CEEH1_CAEEL
ID CEEH1_CAEEL Reviewed; 404 AA.
AC G5EBI4;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Epoxide hydrolase 1 {ECO:0000312|WormBase:K02F3.6};
DE EC=3.3.2.10 {ECO:0000269|PubMed:18267101};
DE AltName: Full=CEEH1 {ECO:0000303|PubMed:18267101};
GN Name=ceeh-1 {ECO:0000312|WormBase:K02F3.6};
GN ORFNames=K02F3.6 {ECO:0000312|WormBase:K02F3.6};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:ABV45408.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=18267101; DOI=10.1016/j.abb.2008.01.016;
RA Harris T.R., Aronov P.A., Jones P.D., Tanaka H., Arand M., Hammock B.D.;
RT "Identification of two epoxide hydrolases in Caenorhabditis elegans that
RT metabolize mammalian lipid signaling molecules.";
RL Arch. Biochem. Biophys. 472:139-149(2008).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
CC -!- FUNCTION: Catalyzes the hydrolysis of epoxide-containing fatty acids.
CC Active against epoxyeicosatrienoic acids (EETs) including 8,9-epoxy-
CC (5Z,11Z,14Z)-eicosatrienoate (8,9-EET), 11,12-epoxy-(5Z,8Z,14Z)-
CC eicosatrienoate (11,12-EET) and 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC (14,15-EET) and the linoleic acid metabolites 12,13-epoxy-(9Z)-
CC octadecenoate (12,13-EpOME) and 9,10-epoxy-(12Z)-octadecenoate (9,10-
CC EpOME). These epoxides function as lipid signaling molecules, the
CC enzyme can deplete the supply of the epoxide signal by transforming
CC them into diol species that are more readily eliminated through
CC excretion. {ECO:0000269|PubMed:18267101}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an epoxide + H2O = an ethanediol; Xref=Rhea:RHEA:19037,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32955, ChEBI:CHEBI:140594;
CC EC=3.3.2.10; Evidence={ECO:0000269|PubMed:18267101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19038;
CC Evidence={ECO:0000305|PubMed:18267101};
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:18267101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049;
CC Evidence={ECO:0000305|PubMed:18267101};
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:18267101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045;
CC Evidence={ECO:0000305|PubMed:18267101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = 14,15-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:44040,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:84024, ChEBI:CHEBI:84029;
CC Evidence={ECO:0000269|PubMed:18267101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44041;
CC Evidence={ECO:0000305|PubMed:18267101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12,13-epoxy-(9Z)-octadecenoate + H2O = 12,13-dihydroxy-(9Z)-
CC octadecenoate; Xref=Rhea:RHEA:44036, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:84026, ChEBI:CHEBI:84028;
CC Evidence={ECO:0000269|PubMed:18267101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44037;
CC Evidence={ECO:0000305|PubMed:18267101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9,10-epoxy-(12Z)-octadecenoate + H2O = 9,10-dihydroxy-(12Z)-
CC octadecenoate; Xref=Rhea:RHEA:44032, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:84023, ChEBI:CHEBI:84027;
CC Evidence={ECO:0000269|PubMed:18267101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44033;
CC Evidence={ECO:0000305|PubMed:18267101};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=160 uM for trans-1,3-diphenylpropene oxide
CC {ECO:0000269|PubMed:18267101};
CC KM=11.4 uM for 12,13-epoxy-9-octadecenoate
CC {ECO:0000269|PubMed:18267101};
CC KM=7.5 uM for 9,10-epoxy-12-octadecenoate
CC {ECO:0000269|PubMed:18267101};
CC Note=kcat is 12 sec(-1) with trans-1,3-diphenylpropene oxide as
CC substrate. kcat is 0.11 sec(-1) with 12,13-epoxy-9-octadecenoate as
CC substrate. kcat is 0.22 sec(-1) with 9,10-epoxy-12-octadecenoate as
CC substrate. {ECO:0000269|PubMed:18267101};
CC -!- PATHWAY: Lipid metabolism. {ECO:0000305|PubMed:18267101}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: RNAi knockdown of both ceeh-1 and ceeh-2 results
CC in the accumulation of 9,10-EpOME and 12,13-EpOME.
CC {ECO:0000269|PubMed:18267101}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide hydrolase
CC family. {ECO:0000305}.
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DR EMBL; EU151493; ABV45408.1; -; mRNA.
DR EMBL; FO080195; CCD61875.1; -; Genomic_DNA.
DR RefSeq; NP_497268.1; NM_064867.4.
DR AlphaFoldDB; G5EBI4; -.
DR SMR; G5EBI4; -.
DR STRING; 6239.K02F3.6; -.
DR SwissLipids; SLP:000001026; -.
DR ESTHER; caeel-K02F3.6; Epoxide_hydrolase.
DR EPD; G5EBI4; -.
DR PaxDb; G5EBI4; -.
DR PeptideAtlas; G5EBI4; -.
DR EnsemblMetazoa; K02F3.6.1; K02F3.6.1; WBGene00019329.
DR EnsemblMetazoa; K02F3.6.2; K02F3.6.2; WBGene00019329.
DR GeneID; 175239; -.
DR KEGG; cel:CELE_K02F3.6; -.
DR CTD; 175239; -.
DR WormBase; K02F3.6; CE28941; WBGene00019329; ceeh-1.
DR eggNOG; KOG4178; Eukaryota.
DR HOGENOM; CLU_020336_7_3_1; -.
DR InParanoid; G5EBI4; -.
DR OMA; HGWPQHH; -.
DR OrthoDB; 616687at2759; -.
DR PhylomeDB; G5EBI4; -.
DR SABIO-RK; G5EBI4; -.
DR PRO; PR:G5EBI4; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00019329; Expressed in material anatomical entity and 5 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004301; F:epoxide hydrolase activity; IDA:WormBase.
DR GO; GO:0016787; F:hydrolase activity; IBA:GO_Central.
DR GO; GO:0044255; P:cellular lipid metabolic process; IDA:WormBase.
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 Pfam; PF00561; Abhydrolase_1; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Lipid metabolism; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..404
FT /note="Epoxide hydrolase 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000432072"
FT TRANSMEM 74..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 140..389
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 215
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT ACT_SITE 327
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT ACT_SITE 382
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P34914"
SQ SEQUENCE 404 AA; 47865 MW; 0434E581F585E826 CRC64;
MLFESIYIQC LNKFSKYKKF VCHTTCNCPN YKIIGYLLYF LCLCRPINCS LPLSRHDLAF
GSFSYYLTMF LYRILVRLLQ FYYFVKFSAI LFLGFAVKGR SLFEKKQREK PNVLEGWDSR
YIKLKKVRLH YVQTGSDDKP LMLFIHGYPE FWYSWRFQLK EFADKYRCVA IDQRGYNLSD
KPKHVDNYSI DELTGDIRDV IEGLGYDKAI VVAHDWGGLV AWQFAEQYPE MVDKLICCNI
PRPGSFRKRI YTSWSQFRKS WYMFFYQNEK IPEMLCSADD MKMLELCFRA KEIGIQNNKN
FTDEDLEAWK YSFSMNGASF KYPINYYRNI FNAKKQQADL VLEMPTLIIW GTADGALDIE
AAVDSLNTLK QGTMKKIEGA SHWVQQDEPE MVNEHIKKFL NKYQ
