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 24-JAN-2024, entry version 153. 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}. 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; 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; 9606-ENSP00000221730; -. DR PeptideAtlas; Q9H6B9; -. DR ProteomicsDB; 80974; -. DR Antibodypedia; 26990; 137 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 AGR; HGNC:23760; -. DR CTD; 79852; -. DR DisGeNET; 79852; -. DR GeneCards; EPHX3; -. DR HGNC; HGNC:23760; EPHX3. DR HPA; ENSG00000105131; Tissue enhanced (esophagus, 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; EEMHQYM; -. DR OrthoDB; 2443908at2759; -. DR PhylomeDB; Q9H6B9; -. DR TreeFam; TF314403; -. DR BioCyc; MetaCyc:ENSG00000105131-MONOMER; -. DR BRENDA; 3.3.2.10; 2681. DR PathwayCommons; Q9H6B9; -. DR SABIO-RK; Q9H6B9; -. DR BioGRID-ORCS; 79852; 11 hits in 1149 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 108 other cell types or tissues. DR ExpressionAtlas; Q9H6B9; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; 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; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR000073; AB_hydrolase_1. DR InterPro; IPR000639; Epox_hydrolase-like. DR PANTHER; PTHR43329; EPOXIDE HYDROLASE; 1. DR PANTHER; PTHR43329:SF10; EPOXIDE HYDROLASE 3; 1. DR Pfam; PF00561; Abhydrolase_1; 1. DR PRINTS; PR00111; ABHYDROLASE. DR PRINTS; PR00412; EPOXHYDRLASE. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR Genevisible; Q9H6B9; HS. 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 //