HYEP_RABIT
ID HYEP_RABIT Reviewed; 455 AA.
AC P04068;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 2.
DT 25-MAY-2022, entry version 130.
DE RecName: Full=Epoxide hydrolase 1;
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;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2729997; DOI=10.1016/0003-9861(89)90287-7;
RA Hassett C., Turnblom S.M., Deangeles A., Omiecinski C.J.;
RT "Rabbit microsomal epoxide hydrolase: isolation and characterization of the
RT xenobiotic metabolizing enzyme cDNA.";
RL Arch. Biochem. Biophys. 271:380-389(1989).
RN [2]
RP PROTEIN SEQUENCE.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=6693396; DOI=10.1016/s0021-9258(17)43528-9;
RA Heinemann F.S., Ozols J.;
RT "The covalent structure of hepatic microsomal epoxide hydrolase. II. The
RT complete amino acid sequence.";
RL J. Biol. Chem. 259:797-804(1984).
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}.
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DR EMBL; M21496; AAA31392.1; -; mRNA.
DR PIR; S04342; YXRBH.
DR RefSeq; NP_001075744.1; NM_001082275.1.
DR AlphaFoldDB; P04068; -.
DR SMR; P04068; -.
DR STRING; 9986.ENSOCUP00000010259; -.
DR ESTHER; rabit-hyep; Epoxide_hydrolase.
DR MEROPS; S33.971; -.
DR GeneID; 100009104; -.
DR KEGG; ocu:100009104; -.
DR CTD; 2052; -.
DR eggNOG; KOG2565; Eukaryota.
DR InParanoid; P04068; -.
DR OrthoDB; 898504at2759; -.
DR BRENDA; 3.3.2.9; 1749.
DR Proteomes; UP000001811; Unplaced.
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:0033961; F:cis-stilbene-oxide hydrolase activity; ISS:UniProtKB.
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: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 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_0000080858"
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 CONFLICT 68..70
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="Y -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 201..203
FT /note="SVS -> NVV (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="M -> RISSY (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 248..249
FT /note="LN -> DL (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="R -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 366..371
FT /note="SIVSSQ -> WIRTHY (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 52512 MW; 8A1F556275389AD2 CRC64;
MLLELLLASV LGFVIYWFVS GDKEESLPLE DGWWGPGSRP VGLEDESIRP FKVETSDEEI
NDLHQRIDRI RLTPPLENSR FHYGFNSNYL KKILSYWRHE FDWKKQVEIL NSYPHFKTKI
EGLDIHFIHV KPPQVPPGRT PKPLLMVHGW PGSFFEFYKI IPLLTDPKSH GLSDEHIFEV
ICPSIPGYGF SQASSKKGFN SVSTARIFYK LMLRLGFQEF YIQGGDWGAL VCTNMAQLVP
SHVKGLHLNM ALILRNHYTL TLLLGRRIGG LLGYTERDME LLYPFKEKVF YSLMRESGYM
HIRATKPDTV GCALNDSPVG LAAYILEKFS TWTNSEFRDL EDGGLERKFS LQDLLTNIMI
YWTTGSIVSS QRYYKENLGQ GFMAHKHERL KVHVPTGFAA FPCEIMHVPE KWVRTKYPQL
ISYSYMPRGG HFAAFEEPEL LARDICKFVG LVERQ
