You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP01790
Secondary Accession Numbers
  • 7147
Name Bifunctional epoxide hydrolase 2
Synonyms
  1. CEH
  2. Cytosolic epoxide hydrolase
  3. Epoxide hydratase
  4. SEH
  5. Soluble epoxide hydrolase
Gene Name EPHX2
Protein Type Unknown
Biological Properties
General Function Involved in catalytic activity
Specific Function 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.
Pathways
  • Acetaminophen Action Pathway
  • Acetylsalicylic Acid Action Pathway
  • Antipyrine Action Pathway
  • Antrafenine Action Pathway
  • Arachidonic acid metabolism
  • Arachidonic Acid Metabolism
  • Bromfenac Action Pathway
  • Carprofen Action Pathway
  • Celecoxib Action Pathway
  • Diclofenac Action Pathway
  • Diflunisal Action Pathway
  • Etodolac Action Pathway
  • Etoricoxib Action Pathway
  • Fenoprofen Action Pathway
  • Flurbiprofen Action Pathway
  • Ibuprofen Action Pathway
  • Indomethacin Action Pathway
  • Ketoprofen Action Pathway
  • Ketorolac Action Pathway
  • Leukotriene C4 Synthesis Deficiency
  • Lornoxicam Action Pathway
  • Lumiracoxib Action Pathway
  • Magnesium salicylate Action Pathway
  • Mefenamic Acid Action Pathway
  • Meloxicam Action Pathway
  • Nabumetone Action Pathway
  • Naproxen Action Pathway
  • Nepafenac Action Pathway
  • Oxaprozin Action Pathway
  • Peroxisome
  • Phenylbutazone Action Pathway
  • Piroxicam Action Pathway
  • Rofecoxib Action Pathway
  • Salicylate-sodium Action Pathway
  • Salicylic Acid Action Pathway
  • Salsalate Action Pathway
  • Sulindac Action Pathway
  • Suprofen Action Pathway
  • Tenoxicam Action Pathway
  • Tiaprofenic Acid Action Pathway
  • Tolmetin Action Pathway
  • Trisalicylate-choline Action Pathway
  • Valdecoxib Action Pathway
Reactions
An epoxide + Water → a glycol details
(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + Water → (9S,10S)-9,10-dihydroxyoctadecanoate + Phosphate details
Oxirane + Water → Ethylene glycol details
14,15-Epoxy-5,8,11-eicosatrienoic acid + Water → 14,15-DiHETrE details
11,12-Epoxyeicosatrienoic acid + Water → 11,12-DiHETrE details
8,9-Epoxyeicosatrienoic acid + Water → 8,9-DiHETrE details
5,6-Epoxy-8,11,14-eicosatrienoic acid + Water → 5,6-DHET details
GO Classification
Biological Process
drug metabolic process
phospholipid dephosphorylation
stilbene catabolic process
inflammatory response
reactive oxygen species metabolic process
positive regulation of vasodilation
xenobiotic metabolic process
cellular calcium ion homeostasis
cholesterol homeostasis
regulation of blood pressure
response to toxin
positive regulation of gene expression
regulation of cholesterol metabolic process
Cellular Component
cytosol
focal adhesion
nucleolus
Golgi apparatus
peroxisome
Function
catalytic activity
hydrolase activity
Molecular Function
magnesium ion binding
epoxide hydrolase activity
10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity
lipid phosphatase activity
toxin binding
4-nitrophenylphosphatase activity
protein homodimerization activity
Process
metabolic process
Cellular Location
  1. Cytoplasm
  2. Peroxisome
Gene Properties
Chromosome Location 8
Locus 8p21
SNPs EPHX2
Gene Sequence
>1668 bp
ATGACGCTGCGCGCGGCCGTCTTCGACCTTGACGGGGTGCTGGCGCTGCCAGCGGTGTTC
GGCGTCCTCGGCCGCACGGAGGAGGCCCTGGCGCTGCCCAGAGGACTTCTGAATGATGCT
TTCCAGAAAGGGGGACCAGAGGGTGCCACTACCCGGCTTATGAAAGGAGAGATCACACTT
TCCCAGTGGATACCACTCATGGAAGAAAACTGCAGGAAGTGCTCCGAGACCGCTAAAGTC
TGCCTCCCCAAGAATTTCTCCATAAAAGAAATCTTTGACAAGGCGATTTCAGCCAGAAAG
ATCAACCGCCCCATGCTCCAGGCAGCTCTCATGCTCAGGAAGAAAGGATTCACTACTGCC
ATCCTCACCAACACCTGGCTGGACGACCGTGCTGAGAGAGATGGCCTGGCCCAGCTGATG
TGTGAGCTGAAGATGCACTTTGACTTCCTGATAGAGTCGTGTCAGGTGGGAATGGTCAAA
CCTGAACCTCAGATCTACAAGTTTCTGCTGGACACCCTGAAGGCCAGCCCCAGTGAGGTC
GTTTTTTTGGATGACATCGGGGCTAATCTGAAGCCAGCCCGTGACTTGGGAATGGTCACC
ATCCTGGTCCAGGACACTGACACGGCCCTGAAAGAACTGGAGAAAGTGACCGGAATCCAG
CTTCTCAATACCCCGGCCCCTCTGCCGACCTCTTGCAATCCAAGTGACATGAGCCATGGG
TACGTGACAGTAAAGCCCAGGGTCCGTCTGCATTTTGTGGAGCTGGGCTCCGGCCCTGCT
GTGTGCCTCTGCCATGGATTTCCCGAGAGTTGGTATTCTTGGAGGTACCAGATCCCTGCT
CTGGCCCAGGCAGGTTACCGGGTCCTAGCTATGGACATGAAAGGCTATGGAGAGTCATCT
GCTCCTCCCGAAATAGAAGAATATTGCATGGAAGTGTTATGTAAGGAGATGGTAACCTTC
CTGGATAAACTGGGCCTCTCTCAAGCAGTGTTCATTGGCCATGACTGGGGTGGCATGCTG
GTGTGGTACATGGCTCTCTTCTACCCCGAGAGAGTGAGGGCGGTGGCCAGTTTGAATACT
CCCTTCATACCAGCAAATCCCAACATGTCCCCTTTGGAGAGTATCAAAGCCAACCCAGTA
TTTGATTACCAGCTCTACTTCCAAGAACCAGGAGTGGCTGAGGCTGAACTGGAACAGAAC
CTGAGTCGGACTTTCAAAAGCCTCTTCAGAGCAAGCGATGAGAGTGTTTTATCCATGCAT
AAAGTCTGTGAAGCGGGAGGACTTTTTGTAAATAGCCCAGAAGAGCCCAGCCTCAGCAGG
ATGGTCACTGAGGAGGAAATCCAGTTCTATGTGCAGCAGTTCAAGAAGTCTGGTTTCAGA
GGTCCTCTAAACTGGTACCGAAACATGGAAAGGAACTGGAAGTGGGCTTGCAAAAGCTTG
GGACGGAAGATCCTGATTCCGGCCCTGATGGTCACGGCGGAGAAGGACTTCGTGCTCGTT
CCTCAGATGTCCCAGCACATGGAGGACTGGATTCCCCACCTGAAAAGGGGACACATTGAG
GACTGTGGGCACTGGACACAGATGGACAAGCCAACCGAGGTGAATCAGATCCTCATTAAG
TGGCTGGATTCTGATGCCCGGAACCCACCGGTGGTCTCAAAGATGTAG
Protein Properties
Number of Residues 555
Molecular Weight 62615.22
Theoretical pI 6.281
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Epoxide hydrolase 2
MTLRAAVFDLDGVLALPAVFGVLGRTEEALALPRGLLNDAFQKGGPEGATTRLMKGEITL
SQWIPLMEENCRKCSETAKVCLPKNFSIKEIFDKAISARKINRPMLQAALMLRKKGFTTA
ILTNTWLDDRAERDGLAQLMCELKMHFDFLIESCQVGMVKPEPQIYKFLLDTLKASPSEV
VFLDDIGANLKPARDLGMVTILVQDTDTALKELEKVTGIQLLNTPAPLPTSCNPSDMSHG
YVTVKPRVRLHFVELGSGPAVCLCHGFPESWYSWRYQIPALAQAGYRVLAMDMKGYGESS
APPEIEEYCMEVLCKEMVTFLDKLGLSQAVFIGHDWGGMLVWYMALFYPERVRAVASLNT
PFIPANPNMSPLESIKANPVFDYQLYFQEPGVAEAELEQNLSRTFKSLFRASDESVLSMH
KVCEAGGLFVNSPEEPSLSRMVTEEEIQFYVQQFKKSGFRGPLNWYRNMERNWKWACKSL
GRKILIPALMVTAEKDFVLVPQMSQHMEDWIPHLKRGHIEDCGHWTQMDKPTEVNQILIK
WLDSDARNPPVVSKM
GenBank ID Protein 10197680
UniProtKB/Swiss-Prot ID P34913
UniProtKB/Swiss-Prot Entry Name HYES_HUMAN
PDB IDs
GenBank Gene ID AF233334
GeneCard ID EPHX2
GenAtlas ID EPHX2
HGNC ID HGNC:3402
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Beetham JK, Tian T, Hammock BD: cDNA cloning and expression of a soluble epoxide hydrolase from human liver. Arch Biochem Biophys. 1993 Aug 15;305(1):197-201. [PubMed:8342951 ]
  4. Sandberg M, Meijer J: Structural characterization of the human soluble epoxide hydrolase gene (EPHX2). Biochem Biophys Res Commun. 1996 Apr 16;221(2):333-9. [PubMed:8619856 ]
  5. Sandberg M, Hassett C, Adman ET, Meijer J, Omiecinski CJ: Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms. J Biol Chem. 2000 Sep 15;275(37):28873-81. [PubMed:10862610 ]
  6. Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M: The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1552-7. Epub 2003 Feb 6. [PubMed:12574508 ]
  7. Gomez GA, Morisseau C, Hammock BD, Christianson DW: Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry. 2004 Apr 27;43(16):4716-23. [PubMed:15096040 ]