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P07099 (HYEP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Epoxide hydrolase 1

EC=3.3.2.9
Alternative name(s):
Epoxide hydratase
Microsomal epoxide hydrolase
Gene names
Name:EPHX1
Synonyms:EPHX, EPOX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length455 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.

Catalytic activity

Cis-stilbene oxide + H2O = (+)-(1R,2R)-1,2-diphenylethane-1,2-diol.

Subcellular location

Microsome membrane; Single-pass type II membrane protein. Endoplasmic reticulum membrane; Single-pass type II membrane protein Potential.

Tissue specificity

Found in liver. Ref.13

Involvement in disease

In some populations, the high activity haplotype tyr113/his139 is overrepresented among women suffering from pregnancy-induced hypertension (pre-eclampsia) when compared with healthy controls. Ref.15

Familial hypercholanemia (FHCA) [MIM:607748]: A disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15

Sequence similarities

Belongs to the peptidase S33 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 455455Epoxide hydrolase 1
PRO_0000080855

Regions

Transmembrane2 – 2019Helical; Signal-anchor; Potential

Amino acid modifications

Modified residue2951Omega-N-methylated arginine By similarity

Natural variations

Natural variant431R → T. Ref.8
Corresponds to variant rs3738046 [ dbSNP | Ensembl ].
VAR_023303
Natural variant441E → Q. Ref.16
VAR_018347
Natural variant491R → C in allele EPHX1*2. Ref.12
Corresponds to variant rs2234697 [ dbSNP | Ensembl ].
VAR_013298
Natural variant1131Y → H in allele EPHX1*3; 55% of wild type enzyme activity. Ref.4 Ref.8 Ref.12 Ref.15 Ref.17
Corresponds to variant rs1051740 [ dbSNP | Ensembl ].
VAR_005295
Natural variant1391H → R in allele EPHX1*4; 62% of wild type enzyme activity. Ref.4 Ref.8 Ref.12 Ref.15 Ref.17
Corresponds to variant rs2234922 [ dbSNP | Ensembl ].
VAR_005296
Natural variant2601L → P in allele EPHX1*1G. Ref.12
VAR_013299
Natural variant2751T → A.
Corresponds to variant rs35073925 [ dbSNP | Ensembl ].
VAR_051828
Natural variant2851V → L. Ref.8
Corresponds to variant rs45449793 [ dbSNP | Ensembl ].
VAR_023304
Natural variant3961T → I Either a rare polymorphism or a sequencing error. Ref.4
VAR_005297
Natural variant4081T → M. Ref.8
Corresponds to variant rs45495897 [ dbSNP | Ensembl ].
VAR_023305
Natural variant4521L → Q. Ref.8
Corresponds to variant rs45563137 [ dbSNP | Ensembl ].
VAR_023306
Natural variant4541R → Q in allele EPHX1*5. Ref.12
Corresponds to variant rs2234701 [ dbSNP | Ensembl ].
VAR_013300

Experimental info

Sequence conflict151I → V in BAG36227. Ref.7
Sequence conflict1121R → K Ref.11
Sequence conflict1481H → N Ref.3
Sequence conflict1481H → N Ref.11
Sequence conflict2431V → L Ref.11
Sequence conflict3481K → S in CAA68486. Ref.3
Sequence conflict4061L → F in CAA68486. Ref.3
Sequence conflict4201L → V in CAA68486. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P07099 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: 88E333838C841390

FASTA45552,949
        10         20         30         40         50         60 
MWLEILLTSV LGFAIYWFIS RDKEETLPLE DGWWGPGTRS AAREDDSIRP FKVETSDEEI 

        70         80         90        100        110        120 
HDLHQRIDKF RFTPPLEDSC FHYGFNSNYL KKVISYWRNE FDWKKQVEIL NRYPHFKTKI 

       130        140        150        160        170        180 
EGLDIHFIHV KPPQLPAGHT PKPLLMVHGW PGSFYEFYKI IPLLTDPKNH GLSDEHVFEV 

       190        200        210        220        230        240 
ICPSIPGYGF SEASSKKGFN SVATARIFYK LMLRLGFQEF YIQGGDWGSL ICTNMAQLVP 

       250        260        270        280        290        300 
SHVKGLHLNM ALVLSNFSTL TLLLGQRFGR FLGLTERDVE LLYPVKEKVF YSLMRESGYM 

       310        320        330        340        350        360 
HIQCTKPDTV GSALNDSPVG LAAYILEKFS TWTNTEFRYL EDGGLERKFS LDDLLTNVML 

       370        380        390        400        410        420 
YWTTGTIISS QRFYKENLGQ GWMTQKHERM KVYVPTGFSA FPFELLHTPE KWVRFKYPKL 

       430        440        450 
ISYSYMVRGG HFAAFEEPEL LAQDIRKFLS VLERQ 

« Hide

References

« Hide 'large scale' references
[1]"Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, complementary DNA-directed expression in COS-1 cells, and chromosomal localization."
Skoda R.C., Demierre A., McBride O.W., Gonzalez F.J., Meyer U.A.
J. Biol. Chem. 263:1549-1554(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-19.
[2]"Nucleotide sequence of a human microsomal epoxide hydrolase cDNA clone."
Wilson N.M., Omiecinski C.J.
Submitted (JUL-1988) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal liver.
[3]"Nucleotide and deduced amino acid sequence of human liver microsomal epoxide hydrolase."
Jackson M.R., Craft J.A., Burchell B.
Nucleic Acids Res. 15:7188-7188(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[4]"Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants."
Hassett C., Aicher L., Sidhu J.S., Omiecinski C.J.
Hum. Mol. Genet. 3:421-428(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-113; ARG-139 AND ILE-396.
Tissue: Liver.
[5]Erratum
Hassett C., Aicher L., Sidhu J.S., Omiecinski C.J.
Hum. Mol. Genet. 3:1214-1214(1994)
[6]"The human microsomal epoxide hydrolase gene (EPHX1): complete nucleotide sequence and structural characterization."
Hassett C., Robinson K.B., Beck N.B., Omiecinski C.J.
Genomics 23:433-442(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex.
[8]NIEHS SNPs program
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-43; HIS-113; ARG-139; LEU-285; MET-408 AND GLN-452.
[9]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin, Testis and Uterus.
[11]"Partial nucleotide sequence of a cloned cDNA for human liver microsomal epoxide hydrolase."
Craft J.A., Jackson M.R., Burchell B.
Biochem. Soc. Trans. 15:708-709(1987)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-327.
Tissue: Liver.
[12]"Identification of 6 new polymorphisms, g.11177G>A, g.14622C>T (R49C), g.17540T>C, g.17639T>C, g.30929T>C, g.31074G>A (R454Q), in the human microsomal epoxide hydrolase gene (EPHX1) in a French population."
Belmahdi F., Chevalier D., Lo-Guidice J.-M., Allorge D., Cauffiez C., Lafitte J.-J., Broly F.
Hum. Mutat. 16:450-450(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-197; 242-310 AND 348-455, VARIANTS CYS-49; HIS-113; ARG-139; PRO-260 AND GLN-454.
[13]"Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia."
Zhu Q.S., Xing W., Qian B., von Dippe P., Shneider B.L., Fox V.L., Levy D.
Biochim. Biophys. Acta 1638:208-216(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HYPERCHOLANEMIA, TISSUE SPECIFICITY.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are jointly associated with preeclampsia."
Laasanen J., Romppanen E.-L., Hiltunen M., Helisalmi S., Mannermaa A., Punnonen K., Heinonen S.
Eur. J. Hum. Genet. 10:569-573(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-113 AND ARG-139, DISEASE.
[16]"Five novel single nucleotide polymorphisms in the EPHX1 gene encoding microsomal epoxide hydrolase."
Shiseki K., Itoda M., Saito Y., Nakajima Y., Maekawa K., Kimura H., Goto Y., Saitoh O., Katoh M., Ohnuma T., Kawai M., Sugai K., Ohtsuki T., Suzuki C., Minami N., Ozawa S., Sawada J.
Drug Metab. Pharmacokinet. 18:150-153(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-44.
[17]"Functional analysis of human microsomal epoxide hydrolase genetic variants."
Hosagrahara V.P., Rettie A.E., Hassett C., Omiecinski C.J.
Chem. Biol. Interact. 150:149-159(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS HIS-113 AND ARG-139.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03518 mRNA. Translation: AAA61305.1.
X07936 mRNA. Translation: CAA30759.1.
Y00424 mRNA. Translation: CAA68486.1.
L25878 mRNA. Translation: AAA52389.1.
L25879 mRNA. Translation: AAA52390.1.
U06661 expand/collapse EMBL AC list , U06656, U06657, U06658, U06659, U06660 Genomic DNA. Translation: AAB60649.1.
AK313436 mRNA. Translation: BAG36227.1.
AY948961 Genomic DNA. Translation: AAX81410.1.
AL591895 Genomic DNA. Translation: CAH71994.1.
BC003567 mRNA. Translation: AAH03567.1.
BC008291 mRNA. Translation: AAH08291.1.
BC095430 mRNA. Translation: AAH95430.1.
M36374 mRNA. Translation: AAA59580.1.
AF253417 Genomic DNA. Translation: AAC41694.1.
AF276626 Genomic DNA. Translation: AAF87726.1.
AF276627 Genomic DNA. Translation: AAF87727.1.
AF276628 Genomic DNA. Translation: AAF87728.1.
AF276629 Genomic DNA. Translation: AAF87729.1.
AF276630 Genomic DNA. Translation: AAF87730.1.
AF276631 Genomic DNA. Translation: AAF87731.1.
AF276632 Genomic DNA. Translation: AAF87732.1.
AF276633 Genomic DNA. Translation: AAF87733.1.
AF276634 Genomic DNA. Translation: AAF87734.1.
AF276635 Genomic DNA. Translation: AAF87735.1.
AF276636 Genomic DNA. Translation: AAF87736.1.
AF276637 Genomic DNA. Translation: AAF87737.1.
AF276638 Genomic DNA. Translation: AAF87738.1.
PIRA29939.
RefSeqNP_000111.1. NM_000120.3.
NP_001129490.1. NM_001136018.2.
UniGeneHs.89649.

3D structure databases

ProteinModelPortalP07099.
SMRP07099. Positions 47-454.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108366. 7 interactions.
IntActP07099. 2 interactions.

Chemistry

BindingDBP07099.
ChEMBLCHEMBL1968.

Protein family/group databases

MEROPSS33.971.

PTM databases

PhosphoSiteP07099.

Polymorphism databases

DMDM123926.

Proteomic databases

PaxDbP07099.
PeptideAtlasP07099.
PRIDEP07099.

Protocols and materials databases

DNASU2052.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000272167; ENSP00000272167; ENSG00000143819.
ENST00000366837; ENSP00000355802; ENSG00000143819.
GeneID2052.
KEGGhsa:2052.
UCSCuc001hpk.3. human.

Organism-specific databases

CTD2052.
GeneCardsGC01P225997.
HGNCHGNC:3401. EPHX1.
HPAHPA020593.
MIM132810. gene+phenotype.
607748. phenotype.
neXtProtNX_P07099.
Orphanet238475. Familial hypercholanemia.
1912. Fetal hydantoin syndrome.
PharmGKBPA27829.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0596.
HOVERGENHBG002366.
InParanoidP07099.
KOK01253.
OMAIYFNEVD.
PhylomeDBP07099.
TreeFamTF313813.

Enzyme and pathway databases

SABIO-RKP07099.

Gene expression databases

ArrayExpressP07099.
BgeeP07099.
GenevestigatorP07099.

Family and domain databases

InterProIPR000073. AB_hydrolase_1.
IPR000639. Epox_hydrolase-like.
IPR010497. Epoxide_hydro_N.
IPR016292. Epoxide_hydrolase.
[Graphical view]
PfamPF00561. Abhydrolase_1. 1 hit.
PF06441. EHN. 1 hit.
[Graphical view]
PIRSFPIRSF001112. Epoxide_hydrolase. 1 hit.
PRINTSPR00412. EPOXHYDRLASE.
ProtoNetSearch...

Other

ChiTaRSEPHX1. human.
GeneWikiEPHX1.
GenomeRNAi2052.
NextBio8343.
PROP07099.
SOURCESearch...

Entry information

Entry nameHYEP_HUMAN
AccessionPrimary (citable) accession number: P07099
Secondary accession number(s): B2R8N0 expand/collapse secondary AC list , Q5VTJ6, Q9NP75, Q9NPE7, Q9NQU6, Q9NQU7, Q9NQU8, Q9NQU9, Q9NQV0, Q9NQV1, Q9NQV2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: November 1, 1988
Last modified: April 16, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM