HYEP_MOUSE
ID HYEP_MOUSE Reviewed; 455 AA.
AC Q9D379; P97869;
DT 15-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 164.
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|MGI:MGI:95405};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=11003708; DOI=10.1007/s003350010169;
RA Hartsfield J.K. Jr., Everett E.T.;
RT "The Ephx1(d) allele encoding an Arg338Cys substitution is associated with
RT heat lability.";
RL Mamm. Genome 11:915-918(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, and Mammary tumor;
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 [5]
RP PROTEIN SEQUENCE OF 339-347, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-439, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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. May play a role in the
CC metabolism of endogenous lipids such as epoxide-containing fatty acids.
CC Metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG)
CC to free arachidonic acid (AA) and glycerol (By similarity).
CC {ECO:0000250|UniProtKB:P07099, ECO:0000250|UniProtKB:P07687}.
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:0000250|UniProtKB:P07099,
CC ECO:0000250|UniProtKB:P07687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23901;
CC Evidence={ECO:0000250|UniProtKB:P07099};
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:0000250|UniProtKB:P07099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049;
CC Evidence={ECO:0000250|UniProtKB:P07099};
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:0000250|UniProtKB:P07099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045;
CC Evidence={ECO:0000250|UniProtKB:P07099};
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:0000250|UniProtKB:P07099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000250|UniProtKB:P07099};
CC -!- ACTIVITY REGULATION: Inhibited by 10-hydroxystearamide and methoxy-
CC arachidonyl fluorophosphate. {ECO:0000250|UniProtKB:P07099}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P07687}; Single-pass type III membrane protein
CC {ECO:0000250|UniProtKB:P07687}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P07687}; Single-pass type III membrane protein
CC {ECO:0000250|UniProtKB:P07687}.
CC -!- SIMILARITY: Belongs to the peptidase S33 family. {ECO:0000305}.
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; U89491; AAB49762.1; -; mRNA.
DR EMBL; AK018249; BAB31132.1; -; mRNA.
DR EMBL; CH466555; EDL13136.1; -; Genomic_DNA.
DR EMBL; BC045194; AAH45194.1; -; mRNA.
DR EMBL; BC061493; AAH61493.1; -; mRNA.
DR CCDS; CCDS15579.1; -.
DR RefSeq; NP_001299847.1; NM_001312918.1.
DR RefSeq; NP_034275.1; NM_010145.3.
DR AlphaFoldDB; Q9D379; -.
DR SMR; Q9D379; -.
DR BioGRID; 199480; 3.
DR IntAct; Q9D379; 5.
DR STRING; 10090.ENSMUSP00000047551; -.
DR BindingDB; Q9D379; -.
DR ChEMBL; CHEMBL1075293; -.
DR DrugCentral; Q9D379; -.
DR ESTHER; mouse-EPHX1; Epoxide_hydrolase.
DR MEROPS; S33.971; -.
DR iPTMnet; Q9D379; -.
DR PhosphoSitePlus; Q9D379; -.
DR SwissPalm; Q9D379; -.
DR EPD; Q9D379; -.
DR jPOST; Q9D379; -.
DR MaxQB; Q9D379; -.
DR PaxDb; Q9D379; -.
DR PeptideAtlas; Q9D379; -.
DR PRIDE; Q9D379; -.
DR ProteomicsDB; 273295; -.
DR Antibodypedia; 34646; 459 antibodies from 29 providers.
DR DNASU; 13849; -.
DR Ensembl; ENSMUST00000036928; ENSMUSP00000047551; ENSMUSG00000038776.
DR GeneID; 13849; -.
DR KEGG; mmu:13849; -.
DR UCSC; uc007dwz.1; mouse.
DR CTD; 2052; -.
DR MGI; MGI:95405; Ephx1.
DR VEuPathDB; HostDB:ENSMUSG00000038776; -.
DR eggNOG; KOG2565; Eukaryota.
DR GeneTree; ENSGT00390000002210; -.
DR InParanoid; Q9D379; -.
DR OMA; SAARFYW; -.
DR OrthoDB; 898504at2759; -.
DR PhylomeDB; Q9D379; -.
DR TreeFam; TF313813; -.
DR BRENDA; 3.3.2.9; 3474.
DR Reactome; R-MMU-211945; Phase I - Functionalization of compounds.
DR SABIO-RK; Q9D379; -.
DR BioGRID-ORCS; 13849; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Ephx1; mouse.
DR PRO; PR:Q9D379; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9D379; protein.
DR Bgee; ENSMUSG00000038776; Expressed in choroid plexus of fourth ventricle and 215 other tissues.
DR ExpressionAtlas; Q9D379; baseline and differential.
DR Genevisible; Q9D379; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0033961; F:cis-stilbene-oxide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004301; F:epoxide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006725; P:cellular aromatic compound metabolic process; IMP:MGI.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0034312; P:diol biosynthetic process; ISO:MGI.
DR GO; GO:0097176; P:epoxide metabolic process; ISO:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:MGI.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000639; Epox_hydrolase-like.
DR InterPro; IPR010497; Epoxide_hydro_N.
DR InterPro; IPR016292; Epoxide_hydrolase.
DR Pfam; PF06441; EHN; 1.
DR PIRSF; PIRSF001112; Epoxide_hydrolase; 1.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Acetylation; 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_0000080856"
FT TRANSMEM 1..21
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
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 MOD_RES 439
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 410
FT /note="E -> K (in Ref. 2; BAB31132)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 52577 MW; 1567F619D9114C58 CRC64;
MWLELILASV LGFVIYWFVS RDKEETLPLE DGWWGPGSKP SAKEDESIRP FKVETSDEEI
KDLHQRIDRF RASPPLEGSR FHYGFNSSYL KKVVSFWRNE FDWRKQVEIL NQYPHFKTKI
EGLDIHFIHV KPPQLPSGRT PKPLLMVHGW PGSFYEFYKI IPLLTDPKTH GLSDEHVFEV
ICPSIPGYGF SEASSKKGLN SVATARIFYK LMSRLGFQKF YIQGGDWGSL ICTNIAQMVP
NHVKGLHLNM SFISRNIYSL TPLLGQRFGR FLGYTEKDLE LLYPFKEKVF YNIMRESGYL
HIQATKPDTV GCALNDSPVG LAAYILEKFS TWTKSEYREL EDGGLERKFS LEDLLTNIMI
YWTTGTIVSS QRFYKENLGQ GVMVHRHEGM KVFVPTGYSA FPSEILHAPE KWVKVKYPKL
ISYSYMERGG HFAAFEEPKL LAQDIRKFVS LAELQ
