ID HYEP_HUMAN Reviewed; 455 AA. AC P07099; B2R8N0; Q5VTJ6; Q9NP75; Q9NPE7; Q9NQU6; Q9NQU7; Q9NQU8; Q9NQU9; AC Q9NQV0; Q9NQV1; Q9NQV2; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1988, sequence version 1. DT 27-MAR-2024, entry version 219. DE RecName: Full=Epoxide hydrolase 1 {ECO:0000305}; DE EC=3.3.2.9 {ECO:0000250|UniProtKB:P07687}; DE AltName: Full=Epoxide hydratase; DE AltName: Full=Microsomal epoxide hydrolase; DE Short=mEH {ECO:0000305}; GN Name=EPHX1 {ECO:0000312|HGNC:HGNC:3401}; Synonyms=EPHX, EPOX; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-19. RX PubMed=2891713; DOI=10.1016/s0021-9258(19)57339-2; RA Skoda R.C., Demierre A., McBride O.W., Gonzalez F.J., Meyer U.A.; RT "Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, RT complementary DNA-directed expression in COS-1 cells, and chromosomal RT localization."; RL J. Biol. Chem. 263:1549-1554(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal liver; RA Wilson N.M., Omiecinski C.J.; RT "Nucleotide sequence of a human microsomal epoxide hydrolase cDNA clone."; RL Submitted (JUL-1988) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=3502697; DOI=10.1093/nar/15.17.7188; RA Jackson M.R., Craft J.A., Burchell B.; RT "Nucleotide and deduced amino acid sequence of human liver microsomal RT epoxide hydrolase."; RL Nucleic Acids Res. 15:7188-7188(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS HIS-113; ARG-139 AND ILE-396. RC TISSUE=Liver; RX PubMed=7516776; DOI=10.1093/hmg/3.3.421; RA Hassett C., Aicher L., Sidhu J.S., Omiecinski C.J.; RT "Human microsomal epoxide hydrolase: genetic polymorphism and functional RT expression in vitro of amino acid variants."; RL Hum. Mol. Genet. 3:421-428(1994). RN [5] RP ERRATUM OF PUBMED:7516776. RA Hassett C., Aicher L., Sidhu J.S., Omiecinski C.J.; RL Hum. Mol. Genet. 3:1214-1214(1994). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7835893; DOI=10.1006/geno.1994.1520; RA Hassett C., Robinson K.B., Beck N.B., Omiecinski C.J.; RT "The human microsomal epoxide hydrolase gene (EPHX1): complete nucleotide RT sequence and structural characterization."; RL Genomics 23:433-442(1994). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain cortex; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-43; HIS-113; ARG-139; RP LEU-285; MET-408 AND GLN-452. RG NIEHS SNPs program; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin, Testis, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-327. RC TISSUE=Liver; RA Craft J.A., Jackson M.R., Burchell B.; RT "Partial nucleotide sequence of a cloned cDNA for human liver microsomal RT epoxide hydrolase."; RL Biochem. Soc. Trans. 15:708-709(1987). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-197; 242-310 AND 348-455, AND RP VARIANTS CYS-49; HIS-113; ARG-139; PRO-260 AND GLN-454. RX PubMed=11058921; RX DOI=10.1002/1098-1004(200011)16:5<450::aid-humu28>3.0.co;2-1; RA Belmahdi F., Chevalier D., Lo-Guidice J.-M., Allorge D., Cauffiez C., RA Lafitte J.-J., Broly F.; RT "Identification of 6 new polymorphisms, g.11177G>A, g.14622C>T (R49C), RT g.17540T>C, g.17639T>C, g.30929T>C, g.31074G>A (R454Q), in the human RT microsomal epoxide hydrolase gene (EPHX1) in a French population."; RL Hum. Mutat. 16:450-450(2000). RN [13] RP POTENTIAL INVOLVEMENT IN HYPERCHOLANEMIA, AND TISSUE SPECIFICITY. RX PubMed=12878321; DOI=10.1016/s0925-4439(03)00085-1; RA Zhu Q.S., Xing W., Qian B., von Dippe P., Shneider B.L., Fox V.L., Levy D.; RT "Inhibition of human m-epoxide hydrolase gene expression in a case of RT hypercholanemia."; RL Biochim. Biophys. Acta 1638:208-216(2003). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=22798687; DOI=10.1194/jlr.m024448; RA Decker M., Adamska M., Cronin A., Di Giallonardo F., Burgener J., RA Marowsky A., Falck J.R., Morisseau C., Hammock B.D., Gruzdev A., RA Zeldin D.C., Arand M.; RT "EH3 (ABHD9): the first member of a new epoxide hydrolase family with high RT activity for fatty acid epoxides."; RL J. Lipid Res. 53:2038-2045(2012). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR RP LOCATION. RX PubMed=24958911; DOI=10.1194/jlr.m051284; RA Nithipatikom K., Endsley M.P., Pfeiffer A.W., Falck J.R., Campbell W.B.; RT "A novel activity of microsomal epoxide hydrolase: metabolism of the RT endocannabinoid 2-arachidonoylglycerol."; RL J. Lipid Res. 55:2093-2102(2014). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [19] RP VARIANTS HIS-113 AND ARG-139, AND DISEASE. RX PubMed=12173035; DOI=10.1038/sj.ejhg.5200849; RA Laasanen J., Romppanen E.-L., Hiltunen M., Helisalmi S., Mannermaa A., RA Punnonen K., Heinonen S.; RT "Two exonic single nucleotide polymorphisms in the microsomal epoxide RT hydrolase gene are jointly associated with preeclampsia."; RL Eur. J. Hum. Genet. 10:569-573(2002). RN [20] RP VARIANT GLN-44. RX PubMed=15618730; DOI=10.2133/dmpk.18.150; RA Shiseki K., Itoda M., Saito Y., Nakajima Y., Maekawa K., Kimura H., RA Goto Y., Saitoh O., Katoh M., Ohnuma T., Kawai M., Sugai K., Ohtsuki T., RA Suzuki C., Minami N., Ozawa S., Sawada J.; RT "Five novel single nucleotide polymorphisms in the EPHX1 gene encoding RT microsomal epoxide hydrolase."; RL Drug Metab. Pharmacokinet. 18:150-153(2003). RN [21] RP CHARACTERIZATION OF VARIANTS HIS-113 AND ARG-139. RX PubMed=15535985; DOI=10.1016/j.cbi.2004.07.004; RA Hosagrahara V.P., Rettie A.E., Hassett C., Omiecinski C.J.; RT "Functional analysis of human microsomal epoxide hydrolase genetic RT variants."; RL Chem. Biol. Interact. 150:149-159(2004). CC -!- FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of CC arene and aliphatic epoxides to less reactive and more water soluble CC dihydrodiols by the trans addition of water (By similarity). Plays a CC role in the metabolism of endogenous lipids such as epoxide-containing CC fatty acids (PubMed:22798687). Metabolizes the abundant endocannabinoid CC 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and CC glycerol (PubMed:24958911). Binds 20(S)-hydroxycholesterol (20(S)-OHC) CC (By similarity). {ECO:0000250|UniProtKB:P07687, CC ECO:0000250|UniProtKB:Q9D379, ECO:0000269|PubMed:22798687, CC ECO:0000269|PubMed:24958911}. CC -!- CATALYTIC ACTIVITY: CC Reaction=cis-stilbene oxide + H2O = (1R,2R)-hydrobenzoin; CC Xref=Rhea:RHEA:23900, ChEBI:CHEBI:15377, ChEBI:CHEBI:50004, CC ChEBI:CHEBI:50014; EC=3.3.2.9; CC Evidence={ECO:0000269|PubMed:24958911}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23901; CC Evidence={ECO:0000269|PubMed:24958911}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3- CC yl)methyl]methanamine + H2O = 2-{[(4- CC methoxybenzyl)(methyl)amino]methyl}-2-methylpropane-1,3-diol; CC Xref=Rhea:RHEA:55764, ChEBI:CHEBI:15377, ChEBI:CHEBI:139161, CC ChEBI:CHEBI:139164; EC=3.3.2.9; CC Evidence={ECO:0000250|UniProtKB:P07687}; CC -!- CATALYTIC ACTIVITY: CC Reaction=8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = 8,9-dihydroxy- CC (5Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:44048, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:84025, ChEBI:CHEBI:84032; CC Evidence={ECO:0000269|PubMed:22798687}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049; CC Evidence={ECO:0000269|PubMed:22798687}; CC -!- CATALYTIC ACTIVITY: CC Reaction=11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = 11,12- CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:44044, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:76625, ChEBI:CHEBI:84031; CC Evidence={ECO:0000269|PubMed:22798687}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045; CC Evidence={ECO:0000269|PubMed:22798687}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+); CC Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392; CC Evidence={ECO:0000269|PubMed:24958911}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; CC Evidence={ECO:0000269|PubMed:24958911}; CC -!- ACTIVITY REGULATION: Inhibited by 10-hydroxystearamide and methoxy- CC arachidonyl fluorophosphate. {ECO:0000269|PubMed:24958911}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.8 uM for 8,9-EET {ECO:0000269|PubMed:22798687}; CC KM=0.4 uM for 11,12-EET {ECO:0000269|PubMed:22798687}; CC KM=0.9 uM for 14,15-EET {ECO:0000269|PubMed:22798687}; CC KM=5.8 uM for leukotoxin {ECO:0000269|PubMed:22798687}; CC Vmax=0.12 umol/min/mg enzyme with 8,9-EET as substrate CC {ECO:0000269|PubMed:22798687}; CC Vmax=0.6 umol/min/mg enzyme with 11,12-EET as substrate CC {ECO:0000269|PubMed:22798687}; CC Vmax=0.04 umol/min/mg enzyme with 14,15-EET as substrate CC {ECO:0000269|PubMed:22798687}; CC Vmax=0.008 umol/min/mg enzyme with leukotoxin as substrate CC {ECO:0000269|PubMed:22798687}; CC -!- INTERACTION: CC P07099; P23560-2: BDNF; NbExp=3; IntAct=EBI-6138796, EBI-12275524; CC P07099; P13569: CFTR; NbExp=5; IntAct=EBI-6138796, EBI-349854; CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:24958911}; CC Single-pass type III membrane protein {ECO:0000255}. Endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P07687}; Single-pass type III CC membrane protein {ECO:0000250|UniProtKB:P07687}. CC -!- TISSUE SPECIFICITY: Found in liver. {ECO:0000269|PubMed:12878321}. CC -!- DISEASE: Note=In some populations, the high activity haplotype CC tyr113/his139 is overrepresented among women suffering from pregnancy- CC induced hypertension (pre-eclampsia) when compared with healthy CC controls. {ECO:0000269|PubMed:12173035}. CC -!- DISEASE: Note=Variations in EPHX1 gene non-coding regions have been CC observed in a patient with hypercholanemia. The pathogenicity of these CC variants has not been confirmed. {ECO:0000269|PubMed:12878321}. CC -!- SIMILARITY: Belongs to the peptidase S33 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ephx1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J03518; AAA61305.1; -; mRNA. DR EMBL; X07936; CAA30759.1; -; mRNA. DR EMBL; Y00424; CAA68486.1; -; mRNA. DR EMBL; L25878; AAA52389.1; -; mRNA. DR EMBL; L25879; AAA52390.1; -; mRNA. DR EMBL; U06661; AAB60649.1; -; Genomic_DNA. DR EMBL; U06656; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06657; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06658; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06659; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06660; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; AK313436; BAG36227.1; -; mRNA. DR EMBL; AY948961; AAX81410.1; -; Genomic_DNA. DR EMBL; AL591895; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003567; AAH03567.1; -; mRNA. DR EMBL; BC008291; AAH08291.1; -; mRNA. DR EMBL; BC095430; AAH95430.1; -; mRNA. DR EMBL; M36374; AAA59580.1; -; mRNA. DR EMBL; AF253417; AAC41694.1; -; Genomic_DNA. DR EMBL; AF276626; AAF87726.1; -; Genomic_DNA. DR EMBL; AF276627; AAF87727.1; -; Genomic_DNA. DR EMBL; AF276628; AAF87728.1; -; Genomic_DNA. DR EMBL; AF276629; AAF87729.1; -; Genomic_DNA. DR EMBL; AF276630; AAF87730.1; -; Genomic_DNA. DR EMBL; AF276631; AAF87731.1; -; Genomic_DNA. DR EMBL; AF276632; AAF87732.1; -; Genomic_DNA. DR EMBL; AF276633; AAF87733.1; -; Genomic_DNA. DR EMBL; AF276634; AAF87734.1; -; Genomic_DNA. DR EMBL; AF276635; AAF87735.1; -; Genomic_DNA. DR EMBL; AF276636; AAF87736.1; -; Genomic_DNA. DR EMBL; AF276637; AAF87737.1; -; Genomic_DNA. DR EMBL; AF276638; AAF87738.1; -; Genomic_DNA. DR CCDS; CCDS1547.1; -. DR PIR; A29939; A29939. DR RefSeq; NP_000111.1; NM_000120.3. DR RefSeq; NP_001129490.1; NM_001136018.3. DR RefSeq; NP_001278092.1; NM_001291163.1. DR AlphaFoldDB; P07099; -. DR SMR; P07099; -. DR BioGRID; 108366; 141. DR IntAct; P07099; 24. DR MINT; P07099; -. DR STRING; 9606.ENSP00000480004; -. DR BindingDB; P07099; -. DR ChEMBL; CHEMBL1968; -. DR DrugBank; DB00808; Indapamide. DR DrugBank; DB00252; Phenytoin. DR DrugCentral; P07099; -. DR SwissLipids; SLP:000001117; -. DR ESTHER; human-EPHX1; Epoxide_hydrolase. DR MEROPS; S33.971; -. DR GlyGen; P07099; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P07099; -. DR PhosphoSitePlus; P07099; -. DR SwissPalm; P07099; -. DR BioMuta; EPHX1; -. DR DMDM; 123926; -. DR CPTAC; CPTAC-1613; -. DR CPTAC; CPTAC-359; -. DR CPTAC; CPTAC-360; -. DR EPD; P07099; -. DR jPOST; P07099; -. DR MassIVE; P07099; -. DR PaxDb; 9606-ENSP00000480004; -. DR PeptideAtlas; P07099; -. DR ProteomicsDB; 51949; -. DR Pumba; P07099; -. DR Antibodypedia; 34646; 503 antibodies from 29 providers. DR DNASU; 2052; -. DR Ensembl; ENST00000272167.10; ENSP00000272167.5; ENSG00000143819.13. DR Ensembl; ENST00000366837.5; ENSP00000355802.4; ENSG00000143819.13. DR Ensembl; ENST00000614058.4; ENSP00000480004.1; ENSG00000143819.13. DR GeneID; 2052; -. DR KEGG; hsa:2052; -. DR MANE-Select; ENST00000272167.10; ENSP00000272167.5; NM_001136018.4; NP_001129490.1. DR AGR; HGNC:3401; -. DR CTD; 2052; -. DR DisGeNET; 2052; -. DR GeneCards; EPHX1; -. DR HGNC; HGNC:3401; EPHX1. DR HPA; ENSG00000143819; Tissue enhanced (adrenal gland, liver). DR MalaCards; EPHX1; -. DR MIM; 132810; gene. DR neXtProt; NX_P07099; -. DR OpenTargets; ENSG00000143819; -. DR Orphanet; 238475; Familial hypercholanemia. DR PharmGKB; PA27829; -. DR VEuPathDB; HostDB:ENSG00000143819; -. DR eggNOG; KOG2565; Eukaryota. DR GeneTree; ENSGT00390000002210; -. DR HOGENOM; CLU_019414_3_0_1; -. DR InParanoid; P07099; -. DR OMA; WVKQKYH; -. DR OrthoDB; 5472392at2759; -. DR PhylomeDB; P07099; -. DR TreeFam; TF313813; -. DR BioCyc; MetaCyc:HS07112-MONOMER; -. DR BRENDA; 3.3.2.9; 2681. DR PathwayCommons; P07099; -. DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds. DR SABIO-RK; P07099; -. DR SignaLink; P07099; -. DR BioGRID-ORCS; 2052; 18 hits in 1161 CRISPR screens. DR ChiTaRS; EPHX1; human. DR GeneWiki; EPHX1; -. DR GenomeRNAi; 2052; -. DR Pharos; P07099; Tchem. DR PRO; PR:P07099; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P07099; Protein. DR Bgee; ENSG00000143819; Expressed in right adrenal gland cortex and 186 other cell types or tissues. DR ExpressionAtlas; P07099; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0033961; F:cis-stilbene-oxide hydrolase activity; IDA:UniProtKB. DR GO; GO:0004301; F:epoxide hydrolase activity; IDA:UniProtKB. DR GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB. DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB. DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-KW. DR GO; GO:0097176; P:epoxide metabolic process; IDA:UniProtKB. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR000073; AB_hydrolase_1. DR InterPro; IPR000639; Epox_hydrolase-like. DR InterPro; IPR016292; Epoxide_hydrolase. DR PANTHER; PTHR21661:SF78; EPOXIDE HYDROLASE 1; 1. DR PANTHER; PTHR21661; EPOXIDE HYDROLASE 1-RELATED; 1. DR Pfam; PF00561; Abhydrolase_1; 1. DR PIRSF; PIRSF001112; Epoxide_hydrolase; 1. DR PRINTS; PR00412; EPOXHYDRLASE. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR Genevisible; P07099; HS. PE 1: Evidence at protein level; KW Aromatic hydrocarbons catabolism; Detoxification; KW Direct protein sequencing; Endoplasmic reticulum; Hydrolase; KW Lipid metabolism; Membrane; Methylation; Microsome; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..455 FT /note="Epoxide hydrolase 1" FT /id="PRO_0000080855" FT TRANSMEM 1..21 FT /note="Helical; Signal-anchor for type III membrane FT protein" FT /evidence="ECO:0000250|UniProtKB:P07687" FT TOPO_DOM 22..455 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P07687" FT ACT_SITE 226 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P07687" FT ACT_SITE 374 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P34913" FT ACT_SITE 431 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P07687" FT MOD_RES 295 FT /note="Dimethylated arginine" FT /evidence="ECO:0000250|UniProtKB:P07687" FT VARIANT 43 FT /note="R -> T (in dbSNP:rs3738046)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_023303" FT VARIANT 44 FT /note="E -> Q (in dbSNP:rs745306359)" FT /evidence="ECO:0000269|PubMed:15618730" FT /id="VAR_018347" FT VARIANT 49 FT /note="R -> C (in allele EPHX1*2; dbSNP:rs2234697)" FT /evidence="ECO:0000269|PubMed:11058921" FT /id="VAR_013298" FT VARIANT 113 FT /note="Y -> H (in allele EPHX1*3; benign; frequent in the FT human population; 55% of wild type enzyme activity; FT dbSNP:rs1051740)" FT /evidence="ECO:0000269|PubMed:11058921, FT ECO:0000269|PubMed:12173035, ECO:0000269|PubMed:15535985, FT ECO:0000269|PubMed:7516776, ECO:0000269|Ref.8" FT /id="VAR_005295" FT VARIANT 139 FT /note="H -> R (in allele EPHX1*4; benign; frequent in the FT human population; 62% of wild type enzyme activity; FT dbSNP:rs2234922)" FT /evidence="ECO:0000269|PubMed:11058921, FT ECO:0000269|PubMed:12173035, ECO:0000269|PubMed:15535985, FT ECO:0000269|PubMed:7516776, ECO:0000269|Ref.8" FT /id="VAR_005296" FT VARIANT 260 FT /note="L -> P (in allele EPHX1*1G)" FT /evidence="ECO:0000269|PubMed:11058921" FT /id="VAR_013299" FT VARIANT 275 FT /note="T -> A (in dbSNP:rs35073925)" FT /id="VAR_051828" FT VARIANT 285 FT /note="V -> L (in dbSNP:rs45449793)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_023304" FT VARIANT 396 FT /note="T -> I (either a rare variant or a sequencing FT error)" FT /evidence="ECO:0000269|PubMed:7516776" FT /id="VAR_005297" FT VARIANT 408 FT /note="T -> M (in dbSNP:rs45495897)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_023305" FT VARIANT 452 FT /note="L -> Q (in dbSNP:rs45563137)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_023306" FT VARIANT 454 FT /note="R -> Q (in allele EPHX1*5; dbSNP:rs2234701)" FT /evidence="ECO:0000269|PubMed:11058921" FT /id="VAR_013300" FT CONFLICT 15 FT /note="I -> V (in Ref. 7; BAG36227)" FT /evidence="ECO:0000305" FT CONFLICT 112 FT /note="R -> K (in Ref. 11)" FT /evidence="ECO:0000305" FT CONFLICT 148 FT /note="H -> N (in Ref. 3 and 11)" FT /evidence="ECO:0000305" FT CONFLICT 243 FT /note="V -> L (in Ref. 11)" FT /evidence="ECO:0000305" FT CONFLICT 348 FT /note="K -> S (in Ref. 3; CAA68486)" FT /evidence="ECO:0000305" FT CONFLICT 406 FT /note="L -> F (in Ref. 3; CAA68486)" FT /evidence="ECO:0000305" FT CONFLICT 420 FT /note="L -> V (in Ref. 3; CAA68486)" FT /evidence="ECO:0000305" SQ SEQUENCE 455 AA; 52949 MW; 88E333838C841390 CRC64; MWLEILLTSV LGFAIYWFIS RDKEETLPLE DGWWGPGTRS AAREDDSIRP FKVETSDEEI HDLHQRIDKF RFTPPLEDSC FHYGFNSNYL KKVISYWRNE FDWKKQVEIL NRYPHFKTKI EGLDIHFIHV KPPQLPAGHT PKPLLMVHGW PGSFYEFYKI IPLLTDPKNH GLSDEHVFEV ICPSIPGYGF SEASSKKGFN SVATARIFYK LMLRLGFQEF YIQGGDWGSL ICTNMAQLVP SHVKGLHLNM ALVLSNFSTL TLLLGQRFGR FLGLTERDVE LLYPVKEKVF YSLMRESGYM HIQCTKPDTV GSALNDSPVG LAAYILEKFS TWTNTEFRYL EDGGLERKFS LDDLLTNVML YWTTGTIISS QRFYKENLGQ GWMTQKHERM KVYVPTGFSA FPFELLHTPE KWVRFKYPKL ISYSYMVRGG HFAAFEEPEL LAQDIRKFLS VLERQ //