EPHX3_MOUSE
ID EPHX3_MOUSE Reviewed; 367 AA.
AC Q3V1F8;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 25-MAY-2022, entry version 102.
DE RecName: Full=Epoxide hydrolase 3;
DE Short=EH3 {ECO:0000303|PubMed:22798687};
DE EC=3.3.2.10 {ECO:0000250|UniProtKB:Q9H6B9};
DE AltName: Full=Abhydrolase domain-containing protein 9;
GN Name=Ephx3; Synonyms=Abhd9;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 [2]
RP TISSUE SPECIFICITY.
RX PubMed=22798687; DOI=10.1194/jlr.m024448;
RA Decker M., Adamska M., Cronin A., Di Giallonardo F., Burgener J.,
RA Marowsky A., Falck J.R., Morisseau C., Hammock B.D., Gruzdev A.,
RA Zeldin D.C., Arand M.;
RT "EH3 (ABHD9): the first member of a new epoxide hydrolase family with high
RT activity for fatty acid epoxides.";
RL J. Lipid Res. 53:2038-2045(2012).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=28384353; DOI=10.1371/journal.pone.0175348;
RA Hoopes S.L., Gruzdev A., Edin M.L., Graves J.P., Bradbury J.A., Flake G.P.,
RA Lih F.B., DeGraff L.M., Zeldin D.C.;
RT "Generation and characterization of epoxide hydrolase 3 (EPHX3)-deficient
RT mice.";
RL PLoS ONE 12:E0175348-E0175348(2017).
CC -!- FUNCTION: Catalyzes the hydrolysis of epoxide-containing fatty acids.
CC Active in vitro against epoxyeicosatrienoic acids (EETs) including 8,9-
CC EET, 9,10-EET, 11,12-EET and 14,15-EET and leukotoxin.
CC {ECO:0000250|UniProtKB:Q9H6B9}.
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:Q9H6B9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19038;
CC Evidence={ECO:0000250|UniProtKB:Q9H6B9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9,10-epoxyoctadecanoate + H2O = 9,10-dihydroxyoctadecanoate;
CC Xref=Rhea:RHEA:45352, ChEBI:CHEBI:15377, ChEBI:CHEBI:85195,
CC ChEBI:CHEBI:85197; Evidence={ECO:0000250|UniProtKB:Q9H6B9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45353;
CC Evidence={ECO:0000250|UniProtKB:Q9H6B9};
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:Q9H6B9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44033;
CC Evidence={ECO:0000250|UniProtKB:Q9H6B9};
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:Q9H6B9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049;
CC Evidence={ECO:0000250|UniProtKB:Q9H6B9};
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:Q9H6B9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045;
CC Evidence={ECO:0000250|UniProtKB:Q9H6B9};
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:Q9H6B9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44041;
CC Evidence={ECO:0000250|UniProtKB:Q9H6B9};
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 and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)
CC octanoic acid (AUOA). {ECO:0000250|UniProtKB:Q9H6B9}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:Q9H6B9}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skin, esophagus, lung
CC and tongue and to a lesser extent in pancreas and eye.
CC {ECO:0000269|PubMed:22798687}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the
CC expected Mendelian rate. No defect in the metabolism of epoxygenated
CC fatty acid epoxide. {ECO:0000269|PubMed:28384353}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide hydrolase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE21193.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AK132483; BAE21193.1; ALT_INIT; mRNA.
DR RefSeq; NP_001028335.1; NM_001033163.3.
DR AlphaFoldDB; Q3V1F8; -.
DR SMR; Q3V1F8; -.
DR STRING; 10090.ENSMUSP00000085013; -.
DR ESTHER; mouse-ephx3; Epoxide_hydrolase.
DR iPTMnet; Q3V1F8; -.
DR PhosphoSitePlus; Q3V1F8; -.
DR MaxQB; Q3V1F8; -.
DR PaxDb; Q3V1F8; -.
DR PRIDE; Q3V1F8; -.
DR ProteomicsDB; 275631; -.
DR GeneID; 71932; -.
DR KEGG; mmu:71932; -.
DR CTD; 79852; -.
DR MGI; MGI:1919182; Ephx3.
DR eggNOG; KOG4178; Eukaryota.
DR InParanoid; Q3V1F8; -.
DR OrthoDB; 616687at2759; -.
DR PhylomeDB; Q3V1F8; -.
DR TreeFam; TF314403; -.
DR BRENDA; 3.3.2.10; 3474.
DR BioGRID-ORCS; 71932; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q3V1F8; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q3V1F8; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
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:0004301; F:epoxide hydrolase activity; ISO:MGI.
DR GO; GO:0016787; F:hydrolase activity; IBA:GO_Central.
DR GO; GO:0097176; P:epoxide metabolic process; ISO:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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; PF12697; Abhydrolase_6; 1.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Hydrolase; Lipid metabolism; Membrane; Microsome;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..367
FT /note="Epoxide hydrolase 3"
FT /id="PRO_0000264233"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 180
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT ACT_SITE 288
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT ACT_SITE 344
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P34913"
SQ SEQUENCE 367 AA; 41853 MW; 41C068E3D1D1B33D CRC64;
MPEFVVTALL APSRLSLKLL RALVMSLVYL AALVAAFVYS CIALTHVMCR PRRGCCGRQR
LSPPECLRDP TLGEHCFLTL RVSVPPVKSS GLRLHYVSAG HGNGPLMLFL HGFPENWFSW
RYQLREFQSH FHVVAVDMRG YSPSDAPKEV DCYTIDLLLD DIKDTILGLG YSKCILVSHD
WGASLAWEFS IYYPSLVERM VVANGPPMSV IQEYSIHHIG QIFRSNYMFL FQLPWLPEKL
LSMSDFQILK DTFTHRKNGI PGLTPSELEA FLYHFSQPGC LTGPINYYRN VFRNFPLEPK
KLSTPTLLLW GEKDFAFQQG LVEAIGRHFV PGRLESHILP GSGHWIPQSH PQEMHQYMWA
FLQDLLG
