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Protein

Bifunctional epoxide hydrolase 2

Gene

Ephx2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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.

Catalytic activityi

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

Cofactori

Kineticsi

  1. KM=0.235 mM for p-nitrophenyl phosphate
  1. Vmax=1450 nmol/min/mg enzyme

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 donorBy similarity
Active sitei523 – 5231Proton acceptor

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
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. 5301.
SABIO-RKP80299.

Protein family/group databases

ESTHERiratno-hyes. Epoxide_hydrolase.
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620732. Ephx2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
  • peroxisome Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Peroxisome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi332 – 3321H → Q: Reduces epoxide hydrolase activity by 95%.
Mutagenesisi333 – 3331D → G: Loss of epoxide hydrolase activity. 1 Publication
Mutagenesisi334 – 3341W → F: Slight reduction of epoxide hydrolase activity. 1 Publication
Mutagenesisi433 – 4331E → Q or K: Slight loss of epoxide hydrolase activity. 1 Publication
Mutagenesisi434 – 4341D → Y: Slight loss of epoxide hydrolase activity. 1 Publication
Mutagenesisi493 – 4931E → Q or K: No effect. 1 Publication
Mutagenesisi495 – 4951D → H: Loss of epoxide hydrolase activity. 1 Publication
Mutagenesisi517 – 5171H → Y: Reduces epoxide hydrolase activity by 50%. Loss of activity; when associated with Y-521. 1 Publication
Mutagenesisi521 – 5211C → Y: Loss of epoxide hydrolase activity; when associated with Y-517. 1 Publication
Mutagenesisi523 – 5231H → D, N or Y: Loss of epoxide hydrolase activity. 1 Publication
Mutagenesisi526 – 5261Q → H: Reduces epoxide hydrolase activity by 80%; when associated with T-542. 1 Publication
Mutagenesisi540 – 5401W → L or S: Reduces epoxide hydrolase activity by 95%. 1 Publication
Mutagenesisi542 – 5421K → T: Reduces epoxide hydrolase activity by 80%; when associated with H-526. 1 Publication

Chemistry

ChEMBLiCHEMBL5669.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 554554Bifunctional epoxide hydrolase 2PRO_0000084114Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei55 – 551N6-succinyllysineBy similarity
Modified residuei176 – 1761N6-acetyllysine; alternateBy similarity
Modified residuei176 – 1761N6-succinyllysine; alternateBy similarity
Modified residuei191 – 1911N6-acetyllysineBy similarity
Modified residuei215 – 2151N6-acetyllysineBy similarity
Modified residuei368 – 3681PhosphoserineBy similarity
Modified residuei420 – 4201N6-succinyllysineBy similarity
Modified residuei454 – 4541N6-succinyllysineBy similarity
Modified residuei504 – 5041N6-succinyllysineBy similarity
Lipidationi521 – 5211S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteineBy similarity
Modified residuei553 – 5531N6-succinyllysineBy similarity

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

iPTMnetiP80299.
PhosphoSiteiP80299.

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

BindingDBiP80299.

Structurei

3D structure databases

ProteinModelPortaliP80299.
SMRiP80299. Positions 4-544.
ModBaseiSearch...
MobiDBiSearch...

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

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. 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.
IPR011945. HAD-SF_ppase_IA/epoxid_hydro_N.
IPR023198. PGP_dom2.
[Graphical view]
PfamiPF00561. Abhydrolase_1. 1 hit.
PF13419. HAD_2. 1 hit.
[Graphical view]
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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP80299.
SMRiP80299. Positions 4-544.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000023385.

Chemistry

BindingDBiP80299.
ChEMBLiCHEMBL5669.

Protein family/group databases

ESTHERiratno-hyes. Epoxide_hydrolase.
MEROPSiS33.973.

PTM databases

iPTMnetiP80299.
PhosphoSiteiP80299.

Proteomic databases

PaxDbiP80299.
PRIDEiP80299.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi65030.
KEGGirno:65030.
UCSCiRGD:620732. rat.

Organism-specific databases

CTDi2053.
RGDi620732. Ephx2.

Phylogenomic databases

eggNOGiKOG3085. Eukaryota.
KOG4178. Eukaryota.
COG1011. LUCA.
HOGENOMiHOG000028073.
HOVERGENiHBG006095.
InParanoidiP80299.
KOiK08726.
PhylomeDBiP80299.

Enzyme and pathway databases

BRENDAi3.3.2.10. 5301.
SABIO-RKP80299.

Miscellaneous databases

PROiP80299.

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.
IPR011945. HAD-SF_ppase_IA/epoxid_hydro_N.
IPR023198. PGP_dom2.
[Graphical view]
PfamiPF00561. Abhydrolase_1. 1 hit.
PF13419. HAD_2. 1 hit.
[Graphical view]
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.
ProtoNetiSearch...

Entry informationi

Entry nameiHYES_RAT
AccessioniPrimary (citable) accession number: P80299
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: September 7, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.