Entry
Name
leukotriene-A4 hydrolase;
LTA4 hydrolase;
LTA4H;
leukotriene A4 hydrolase
Class
Hydrolases;
Acting on ether bonds;
Ether hydrolases
BRITE hierarchy
Sysname
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase
Reaction(IUBMB)
leukotriene A4 + H2O = leukotriene B4 [RN:
R03057 ]
Reaction(KEGG)
Substrate
Product
Comment
This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates [6] (see EC
3.4.11.6 , aminopeptidase B). It also converts leukotriene A4 into leukotriene B4, unlike EC
3.3.2.10 , soluble epoxide hydrolase, which converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. 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) [5].
History
EC 3.3.2.6 created 1989, modified 2006
Pathway
ec00590 Arachidonic acid metabolism
Orthology
K01254 leukotriene-A4 hydrolase
Genes
PROB : 127231843 127237881(Lta4h)
MMF : 118624316(LTA4H) 118642487
BGAR : 122925883 122928089(LTA4H)
SRX : 107725980(lta4h) 107744078
SANH : 107656327 107658863
SGH : 107581265 107584011(lta4h)
CCAR : 109064051 109064070
CAUA : 113047946 113058671
CGIB : 127956839 127977404
MASI : 127435136 127436656
PHYP : 113532069(lta4h) 113539473(rnpep)
TNG : GSTEN00001493G001 GSTEN00005050G001
ALIM : 106511529 106530283(lta4h)
SASA : 100195091(lkha4) 106576033
STRU : 115180638 115198687 115198688
SALP : 111950871(lta4h) 111951309
CCLU : 121543706 121546278
SFM : 108926655(lta4h) 108931362
PSPA : 121318281 121319837
ARUT : 117414843 117419638
BBEL : 109472094 109476781
DME : Dmel_CG10602(CG10602)
DSI : Dsimw501_GD21803(Dsim_GD21803)
CCAT : 101457541 101457728
TDA : 119669021 119669022 119687685
CLON : 129615082 129615143
AALB : 109398621 109404731
AEC : 105150328 105150329 105150330 105153682
PBAR : 105428205 105433948
LSIN : 126977831 126977833
DPX : DAPPUDRAFT_313156(LTA4)
VDE : 111246726 111250533 111254527
VJA : 111270094 111270397 111273644
CEL : CELE_C42C1.11(ltah-1.1) CELE_ZC416.6(ltah-1.2)
CRQ : GCK72_014104 GCK72_015034
BMY : BM_BM13802(Bma-ltah-1.2)
CANU : 128159386 128159391
MMER : 123529512 128547695
MAEA : 128216682 128217740 128218198
ALY : 9307642 9309643 9309646
CSAT : 104705604 104709116 104735355 104769569
BNA : 106372289 106384246 125593126
MDM : 103433188 103433303 103446928
MSYL : 126630748 126633536 126633543
PXB : 103948321 103966665 103966666
CMAX : 111487203 111489203
CMOS : 111444926 111455330
CPEP : 111803208 111808295
MESC : 110605952 110607370 110607371
PALZ : 118052241 118059921
NTA : 107769631 107776257 107784886 107814668
NAU : 109228848 109238181 109238182
SIND : 105166640 105166641
SSPL : 121742597 121743008
SHIS : 125189053 125219953
CSIN : 114322590 114322592 114323259
MING : 122058452 122087507
PSOM : 113308480 113321597
TAES : 123105647 123113966 123123464
MFLO : 136491468 136515549 136537736
PVIR : 120649289 120690463
SMO : SELMODRAFT_82151 SELMODRAFT_88325
CVR : CHLNCDRAFT_144199 CHLNCDRAFT_22427
GSL : Gasu_15220 Gasu_16140
CGR : 2888012(GVI51_G01287)
NCS : NCAS_0G03220(NCAS0G03220)
NDI : NDAI_0D01240(NDAI0D01240)
TPF : TPHA_0D01620(TPHA0D01620)
TBL : TBLA_0G02440(TBLA0G02440)
KAF : KAFR_0H03440(KAFR0H03440)
KNG : KNAG_0H02150(KNAG0H02150)
DHA : DEHA2B14960g DEHA2G15400g
PIC : PICST_76777(LKA4) PICST_82220(LTA4)
PGU : PGUG_02354 PGUG_04447
SPAA : SPAPADRAFT_139780 SPAPADRAFT_62752
LEL : PVL30_000400(LAP2_2)
LBG : 92205877(LODBEIA_P06810) 92205960(LODBEIA_P07640)
CAL : CAALFM_C110490WA(LKH1)
CTEN : 18247450(LAP2_2) 18248600(LAP2_1)
YLI : 2908541(YALI2_F01000g)
NTE : NEUTE1DRAFT127403(NEUTE1DRAFT_127403)
SMP : 10803512(SMAC4_06601)
PBEL : QC761_210380(LAP2_1)
PPSD : QC762_210380(LAP2_1)
PPSP : QC763_210380(LAP2_1)
PPSA : QC764_210380(LAP2_1)
NHE : NECHADRAFT_104478 NECHADRAFT_89546
FFC : NCS54_00700800 NCS54_00912800
FKR : NCS57_00740900 NCS57_00930700
TATV : 25779635(TrAtP1_003306)
TASP : 36615246(TrAFT101_006993)
PCHM : VFPPC_06484 VFPPC_07282
PLJ : 28890819(PLICBS_004848)
CDET : 87950123(CDEST_13623)
BFU : BCIN_09g05630(Bclap2)
TRG : TRUGW13939_06125 TRUGW13939_10556
PTRR : 6349413(PtrM4_073020)
CDEP : 91089584(L203_105375)
KMG : 30160170(I203_104698)
KNE : 92180949(IAR55_003691)
CCAC : CcaHIS019_0212700(LAP2)
PCO : PHACADRAFT_203757 PHACADRAFT_246632
FME : FOMMEDRAFT_107254 FOMMEDRAFT_83411
RSX : RhiXN_01161 RhiXN_08665
ABP : AGABI1DRAFT103588(AGABI1DRAFT_103588)
ABV : AGABI2DRAFT198496(AGABI2DRAFT_198496)
SCM : SCHCO_02613207(SCHCODRAFT_02613207)
CPUT : CONPUDRAFT_124530 CONPUDRAFT_94541
SLA : SERLADRAFT_363710 SERLADRAFT_363857
RIE : OCT59_008754 OCT59_020191 OCT59_028076
TET : TTHERM_00579060 TTHERM_00579070 TTHERM_00637080
PTM : GSPATT00005113001 GSPATT00007464001 GSPATT00010851001 GSPATT00015207001 GSPATT00020188001 GSPATT00022408001 GSPATT00022872001 GSPATT00027103001 GSPATT00032737001 GSPATT00032843001 GSPATT00034053001 GSPATT00036790001
TPS : THAPSDRAFT_269777(LTA4)
PIF : PITG_15392 PITG_15413 PITG_21284 PITG_21860
PSOJ : PHYSODRAFT_310648 PHYSODRAFT_555820
BLAC : 94351288(CCR75_007559)
SPAR : SPRG_04360 SPRG_06006
EHX : EMIHUDRAFT_194303(MAP3) EMIHUDRAFT_256380(MAP4) EMIHUDRAFT_433828(MAP2)
SBM : Shew185_1367 Shew185_2628
SBN : Sbal195_1406 Sbal195_2703
SBP : Sbal223_1757 Sbal223_2977
SBT : Sbal678_1441 Sbal678_2708
SBS : Sbal117_1491 Sbal117_2725
SBB : Sbal175_1741 Sbal175_2955
SPC : Sputcn32_1299 Sputcn32_2314
SHP : Sput200_1305 Sput200_2340
SHE : Shewmr4_2267 Shewmr4_2706
SHM : Shewmr7_2339 Shewmr7_2774
SHN : Shewana3_2457 Shewana3_2876
SHW : Sputw3181_1694 Sputw3181_2804
SHF : CEQ32_06290 CEQ32_08355
SBJ : CF168_06475 CF168_08625
SHEW : CKQ84_00805 CKQ84_17390
SKH : STH12_00626(pepN_1) STH12_01720(pepN_3)
SCYP : JYB88_10270 JYB88_12495
SSEM : JYB85_07545 JYB85_12800
SXM : MKD32_11995 MKD32_13995
SHEJ : MZ182_06200 MZ182_11610
SDEO : D0436_13060 D0436_15290
SMAY : K0H60_12360 K0H60_14480
SOG : RA178_08985 RA178_15525
PSEN : PNC201_00985(pepN1)
AMAG : I533_04015 I533_04070
MICC : AUP74_01229(pepN_4)
LADL : NCTC12735_01052(pepN_1)
HYF : DTO96_100431(pepN_1)
MVAR : MasN3_06020(pepN_1)
BVY : NCTC9239_02926(pepN_2)
TSV : DSM104635_01301(pepN_2)
MFF : MFFC18_16550(pepN_2)
ABAC : LuPra_00324(pepN_1)
KOS : KORDIASMS9_02880(pepN)
KAN : IMCC3317_10440(pepN_2)
» show all
Taxonomy
Reference
Authors
Evans JF, Dupuis P, Ford-Hutchinson AW
Title
Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils.
Journal
Sequence
Reference
Authors
Minami M, Ohno S, Kawasaki H, Radmark O, Samuelsson B, Jornvall H, Shimizu T, Seyama Y, Suzuki K
Title
Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis.
Journal
J Biol Chem 262:13873-6 (1987)
Sequence
Reference
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
Authors
Newman JW, Morisseau C, Hammock BD.
Title
Epoxide hydrolases: their roles and interactions with lipid metabolism.
Journal
Reference
Authors
Fretland AJ, Omiecinski CJ.
Title
Epoxide hydrolases: biochemistry and molecular biology.
Journal
Reference
Authors
Orning L, Gierse JK, Fitzpatrick FA.
Title
The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity.
Journal
J Biol Chem 269:11269-73 (1994)
Reference
Authors
Ohishi N, Izumi T, Minami M, Kitamura S, Seyama Y, Ohkawa S, Terao S, Yotsumoto H, Takaku F, Shimizu T.
Title
Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers.
Journal
J Biol Chem 262:10200-5 (1987)
Other DBs
ExplorEnz - The Enzyme Database: 3.3.2.6
ExPASy - ENZYME nomenclature database: 3.3.2.6
BRENDA, the Enzyme Database: 3.3.2.6
LinkDB
All DBs