/group databases

ESTHERiratno-hyes Epoxide_hydrolase
MEROPSiS33.973

Chemistry databases

SwissLipidsiSLP:000001643

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional epoxide hydrolase 2
Including the following 2 domains:
Cytosolic epoxide hydrolase 2 (EC:3.3.2.101 Publication)
Short name:
CEH
Alternative name(s):
Epoxide hydratase
Soluble epoxide hydrolase
Short name:
SEH
Lipid-phosphate phosphatase (EC:3.1.3.761 Publication)
Gene namesi
Name:Ephx2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620732 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi332H → Q: Reduces epoxide hydrolase activity by 95%. 1
Mutagenesisi333D → G: Loss of epoxide hydrolase activity. 1 Publication1
Mutagenesisi334W → F: Slight reduction of epoxide hydrolase activity. 1 Publication1
Mutagenesisi433E → Q or K: Slight loss of epoxide hydrolase activity. 1 Publication1
Mutagenesisi434D → Y: Slight loss of epoxide hydrolase activity. 1 Publication1
Mutagenesisi493E → Q or K: No effect. 1 Publication1
Mutagenesisi495D → H: Loss of epoxide hydrolase activity. 1 Publication1
Mutagenesisi517H → Y: Reduces epoxide hydrolase activity by 50%. Loss of activity; when associated with Y-521. 1 Publication1
Mutagenesisi521C → Y: Loss of epoxide hydrolase activity; when associated with Y-517. 1 Publication1
Mutagenesisi523H → D, N or Y: Loss of epoxide hydrolase activity. 1 Publication1
Mutagenesisi526Q → H: Reduces epoxide hydrolase activity by 80%; when associated with T-542. 1 Publication1
Mutagenesisi540W → L or S: Reduces epoxide hydrolase activity by 95%. 1 Publication1
Mutagenesisi542K → T: Reduces epoxide hydrolase activity by 80%; when associated with H-526. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5669

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000841141 – 554Bifunctional epoxide hydrolase 2Add BLAST554

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei55N6-succinyllysineBy similarity1
Modified residuei176N6-acetyllysine; alternateBy similarity1
Modified residuei176N6-succinyllysine; alternateBy similarity1
Modified residuei191N6-acetyllysineBy similarity1
Modified residuei215N6-acetyllysineBy similarity1
Modified residuei368PhosphoserineBy similarity1
Modified residuei420N6-succinyllysineBy similarity1
Modified residuei454N6-succinyllysineBy similarity1
Modified residuei504N6-succinyllysineBy similarity1
Lipidationi521S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteineBy similarity1
Modified residuei553N6-succinyllysineBy similarity1

Post-translational modificationi

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

PaxDbiP80299
PRIDEiP80299

PTM databases

CarbonylDBiP80299
iPTMnetiP80299
PhosphoSitePlusiP80299

Expressioni

Inductioni

By compounds that cause peroxisome proliferation such as clofibrate, tiadenol and fenofibrate.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000023385

Chemistry databases

BindingDBiP80299

Structurei

3D structure databases

ProteinModelPortaliP80299
SMRiP80299
ModBaseiSearch...
MobiDBiSearch...

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
HOGENOMiHOG000028073
HOVERGENiHBG006095
InParanoidiP80299
KOiK08726
PhylomeDBiP80299

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
IPR011945 HAD-SF_ppase_IA/epoxid_hydro_N
IPR023214 HAD_sf
IPR023198 PGP-like_dom2
PfamiView protein in Pfam
PF00561 Abhydrolase_1, 1 hit
PRINTSiPR00111 ABHYDROLASE
PR00412 EPOXHYDRLASE
SUPFAMiSSF53474 SSF53474, 2 hits
SSF56784 SSF56784, 1 hit
TIGRFAMsiTIGR02247 HAD-1A3-hyp, 1 hit
TIGR01509 HAD-SF-IA-v3, 1 hit

Sequencei

Sequence statusi: Complete.

P80299-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALRVAAFDL DGVLALPSIA GVLRHTEEAL ALPRDFLLGA FQMKFPEGPT
60 70 80 90 100
EQLMKGKITF SQWVPLMDES CRKSSKACGA SLPENFSISE IFSQAMAARS
110 120 130 140 150
INRPMLQAAA ALKKKGFTTC IVTNNWLDDS DKRDILAQMM CELSQHFDFL
160 170 180 190 200
IESCQVGMIK PEPQIYKFVL DTLKAKPNEV VFLDDFGSNL KPARDMGMVT
210 220 230 240 250
ILVRDTASAL RELEKVTGTQ FPEAPLPVPC SPNDVSHGYV TVKPGIRLHF
260 270 280 290 300
VEMGSGPAIC LCHGFPESWF SWRYQIPALA QAGFRVLAID MKGYGDSSSP
310 320 330 340 350
PEIEEYAMEL LCEEMVTFLN KLGIPQAVFI GHDWAGVLVW NMALFHPERV
360 370 380 390 400
RAVASLNTPL MPPNPEVSPM EVIRSIPVFN YQLYFQEPGV AEAELEKNMS
410 420 430 440 450
RTFKSFFRTS DDMGLLTVNK ATEMGGILVG TPEDPKVSKI TTEEEIEYYI
460 470 480 490 500
QQFKKSGFRG PLNWYRNTER NWKWSCKALG RKILVPALMV TAEKDIVLRP
510 520 530 540 550
EMSKNMENWI PFLKRGHIED CGHWTQIEKP AEVNQILIKW LKTEIQNPSV

TSKI
Length:554
Mass (Da):62,340
Last modified:February 1, 1994 - v1
Checksum:i145FDCA53F582138
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X65083 mRNA Translation: CAA46211.1
X60328 mRNA Translation: CAA42898.1
PIRiA47503
RefSeqiNP_075225.1, NM_022936.1
UniGeneiRn.54495

Genome annotation databases

GeneIDi65030
KEGGirno:65030
UCSCiRGD:620732 rat

Similar proteinsi

Entry informationi

Entry nameiHYES_RAT
AccessioniPrimary (citable) accession number: P80299
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: May 23, 2018
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health