Gene/Proteome Database (LMPD)
LMPD ID
LMP003143
Gene ID
Species
Homo sapiens (Human)
Gene Name
epoxide hydrolase 2, cytoplasmic
Gene Symbol
Synonyms
CEH; SEH
Alternate Names
bifunctional epoxide hydrolase 2; epoxide hydratase; epoxide hydrolase, soluble; epoxide hydrolase 2, cytosolic
Chromosome
8
Map Location
8p21
EC Number
3.3.2.10
Summary
This gene encodes a member of the epoxide hydrolase family. The protein, found in both the cytosol and peroxisomes, binds to specific epoxides and converts them to the corresponding dihydrodiols. Mutations in this gene have been associated with familial hypercholesterolemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]
Orthologs
Proteins
| bifunctional epoxide hydrolase 2 isoform a | |
|---|---|
| Refseq ID | NP_001970 |
| Protein GI | 27597073 |
| UniProt ID | P34913 |
| mRNA ID | NM_001979 |
| Length | 555 |
| RefSeq Status | REVIEWED |
| MTLRAAVFDLDGVLALPAVFGVLGRTEEALALPRGLLNDAFQKGGPEGATTRLMKGEITLSQWIPLMEENCRKCSETAKVCLPKNFSIKEIFDKAISARKINRPMLQAALMLRKKGFTTAILTNTWLDDRAERDGLAQLMCELKMHFDFLIESCQVGMVKPEPQIYKFLLDTLKASPSEVVFLDDIGANLKPARDLGMVTILVQDTDTALKELEKVTGIQLLNTPAPLPTSCNPSDMSHGYVTVKPRVRLHFVELGSGPAVCLCHGFPESWYSWRYQIPALAQAGYRVLAMDMKGYGESSAPPEIEEYCMEVLCKEMVTFLDKLGLSQAVFIGHDWGGMLVWYMALFYPERVRAVASLNTPFIPANPNMSPLESIKANPVFDYQLYFQEPGVAEAELEQNLSRTFKSLFRASDESVLSMHKVCEAGGLFVNSPEEPSLSRMVTEEEIQFYVQQFKKSGFRGPLNWYRNMERNWKWACKSLGRKILIPALMVTAEKDFVLVPQMSQHMEDWIPHLKRGHIEDCGHWTQMDKPTEVNQILIKWLDSDARNPPVVSKM | |
| bifunctional epoxide hydrolase 2 isoform b | |
|---|---|
| Refseq ID | NP_001243411 |
| Protein GI | 374532800 |
| UniProt ID | P34913 |
| mRNA ID | NM_001256482 |
| Length | 502 |
| RefSeq Status | REVIEWED |
| MKGEITLSQWIPLMEENCRKCSETAKVCLPKNFSIKEIFDKAISARKINRPMLQAALMLRKKGFTTAILTNTWLDDRAERDGLAQLMCELKMHFDFLIESCQVGMVKPEPQIYKFLLDTLKASPSEVVFLDDIGANLKPARDLGMVTILVQDTDTALKELEKVTGIQLLNTPAPLPTSCNPSDMSHGYVTVKPRVRLHFVELGSGPAVCLCHGFPESWYSWRYQIPALAQAGYRVLAMDMKGYGESSAPPEIEEYCMEVLCKEMVTFLDKLGLSQAVFIGHDWGGMLVWYMALFYPERVRAVASLNTPFIPANPNMSPLESIKANPVFDYQLYFQEPGVAEAELEQNLSRTFKSLFRASDESVLSMHKVCEAGGLFVNSPEEPSLSRMVTEEEIQFYVQQFKKSGFRGPLNWYRNMERNWKWACKSLGRKILIPALMVTAEKDFVLVPQMSQHMEDWIPHLKRGHIEDCGHWTQMDKPTEVNQILIKWLDSDARNPPVVSKM | |
| bifunctional epoxide hydrolase 2 isoform b | |
|---|---|
| Refseq ID | NP_001243413 |
| Protein GI | 374532804 |
| UniProt ID | P34913 |
| mRNA ID | NM_001256484 |
| Length | 502 |
| RefSeq Status | REVIEWED |
| Protein sequence is identical to GI:374532800 (mRNA isoform) | |
| bifunctional epoxide hydrolase 2 isoform c | |
|---|---|
| Refseq ID | NP_001243412 |
| Protein GI | 374532802 |
| UniProt ID | P34913 |
| mRNA ID | NM_001256483 |
| Length | 489 |
| RefSeq Status | REVIEWED |
| MEENCRKCSETAKVCLPKNFSIKEIFDKAISARKINRPMLQAALMLRKKGFTTAILTNTWLDDRAERDGLAQLMCELKMHFDFLIESCQVGMVKPEPQIYKFLLDTLKASPSEVVFLDDIGANLKPARDLGMVTILVQDTDTALKELEKVTGIQLLNTPAPLPTSCNPSDMSHGYVTVKPRVRLHFVELGSGPAVCLCHGFPESWYSWRYQIPALAQAGYRVLAMDMKGYGESSAPPEIEEYCMEVLCKEMVTFLDKLGLSQAVFIGHDWGGMLVWYMALFYPERVRAVASLNTPFIPANPNMSPLESIKANPVFDYQLYFQEPGVAEAELEQNLSRTFKSLFRASDESVLSMHKVCEAGGLFVNSPEEPSLSRMVTEEEIQFYVQQFKKSGFRGPLNWYRNMERNWKWACKSLGRKILIPALMVTAEKDFVLVPQMSQHMEDWIPHLKRGHIEDCGHWTQMDKPTEVNQILIKWLDSDARNPPVVSKM | |
Gene Information
Entrez Gene ID
Gene Name
epoxide hydrolase 2, cytoplasmic
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005829 | IDA:UniProtKB | C | cytosol |
| GO:0070062 | IDA:UniProtKB | C | extracellular vesicular exosome |
| GO:0005777 | IDA:UniProtKB | C | peroxisome |
| GO:0033885 | IEA:UniProtKB-EC | F | 10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity |
| GO:0004301 | IDA:UniProtKB | F | epoxide hydrolase activity |
| GO:0042577 | IDA:UniProtKB | F | lipid phosphatase activity |
| GO:0000287 | IDA:UniProtKB | F | magnesium ion binding |
| GO:0016791 | IDA:UniProtKB | F | phosphatase activity |
| GO:0042803 | IDA:UniProtKB | F | protein homodimerization activity |
| GO:0005102 | IPI:UniProtKB | F | receptor binding |
| GO:0015643 | IDA:UniProtKB | F | toxic substance binding |
| GO:0019369 | TAS:Reactome | P | arachidonic acid metabolic process |
| GO:0006874 | NAS:UniProtKB | P | cellular calcium ion homeostasis |
| GO:0042632 | IDA:UniProtKB | P | cholesterol homeostasis |
| GO:0016311 | IDA:UniProtKB | P | dephosphorylation |
| GO:0017144 | NAS:UniProtKB | P | drug metabolic process |
| GO:0019373 | TAS:Reactome | P | epoxygenase P450 pathway |
| GO:0006954 | NAS:UniProtKB | P | inflammatory response |
| GO:0046839 | IDA:UniProtKB | P | phospholipid dephosphorylation |
| GO:0010628 | IDA:UniProtKB | P | positive regulation of gene expression |
| GO:0045909 | NAS:UniProtKB | P | positive regulation of vasodilation |
| GO:0072593 | NAS:UniProtKB | P | reactive oxygen species metabolic process |
| GO:0008217 | NAS:UniProtKB | P | regulation of blood pressure |
| GO:0090181 | IMP:UniProtKB | P | regulation of cholesterol metabolic process |
| GO:0009636 | NAS:UniProtKB | P | response to toxic substance |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0046272 | IDA:UniProtKB | P | stilbene catabolic process |
| GO:0006805 | NAS:UniProtKB | P | xenobiotic metabolic process |
KEGG Pathway Links
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_150417 | Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR029058 | Alpha/Beta hydrolase fold |
| IPR000073 | Alpha/beta hydrolase fold-1 |
| IPR000639 | Epoxide hydrolase-like |
| IPR006439 | HAD hydrolase, subfamily IA |
| IPR023214 | HAD-like domain |
| IPR023198 | Phosphoglycolate phosphatase, domain 2 |
| IPR011945 | Predicted HAD-superfamily phosphatase, subfamily IA/Epoxide hydrolase, N-terminal |
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P34913-1; Sequence=Displayed; Name=2; IsoId=P34913-2; Sequence=VSP_045598; Note=No experimental confirmation available.; Name=3; IsoId=P34913-3; Sequence=VSP_045597; Note=No experimental confirmation available.; |
| Biophysicochemical Properties | Kinetic parameters: KM=21 uM for threo-9,10-phosphonooxy-hydroxy-octadecanoic acid {ECO |
| Catalytic Activity | (9S,10S)-10-hydroxy-9- (phosphonooxy)octadecanoate + H(2)O = (9S,10S)-9,10- dihydroxyoctadecanoate + phosphate. |
| Catalytic Activity | An epoxide + H(2)O = a glycol. |
| Cofactor | Name=Mg(2+); Xref=ChEBI |
| Domain | The N-terminal domain has phosphatase activity. The C- terminal domain has epoxide hydrolase activity. |
| Function | Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo- 9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro- 9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy- octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate. {ECO |
| Induction | By compounds that cause peroxisome proliferation such as clofibrate, tiadenol and fenofibrate. |
| Ptm | The N-terminus is blocked. |
| Ptm | The covalent modification of cysteine by 15-deoxy-Delta12,14- prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S- nitrosylation and S-palmitoylation (Probable). |
| Similarity | Belongs to the AB hydrolase superfamily. Epoxide hydrolase family. |
| Subcellular Location | Cytoplasm. Peroxisome. |
| Subunit | Homodimer. {ECO |
| Web Resource | Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ephx2/"; |
Identical and Related Proteins
Unique RefSeq proteins for LMP003143 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 27597073 | RefSeq | NP_001970 | 555 | bifunctional epoxide hydrolase 2 isoform a |
| 374532800 | RefSeq | NP_001243411 | 502 | bifunctional epoxide hydrolase 2 isoform b |
| 374532802 | RefSeq | NP_001243412 | 489 | bifunctional epoxide hydrolase 2 isoform c |
Identical Sequences to LMP003143 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:374532800 | GenBank | EAW63549.1 | 502 | epoxide hydrolase 2, cytoplasmic, isoform CRA_c [Homo sapiens] |
| GI:374532802 | GenBank | EAW63551.1 | 489 | epoxide hydrolase 2, cytoplasmic, isoform CRA_e [Homo sapiens] |
| GI:27597073 | GenBank | AGN61907.1 | 555 | Sequence 1 from patent US 8455652 |
| GI:27597073 | GenBank | AGU04324.1 | 555 | Sequence 1 from patent US 8476043 |
| GI:27597073 | GenBank | AHD71379.1 | 555 | Sequence 6073 from patent US 8586006 |
| GI:27597073 | GenBank | AIC48706.1 | 555 | EPHX2, partial [synthetic construct] |
| GI:27597073 | PDB | 4OCZ | 555 | Chain A, Crystal Structure Of Human Soluble Epoxide Hydrolase Complexed With 1- (1-isobutyrylpiperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)urea |
| GI:27597073 | PDB | 4OD0 | 555 | Chain A, Crystal Structure Of Human Soluble Epoxide Hydrolase Complexed With 1- (1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea |
| GI:374532800 | RefSeq | NP_001243413.1 | 502 | bifunctional epoxide hydrolase 2 isoform b [Homo sapiens] |
Related Sequences to LMP003143 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:374532800 | GenBank | AAH07708.1 | 555 | Epoxide hydrolase 2, cytoplasmic [Homo sapiens] |
| GI:374532802 | GenBank | AAH07708.1 | 555 | Epoxide hydrolase 2, cytoplasmic [Homo sapiens] |
| GI:374532802 | GenBank | AAH11628.1 | 555 | Epoxide hydrolase 2, cytoplasmic [Homo sapiens] |
| GI:374532800 | GenBank | AAH11628.1 | 555 | Epoxide hydrolase 2, cytoplasmic [Homo sapiens] |
| GI:374532802 | GenBank | AAH13874.1 | 555 | Epoxide hydrolase 2, cytoplasmic [Homo sapiens] |
| GI:374532800 | GenBank | AAH13874.1 | 555 | Epoxide hydrolase 2, cytoplasmic [Homo sapiens] |
| GI:27597073 | GenBank | AAP36260.1 | 556 | Homo sapiens epoxide hydrolase 2, cytoplasmic, partial [synthetic construct] |
| GI:27597073 | GenBank | AAX29746.1 | 556 | epoxide hydrolase 2 cytoplasmic, partial [synthetic construct] |
| GI:27597073 | GenBank | AAX29747.1 | 556 | epoxide hydrolase 2 cytoplasmic, partial [synthetic construct] |
| GI:27597073 | GenBank | EJO89151.1 | 292 | 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase [Mycobacterium colombiense CECT 3035] |
| GI:374532802 | GenBank | AGU04324.1 | 555 | Sequence 1 from patent US 8476043 |
| GI:374532800 | GenBank | AGU04324.1 | 555 | Sequence 1 from patent US 8476043 |
| GI:374532800 | PDB | 3I1Y | 555 | Chain A, Crystal Structure Of Soluble Epoxide Hydrolase |
| GI:374532802 | PDB | 3I1Y | 555 | Chain A, Crystal Structure Of Soluble Epoxide Hydrolase |
| GI:374532802 | PDB | 3I28 | 555 | Chain A, Crystal Structure Of Soluble Epoxide Hydrolase |
| GI:374532800 | PDB | 3I28 | 555 | Chain A, Crystal Structure Of Soluble Epoxide Hydrolase |
| GI:27597073 | PDB | 3WK5 | 561 | Chain A, Crystal Structure Of Soluble Epoxide Hydrolase In Complex With Fragment Inhibitor |
| GI:27597073 | RefSeq | WP_007772388.1 | 292 | 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase [Mycobacterium colombiense] |