KEGG   ENZYME: 3.3.2.10
Entry
EC 3.3.2.10                 Enzyme                                 

Name
soluble epoxide hydrolase;
epoxide hydrase (ambiguous);
epoxide hydratase (ambiguous);
arene-oxide hydratase (ambiguous);
aryl epoxide hydrase (ambiguous);
trans-stilbene oxide hydrolase;
sEH;
cytosolic epoxide hydrolase
Class
Hydrolases;
Acting on ether bonds;
Ether hydrolases
Sysname
epoxide hydrolase
Reaction(IUBMB)
an epoxide + H2O = a glycol [RN:R02822]
Reaction(KEGG)
Substrate
epoxide [CPD:C00722];
H2O [CPD:C00001]
Product
glycol [CPD:C15588]
Comment
Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl---enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [7].
History
EC 3.3.2.10 created 2006 (EC 3.3.2.3 created 1978, part incorporated 2006)
Pathway
ec00590  Arachidonic acid metabolism
ec00625  Chloroalkane and chloroalkene degradation
ec01100  Metabolic pathways
ec01120  Microbial metabolism in diverse environments
Orthology
K08726  soluble epoxide hydrolase / lipid-phosphate phosphatase
K22368  epoxide hydrolase 3
Genes
HSA: 2053(EPHX2) 79852(EPHX3)
PTR: 455793(EPHX3) 464074(EPHX2)
PPS: 100990932(EPHX2)
GGO: 101136750(EPHX2)
PON: 100172736(EPHX2) 100455128(EPHX3)
NLE: 100585861(EPHX2) 100592370(EPHX3)
MCC: 712926(EPHX2) 718176(EPHX3)
MCF: 102124136(EPHX3) 102134633(EPHX2)
CSAB: 103215526(EPHX2) 103234067(EPHX3)
RRO: 104661024(EPHX3) 104673945(EPHX2)
RBB: 108523071(EPHX3) 108537568(EPHX2)
CJC: 100402999(EPHX2) 100405833(EPHX3)
SBQ: 101033420(EPHX2) 101039796(EPHX3)
MMU: 13850(Ephx2) 71932(Ephx3)
MCAL: 110284324(Ephx3) 110309184(Ephx2)
MPAH: 110325104(Ephx2) 110335924(Ephx3)
RNO: 366836(Ephx3) 65030(Ephx2)
MUN: 110548893(Ephx3) 110559220(Ephx2)
CGE: 100753937(Ephx3) 100757328(Ephx2)
NGI: 103730002(Ephx2) 103731623(Ephx3)
HGL: 101715352(Ephx2) 101722570(Ephx3)
CCAN: 109681381(Ephx3) 109683973
OCU: 100350230(EPHX2) 100352464(EPHX3)
TUP: 102480725(EPHX2) 102499982(EPHX3)
CFA: 100684177(EPHX3) 477373(EPHX2)
VVP: 112913147(EPHX3) 112926786(EPHX2)
AML: 100483292(EPHX3) 100483572(EPHX2)
UMR: 103675990(EPHX2) 103677203(EPHX3)
UAH: 113248703(EPHX3) 113269956(EPHX2)
ORO: 101373863(EPHX2) 101374433(EPHX3)
FCA: 101092355(EPHX2) 101099782(EPHX3)
PTG: 102954012(EPHX3) 102957184(EPHX2)
PPAD: 109247513 109262341(EPHX2)
AJU: 106973110(EPHX2) 113596564(EPHX3)
BTA: 511716(EPHX2) 617882(EPHX3)
BOM: 102265452(EPHX3) 102267808(EPHX2)
BIU: 109561482(EPHX3) 109563159(EPHX2)
BBUB: 102390473(EPHX3) 102411270(EPHX2)
CHX: 102184515(EPHX3) 102185835(EPHX2)
OAS: 101106654(EPHX2) 101120077(EPHX3)
SSC: 100625866(EPHX3) 414425(EPHX2)
CFR: 102517269(EPHX2) 102521591(EPHX3)
CDK: 105102229(EPHX2) 105105142(EPHX3)
BACU: 102998957(EPHX3) 103015729(EPHX2)
LVE: 103082628(EPHX2) 103086935(EPHX3)
OOR: 101277852(EPHX3) 101282222(EPHX2)
DLE: 111166730(EPHX3) 111185405(EPHX2)
PCAD: 102974927(EPHX3) 102997018(EPHX2)
ECB: 100060414(EPHX2) 100063124(EPHX3)
EPZ: 103550424(EPHX2) 103563921(EPHX3)
EAI: 106832514(EPHX2) 106839070(EPHX3)
MYB: 102255588(EPHX2) 102264163(EPHX3)
MYD: 102755564(EPHX2) 102768225(EPHX3)
MNA: 107534291(EPHX3) 107538569(EPHX2)
HAI: 109376078(EPHX3) 109379561(EPHX2)
DRO: 112305266(EPHX3) 112312409(EPHX2)
PALE: 102886924(EPHX2) 102895797(EPHX3)
RAY: 107507539(EPHX2) 107517222(EPHX3)
MJV: 108394328(EPHX2) 108408748(EPHX3)
LAV: 100658579(EPHX2) 100672531(EPHX3)
MDO: 100012757(EPHX3) 100030580(EPHX2)
PCW: 110196222(EPHX3) 110206532(EPHX2)
OAA: 100093187(EPHX2) 100093585(EPHX3)
GGA: 421999(EPHX2)
MGP: 100550075(EPHX2)
CJO: 107312419(EPHX2)
NMEL: 110396327(EPHX2)
APLA: 101802271(EPHX2)
TGU: 115494601(EPHX2)
LSR: 110477399(EPHX2)
SCAN: 103825122(EPHX2)
FAB: 101820851(EPHX2)
PHI: 102113903(EPHX2)
CCAE: 111927478(EPHX2)
FPG: 101922601(EPHX2)
FCH: 102047869(EPHX2)
CLV: 102084991(EPHX2)
EGZ: 104132029(EPHX2)
NNI: 104014768(EPHX2)
ACUN: 113478826(EPHX2)
AAM: 106486373(EPHX2)
ASN: 102380849 102382847(EPHX2)
AMJ: 102558789(EPHX2) 102571865(EPHX3)
PSS: 102463793(EPHX2)
CMY: 102944771(EPHX2)
CPIC: 101948727
ACS: 100564154(ephx2) 100568091(ephx3)
PVT: 110080425(EPHX3) 110089501(EPHX2)
PBI: 103065207
PMUR: 107296270
TSR: 106551030(EPHX2)
PMUA: 114594946(EPHX2)
GJA: 107118053(EPHX2) 107118743
XLA: 108712668(ephx3.S) 447032(ephx2.L)
XTR: 448759(ephx2) 779884(ephx3)
NPR: 108797013 108798538(EPHX2)
DRE: 494099(ephx2)
SRX: 107717245(ephx2) 107733988
SGH: 107552031 107594076(ephx2)
CCAR: 109107424
IPU: 108270338(ephx2)
PHYP: 113538653(ephx2)
AMEX: 103037948(ephx2)
EEE: 113572683(ephx2)
TRU: 101078765(ephx2)
LCO: 104928568(ephx2)
NCC: 104958265(ephx2)
MZE: 101483599(ephx2)
ONL: 100705182(ephx2)
OLA: 101157276(ephx2)
XMA: 102235090(ephx2)
XCO: 114140564(ephx2)
PRET: 103456621(ephx2)
CVG: 107096825(ephx2)
NFU: 107384625(ephx2)
KMR: 108246829(ephx2)
ALIM: 106527033(ephx2)
AOCE: 111573235(ephx2)
LCF: 108873166(ephx2)
SDU: 111234755(ephx2)
SLAL: 111672419(ephx2)
MALB: 109955803(ephx2)
SASA: 106604359(HYES) 106611412(HYES)
SALP: 112071651(ephx2)
ELS: 105028738(ephx2)
BFO: 118420112
CIN: 113474027
SPU: 590472(EH1) 752510(eh2)
SKO: 100367532
NVE: 5521988
EPA: 110251610
PDAM: 113686980
SPIS: 111334437
DZI: 111302718
ADU: 107492180
PXB: 103939771
CMAX: 111482470
JCU: 105643456
HAN: 110941524
CCAV: 112528667
BDI: 100841009
SBI: 8071538
NCR: NCU02924
NTE: NEUTE1DRAFT119163(NEUTE1DRAFT_119163)
SSCK: SPSK_04392
MAW: MAC_03724
ANG: ANI_1_1944014(An01g14420)
PNO: SNOG_12792 SNOG_13782(SNOG_13781) SNOG_14994
ABP: AGABI1DRAFT110229(AGABI1DRAFT_110229) AGABI1DRAFT38499(AGABI1DRAFT_38499) AGABI1DRAFT70817(AGABI1DRAFT_70817)
ABV: AGABI2DRAFT184905(AGABI2DRAFT_184905) AGABI2DRAFT189875(AGABI2DRAFT_189875) AGABI2DRAFT78715(AGABI2DRAFT_78715)
 » show all
Reference
1  [PMID:12574510]
  Authors
Newman JW, Morisseau C, Harris TR, Hammock BD.
  Title
The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity.
  Journal
Proc Natl Acad Sci U S A 100:1558-63 (2003)
DOI:10.1073/pnas.0437724100
  Sequence
[hsa:2053]
Reference
2  [PMID:12574508]
  Authors
Cronin A, Mowbray S, Durk H, Homburg S, Fleming I, Fisslthaler B, Oesch F, Arand M.
  Title
The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.
  Journal
Proc Natl Acad Sci U S A 100:1552-7 (2003)
DOI:10.1073/pnas.0437829100
  Sequence
[hsa:2053] [rno:65030]
Reference
3  [PMID:4584115]
  Authors
Oesch F.
  Title
Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.
  Journal
Xenobiotica 3:305-40 (1973)
DOI:10.3109/00498257309151525
Reference
4  [PMID:15822179]
  Authors
Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Journal
Annu Rev Pharmacol Toxicol 45:311-33 (2005)
DOI:10.1146/annurev.pharmtox.45.120403.095920
Reference
5  [PMID:11090543]
  Authors
Yu Z, Xu F, Huse LM, Morisseau C, Draper AJ, Newman JW, Parker C, Graham L, Engler MM, Hammock BD, Zeldin DC, Kroetz DL.
  Title
Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.
  Journal
Circ Res 87:992-8 (2000)
DOI:10.1161/01.res.87.11.992
Reference
6
  Authors
Lacourciere, G.M. and Armstrong, R.N.
  Title
The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate.
  Journal
J Am Chem Soc 115:10466-10456 (1993)
Reference
7  [PMID:11154734]
  Authors
Fretland AJ, Omiecinski CJ.
  Title
Epoxide hydrolases: biochemistry and molecular biology.
  Journal
Chem Biol Interact 129:41-59 (2000)
DOI:10.1016/S0009-2797(00)00197-6
Reference
8  [PMID:7840649]
  Authors
Zeldin DC, Wei S, Falck JR, Hammock BD, Snapper JR, Capdevila JH.
  Title
Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis.
  Journal
Arch Biochem Biophys 316:443-51 (1995)
DOI:10.1006/abbi.1995.1059
Reference
9  [PMID:3009453]
  Authors
Haeggstrom J, Meijer J, Radmark O.
  Title
Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase.
  Journal
J Biol Chem 261:6332-7 (1986)
Reference
10 [PMID:15748653]
  Authors
Newman JW, Morisseau C, Hammock BD.
  Title
Epoxide hydrolases: their roles and interactions with lipid metabolism.
  Journal
Prog Lipid Res 44:1-51 (2005)
DOI:10.1016/j.plipres.2004.10.001
Other DBs
ExplorEnz - The Enzyme Database: 3.3.2.10
IUBMB Enzyme Nomenclature: 3.3.2.10
ExPASy - ENZYME nomenclature database: 3.3.2.10
UM-BBD (Biocatalysis/Biodegradation Database): 3.3.2.10
BRENDA, the Enzyme Database: 3.3.2.10
CAS: 9048-63-9

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