HYES_MOUSE
ID HYES_MOUSE Reviewed; 554 AA.
AC P34914; Q8CGV0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Bifunctional epoxide hydrolase 2 {ECO:0000305};
DE Includes:
DE RecName: Full=Cytosolic epoxide hydrolase 2;
DE Short=CEH;
DE EC=3.3.2.10 {ECO:0000269|PubMed:21217101};
DE AltName: Full=Epoxide hydratase;
DE AltName: Full=Soluble epoxide hydrolase {ECO:0000303|PubMed:21217101};
DE Short=SEH {ECO:0000303|PubMed:21217101};
DE Includes:
DE RecName: Full=Lipid-phosphate phosphatase;
DE EC=3.1.3.76 {ECO:0000250|UniProtKB:P34913};
GN Name=Ephx2 {ECO:0000312|MGI:MGI:99500}; Synonyms=Eph2;
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] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP INDUCTION.
RC TISSUE=Liver;
RX PubMed=8349642; DOI=10.1016/s0021-9258(19)85378-4;
RA Grant D.F., Storms D.H., Hammock B.D.;
RT "Molecular cloning and expression of murine liver soluble epoxide
RT hydrolase.";
RL J. Biol. Chem. 268:17628-17633(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=NMRI;
RX PubMed=8750907; DOI=10.1007/s002040050250;
RA Johansson C., Stark A., Sandberg M., Ek B., Rask L., Meijer J.;
RT "Tissue specific basal expression of soluble murine epoxide hydrolase and
RT effects of clofibrate on the mRNA levels in extrahepatic tissues and
RT liver.";
RL Arch. Toxicol. 70:61-63(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=C57BL/6J;
RX PubMed=15601917; DOI=10.1095/biolreprod.104.035899;
RA Hennebold J.D., Mah K., Perez W., Vance J.E., Stouffer R.L., Morisseau C.,
RA Hammock B.D., Adashi E.Y.;
RT "Identification and characterization of an ovary-selective isoform of
RT epoxide hydrolase.";
RL Biol. Reprod. 72:968-975(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Colon;
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 FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=7840649; DOI=10.1006/abbi.1995.1059;
RA Zeldin D.C., Wei S., Falck J.R., Hammock B.D., Snapper J.R.,
RA Capdevila J.H.;
RT "Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase:
RT substrate structural determinants of asymmetric catalysis.";
RL Arch. Biochem. Biophys. 316:443-451(1995).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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 [8]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=21217101; DOI=10.1194/jlr.m009639;
RA Cronin A., Decker M., Arand M.;
RT "Mammalian soluble epoxide hydrolase is identical to liver hepoxilin
RT hydrolase.";
RL J. Lipid Res. 52:712-719(2011).
RN [9]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-55; LYS-176; LYS-371; LYS-420;
RP LYS-454; LYS-504; LYS-508 AND LYS-553, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-176; LYS-191; LYS-215 AND
RP LYS-508, AND IDENTIFICATION BY MASS 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).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND ACTIVE SITE.
RC TISSUE=Liver;
RX PubMed=10485878; DOI=10.1073/pnas.96.19.10637;
RA Argiriadi M.A., Morisseau C., Hammock B.D., Christianson D.W.;
RT "Detoxification of environmental mutagens and carcinogens: structure,
RT mechanism, and evolution of liver epoxide hydrolase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10637-10642(1999).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH EPOXIDE HYDROLASE
RP INHIBITOR, AND ACTIVE SITE.
RX PubMed=10747889; DOI=10.1074/jbc.m000278200;
RA Argiriadi M.A., Morisseau C., Goodrow M.H., Dowdy D.L., Hammock B.D.,
RA Christianson D.W.;
RT "Binding of alkylurea inhibitors to epoxide hydrolase implicates active
RT site tyrosines in substrate activation.";
RL J. Biol. Chem. 275:15265-15270(2000).
CC -!- FUNCTION: Bifunctional enzyme. The C-terminal domain has epoxide
CC hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and
CC arene oxides (PubMed:7840649, PubMed:21217101). Plays a role in
CC xenobiotic metabolism by degrading potentially toxic epoxides (By
CC similarity). Also determines steady-state levels of physiological
CC mediators (By similarity). {ECO:0000250|UniProtKB:P34913,
CC ECO:0000250|UniProtKB:P80299, ECO:0000269|PubMed:21217101,
CC ECO:0000269|PubMed:7840649}.
CC -!- FUNCTION: Bifunctional enzyme. The N-terminal domain has lipid
CC phosphatase activity, with the highest activity towards threo-9,10-
CC phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-
CC phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-
CC enoic acid and 12-phosphonooxy-octadec-9E-enoic acid (By similarity).
CC Has phosphatase activity toward lyso-glycerophospholipids with also
CC some lower activity toward lysolipids of sphingolipid and isoprenoid
CC phosphates (By similarity). {ECO:0000250|UniProtKB:P34913}.
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=8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate + H2O =
CC (8,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50896, ChEBI:CHEBI:15377, ChEBI:CHEBI:78100,
CC ChEBI:CHEBI:132127; Evidence={ECO:0000269|PubMed:21217101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50897;
CC Evidence={ECO:0000269|PubMed:21217101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate + H2O
CC = (10,11S,12R)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50900, ChEBI:CHEBI:15377, ChEBI:CHEBI:78084,
CC ChEBI:CHEBI:78099; Evidence={ECO:0000269|PubMed:21217101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50901;
CC Evidence={ECO:0000269|PubMed:21217101};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8S,9S)-
CC dihydroxy-(5Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53972,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131974, ChEBI:CHEBI:138002;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53973;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53980,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131969, ChEBI:CHEBI:138004;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53981;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53984,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131969, ChEBI:CHEBI:138005;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53985;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14R,15R)-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53992,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131964, ChEBI:CHEBI:138003;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53993;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = (14S,15S)-
CC dihydroxy-(5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53996,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131964, ChEBI:CHEBI:138006;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53997;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11S,12S)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:54004,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131970, ChEBI:CHEBI:138005;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54005;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = (11R,12R)-
CC dihydroxy-(5Z,8Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:54000,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131970, ChEBI:CHEBI:138004;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54001;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = (8R,9R)-
CC dihydroxy-(5Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:54016,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:131974, ChEBI:CHEBI:138008;
CC Evidence={ECO:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54017;
CC Evidence={ECO:0000305|PubMed:7840649};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-phosphooxy-(9Z)-octadecenoate + H2O = 12-hydroxy-(9Z)-
CC octadecenoate + phosphate; Xref=Rhea:RHEA:45272, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:85141, ChEBI:CHEBI:85150;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45273;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-phosphooxy-(9E)-octadecenoate + H2O = 12-hydroxy-(9E)-
CC octadecenoate + phosphate; Xref=Rhea:RHEA:45276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:85137, ChEBI:CHEBI:85152;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45277;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-(phosphooxy)octadecanoate + H2O = 12-hydroxyoctadecanoate +
CC phosphate; Xref=Rhea:RHEA:45280, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84201, ChEBI:CHEBI:85134;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45281;
CC Evidence={ECO:0000250|UniProtKB:P34913};
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:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049;
CC Evidence={ECO:0000250|UniProtKB:P34913};
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:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045;
CC Evidence={ECO:0000250|UniProtKB:P34913};
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:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44041;
CC Evidence={ECO:0000250|UniProtKB:P34913};
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:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44033;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycerol 3-phosphate + H2O = 1-
CC tetradecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:53592,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72683,
CC ChEBI:CHEBI:75536; Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53593;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-sn-glycero-3-phosphate + H2O = 1-octadecanoyl-
CC sn-glycerol + phosphate; Xref=Rhea:RHEA:53596, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:74565, ChEBI:CHEBI:75550;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53597;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:53600, ChEBI:CHEBI:15377, ChEBI:CHEBI:34071,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:74938;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53601;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-
CC sn-glycerol + phosphate; Xref=Rhea:RHEA:53604, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57518, ChEBI:CHEBI:75542;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53605;
CC Evidence={ECO:0000250|UniProtKB:P34913};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544,
CC ChEBI:CHEBI:75757; Evidence={ECO:0000250|UniProtKB:P34913};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836;
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:0000269|PubMed:7840649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53977;
CC Evidence={ECO:0000305|PubMed:7840649};
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) (By similarity). Phosphatase activity is inhibited
CC by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic
CC acids and fatty acids such as palmitic acid and lauric acid
CC (PubMed:21217101). {ECO:0000250|UniProtKB:P34913,
CC ECO:0000269|PubMed:21217101}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4 uM for 14(R),15(S)-EET {ECO:0000269|PubMed:7840649};
CC KM=5 uM for 14(S),15(R)-EET {ECO:0000269|PubMed:7840649};
CC KM=3 uM for 11(R),12(R)-EET {ECO:0000269|PubMed:7840649};
CC KM=4 uM for 11(S),12(R)-EET {ECO:0000269|PubMed:7840649};
CC KM=41 uM for 8(R),9(S)-EET {ECO:0000269|PubMed:7840649};
CC KM=5 uM for 8(S),9(R)-EET {ECO:0000269|PubMed:7840649};
CC Vmax=9.03 umol/min/mg enzyme with 14(R),15(S)-EET as substrate
CC {ECO:0000269|PubMed:7840649};
CC Vmax=1.36 umol/min/mg enzyme with 14(S),15(R)-EET as substrate
CC {ECO:0000269|PubMed:7840649};
CC Vmax=0.82 umol/min/mg enzyme with 11(R),12(R)-EET as substrate
CC {ECO:0000269|PubMed:7840649};
CC Vmax=3.02 umol/min/mg enzyme with 11(S),12(R)-EET as substrate
CC {ECO:0000269|PubMed:7840649};
CC Vmax=0.83 umol/min/mg enzyme with 8(R),9(S)-EET as substrate
CC {ECO:0000269|PubMed:7840649};
CC Vmax=3.10 umol/min/mg enzyme with 8(S),9(R)-EET as substrate
CC {ECO:0000269|PubMed:7840649};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10747889,
CC ECO:0000269|PubMed:21217101}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21217101,
CC ECO:0000269|PubMed:7840649}. Peroxisome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ephx2A;
CC IsoId=P34914-1; Sequence=Displayed;
CC Name=2; Synonyms=Ephx2B;
CC IsoId=P34914-2; Sequence=VSP_013904;
CC -!- TISSUE SPECIFICITY: Detected in liver, intestine, ovary and kidney.
CC Detected at low levels in heart and muscle.
CC {ECO:0000269|PubMed:15601917, ECO:0000269|PubMed:21217101,
CC ECO:0000269|PubMed:7840649, ECO:0000269|PubMed:8750907}.
CC -!- INDUCTION: Up-regulated during the luteal phase of the stimulated
CC estrus cycle and by compounds that cause peroxisome proliferation, such
CC as clofibrate, tiadenol and fenofibrate. {ECO:0000269|PubMed:15601917,
CC ECO:0000269|PubMed:8349642, ECO:0000269|PubMed:8750907}.
CC -!- DOMAIN: The N-terminal domain has phosphatase activity. The C-terminal
CC domain has epoxide hydrolase activity.
CC -!- PTM: The N-terminus is blocked.
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 -!- DISRUPTION PHENOTYPE: In knockout mice, hepoxilin turnover to
CC trioxilins is greatly abolished (PubMed:21217101). In livers, the
CC activity toward HxA3 (8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-
CC eicosatrienoate) and HxB3 (10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-
CC eicosatrienoate) is greatly reduced compared with the WT mice
CC (PubMed:21217101). {ECO:0000269|PubMed:21217101}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide hydrolase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; L05781; AAA37555.1; -; mRNA.
DR EMBL; Z37107; CAA85471.1; -; mRNA.
DR EMBL; AY098585; AAM28238.1; -; mRNA.
DR EMBL; BC015087; AAH15087.1; -; mRNA.
DR CCDS; CCDS27218.1; -. [P34914-1]
DR CCDS; CCDS88694.1; -. [P34914-2]
DR PIR; A47504; A47504.
DR RefSeq; NP_001258332.1; NM_001271403.1. [P34914-2]
DR RefSeq; NP_031966.2; NM_007940.4. [P34914-1]
DR PDB; 1CQZ; X-ray; 2.80 A; A/B=1-554.
DR PDB; 1CR6; X-ray; 2.80 A; A/B=1-554.
DR PDB; 1EK1; X-ray; 3.10 A; A/B=1-554.
DR PDB; 1EK2; X-ray; 3.00 A; A/B=1-554.
DR PDBsum; 1CQZ; -.
DR PDBsum; 1CR6; -.
DR PDBsum; 1EK1; -.
DR PDBsum; 1EK2; -.
DR AlphaFoldDB; P34914; -.
DR SMR; P34914; -.
DR BioGRID; 199481; 3.
DR IntAct; P34914; 3.
DR MINT; P34914; -.
DR STRING; 10090.ENSMUSP00000069209; -.
DR BindingDB; P34914; -.
DR ChEMBL; CHEMBL4140; -.
DR GuidetoPHARMACOLOGY; 2970; -.
DR SwissLipids; SLP:000001106; -.
DR ESTHER; mouse-hyes; Epoxide_hydrolase.
DR MEROPS; S33.973; -.
DR iPTMnet; P34914; -.
DR MetOSite; P34914; -.
DR PhosphoSitePlus; P34914; -.
DR SwissPalm; P34914; -.
DR SWISS-2DPAGE; P34914; -.
DR jPOST; P34914; -.
DR MaxQB; P34914; -.
DR PaxDb; P34914; -.
DR PeptideAtlas; P34914; -.
DR PRIDE; P34914; -.
DR ProteomicsDB; 267029; -. [P34914-1]
DR ProteomicsDB; 267030; -. [P34914-2]
DR Antibodypedia; 4070; 433 antibodies from 34 providers.
DR DNASU; 13850; -.
DR Ensembl; ENSMUST00000070515; ENSMUSP00000069209; ENSMUSG00000022040. [P34914-1]
DR Ensembl; ENSMUST00000224698; ENSMUSP00000153161; ENSMUSG00000022040. [P34914-2]
DR GeneID; 13850; -.
DR KEGG; mmu:13850; -.
DR UCSC; uc007ujv.2; mouse. [P34914-1]
DR UCSC; uc033grp.1; mouse. [P34914-2]
DR CTD; 2053; -.
DR MGI; MGI:99500; Ephx2.
DR VEuPathDB; HostDB:ENSMUSG00000022040; -.
DR eggNOG; KOG3085; Eukaryota.
DR eggNOG; KOG4178; Eukaryota.
DR GeneTree; ENSGT00940000158614; -.
DR HOGENOM; CLU_036085_1_1_1; -.
DR InParanoid; P34914; -.
DR OMA; YAMEVLC; -.
DR PhylomeDB; P34914; -.
DR TreeFam; TF315395; -.
DR BRENDA; 3.3.2.10; 3474.
DR Reactome; R-MMU-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-MMU-9018682; Biosynthesis of maresins.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR BioGRID-ORCS; 13850; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Ephx2; mouse.
DR EvolutionaryTrace; P34914; -.
DR PRO; PR:P34914; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P34914; protein.
DR Bgee; ENSMUSG00000022040; Expressed in small intestine Peyer's patch and 235 other tissues.
DR ExpressionAtlas; P34914; baseline and differential.
DR Genevisible; P34914; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; ISO:MGI.
DR GO; GO:0033885; F:10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004301; F:epoxide hydrolase activity; IMP:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IBA:GO_Central.
DR GO; GO:0042577; F:lipid phosphatase activity; ISS:UniProtKB.
DR GO; GO:0052642; F:lysophosphatidic acid phosphatase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0015643; F:toxic substance binding; ISO:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; ISS:UniProtKB.
DR GO; GO:0097176; P:epoxide metabolic process; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISO:MGI.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISO:MGI.
DR GO; GO:0046839; P:phospholipid dephosphorylation; ISS:UniProtKB.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0002539; P:prostaglandin production involved in inflammatory response; ISO:MGI.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0046272; P:stilbene catabolic process; ISO:MGI.
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; 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; TIGR01509; HAD-SF-IA-v3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Aromatic hydrocarbons catabolism; Cytoplasm; Detoxification;
KW Direct protein sequencing; Hydrolase; Lipid metabolism; Lipoprotein;
KW Magnesium; Metal-binding; Multifunctional enzyme; Peroxisome;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..554
FT /note="Bifunctional epoxide hydrolase 2"
FT /id="PRO_0000084112"
FT DOMAIN 257..530
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT REGION 1..224
FT /note="Phosphatase"
FT REGION 233..554
FT /note="Epoxide hydrolase"
FT MOTIF 552..554
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 333
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:10485878,
FT ECO:0000269|PubMed:10747889"
FT ACT_SITE 465
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:10485878,
FT ECO:0000269|PubMed:10747889"
FT ACT_SITE 523
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:10485878,
FT ECO:0000269|PubMed:10747889"
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 381
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT MOD_RES 55
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 176
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 176
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 191
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 215
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 371
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 420
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 454
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 504
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 508
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 508
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 553
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT LIPID 521
FT /note="S-(15-deoxy-Delta12,14-prostaglandin J2-9-
FT yl)cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..62
FT /note="MALRVAAFDLDGVLALPSIAGAFRRSEEALALPRDFLLGAYQTEFPEGPTEQ
FT LMKGKITFSQ -> MRFAAMAAFSVFFVSKGLLMNSNIWCVGQEGPSQEDTDTIHTSE
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15601917"
FT /id="VSP_013904"
FT CONFLICT 77
FT /note="A -> T (in Ref. 2; CAA85471)"
FT /evidence="ECO:0000305"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:1CR6"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 20..28
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 34..37
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 38..41
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 51..56
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:1EK1"
FT HELIX 64..74
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1CR6"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 148..152
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 163..173
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 177..187
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 191..195
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 208..215
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:1EK2"
FT STRAND 232..241
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 256..262
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 269..274
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 275..281
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 285..290
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 308..322
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 327..332
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 334..345
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:1EK2"
FT STRAND 350..357
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 369..375
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 380..385
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 390..397
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 399..406
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:1CQZ"
FT TURN 427..430
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 439..441
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 443..456
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 459..462
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 463..467
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 468..475
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 476..478
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 487..492
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 496..498
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 500..503
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:1CQZ"
FT STRAND 514..518
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 525..528
FT /evidence="ECO:0007829|PDB:1CQZ"
FT HELIX 530..543
FT /evidence="ECO:0007829|PDB:1CQZ"
SQ SEQUENCE 554 AA; 62515 MW; 2F3A3F7DACE47C93 CRC64;
MALRVAAFDL DGVLALPSIA GAFRRSEEAL ALPRDFLLGA YQTEFPEGPT EQLMKGKITF
SQWVPLMDES YRKSSKACGA NLPENFSISQ IFSQAMAARS INRPMLQAAI ALKKKGFTTC
IVTNNWLDDG DKRDSLAQMM CELSQHFDFL IESCQVGMIK PEPQIYNFLL DTLKAKPNEV
VFLDDFGSNL KPARDMGMVT ILVHNTASAL RELEKVTGTQ FPEAPLPVPC NPNDVSHGYV
TVKPGIRLHF VEMGSGPALC LCHGFPESWF SWRYQIPALA QAGFRVLAID MKGYGDSSSP
PEIEEYAMEL LCKEMVTFLD KLGIPQAVFI GHDWAGVMVW NMALFYPERV RAVASLNTPF
MPPDPDVSPM KVIRSIPVFN YQLYFQEPGV AEAELEKNMS RTFKSFFRAS DETGFIAVHK
ATEIGGILVN TPEDPNLSKI TTEEEIEFYI QQFKKTGFRG PLNWYRNTER NWKWSCKGLG
RKILVPALMV TAEKDIVLRP EMSKNMEKWI PFLKRGHIED CGHWTQIEKP TEVNQILIKW
LQTEVQNPSV TSKI
