HYEP_HUMAN
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 03-AUG-2022, entry version 210.
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). {ECO:0000250|UniProtKB:P07687,
CC ECO:0000269|PubMed:22798687, 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 -!- 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; 118.
DR IntAct; P07099; 22.
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; P07099; -.
DR PeptideAtlas; P07099; -.
DR PRIDE; P07099; -.
DR ProteomicsDB; 51949; -.
DR Antibodypedia; 34646; 459 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 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; WPSLFVP; -.
DR OrthoDB; 898504at2759; -.
DR PhylomeDB; P07099; -.
DR TreeFam; TF313813; -.
DR BioCyc; MetaCyc:HS07112-MON; -.
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 1081 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 184 other tissues.
DR ExpressionAtlas; P07099; baseline and differential.
DR Genevisible; P07099; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR000639; Epox_hydrolase-like.
DR InterPro; IPR016292; Epoxide_hydrolase.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR PIRSF; PIRSF001112; Epoxide_hydrolase; 1.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
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 variant; frequent
FT in the 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 variant; frequent
FT in the 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
