epoxide hydrolase 2

Target id: 2970

Nomenclature: epoxide hydrolase 2

Family: Hydrolases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     epoxide hydrolase 2 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 555 8p21.2-p21.1 EPHX2 epoxide hydrolase 2
Mouse - 554 14 D1; 14 34.36 cM Ephx2 epoxide hydrolase 2
Rat - 554 15p12 Ephx2 epoxide hydrolase 2
Gene and Protein Information Comments
Three protein isoforms are reported from the human gene, with isoform a (555 amino acids) being the longest. The mouse gene produces 4 transcripts and protein isoforms, isoform a being the longest at 554 amino acids.
Previous and Unofficial Names
epoxide hydrolase 2, cytoplasmic | sEH | soluble epoxide hydrolase | bifunctional epoxide hydrolase 2
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction
EC Number:
Description Reaction Reference
Lipid-phosphate phosphatase activity (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H(2)O <=> (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate
EC Number:
Description Reaction Reference
Epoxide hydrase activity An epoxide + H(2)O <=> a glycol

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Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
BI-1935 Hs Inhibition 8.1 pIC50 7
pIC50 8.1 (IC50 7x10-9 M) [7]
Description: In a biochemical h-sEH binding assay.
GSK2256294 Hs Inhibition 7.0 pIC50 1
pIC50 7.0 (IC50 1.1x10-7 M) [1]
Description: In a biochemical enzyme assay.
Immunopharmacology Comments
Its role in metabolism of arachadonic acid EET metabolites, means that sEH participates in the regulation of prostaglandin and leukotriene production and therefore in immune homeostasis. Small molecule sEH inhibitors can be used as chemical probes to investigate EET (immuno)biology [5].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
GO Annotation:  Associated to GO processes
GO Processes:  inflammatory response (GO:0006954) NAS
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A nonsynonymous SNP associated wih coronary artery calcification in African American patients.
Amino acid change:  R287Q
References:  2
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A nonsynonymous SNP associated wih the risk of developing coronary heart disease in Caucasian patients, and with a higher risk of hypertension and ischemic stroke in male homozygotes
Amino acid change:  K55R
References:  4
General Comments
Epoxide hydrolase 2 (sEH) performs two enzymatic functions. The C terminal contains an epoxide hydrolase domain and the N terminal has a lipid phosphatase domain [6]. sEH plays a major role in the metabolism of endogenous chemical mediators originated from arachidonic acid, including epoxyeicosatrienoic acids (EETs, which are arachidonic acid metabolites produced by certain Cyp450 enzymes) and squalene oxide (a key intermediate in cholesterol biosynthesis). Through metabolism of EETs and other lipid mediators, sEH plays a role in several pathologies, including hypertension, cardiac hypertrophy, and arteriosclerosis [3]. It also appears to be involved in pain mechanisms. Inhibition of sEH is expected to increase EETs levels, thereby potentiating their in vivo anti-inflammatory and vasodilatory effects. Novel drugs targeting sEH have progressed to clinical trial for inflammatory and cardiovascular diseases.


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1. Blocher R, Lamers C, Wittmann SK, Diehl O, Hanke T, Merk D, Steinhilber D, Schubert-Zsilavecz M, Kahnt AS, Proschak E. (2016) Design and synthesis of fused soluble epoxide hydrolase/peroxisome proliferator-activated receptor modulators. Medchemcomm7: 1209-1216.

2. Fornage M, Boerwinkle E, Doris PA, Jacobs D, Liu K, Wong ND. (2004) Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Circulation109 (3): 335-9. [PMID:14732757]

3. Imig JD, Hammock BD. (2009) Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov8 (10): 794-805. [PMID:19794443]

4. Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, Hammock BD, Couper DJ, Heiss G, Zeldin DC. (2006) Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study. Hum. Mol. Genet.15 (10): 1640-9. [PMID:16595607]

5. Morisseau C, Hammock BD. (2013) Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu. Rev. Pharmacol. Toxicol.53: 37-58. [PMID:23020295]

6. Newman JW, Morisseau C, Harris TR, Hammock BD. (2003) The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc. Natl. Acad. Sci. U.S.A.100 (4): 1558-63. [PMID:12574510]

7. Taylor SJ, Soleymanzadeh F, Eldrup AB, Farrow NA, Muegge I, Kukulka A, Kabcenell AK, De Lombaert S. (2009) Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase. Bioorg. Med. Chem. Lett.19 (20): 5864-8. [PMID:19758802]

How to cite this page

Hydrolases: epoxide hydrolase 2. Last modified on 28/11/2017. Accessed on 25/02/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2970.