ID HYEP_HUMAN Reviewed; 455 AA. AC P07099; Q5VTJ6; Q9NP75; Q9NPE7; Q9NQU6; Q9NQU7; Q9NQU8; Q9NQU9; AC Q9NQV0; Q9NQV1; Q9NQV2; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1988, sequence version 1. DT 10-JUN-2008, entry version 95. DE Epoxide hydrolase 1 (EC 3.3.2.9) (Microsomal epoxide hydrolase) DE (Epoxide hydratase). GN Name=EPHX1; Synonyms=EPHX, EPOX; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-19. RX MEDLINE=88087301; PubMed=2891713; RA Skoda R.C., Demierre A., McBride O.W., Gonzalez F.J., Meyer U.A.; RT "Human microsomal xenobiotic epoxide hydrolase. Complementary DNA RT sequence, complementary DNA-directed expression in COS-1 cells, and RT chromosomal localization."; RL J. Biol. Chem. 263:1549-1554(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal liver; RA Wilson N.M., Omiecinski C.J.; RT "Nucleotide sequence of a human microsomal epoxide hydrolase cDNA RT clone."; RL Submitted (JUL-1988) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX MEDLINE=88015564; PubMed=3502697; DOI=10.1093/nar/15.17.7188; RA Jackson M.R., Craft J.A., Burchell B.; RT "Nucleotide and deduced amino acid sequence of human liver microsomal RT epoxide hydrolase."; RL Nucleic Acids Res. 15:7188-7188(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS HIS-113; ARG-139 AND ILE-396. RC TISSUE=Liver; RX MEDLINE=94282033; PubMed=7516776; DOI=10.1093/hmg/3.3.421; RA Hassett C., Aicher L., Sidhu J.S., Omiecinski C.J.; RT "Human microsomal epoxide hydrolase: genetic polymorphism and RT functional expression in vitro of amino acid variants."; RL Hum. Mol. Genet. 3:421-428(1994). RN [5] RP ERRATUM. RA Hassett C., Aicher L., Sidhu J.S., Omiecinski C.J.; RL Hum. Mol. Genet. 3:1214-1214(1994). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=95137590; PubMed=7835893; DOI=10.1006/geno.1994.1520; RA Hassett C., Robinson K.B., Beck N.B., Omiecinski C.J.; RT "The human microsomal epoxide hydrolase gene (EPHX1): complete RT nucleotide sequence and structural characterization."; RL Genomics 23:433-442(1994). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-43; HIS-113; RP ARG-139; LEU-285; MET-408 AND GLN-452. RA Livingston R.J., Rieder M.J., Rajkumar N., Downing T.K., Olson A.N., RA Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., RA Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.; RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin, Testis, and Uterus; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-327. RC TISSUE=Liver; RA Craft J.A., Jackson M.R., Burchell B.; RT "Partial nucleotide sequence of a cloned cDNA for human liver RT microsomal epoxide hydrolase."; RL Biochem. Soc. Trans. 15:708-709(1987). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-197; 242-310 AND 348-455, AND RP VARIANTS CYS-49; HIS-113; ARG-139; PRO-260 AND GLN-454. RX MEDLINE=20514582; PubMed=11058921; RX DOI=10.1002/1098-1004(200011)16:5<450::AID-HUMU28>3.0.CO;2-1; RA Belmahdi F., Chevalier D., Lo-Guidice J.-M., Allorge D., Cauffiez C., RA Lafitte J.-J., Broly F.; RT "Identification of 6 new polymorphisms, g.11177G>A, g.14622C>T (R49C), RT g.17540T>C, g.17639T>C, g.30929T>C, g.31074G>A (R454Q), in the human RT microsomal epoxide hydrolase gene (EPHX1) in a French population."; RL Hum. Mutat. 16:450-450(2000). RN [12] RP INVOLVEMENT IN HYPERCHOLANEMIA, AND TISSUE SPECIFICITY. RX MEDLINE=22760294; PubMed=12878321; DOI=10.1016/S0925-4439(03)00085-1; RA Zhu Q.S., Xing W., Qian B., von Dippe P., Shneider B.L., Fox V.L., RA Levy D.; RT "Inhibition of human m-epoxide hydrolase gene expression in a case of RT hypercholanemia."; RL Biochim. Biophys. Acta 1638:208-216(2003). RN [13] RP VARIANTS HIS-113 AND ARG-139. RX PubMed=12173035; DOI=10.1038/sj.ejhg.5200849; RA Laasanen J., Romppanen E.-L., Hiltunen M., Helisalmi S., Mannermaa A., RA Punnonen K., Heinonen S.; RT "Two exonic single nucleotide polymorphisms in the microsomal epoxide RT hydrolase gene are jointly associated with preeclampsia."; RL Eur. J. Hum. Genet. 10:569-573(2002). RN [14] RP VARIANT GLN-44. RX PubMed=15618730; DOI=10.2133/dmpk.18.150; RA Shiseki K., Itoda M., Saito Y., Nakajima Y., Maekawa K., Kimura H., RA Goto Y., Saitoh O., Katoh M., Ohnuma T., Kawai M., Sugai K., RA Ohtsuki T., Suzuki C., Minami N., Ozawa S., Sawada J.; RT "Five novel single nucleotide polymorphisms in the EPHX1 gene encoding RT microsomal epoxide hydrolase."; RL Drug Metab. Pharmacokinet. 18:150-153(2003). CC -!- FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis CC of arene and aliphatic epoxides to less reactive and more water CC soluble dihydrodiols by the trans addition of water. CC -!- CATALYTIC ACTIVITY: Cis-stilbene oxide + H(2)O = (+)-(1R,2R)-1,2- CC diphenylethane-1,2-diol. CC -!- SUBCELLULAR LOCATION: Microsome membrane; Single-pass membrane CC protein. CC -!- TISSUE SPECIFICITY: Found in liver. CC -!- DISEASE: Genetic variation in EPHX1 may be associated with CC susceptibility to a form of pregnancy-induced hypertension known CC as preeclampsia [MIM:189800]. Hypertension occurs in 5-7% of all CC pregnancies where it is a leading cause of maternal, fetal and CC neonatal morbidity and mortality. Among pregnancy-induced CC hypertension cases, severe preeclampsia is characterized by the CC development of hypertension and proteinuria after the 20th week of CC pregnancy and is the most distinctive, life-threatening form. CC -!- DISEASE: Defects in EPHX1 are a cause of familial hypercholanemia CC (FHCA) [MIM:607748]. FHCA is a disorder characterized by elevated CC serum bile acid concentrations, itching, and fat malabsorption. CC -!- SIMILARITY: Belongs to the peptidase S33 family. 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; J03518; AAA61305.1; -; mRNA. DR EMBL; X07936; CAA30759.1; -; mRNA. DR EMBL; Y00424; CAA68486.1; -; mRNA. DR EMBL; L25878; AAA52389.1; -; mRNA. DR EMBL; L25879; AAA52390.1; -; mRNA. DR EMBL; U06661; AAB60649.1; -; Genomic_DNA. DR EMBL; U06656; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06657; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06658; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06659; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; U06660; AAB60649.1; JOINED; Genomic_DNA. DR EMBL; AL591895; CAH71994.1; -; Genomic_DNA. DR EMBL; AY948961; AAX81410.1; -; Genomic_DNA. DR EMBL; BC003567; AAH03567.1; -; mRNA. DR EMBL; BC008291; AAH08291.1; -; mRNA. DR EMBL; BC095430; AAH95430.1; -; mRNA. DR EMBL; M36374; AAA59580.1; -; mRNA. DR EMBL; AF253417; AAC41694.1; -; Genomic_DNA. DR EMBL; AF276626; AAF87726.1; -; Genomic_DNA. DR EMBL; AF276627; AAF87727.1; -; Genomic_DNA. DR EMBL; AF276628; AAF87728.1; -; Genomic_DNA. DR EMBL; AF276629; AAF87729.1; -; Genomic_DNA. DR EMBL; AF276630; AAF87730.1; -; Genomic_DNA. DR EMBL; AF276631; AAF87731.1; -; Genomic_DNA. DR EMBL; AF276632; AAF87732.1; -; Genomic_DNA. DR EMBL; AF276633; AAF87733.1; -; Genomic_DNA. DR EMBL; AF276634; AAF87734.1; -; Genomic_DNA. DR EMBL; AF276635; AAF87735.1; -; Genomic_DNA. DR EMBL; AF276636; AAF87736.1; -; Genomic_DNA. DR EMBL; AF276637; AAF87737.1; -; Genomic_DNA. DR EMBL; AF276638; AAF87738.1; -; Genomic_DNA. DR PIR; A29939; A29939. DR RefSeq; NP_000111.1; -. DR UniGene; Hs.89649; -. DR MEROPS; S33.971; -. DR PeptideAtlas; P07099; -. DR Ensembl; ENSG00000143819; Homo sapiens. DR GeneID; 2052; -. DR KEGG; hsa:2052; -. DR H-InvDB; HIX0001636; -. DR HGNC; HGNC:3401; EPHX1. DR MIM; 132810; gene+phenotype. DR MIM; 607748; phenotype. DR Orphanet; 1912; Fetal hydantoin syndrome. DR PharmGKB; PA27829; -. DR HOVERGEN; P07099; -. DR CleanEx; HS_EPHX1; -. DR GermOnline; ENSG00000143819; Homo sapiens. DR GO; GO:0004301; F:epoxide hydrolase activity; TAS:ProtInc. DR InterPro; IPR000073; AB_hydrolase_1. DR InterPro; IPR000639; Epox_hydrolase-like. DR InterPro; IPR010497; Epoxide_hydro_N. DR InterPro; IPR016292; Epoxide_hydrolase. DR Pfam; PF00561; Abhydrolase_1; 1. DR Pfam; PF06441; EHN; 1. DR PIRSF; PIRSF001112; Epoxide_hydrolase; 1. DR PRINTS; PR00412; EPOXHYDRLASE. PE 1: Evidence at protein level; KW Aromatic hydrocarbons catabolism; Detoxification; KW Direct protein sequencing; Endoplasmic reticulum; Hydrolase; Membrane; KW Methylation; Microsome; Polymorphism; Signal-anchor; Transmembrane. FT CHAIN 1 455 Epoxide hydrolase 1. FT /FTId=PRO_0000080855. FT TRANSMEM 2 20 Signal-anchor (Potential). FT MOD_RES 295 295 Omega-N-methylated arginine (By FT similarity). FT VARIANT 43 43 R -> T. FT /FTId=VAR_023303. FT VARIANT 44 44 E -> Q. FT /FTId=VAR_018347. FT VARIANT 49 49 R -> C (in allele EPHX1*2; FT dbSNP:rs2234697). FT /FTId=VAR_013298. FT VARIANT 113 113 Y -> H (in allele EPHX1*3; partial loss FT of enzyme activity; dbSNP:rs1051740). FT /FTId=VAR_005295. FT VARIANT 139 139 H -> R (in allele EPHX1*4; small increase FT in enzyme activity; dbSNP:rs2234922). FT /FTId=VAR_005296. FT VARIANT 260 260 L -> P (in allele EPHX1*1G). FT /FTId=VAR_013299. FT VARIANT 285 285 V -> L. FT /FTId=VAR_023304. FT VARIANT 396 396 T -> I (either a rare polymorphism or a FT sequencing error). FT /FTId=VAR_005297. FT VARIANT 408 408 T -> M. FT /FTId=VAR_023305. FT VARIANT 452 452 L -> Q. FT /FTId=VAR_023306. FT VARIANT 454 454 R -> Q (in allele EPHX1*5; FT dbSNP:rs2234701). FT /FTId=VAR_013300. FT CONFLICT 112 112 R -> K (in Ref. 10). FT CONFLICT 148 148 H -> N (in Ref. 3 and 10). FT CONFLICT 243 243 V -> L (in Ref. 10). FT CONFLICT 348 348 K -> S (in Ref. 3; CAA68486). FT CONFLICT 406 406 L -> F (in Ref. 3; CAA68486). FT CONFLICT 420 420 L -> V (in Ref. 3; CAA68486). SQ SEQUENCE 455 AA; 52949 MW; 88E333838C841390 CRC64; MWLEILLTSV LGFAIYWFIS RDKEETLPLE DGWWGPGTRS AAREDDSIRP FKVETSDEEI HDLHQRIDKF RFTPPLEDSC FHYGFNSNYL KKVISYWRNE FDWKKQVEIL NRYPHFKTKI EGLDIHFIHV KPPQLPAGHT PKPLLMVHGW PGSFYEFYKI IPLLTDPKNH GLSDEHVFEV ICPSIPGYGF SEASSKKGFN SVATARIFYK LMLRLGFQEF YIQGGDWGSL ICTNMAQLVP SHVKGLHLNM ALVLSNFSTL TLLLGQRFGR FLGLTERDVE LLYPVKEKVF YSLMRESGYM HIQCTKPDTV GSALNDSPVG LAAYILEKFS TWTNTEFRYL EDGGLERKFS LDDLLTNVML YWTTGTIISS QRFYKENLGQ GWMTQKHERM KVYVPTGFSA FPFELLHTPE KWVRFKYPKL ISYSYMVRGG HFAAFEEPEL LAQDIRKFLS VLERQ //