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Identification
HMDB Protein ID HMDBP01791
Secondary Accession Numbers
  • 7148
Name Epoxide hydrolase 1
Synonyms
  1. Epoxide hydratase
  2. Microsomal epoxide hydrolase
Gene Name EPHX1
Protein Type Enzyme
Biological Properties
General Function Involved in catalytic activity
Specific Function Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
Pathways
  • Bile secretion
  • Carbamazepine Metabolism Pathway
  • Chemical carcinogenesis
  • Metabolism of xenobiotics by cytochrome P450
  • Phenytoin (Antiarrhythmic) Action Pathway
Reactions
Cis-stilbene oxide + Water → (+)-(1R,2R)-1,2-Diphenylethane-1,2-diol details
Naphthalene epoxide + Water → 1,2-Dihydronaphthalene-1,2-diol details
(1S,2R)-Naphthalene 1,2-oxide + Water → 1,2-Dihydronaphthalene-1,2-diol details
1-Nitronaphthalene-5,6-oxide + Water → 1-Nitro-5,6-dihydroxy-dihydronaphthalene details
Bromobenzene-3,4-oxide + Water → Bromobenzene-3,4-dihydrodiol details
Bromobenzene-2,3-oxide + Water → Bromobenzene-2,3-dihydrodiol details
Benzo[a]pyrene-7,8-oxide + Water → Benzo[a]pyrene-7,8-diol details
2,3-Epoxyaflatoxin B1 + Water → Aflatoxin B1 diol details
1a,11b-Dihydro-4,9-dimethylbenz[a]anthra[3,4-b]oxirene + Water → trans-3,4-Dihydro-3,4-dihydroxy-7,12-dimethylbenz[a]anthracene details
7,12-Dimethylbenz[a]anthracene 5,6-oxide + Water → trans-5,6-Dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene details
GO Classification
Biological Process
aromatic compound catabolic process
response to toxin
response to organic cyclic compound
Cellular Component
endoplasmic reticulum membrane
integral to membrane
Component
membrane
cell part
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on ether bonds
ether hydrolase activity
epoxide hydrolase activity
Molecular Function
cis-stilbene-oxide hydrolase activity
epoxide hydrolase activity
Process
response to stimulus
response to chemical stimulus
response to toxin
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Single-pass type II membrane protein
  3. Microsome membrane
  4. Single-pass type II membrane protein (Potential)
Gene Properties
Chromosome Location 1
Locus 1q42.1
SNPs EPHX1
Gene Sequence
>1368 bp
ATGTGGCTAGAAATCCTCCTCACTTCAGTGCTGGGCTTTGCCATCTACTGGTTCATCTCC
CGGGACAAAGAGGAAACTTTGCCACTTGAAGATGGGTGGTGGGGGCCAGGCACGAGGTCC
GCAGCCAGGGAGGACGACAGCATCCGCCCTTTCAAGGTGGAAACGTCAGATGAGGAGATC
CACGACTTACACCAGAGGATCGATAAGTTCCGTTTCACCCCACCTTTGGAGGACAGCTGC
TTCCACTATGGCTTCAACTCCAACTACCTGAAGAAAGTCATCTCCTACTGGCGGAATGAA
TTTGACTGGAAGAAGCAGGTGGAGATTCTCAACAGATACCCTCACTTCAAGACTAAGATT
GAAGGGCTGGACATCCACTTCATCCACGTGAAGCCCCCCCAGCTGCCCGCAGGCCATACC
CCGAAGCCCTTGCTGATGGTGCACGGCTGGCCCGGCTCTTTCTACGAGTTTTATAAGATC
ATCCCACTCCTGACTGACCCCAAGAACCATGGCCTGAGCGATGAGCACGTTTTTGAAGTC
ATCTGCCCTTCCATCCCTGGCTATGGCTTCTCAGAGGCATCCTCCAAGAAGGGGTTCAAC
TCGGTGGCCACCGCCAGGATCTTTTACAAGCTGATGCTGCGGCTGGGCTTCCAGGAATTC
TACATTCAAGGAGGGGACTGGGGGTCCCTGATCTGCACTAATATGGCCCAGCTGGTGCCC
AGCCACGTGAAAGGCCTGCACTTGAACATGGCTTTGGTTTTAAGCAACTTCTCTACCCTG
ACCCTCCTCCTGGGACAGCGTTTCGGGAGGTTTCTTGGCCTCACTGAGAGGGATGTGGAG
CTGCTGTACCCCGTCAAGGAGAAGGTATTCTACAGCCTGATGAGGGAGAGCGGCTACATG
CACATCCAGTGCACCAAGCCTGACACCGTAGGCTCTGCTCTGAATGACTCTCCTGTGGGT
CTGGCTGCCTATATTCTAGAGAAGTTTTCCACCTGGACCAATACGGAATTCCGATACCTG
GAGGATGGAGGCCTGGAAAGGAAGTTCTCCCTGGACGACCTGCTGACCAACGTCATGCTC
TACTGGACAACAGGCACCATCATCTCCTCCCAGCGCTTCTACAAGGAGAACCTGGGACAG
GGCTGGATGACCCAGAAGCATGAGCGGATGAAGGTCTATGTGCCCACTGGCTTCTCTGCC
TTCCCTTTTGAGCTATTGCACACGCCTGAAAAGTGGGTGAGGTTCAAGTACCCAAAGCTC
ATCTCCTATTCCTACATGGTTCGTGGGGGCCACTTTGCGGCCTTTGAGGAGCCGGAGCTG
CTCGCCCAGGACATCCGCAAGTTCCTGTCGGTGCTGGAGCGGCAATGA
Protein Properties
Number of Residues 455
Molecular Weight 52948.48
Theoretical pI 7.256
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Epoxide hydrolase 1
MWLEILLTSVLGFAIYWFISRDKEETLPLEDGWWGPGTRSAAREDDSIRPFKVETSDEEI
HDLHQRIDKFRFTPPLEDSCFHYGFNSNYLKKVISYWRNEFDWKKQVEILNRYPHFKTKI
EGLDIHFIHVKPPQLPAGHTPKPLLMVHGWPGSFYEFYKIIPLLTDPKNHGLSDEHVFEV
ICPSIPGYGFSEASSKKGFNSVATARIFYKLMLRLGFQEFYIQGGDWGSLICTNMAQLVP
SHVKGLHLNMALVLSNFSTLTLLLGQRFGRFLGLTERDVELLYPVKEKVFYSLMRESGYM
HIQCTKPDTVGSALNDSPVGLAAYILEKFSTWTNTEFRYLEDGGLERKFSLDDLLTNVML
YWTTGTIISSQRFYKENLGQGWMTQKHERMKVYVPTGFSAFPFELLHTPEKWVRFKYPKL
ISYSYMVRGGHFAAFEEPELLAQDIRKFLSVLERQ
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P07099
UniProtKB/Swiss-Prot Entry Name HYEP_HUMAN
PDB IDs Not Available
GenBank Gene ID J03518
GeneCard ID EPHX1
GenAtlas ID EPHX1
HGNC ID HGNC:3401
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. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414 ]
  3. Skoda RC, Demierre A, McBride OW, Gonzalez FJ, Meyer UA: Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, complementary DNA-directed expression in COS-1 cells, and chromosomal localization. J Biol Chem. 1988 Jan 25;263(3):1549-54. [PubMed:2891713 ]
  4. Jackson MR, Craft JA, Burchell B: Nucleotide and deduced amino acid sequence of human liver microsomal epoxide hydrolase. Nucleic Acids Res. 1987 Sep 11;15(17):7188. [PubMed:3502697 ]
  5. Hassett C, Aicher L, Sidhu JS, Omiecinski CJ: Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. Hum Mol Genet. 1994 Mar;3(3):421-8. [PubMed:7516776 ]
  6. Hassett C, Robinson KB, Beck NB, Omiecinski CJ: The human microsomal epoxide hydrolase gene (EPHX1): complete nucleotide sequence and structural characterization. Genomics. 1994 Sep 15;23(2):433-42. [PubMed:7835893 ]
  7. Belmahdi F, Chevalier D, Lo-Guidice JM, Allorge D, Cauffiez C, Lafitte JJ, Broly F: Identification of 6 new polymorphisms, g.11177G>A, g.14622C>T (R49C), g.17540T>C, g.17639T>C, g.30929T>C, g.31074G>A (R454Q), in the human microsomal epoxide hydrolase gene (EPHX1) in a French population. Hum Mutat. 2000 Nov;16(5):450. [PubMed:11058921 ]
  8. Zhu QS, Xing W, Qian B, von Dippe P, Shneider BL, Fox VL, Levy D: Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia. Biochim Biophys Acta. 2003 Jul 30;1638(3):208-16. [PubMed:12878321 ]
  9. Laasanen J, Romppanen EL, Hiltunen M, Helisalmi S, Mannermaa A, Punnonen K, Heinonen S: Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are jointly associated with preeclampsia. Eur J Hum Genet. 2002 Sep;10(9):569-73. [PubMed:12173035 ]
  10. Shiseki K, Itoda M, Saito Y, Nakajima Y, Maekawa K, Kimura H, Goto Y, Saitoh O, Katoh M, Ohnuma T, Kawai M, Sugai K, Ohtsuki T, Suzuki C, Minami N, Ozawa S, Sawada J: Five novel single nucleotide polymorphisms in the EPHX1 gene encoding microsomal epoxide hydrolase. Drug Metab Pharmacokinet. 2003;18(2):150-3. [PubMed:15618730 ]
  11. Hosagrahara VP, Rettie AE, Hassett C, Omiecinski CJ: Functional analysis of human microsomal epoxide hydrolase genetic variants. Chem Biol Interact. 2004 Nov 20;150(2):149-59. [PubMed:15535985 ]