P07099 (HYEP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Epoxide hydrolase 1
EC=3.3.2.9

Alternative name(s):
Epoxide hydratase
Microsomal epoxide hydrolase

Gene names

Name:	EPHX1
Synonyms:	EPHX, EPOX

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	455 AA.
Sequence status	Complete.
Protein existence	Evidence 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.12
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.14 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.14
Sequence similarities	Belongs to the peptidase S33 family.

Ontologies

Keywords
Biological process	Aromatic hydrocarbons catabolism Detoxification
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Methylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	aromatic compound catabolic process Inferred from electronic annotation. Source: UniProtKB-KW response to organic cyclic compound Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cis-stilbene-oxide hydrolase activity Inferred from electronic annotation. Source: EC epoxide hydrolase activity Traceable author statement Ref.4. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 455	455	Epoxide hydrolase 1		PRO_0000080855
Regions
	Transmembrane	2 – 20	19	Helical; Signal-anchor; Potential
Amino acid modifications
	Modified residue	295	1	Omega-N-methylated arginine By similarity
Natural variations
	Natural variant	43	1	R → T. Ref.7 Corresponds to variant rs3738046 [ dbSNP | Ensembl ].		VAR_023303
	Natural variant	44	1	E → Q. Ref.15		VAR_018347
	Natural variant	49	1	R → C in allele EPHX1*2. Ref.11 Corresponds to variant rs2234697 [ dbSNP | Ensembl ].		VAR_013298
	Natural variant	113	1	Y → H in allele EPHX1*3; 55% of wild type enzyme activity. Ref.4 Ref.7 Ref.11 Ref.14 Ref.16 Corresponds to variant rs1051740 [ dbSNP | Ensembl ].		VAR_005295
	Natural variant	139	1	H → R in allele EPHX1*4; 62% of wild type enzyme activity. Ref.4 Ref.7 Ref.11 Ref.14 Ref.16 Corresponds to variant rs2234922 [ dbSNP | Ensembl ].		VAR_005296
	Natural variant	260	1	L → P in allele EPHX1*1G. Ref.11		VAR_013299
	Natural variant	275	1	T → A. Corresponds to variant rs35073925 [ dbSNP | Ensembl ].		VAR_051828
	Natural variant	285	1	V → L. Ref.7 Corresponds to variant rs45449793 [ dbSNP | Ensembl ].		VAR_023304
	Natural variant	396	1	T → I Either a rare polymorphism or a sequencing error. Ref.4		VAR_005297
	Natural variant	408	1	T → M. Ref.7 Corresponds to variant rs45495897 [ dbSNP | Ensembl ].		VAR_023305
	Natural variant	452	1	L → Q. Ref.7 Corresponds to variant rs45563137 [ dbSNP | Ensembl ].		VAR_023306
	Natural variant	454	1	R → Q in allele EPHX1*5. Ref.11 Corresponds to variant rs2234701 [ dbSNP | Ensembl ].		VAR_013300
Experimental info
	Sequence conflict	112	1	R → K Ref.10
	Sequence conflict	148	1	H → N Ref.3
	Sequence conflict	148	1	H → N Ref.10
	Sequence conflict	243	1	V → L Ref.10
	Sequence conflict	348	1	K → S in CAA68486. Ref.3
	Sequence conflict	406	1	L → F in CAA68486. Ref.3
	Sequence conflict	420	1	L → V in CAA68486. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P07099 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 88E333838C841390	FASTA	455	52,949
	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

References

	« Hide 'large scale' referencesShow '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]	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.
[8]	"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. , 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].
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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].
[14]	"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.
[15]	"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.
[16]	"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

NIEHS-SNPs

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 , U06656, U06657, U06658, U06659, U06660 Genomic DNA. Translation: AAB60649.1. AL591895 Genomic DNA. Translation: CAH71994.1. AY948961 Genomic DNA. Translation: AAX81410.1. 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.
IPI	IPI00009896.
PIR	A29939.
RefSeq	NP_000111.1. NM_000120.3. NP_001129490.1. NM_001136018.2.
UniGene	Hs.89649.
3D structure databases
ProteinModelPortal	P07099.
SMR	P07099. Positions 47-454.
ModBase	Search...
Protein-protein interaction databases
IntAct	P07099. 2 interactions.
Protein family/group databases
MEROPS	S33.971.
PTM databases
PhosphoSite	P07099.
Polymorphism databases
DMDM	123926.
Proteomic databases
PaxDb	P07099.
PeptideAtlas	P07099.
PRIDE	P07099.
Protocols and materials databases
DNASU	2052.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000272167; ENSP00000272167; ENSG00000143819. ENST00000366837; ENSP00000355802; ENSG00000143819.
GeneID	2052.
KEGG	hsa:2052.
UCSC	uc001hpk.3. human.
Organism-specific databases
CTD	2052.
GeneCards	GC01P225997.
HGNC	HGNC:3401. EPHX1.
HPA	HPA020593.
MIM	132810. gene+phenotype. 607748. phenotype.
neXtProt	NX_P07099.
Orphanet	238475. Familial hypercholanemia. 1912. Fetal hydantoin syndrome.
PharmGKB	PA27829.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0596.
HOVERGEN	HBG002366.
InParanoid	P07099.
KO	K01253.
OMA	AKPLLMV.
Enzyme and pathway databases
SABIO-RK	P07099.
Gene expression databases
ArrayExpress	P07099.
Bgee	P07099.
Genevestigator	P07099.
GermOnline	ENSG00000143819. Homo sapiens.
Family and domain databases
InterPro	IPR000073. AB_hydrolase_1. IPR000639. Epox_hydrolase-like. IPR010497. Epoxide_hydro_N. IPR016292. Epoxide_hydrolase. [Graphical view]
Pfam	PF00561. Abhydrolase_1. 1 hit. PF06441. EHN. 1 hit. [Graphical view]
PIRSF	PIRSF001112. Epoxide_hydrolase. 1 hit.
PRINTS	PR00412. EPOXHYDRLASE.
ProtoNet	Search...
Other
BindingDB	P07099.
ChEMBL	CHEMBL1968.
ChiTaRS	EPHX1. human.
GenomeRNAi	2052.
NextBio	8343.
SOURCE	Search...

Entry information

Entry name

HYEP_HUMAN

Accession

Primary (citable) accession number: P07099
Secondary accession number(s): 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:	May 1, 2013
This is version 142 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.