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Protein

Leukotriene A-4 hydrolase

Gene

Lta4h

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.1 Publication

Catalytic activityi

(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate.1 Publication

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Enzyme regulationi

Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4.1 Publication

Kineticsi

  1. KM=5 µM for leukotriene A41 Publication
  1. Vmax=1030 nmol/min/mg enzyme for leukotriene A41 Publication

Pathwayi: leukotriene B4 biosynthesis

This protein is involved in the pathway leukotriene B4 biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway leukotriene B4 biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi296Zinc; catalytic1
Active sitei297Proton acceptorPROSITE-ProRule annotation1
Metal bindingi300Zinc; catalytic1
Metal bindingi319Zinc; catalytic1
Sitei376Essential for epoxide hydrolase activity, but not for aminopeptidase activityBy similarity1
Sitei379Covalently modified during suicide inhibition by leukotrienesBy similarity1
Active sitei384Proton donorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processLeukotriene biosynthesis
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-MMU-6798695 Neutrophil degranulation
R-MMU-9018676 Biosynthesis of D-series resolvins
R-MMU-9018681 Biosynthesis of protectins
R-MMU-9018896 Biosynthesis of E-series 18(S)-resolvins
R-MMU-9020265 Biosynthesis of aspirin-triggered D-series resolvins
R-MMU-9023661 Biosynthesis of E-series 18(R)-resolvins
UniPathwayiUPA00878

Protein family/group databases

MEROPSiM01.004

Names & Taxonomyi

Protein namesi
Recommended name:
Leukotriene A-4 hydrolase (EC:3.3.2.6)
Short name:
LTA-4 hydrolase
Alternative name(s):
Leukotriene A(4) hydrolase
Gene namesi
Name:Lta4h
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96836 Lta4h

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi296H → Y: Complete loss of activity. 1 Publication1
Mutagenesisi300H → Y: Complete loss of activity. 1 Publication1
Mutagenesisi319E → Q: Complete loss of activity. 1 Publication1
Mutagenesisi384Y → F, H or Q: Alters leukotriene hydrolase activity, strongly enhancing the formation of a metabolite that is normally produced in trace amounts. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3738

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000951251 – 611Leukotriene A-4 hydrolaseAdd BLAST611

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei73N6-acetyllysineBy similarity1
Modified residuei337N6-acetyllysineBy similarity1
Modified residuei414N6-acetyllysineBy similarity1
Modified residuei416PhosphoserineBy similarity1
Modified residuei573N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-416 inhibits enzymatic activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP24527
MaxQBiP24527
PaxDbiP24527
PeptideAtlasiP24527
PRIDEiP24527

PTM databases

iPTMnetiP24527
PhosphoSitePlusiP24527
SwissPalmiP24527

Expressioni

Gene expression databases

BgeeiENSMUSG00000015889
CleanExiMM_LTA4H
GenevisibleiP24527 MM

Interactioni

Protein-protein interaction databases

IntActiP24527, 3 interactors
MINTiP24527
STRINGi10090.ENSMUSP00000016033

Chemistry databases

BindingDBiP24527

Structurei

3D structure databases

ProteinModelPortaliP24527
SMRiP24527
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 137Substrate bindingBy similarity3
Regioni267 – 272Substrate bindingBy similarity6
Regioni564 – 566Substrate bindingBy similarity3

Sequence similaritiesi

Belongs to the peptidase M1 family.Curated

Phylogenomic databases

eggNOGiKOG1047 Eukaryota
COG0308 LUCA
GeneTreeiENSGT00530000063003
HOGENOMiHOG000293296
HOVERGENiHBG001274
InParanoidiP24527
KOiK01254
OMAiNFEHFWL
OrthoDBiEOG091G02UX
TreeFamiTF300758

Family and domain databases

CDDicd09599 M1_LTA4H, 1 hit
Gene3Di1.10.390.10, 1 hit
1.25.40.320, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR012777 Leukotriene_A4_hydrolase
IPR038502 M1_LTA-4_hydro/amino_C_sf
IPR034015 M1_LTA4H
IPR001930 Peptidase_M1
IPR015211 Peptidase_M1_C
IPR014782 Peptidase_M1_N
IPR027268 Peptidase_M4/M1_CTD_sf
PANTHERiPTHR11533 PTHR11533, 1 hit
PfamiView protein in Pfam
PF09127 Leuk-A4-hydro_C, 1 hit
PF01433 Peptidase_M1, 1 hit
PRINTSiPR00756 ALADIPTASE
SMARTiView protein in SMART
SM01263 Leuk-A4-hydro_C, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
TIGRFAMsiTIGR02411 leuko_A4_hydro, 1 hit
PROSITEiView protein in PROSITE
PS00142 ZINC_PROTEASE, 1 hit

Sequencei

Sequence statusi: Complete.

P24527-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPEVADTCSL ASPASVCRTQ HLHLRCSVDF ARRTLTGTAA LTVQSQEENL
60 70 80 90 100
RSLTLDTKDL TIEKVVINGQ EVKYTLGESQ GYKGSPMEIS LPIALSKNQE
110 120 130 140 150
IVIEISFETS PKSSALQWLT PEQTSGKQHP YLFSQCQAIH CRAILPCQDT
160 170 180 190 200
PSVKLTYTAE VSVPKELVAL MSAIRDGEAP DPEDPSRKIY RFNQRVPIPC
210 220 230 240 250
YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SANEFSETES MLKIAEDLGG
260 270 280 290 300
PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH
310 320 330 340 350
SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FHALGGWGEL
360 370 380 390 400
QNTIKTFGES HPFTKLVVDL KDVDPDVAYS SIPYEKGFAL LFYLEQLLGG
410 420 430 440 450
PEVFLGFLKA YVKKFSYQSV TTDDWKSFLY SHFKDKVDLL NQVDWNTWLY
460 470 480 490 500
APGLPPVKPN YDVTLTNACI ALSQRWVTAK EEDLSSFSIA DLKDLSSHQL
510 520 530 540 550
NEFLAQVLQK APLPLGHIKR MQEVYNFNAI NNSEIRFRWL RLCIQSKWEE
560 570 580 590 600
AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVHTYQ EHKASMHPVT
610
AMLVGRDLKV D
Length:611
Mass (Da):69,051
Last modified:July 27, 2011 - v4
Checksum:iCCF8D30F6FA9721E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti447T → A in AAB59675 (PubMed:1710117).Curated1
Sequence conflicti447T → A in AAH21417 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63848 mRNA Translation: AAB59675.1
AK134931 mRNA Translation: BAE22342.1
BC021417 mRNA Translation: AAH21417.1
CCDSiCCDS24125.1
PIRiJN0066
RefSeqiNP_001300826.1, NM_001313897.1
NP_032543.2, NM_008517.2
UniGeneiMm.271071

Genome annotation databases

EnsembliENSMUST00000016033; ENSMUSP00000016033; ENSMUSG00000015889
GeneIDi16993
KEGGimmu:16993
UCSCiuc007gur.1 mouse

Similar proteinsi

Entry informationi

Entry nameiLKHA4_MOUSE
AccessioniPrimary (citable) accession number: P24527
Secondary accession number(s): Q3UY71, Q8VDR8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 172 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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