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Protein

Leukotriene A-4 hydrolase

Gene

Lta4h

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi296 – 2961Zinc; catalytic
Active sitei297 – 2971Proton acceptorPROSITE-ProRule annotation
Metal bindingi300 – 3001Zinc; catalytic
Metal bindingi319 – 3191Zinc; catalytic
Sitei376 – 3761Essential for epoxide hydrolase activity, but not for aminopeptidase activityBy similarity
Sitei379 – 3791Covalently modified during suicide inhibition by leukotrienesBy similarity
Active sitei384 – 3841Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Leukotriene biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96836. Lta4h.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi296 – 2961H → Y: Complete loss of activity. 1 Publication
Mutagenesisi300 – 3001H → Y: Complete loss of activity. 1 Publication
Mutagenesisi319 – 3191E → Q: Complete loss of activity. 1 Publication
Mutagenesisi384 – 3841Y → F, H or Q: Alters leukotriene hydrolase activity, strongly enhancing the formation of a metabolite that is normally produced in trace amounts. 1 Publication

Chemistry

ChEMBLiCHEMBL3738.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 611610Leukotriene A-4 hydrolasePRO_0000095125Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei73 – 731N6-acetyllysineBy similarity
Modified residuei337 – 3371N6-acetyllysineBy similarity
Modified residuei414 – 4141N6-acetyllysineBy similarity
Modified residuei416 – 4161PhosphoserineBy similarity
Modified residuei573 – 5731N6-acetyllysineBy similarity

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.
PhosphoSiteiP24527.
SwissPalmiP24527.

Expressioni

Gene expression databases

BgeeiENSMUSG00000015889.
CleanExiMM_LTA4H.
GenevisibleiP24527. MM.

Interactioni

Protein-protein interaction databases

IntActiP24527. 3 interactions.
MINTiMINT-1868661.
STRINGi10090.ENSMUSP00000016033.

Chemistry

BindingDBiP24527.

Structurei

3D structure databases

ProteinModelPortaliP24527.
SMRiP24527. Positions 6-610.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni135 – 1373Substrate bindingBy similarity
Regioni267 – 2726Substrate bindingBy similarity
Regioni564 – 5663Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the peptidase M1 family.Curated

Phylogenomic databases

eggNOGiKOG1047. Eukaryota.
COG0308. LUCA.
GeneTreeiENSGT00530000063003.
HOGENOMiHOG000293296.
HOVERGENiHBG001274.
InParanoidiP24527.
KOiK01254.
OMAiEFANSNF.
OrthoDBiEOG091G02UX.
TreeFamiTF300758.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
SMARTiSM01263. Leuk-A4-hydro_C. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
TIGRFAMsiTIGR02411. leuko_A4_hydro. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti447 – 4471T → A in AAB59675 (PubMed:1710117).Curated
Sequence conflicti447 – 4471T → A in AAH21417 (PubMed:15489334).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP24527.
SMRiP24527. Positions 6-610.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP24527. 3 interactions.
MINTiMINT-1868661.
STRINGi10090.ENSMUSP00000016033.

Chemistry

BindingDBiP24527.
ChEMBLiCHEMBL3738.

Protein family/group databases

MEROPSiM01.004.

PTM databases

iPTMnetiP24527.
PhosphoSiteiP24527.
SwissPalmiP24527.

Proteomic databases

EPDiP24527.
MaxQBiP24527.
PaxDbiP24527.
PeptideAtlasiP24527.
PRIDEiP24527.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4048.
MGIiMGI:96836. Lta4h.

Phylogenomic databases

eggNOGiKOG1047. Eukaryota.
COG0308. LUCA.
GeneTreeiENSGT00530000063003.
HOGENOMiHOG000293296.
HOVERGENiHBG001274.
InParanoidiP24527.
KOiK01254.
OMAiEFANSNF.
OrthoDBiEOG091G02UX.
TreeFamiTF300758.

Enzyme and pathway databases

UniPathwayiUPA00878.
ReactomeiR-MMU-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Miscellaneous databases

ChiTaRSiLta4h. mouse.
PROiP24527.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000015889.
CleanExiMM_LTA4H.
GenevisibleiP24527. MM.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
SMARTiSM01263. Leuk-A4-hydro_C. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
TIGRFAMsiTIGR02411. leuko_A4_hydro. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLKHA4_MOUSE
AccessioniPrimary (citable) accession number: P24527
Secondary accession number(s): Q3UY71, Q8VDR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 159 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.