Epoxide hydrolase 1 (EPHX1)
The protein contains 455 amino acids for an estimated molecular weight of 52949 Da.
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 (By similarity). Plays a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids (PubMed:22798687). Metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and glycerol (PubMed:24958911). (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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The reference OMIM entry for this protein is 132810
Epoxide hydrolase 1, microsomal; ephx1
Epoxide hydrolase; ephx
Epoxide hydrolase, microsomal xenobiotic; epox phenytoin toxicity, included
Arene oxide detoxification defect, included
Fetal hydantoin syndrome, included; fhs, included
Dipheny
DESCRIPTION
Epoxide hydrolases (EC 3.3.2.3) play an important role in both the activation and detoxification of exogenous chemicals such as polycyclic aromatic hydrocarbons.CLONING
Jackson et al. (1987) reported the nucleotide sequence of EPOX. The deduced protein is 455 residues long and 82% homologous to rat microsomal epoxide hydrolase. Skoda et al. (1988) isolated cDNA clones for human microsomal epoxide hydrolase and determined the nucleotide sequence. The deduced amino acid sequence of the human enzyme was found to be 80% similar to the previously reported rabbit enzyme and 84% similar to the deduced rat protein sequence. The N-terminal amino acids deduced from the human cDNA were identical to the published 19 N-terminal amino acids of the purified human enzyme. Northern blot analysis showed a single mRNA band of 1.8 kilobases. Southern blot analysis indicated that there is only 1 copy of the gene per haploid genome. Several restriction fragment length polymorphisms were observed with the human EPOX cDNA. Hassett et al. (1994) isolated and sequenced clones that encoded the entire human EPHX1 gene. The primary nuclear transcript, extending from the start of transcription to the site of poly(A) addition, is 20,271 nucleotides long.GENE STRUCTURE
Hassett et al. (1994) determined that the EPHX1 gene contains 9 exons separated by 8 introns; canonical intron/exon boundary sites were observed at each junction. The introns vary in size from 335 to 6,696 basepairs and contain numerous repetitive DNA elements, including 18 Alu sequences (each more than 100 nucleotides long) within 4 of the introns.MAPPING
Brown and Chalmers (1986) measured microsomal epoxide hydrolase activity in human/mouse hybrid cells prepared from human cells expressing 6 to 7 times the activity of the mouse cells. Of 25 clones examined by antihuman and antimouse antisera raised in the rabbit, none expressed human enzyme. This correlated with the loss of human chromosome 6 from each cell line. Brown and Chalmers (1986) concluded that the human gene for epoxide hydrolase may be on chromosome 6. Certain observations in hybrid cells suggested that other gene products can affect the level of activity expressed by the cell. Brown and Chalmers (1986) recognized that assignment of genes to chromosomes on the basis of negative data is not completely satisfactory. They also observed that other chromosomes, particularly chromosome 19, seemed to affect expression. Jackson et al. (1987) assigned the gene to chromosome 1 by somatic cell hybridization. Analysis of 2 hybrids containing spontaneous breaks permitted regional localization of the gene to 1q or proximal to NRAS (164790) on 1p. By fluorescence in situ hybridization, Hartsfield et al. (1998) mapped the EPOX gene to 1q42.1 The mouse equivalent of EPOX, symbolized Eph-1, is located on chromosome 1 (Nadeau, 1988).PHENOTYPE
Strickler et al. (1985) hypothesized a mutant form of microsomal epoxide hydrolase as the molecular basis for abnormal reactions to phenytoin and some other drugs. Phenytoin (diphenylhydantoin, dilantin) is metabolized by cytochrome P-450 monooxygenases to several oxidized products, including parahydroxylated and dihydrodiol metabolites (see 124020). Arene oxides, which are reactive electrophilic compounds, are intermediates in these oxidative reactions. If not detoxified, arene oxide metabolites can covalently bind to cell macromolecules, resulting i ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 132810 was added.