CPLM-006396

Genbank Nucleotide ID

Bifunctional epoxide hydrolase 2

Protein Synonyms/Alias

Cytosolic epoxide hydrolase 2; CEH; Epoxide hydratase; Soluble epoxide hydrolase; SEH; Lipid-phosphate phosphatase

Homo sapiens (Human)

Position	Peptide	Type	References
43	LLNDAFQKGGPEGAT	acetylation	[1]
43	LLNDAFQKGGPEGAT	ubiquitination	[2, 3]
55	GATTRLMKGEITLSQ	ubiquitination	[3]
79	RKCSETAKVCLPKNF	ubiquitination	[3]
84	TAKVCLPKNFSIKEI	ubiquitination	[3]
89	LPKNFSIKEIFDKAI	ubiquitination	[3]
94	SIKEIFDKAISARKI	acetylation	[4]
94	SIKEIFDKAISARKI	ubiquitination	[3]
174	KFLLDTLKASPSEVV	ubiquitination	[3]
191	DDIGANLKPARDLGM	ubiquitination	[3]
245	SHGYVTVKPRVRLHF	ubiquitination	[3]
406	QNLSRTFKSLFRASD	ubiquitination	[3]
421	ESVLSMHKVCEAGGL	ubiquitination	[3]
455	QFYVQQFKKSGFRGP	ubiquitination	[3]
456	FYVQQFKKSGFRGPL	ubiquitination	[3]
474	RNMERNWKWACKSLG	ubiquitination	[3]
478	RNWKWACKSLGRKIL	ubiquitination	[3]
483	ACKSLGRKILIPALM	ubiquitination	[3]
515	EDWIPHLKRGHIEDC	ubiquitination	[3]
530	GHWTQMDKPTEVNQI	ubiquitination	[3]
554	RNPPVVSKM******	ubiquitination	[3]

[1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[4] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]

Functional Description

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.

REGION 1 224 Phosphatase.
REGION 123 124 Phosphate binding.
REGION 235 555 Epoxide hydrolase.
MOTIF 553 555 Microbody targeting signal (Potential).
ACT_SITE 335 335 Nucleophile.
ACT_SITE 466 466 Proton donor.
ACT_SITE 524 524 Proton acceptor.
METAL 9 9 Magnesium.
METAL 11 11 Magnesium.
METAL 185 185 Magnesium.
BINDING 383 383 Substrate.
MOD_RES 43 43 N6-acetyllysine.
LIPID 522 522 S-(15-deoxy-Delta12,14-prostaglandin J2-

3D-structure; Acetylation; Alternative splicing; Aromatic hydrocarbons catabolism; Complete proteome; Cytoplasm; Detoxification; Direct protein sequencing; Hydrolase; Lipid metabolism; Lipoprotein; Magnesium; Metal-binding; Multifunctional enzyme; Peroxisome; Polymorphism; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0005925; C:focal adhesion; IDA:HPA.
GO:0005794; C:Golgi apparatus; IDA:HPA.
GO:0005730; C:nucleolus; IDA:HPA.
GO:0005777; C:peroxisome; IDA:UniProtKB.
GO:0033885; F:10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity; IEA:EC.
GO:0003869; F:4-nitrophenylphosphatase activity; IDA:UniProtKB.
GO:0004301; F:epoxide hydrolase activity; IDA:UniProtKB.
GO:0042577; F:lipid phosphatase activity; IDA:UniProtKB.
GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
GO:0015643; F:toxic substance binding; IDA:UniProtKB.
GO:0006874; P:cellular calcium ion homeostasis; NAS:UniProtKB.
GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
GO:0017144; P:drug metabolic process; NAS:UniProtKB.
GO:0019373; P:epoxygenase P450 pathway; TAS:Reactome.
GO:0006954; P:inflammatory response; NAS:UniProtKB.
GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
GO:0045909; P:positive regulation of vasodilation; NAS:UniProtKB.
GO:0072593; P:reactive oxygen species metabolic process; NAS:UniProtKB.
GO:0008217; P:regulation of blood pressure; NAS:UniProtKB.
GO:0090181; P:regulation of cholesterol metabolic process; IMP:UniProtKB.
GO:0009636; P:response to toxic substance; NAS:UniProtKB.
GO:0046272; P:stilbene catabolic process; IDA:UniProtKB.
GO:0006805; P:xenobiotic metabolic process; NAS:UniProtKB.

IPR000073; AB_hydrolase_1.
IPR000639; Epox_hydrolase-like.
IPR023214; HAD-like_dom.
IPR006402; HAD-SF_hydro_IA_v3.
IPR011945; HAD-SF_ppase_IA/epoxid_hydro_N.
IPR023198; PGP_dom2.

PF00561; Abhydrolase_1
PF13419; HAD_2

PR00111; ABHYDROLASE.
PR00412; EPOXHYDRLASE.