UniProtKB - P24527 (LKHA4_MOUSE)
Protein
Leukotriene A-4 hydrolase
Gene
Lta4h
Organism
Mus musculus (Mouse)
Status
Functioni
Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities (By similarity). Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the proinflammatory mediator leukotriene B4 (LTB4) (PubMed:1881903, PubMed:9287304). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (By similarity). In addition to its proinflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (By similarity).By similarity3 Publications
Catalytic activityi
- EC:3.3.2.62 PublicationsThis reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forwardBy similarity direction.
- (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O = 18S-resolvin E1By similarityThis reaction proceeds in the forwardBy similarity direction.
- Release of the N-terminal residue from a tripeptide.2 Publications EC:3.4.11.4
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Activity regulationi
Inhibited by bestatin (By similarity). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:9287304). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (By similarity).By similarity1 Publication
Kineticsi
- KM=5 µM for leukotriene A41 Publication
- KM=1.59 µM for Pro-Gly-Pro1 Publication
- Vmax=1030 nmol/min/mg enzyme for leukotriene A41 Publication
: leukotriene B4 biosynthesis Pathwayi
This protein is involved in the pathway leukotriene B4 biosynthesis, which is part of Lipid metabolism.2 PublicationsView all proteins of this organism that are known to be involved in the pathway leukotriene B4 biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 296 | Zinc; catalyticBy similarity | 1 | |
Active sitei | 297 | Proton acceptorBy similarity | 1 | |
Metal bindingi | 300 | Zinc; catalyticBy similarity | 1 | |
Metal bindingi | 319 | Zinc; catalyticBy similarity | 1 | |
Sitei | 376 | Essential for epoxide hydrolase activity, but not for aminopeptidase activityBy similarity | 1 | |
Sitei | 379 | Covalently modified during suicide inhibition by leukotrienesBy similarity | 1 | |
Active sitei | 384 | Proton donorBy similarity | 1 |
GO - Molecular functioni
- aminopeptidase activity Source: UniProtKB
- epoxide hydrolase activity Source: UniProtKB
- leukotriene-A4 hydrolase activity Source: UniProtKB
- metalloaminopeptidase activity Source: MGI
- tripeptide aminopeptidase activity Source: UniProtKB-EC
- zinc ion binding Source: UniProtKB
GO - Biological processi
- cellular lipid metabolic process Source: GO_Central
- cellular protein metabolic process Source: MGI
- leukotriene biosynthetic process Source: UniProtKB
- leukotriene metabolic process Source: MGI
- peptide catabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Biological process | Leukotriene biosynthesis |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-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 |
UniPathwayi | UPA00878 |
Protein family/group databases
MEROPSi | M01.004 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Lta4h |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:96836, Lta4h |
Subcellular locationi
Other locations
- Cytoplasm By similarity
Cytosol
- cytosol Source: MGI
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- cytoplasm Source: MGI
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Disruption phenotypei
Deficient mice have normal phenotypes. Inflammatory reactions are reduced as are some other immunological responses.2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 296 | H → Y: Complete loss of LTA4 hydrolase and peptidase enzyme activities. 1 Publication | 1 | |
Mutagenesisi | 300 | H → Y: Complete loss of LTA4 hydrolase and peptidase enzyme activities. 1 Publication | 1 | |
Mutagenesisi | 319 | E → Q: Complete loss of LTA4 hydrolase and peptidase enzyme activities. 1 Publication | 1 | |
Mutagenesisi | 384 | Y → F, H or Q: Alters leukotriene hydrolase activity, strongly enhancing the formation of a metabolite that is normally produced in trace amounts. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3738 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000095125 | 1 – 611 | Leukotriene A-4 hydrolaseAdd BLAST | 611 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 73 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 337 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 414 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 416 | PhosphoserineBy similarity | 1 | |
Modified residuei | 573 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity.By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P24527 |
jPOSTi | P24527 |
MaxQBi | P24527 |
PaxDbi | P24527 |
PeptideAtlasi | P24527 |
PRIDEi | P24527 |
PTM databases
iPTMneti | P24527 |
PhosphoSitePlusi | P24527 |
SwissPalmi | P24527 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000015889, Expressed in bone marrow and 318 other tissues |
Genevisiblei | P24527, MM |
Interactioni
Subunit structurei
Monomer.
By similarityProtein-protein interaction databases
BioGRIDi | 201217, 12 interactors |
IntActi | P24527, 3 interactors |
MINTi | P24527 |
STRINGi | 10090.ENSMUSP00000016033 |
Chemistry databases
BindingDBi | P24527 |
Miscellaneous databases
RNActi | P24527, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 135 – 137 | Substrate bindingBy similarity | 3 | |
Regioni | 267 – 272 | Substrate bindingBy similarity | 6 | |
Regioni | 564 – 566 | Substrate bindingBy similarity | 3 |
Sequence similaritiesi
Belongs to the peptidase M1 family.Curated
Phylogenomic databases
eggNOGi | KOG1047, Eukaryota |
GeneTreei | ENSGT00940000156375 |
HOGENOMi | CLU_014505_0_0_1 |
InParanoidi | P24527 |
OMAi | NSNFRMK |
OrthoDBi | 775595at2759 |
TreeFami | TF300758 |
Family and domain databases
CDDi | cd09599, M1_LTA4H, 1 hit |
Gene3Di | 1.10.390.10, 1 hit 1.25.40.320, 1 hit 2.60.40.1730, 1 hit |
InterProi | View protein in InterPro IPR042097, Aminopeptidase_N-like_N IPR016024, ARM-type_fold IPR012777, LTA4H IPR038502, M1_LTA-4_hydro/amino_C_sf IPR034015, M1_LTA4H IPR001930, Peptidase_M1 IPR015211, Peptidase_M1_C IPR014782, Peptidase_M1_dom IPR027268, Peptidase_M4/M1_CTD_sf |
PANTHERi | PTHR45726, PTHR45726, 1 hit |
Pfami | View protein in Pfam PF09127, Leuk-A4-hydro_C, 1 hit PF01433, Peptidase_M1, 1 hit |
PRINTSi | PR00756, ALADIPTASE |
SMARTi | View protein in SMART SM01263, Leuk-A4-hydro_C, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit SSF63737, SSF63737, 1 hit |
TIGRFAMsi | TIGR02411, leuko_A4_hydro, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
i Sequence
Sequence statusi: Complete.
P24527-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 447 | T → A in AAB59675 (PubMed:1710117).Curated | 1 | |
Sequence conflicti | 447 | T → A in AAH21417 (PubMed:15489334).Curated | 1 |
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 |
CCDSi | CCDS24125.1 |
PIRi | JN0066 |
RefSeqi | NP_001300826.1, NM_001313897.1 NP_032543.2, NM_008517.2 |
Genome annotation databases
Ensembli | ENSMUST00000016033; ENSMUSP00000016033; ENSMUSG00000015889 |
GeneIDi | 16993 |
KEGGi | mmu:16993 |
UCSCi | uc007gur.1, mouse |
Similar proteinsi
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 |
CCDSi | CCDS24125.1 |
PIRi | JN0066 |
RefSeqi | NP_001300826.1, NM_001313897.1 NP_032543.2, NM_008517.2 |
3D structure databases
SMRi | P24527 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 201217, 12 interactors |
IntActi | P24527, 3 interactors |
MINTi | P24527 |
STRINGi | 10090.ENSMUSP00000016033 |
Chemistry databases
BindingDBi | P24527 |
ChEMBLi | CHEMBL3738 |
Protein family/group databases
MEROPSi | M01.004 |
PTM databases
iPTMneti | P24527 |
PhosphoSitePlusi | P24527 |
SwissPalmi | P24527 |
Proteomic databases
EPDi | P24527 |
jPOSTi | P24527 |
MaxQBi | P24527 |
PaxDbi | P24527 |
PeptideAtlasi | P24527 |
PRIDEi | P24527 |
Protocols and materials databases
Antibodypediai | 4453, 490 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000016033; ENSMUSP00000016033; ENSMUSG00000015889 |
GeneIDi | 16993 |
KEGGi | mmu:16993 |
UCSCi | uc007gur.1, mouse |
Organism-specific databases
CTDi | 4048 |
MGIi | MGI:96836, Lta4h |
Phylogenomic databases
eggNOGi | KOG1047, Eukaryota |
GeneTreei | ENSGT00940000156375 |
HOGENOMi | CLU_014505_0_0_1 |
InParanoidi | P24527 |
OMAi | NSNFRMK |
OrthoDBi | 775595at2759 |
TreeFami | TF300758 |
Enzyme and pathway databases
UniPathwayi | UPA00878 |
Reactomei | R-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 |
Miscellaneous databases
BioGRID-ORCSi | 16993, 2 hits in 18 CRISPR screens |
ChiTaRSi | Lta4h, mouse |
PROi | PR:P24527 |
RNActi | P24527, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000015889, Expressed in bone marrow and 318 other tissues |
Genevisiblei | P24527, MM |
Family and domain databases
CDDi | cd09599, M1_LTA4H, 1 hit |
Gene3Di | 1.10.390.10, 1 hit 1.25.40.320, 1 hit 2.60.40.1730, 1 hit |
InterProi | View protein in InterPro IPR042097, Aminopeptidase_N-like_N IPR016024, ARM-type_fold IPR012777, LTA4H IPR038502, M1_LTA-4_hydro/amino_C_sf IPR034015, M1_LTA4H IPR001930, Peptidase_M1 IPR015211, Peptidase_M1_C IPR014782, Peptidase_M1_dom IPR027268, Peptidase_M4/M1_CTD_sf |
PANTHERi | PTHR45726, PTHR45726, 1 hit |
Pfami | View protein in Pfam PF09127, Leuk-A4-hydro_C, 1 hit PF01433, Peptidase_M1, 1 hit |
PRINTSi | PR00756, ALADIPTASE |
SMARTi | View protein in SMART SM01263, Leuk-A4-hydro_C, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit SSF63737, SSF63737, 1 hit |
TIGRFAMsi | TIGR02411, leuko_A4_hydro, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LKHA4_MOUSE | |
Accessioni | P24527Primary (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: | February 10, 2021 | |
This is version 190 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families