EPHX3_HUMAN
ID EPHX3_HUMAN Reviewed; 360 AA.
AC Q9H6B9; A3KMR3;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Epoxide hydrolase 3;
DE Short=EH3 {ECO:0000303|PubMed:22798687};
DE EC=3.3.2.10 {ECO:0000269|PubMed:22798687};
DE AltName: Full=Abhydrolase domain-containing protein 9;
GN Name=EPHX3; Synonyms=ABHD9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Embryonic stem cell;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-173; TYR-220;
RP TYR-280; TYR-281; ASP-307 AND HIS-337.
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).
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:0000269|PubMed:22798687}.
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:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19038;
CC Evidence={ECO:0000305|PubMed:22798687};
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:0000269|PubMed:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45353;
CC Evidence={ECO:0000305|PubMed:22798687};
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:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44033;
CC Evidence={ECO:0000305|PubMed:22798687};
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:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44049;
CC Evidence={ECO:0000305|PubMed:22798687};
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:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44045;
CC Evidence={ECO:0000305|PubMed:22798687};
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:22798687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44041;
CC Evidence={ECO:0000305|PubMed:22798687};
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:0000269|PubMed:22798687}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for 8,9-EET {ECO:0000269|PubMed:22798687};
CC KM=80 uM for 11,12-EET {ECO:0000269|PubMed:22798687};
CC KM=130 uM for 14,15-EET {ECO:0000269|PubMed:22798687};
CC KM=25 uM for leukotoxin {ECO:0000269|PubMed:22798687};
CC Vmax=12 umol/min/mg enzyme with 8,9-EET as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=50 umol/min/mg enzyme with 11,12-EET as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=60 umol/min/mg enzyme with 14,15-EET as substrate
CC {ECO:0000269|PubMed:22798687};
CC Vmax=22 umol/min/mg enzyme with leukotoxin as substrate
CC {ECO:0000269|PubMed:22798687};
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000305|PubMed:22798687};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Epoxide hydrolase
CC family. {ECO:0000305}.
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DR EMBL; AK026061; BAB15342.1; -; mRNA.
DR EMBL; CH471106; EAW84467.1; -; Genomic_DNA.
DR EMBL; BC115002; AAI15003.1; -; mRNA.
DR EMBL; BC132958; AAI32959.1; -; mRNA.
DR EMBL; BC132960; AAI32961.1; -; mRNA.
DR CCDS; CCDS12327.1; -.
DR RefSeq; NP_001136358.1; NM_001142886.1.
DR RefSeq; NP_079070.1; NM_024794.2.
DR AlphaFoldDB; Q9H6B9; -.
DR SMR; Q9H6B9; -.
DR BioGRID; 122942; 2.
DR STRING; 9606.ENSP00000221730; -.
DR SwissLipids; SLP:000001116; -.
DR ESTHER; human-EPHX3; Epoxide_hydrolase.
DR MEROPS; S33.978; -.
DR iPTMnet; Q9H6B9; -.
DR PhosphoSitePlus; Q9H6B9; -.
DR BioMuta; EPHX3; -.
DR DMDM; 74718486; -.
DR EPD; Q9H6B9; -.
DR MassIVE; Q9H6B9; -.
DR MaxQB; Q9H6B9; -.
DR PaxDb; Q9H6B9; -.
DR PeptideAtlas; Q9H6B9; -.
DR PRIDE; Q9H6B9; -.
DR ProteomicsDB; 80974; -.
DR Antibodypedia; 26990; 127 antibodies from 25 providers.
DR DNASU; 79852; -.
DR Ensembl; ENST00000221730.8; ENSP00000221730.2; ENSG00000105131.8.
DR Ensembl; ENST00000435261.5; ENSP00000410323.1; ENSG00000105131.8.
DR Ensembl; ENST00000602233.5; ENSP00000469345.1; ENSG00000105131.8.
DR GeneID; 79852; -.
DR KEGG; hsa:79852; -.
DR MANE-Select; ENST00000221730.8; ENSP00000221730.2; NM_024794.3; NP_079070.1.
DR UCSC; uc002nap.4; human.
DR CTD; 79852; -.
DR DisGeNET; 79852; -.
DR GeneCards; EPHX3; -.
DR HGNC; HGNC:23760; EPHX3.
DR HPA; ENSG00000105131; Group enriched (esophagus, lymphoid tissue, skin, vagina).
DR MIM; 617400; gene.
DR neXtProt; NX_Q9H6B9; -.
DR OpenTargets; ENSG00000105131; -.
DR PharmGKB; PA164719188; -.
DR VEuPathDB; HostDB:ENSG00000105131; -.
DR eggNOG; KOG4178; Eukaryota.
DR GeneTree; ENSGT00940000162086; -.
DR HOGENOM; CLU_020336_7_3_1; -.
DR InParanoid; Q9H6B9; -.
DR OMA; DQLRRSW; -.
DR OrthoDB; 616687at2759; -.
DR PhylomeDB; Q9H6B9; -.
DR TreeFam; TF314403; -.
DR BRENDA; 3.3.2.10; 2681.
DR PathwayCommons; Q9H6B9; -.
DR SABIO-RK; Q9H6B9; -.
DR BioGRID-ORCS; 79852; 11 hits in 1068 CRISPR screens.
DR ChiTaRS; EPHX3; human.
DR GenomeRNAi; 79852; -.
DR Pharos; Q9H6B9; Tbio.
DR PRO; PR:Q9H6B9; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H6B9; protein.
DR Bgee; ENSG00000105131; Expressed in lower esophagus mucosa and 106 other tissues.
DR ExpressionAtlas; Q9H6B9; baseline and differential.
DR Genevisible; Q9H6B9; HS.
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; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0004301; F:epoxide hydrolase activity; IMP:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IBA:GO_Central.
DR GO; GO:0097176; P:epoxide metabolic process; IDA:UniProtKB.
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; PR00111; ABHYDROLASE.
DR PRINTS; PR00412; EPOXHYDRLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Hydrolase; Lipid metabolism; Membrane; Microsome;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..360
FT /note="Epoxide hydrolase 3"
FT /id="PRO_0000264232"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 173
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT ACT_SITE 281
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT ACT_SITE 337
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P34913"
FT MUTAGEN 173
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
FT MUTAGEN 173
FT /note="D->N: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
FT MUTAGEN 220
FT /note="Y->F: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
FT MUTAGEN 280
FT /note="Y->F: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
FT MUTAGEN 281
FT /note="Y->F: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
FT MUTAGEN 307
FT /note="D->A,N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
FT MUTAGEN 337
FT /note="H->Q: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22798687"
SQ SEQUENCE 360 AA; 40909 MW; C465A4B0E2D56BA0 CRC64;
MPELVVTALL APSRLSLKLL RAFMWSLVFS VALVAAAVYG CIALTHVLCR PRRGCCGRRR
SASPACLSDP SLGEHGFLNL KSSGLRLHYV SAGRGNGPLM LFLHGFPENW FSWRYQLREF
QSRFHVVAVD LRGYGPSDAP RDVDCYTIDL LLVDIKDVIL GLGYSKCILV AHDWGALLAW
HFSIYYPSLV ERMVVVSGAP MSVYQDYSLH HISQFFRSHY MFLFQLPWLP EKLLSMSDFQ
ILKTTLTHRK TGIPCLTPSE LEAFLYNFSQ PGGLTGPLNY YRNLFRNFPL EPQELTTPTL
LLWGEKDTYL ELGLVEAIGS RFVPGRLEAH ILPGIGHWIP QSNPQEMHQY MWAFLQDLLD
