HYES_PIG
ID HYES_PIG Reviewed; 555 AA.
AC Q6Q2C2;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Bifunctional epoxide hydrolase 2;
DE Includes:
DE RecName: Full=Cytosolic epoxide hydrolase 2;
DE Short=CEH;
DE EC=3.3.2.10 {ECO:0000250|UniProtKB:P34913};
DE AltName: Full=Epoxide hydratase;
DE AltName: Full=Soluble epoxide hydrolase;
DE Short=SEH;
DE Includes:
DE RecName: Full=Lipid-phosphate phosphatase;
DE EC=3.1.3.76 {ECO:0000250|UniProtKB:P34913};
GN Name=EPHX2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Ovary;
RX PubMed=15308618; DOI=10.1210/en.2004-0710;
RA Newman J.W., Stok J.E., Vidal J.D., Corbin C.J., Huang Q., Hammock B.D.,
RA Conley A.J.;
RT "Cytochrome p450-dependent lipid metabolism in preovulatory follicles.";
RL Endocrinology 145:5097-5105(2004).
CC -!- FUNCTION: Bifunctional enzyme. The C-terminal domain has epoxide
CC hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and
CC arene oxides. Plays a role in xenobiotic metabolism by degrading
CC potentially toxic epoxides (By similarity). Also determines steady-
CC state levels of physiological mediators (PubMed:15308618). The N-
CC terminal domain has lipid phosphatase activity, with the highest
CC activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid,
CC followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-
CC phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic
CC acid (By similarity). {ECO:0000250|UniProtKB:P34913,
CC ECO:0000250|UniProtKB:P80299, ECO:0000305|PubMed:15308618}.
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:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9S,10S)-10-hydroxy-9-(phosphooxy)octadecanoate + H2O =
CC (9S,10S)-9,10-dihydroxyoctadecanoate + phosphate;
CC Xref=Rhea:RHEA:16537, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58796, ChEBI:CHEBI:58797; EC=3.1.3.76;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53976,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131965, ChEBI:CHEBI:138003;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53977;
CC Evidence={ECO:0000250|UniProtKB:P34914};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- ACTIVITY REGULATION: Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-
CC (trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea
CC (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S,
CC 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU),
CC N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S,
CC 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-
CC (((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-
CC yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-
CC (4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB)
CC and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)
CC octanoic acid (AUOA). {ECO:0000250|UniProtKB:P34913}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P34913}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Peroxisome
CC {ECO:0000250}.
CC -!- DOMAIN: The N-terminal domain has phosphatase activity. The C-terminal
CC domain has epoxide hydrolase activity.
CC -!- PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14-
CC prostaglandin-J2 is autocatalytic and reversible. It may occur as an
CC alternative to other cysteine modifications, such as S-nitrosylation
CC and S-palmitoylation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide hydrolase
CC family. {ECO:0000305}.
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DR EMBL; AY566232; AAS68016.1; -; mRNA.
DR RefSeq; NP_001001641.1; NM_001001641.1.
DR AlphaFoldDB; Q6Q2C2; -.
DR SMR; Q6Q2C2; -.
DR STRING; 9823.ENSSSCP00000010323; -.
DR BindingDB; Q6Q2C2; -.
DR ESTHER; pig-q6q2c2; Epoxide_hydrolase.
DR MEROPS; S33.973; -.
DR PaxDb; Q6Q2C2; -.
DR PeptideAtlas; Q6Q2C2; -.
DR PRIDE; Q6Q2C2; -.
DR Ensembl; ENSSSCT00070046106; ENSSSCP00070038885; ENSSSCG00070023132.
DR GeneID; 414425; -.
DR KEGG; ssc:414425; -.
DR CTD; 2053; -.
DR eggNOG; KOG3085; Eukaryota.
DR eggNOG; KOG4178; Eukaryota.
DR InParanoid; Q6Q2C2; -.
DR OrthoDB; 616687at2759; -.
DR Reactome; R-SSC-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-SSC-9018682; Biosynthesis of maresins.
DR Reactome; R-SSC-9033241; Peroxisomal protein import.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 14.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0033885; F:10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004301; F:epoxide hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0042577; F:lipid phosphatase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046839; P:phospholipid dephosphorylation; ISS:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR Gene3D; 1.10.150.240; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
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; IPR036412; HAD-like_sf.
DR InterPro; IPR006439; HAD-SF_hydro_IA.
DR InterPro; IPR011945; HAD-SF_ppase_IA/epoxid_hydro_N.
DR InterPro; IPR041492; HAD_2.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR023198; PGP-like_dom2.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR Pfam; PF13419; HAD_2; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR02247; HAD-1A3-hyp; 1.
DR TIGRFAMs; TIGR01509; HAD-SF-IA-v3; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Aromatic hydrocarbons catabolism; Cytoplasm; Detoxification;
KW Hydrolase; Lipid metabolism; Lipoprotein; Magnesium; Metal-binding;
KW Multifunctional enzyme; Peroxisome; Phosphoprotein; Reference proteome.
FT CHAIN 1..555
FT /note="Bifunctional epoxide hydrolase 2"
FT /id="PRO_0000084113"
FT DOMAIN 259..531
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT REGION 1..224
FT /note="Phosphatase"
FT REGION 235..555
FT /note="Epoxide hydrolase"
FT MOTIF 553..555
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 335
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT ACT_SITE 466
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT ACT_SITE 524
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT BINDING 9
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT BINDING 11
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT BINDING 123..124
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT BINDING 185
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT BINDING 383
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT MOD_RES 191
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 215
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 455
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 505
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT MOD_RES 554
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34914"
FT LIPID 522
FT /note="S-(15-deoxy-Delta12,14-prostaglandin J2-9-
FT yl)cysteine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 555 AA; 62767 MW; 996EF83CBF82FBEF CRC64;
MALRAAVFDL DGVLALPSIT TSWARAEEKL ALPRGFLNEA FKKGGQDGSV ARVMTGEITF
SQWVPFMEED CRKCAEDSGI RLPENFSVKH IFDKALSEKK INYPMLQAAL TLKKKGFSTC
ILTNNWLDDS AQRGSRAQLM CELRPHFDFL IESCRVGMAK PDPQIYKLML DTLKAEPNEV
VFLDDVGTHL KPVRDLGMAT ILVRDTDTAL RELEKVTGVQ LLQTPALPPT SCDPSALSHG
YVLIKPGVRL HFVEMGSGPA VCLCHGFPES WFSWRYQIPA LAQAGFRVLA VDMKGYGESS
APPEIEEYSL EVLCKDMVTF LNKLGLSQAV FIGHDWGGVL VWNMALFYPE RVRAVASLNT
PFMPSNPNVS PMEIIKANPV FDYQLYFQEP GVAEAELEQN LDRTFKNFFR AHDETFLTTN
RVRELGGLFV GTPEEPSLSR LVTEEDIQFY VQQFKKSGFR GPLNWYRNME RNWQWGCKGS
GRKILIPALM VTAENDLVLH PKMSKHMENW IPHLKRGHIK DCGHWTQIDK PAELNRILIE
WLETDARNPL VDSKL
