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Aliases for LTA4H Gene

Aliases for LTA4H Gene

  • Leukotriene A4 Hydrolase 2 3
  • Leukotriene A(4) Hydrolase 4
  • LTA-4 Hydrolase 4
  • EC 3.3.2.6 4
  • LTA4 4

External Ids for LTA4H Gene

Previous GeneCards Identifiers for LTA4H Gene

  • GC12M095829
  • GC12M096758
  • GC12M096327
  • GC12M094897
  • GC12M093456
  • GC12M096394

Summaries for LTA4H Gene

Entrez Gene Summary for LTA4H Gene

  • The protein encoded by this gene is an enzyme that contains both hydrolase and aminopeptidase activities. The hydrolase activity is used in the final step of the biosynthesis of leukotriene B4, a proinflammatory mediator. The aminopeptidase activity has been shown to degrade proline-glycine-proline (PGP), a neutrophil chemoattractant and biomarker for chronic obstructive pulmonary disease (COPD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

GeneCards Summary for LTA4H Gene

LTA4H (Leukotriene A4 Hydrolase) is a Protein Coding gene. Among its related pathways are Metabolism and Linoleic acid metabolism. GO annotations related to this gene include poly(A) RNA binding and peptidase activity. An important paralog of this gene is C9orf3.

UniProtKB/Swiss-Prot for LTA4H Gene

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

Tocris Summary for LTA4H Gene

  • Leukotriene A4 hydrolase, (LTA4 hydrolase, LTA4H) is a zinc-dependent epoxide hydrolase which hydrolyzes LTA4 to form LTB4 during leukotriene biosynthesis. The enzyme is the only member of the leukotriene biosynthetic pathway which is mainly cytoplasmic.

No data available for Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LTA4H Gene

Genomics for LTA4H Gene

Regulatory Elements for LTA4H Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for LTA4H Gene

Chromosome:
12
Start:
96,000,753 bp from pter
End:
96,043,520 bp from pter
Size:
42,768 bases
Orientation:
Minus strand

Genomic View for LTA4H Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for LTA4H Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LTA4H Gene

Proteins for LTA4H Gene

  • Protein details for LTA4H Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P09960-LKHA4_HUMAN
    Recommended name:
    Leukotriene A-4 hydrolase
    Protein Accession:
    P09960
    Secondary Accessions:
    • B4DNQ9
    • F8VV40
    • Q6IAT6
    • Q9UCT7

    Protein attributes for LTA4H Gene

    Size:
    611 amino acids
    Molecular mass:
    69285 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
    Quaternary structure:
    • Monomer.

    Three dimensional structures from OCA and Proteopedia for LTA4H Gene

    Alternative splice isoforms for LTA4H Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LTA4H Gene

Proteomics data for LTA4H Gene at MOPED

Post-translational modifications for LTA4H Gene

  • Phosphorylation at Ser-416 inhibits enzymatic activity.
  • Ubiquitination at Lys 20, Lys 58, Lys 64, Lys 73, Lys 83, Lys 127, Lys 225, Lys 355, Lys 414, Lys 418, Lys 480, Lys 493, Lys 557, Lys 573, Lys 580, and Lys 593
  • Modification sites at PhosphoSitePlus

Other Protein References for LTA4H Gene

Antibody Products

  • R&D Systems Antibodies for LTA4H (Leukotriene A4 Hydrolase/LTA4H)

No data available for DME Specific Peptides for LTA4H Gene

Domains & Families for LTA4H Gene

Graphical View of Domain Structure for InterPro Entry

P09960

UniProtKB/Swiss-Prot:

LKHA4_HUMAN :
  • Belongs to the peptidase M1 family.
Family:
  • Belongs to the peptidase M1 family.
genes like me logo Genes that share domains with LTA4H: view

Function for LTA4H Gene

Molecular function for LTA4H Gene

GENATLAS Biochemistry:
leukotriene A4 hydrolase,highly expressed in spleen,lung,small intestine
UniProtKB/Swiss-Prot CatalyticActivity:
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H(2)O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4, due to the formation of a covalent adduct at Tyr-379.
UniProtKB/Swiss-Prot Function:
Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.

Enzyme Numbers (IUBMB) for LTA4H Gene

Gene Ontology (GO) - Molecular Function for LTA4H Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004177 aminopeptidase activity IDA 15078870
GO:0004301 epoxide hydrolase activity TAS 11154734
GO:0004463 leukotriene-A4 hydrolase activity TAS --
GO:0005488 binding --
GO:0005515 protein binding --
genes like me logo Genes that share ontologies with LTA4H: view
genes like me logo Genes that share phenotypes with LTA4H: view

Animal Models for LTA4H Gene

MGI Knock Outs for LTA4H:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for LTA4H

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for LTA4H Gene

Localization for LTA4H Gene

Subcellular locations from UniProtKB/Swiss-Prot for LTA4H Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for LTA4H Gene COMPARTMENTS Subcellular localization image for LTA4H gene
Compartment Confidence
extracellular 5
cytosol 4
nucleus 4

Gene Ontology (GO) - Cellular Components for LTA4H Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with LTA4H: view

Pathways & Interactions for LTA4H Gene

genes like me logo Genes that share pathways with LTA4H: view

Pathways by source for LTA4H Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

UniProtKB/Swiss-Prot P09960-LKHA4_HUMAN

  • Pathway: Lipid metabolism; leukotriene B4 biosynthesis

Gene Ontology (GO) - Biological Process for LTA4H Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IBA --
GO:0006691 leukotriene metabolic process TAS --
GO:0006954 inflammatory response NAS 11175901
GO:0010043 response to zinc ion IEA --
GO:0019369 arachidonic acid metabolic process TAS --
genes like me logo Genes that share ontologies with LTA4H: view

No data available for SIGNOR curated interactions for LTA4H Gene

Drugs & Compounds for LTA4H Gene

(33) Drugs for LTA4H Gene - From: NovoSeek, HMDB, DrugBank, IUPHAR, ApexBio, DGIdb, PharmGKB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Captopril Approved Pharma Inhibition, Inhibitor, Target ACE inhibitor, ACE inhibitor; also inhibits LTA4 hydrolase 28
Montelukast Approved Pharma Antagonist 257
Dexamethasone Approved, Investigational Pharma Agonist 1806
Zileuton Approved, Investigational, Withdrawn Pharma Inhibition, Inhibitor 5-lipoxygenase (5-LOX) inhibitor, orally active 20
Zinc Approved Pharma 1404

(16) Additional Compounds for LTA4H Gene - From: HMDB and NovoSeek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Leukotriene B4
  • (6z,8e,10e,14z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate
  • (6z,8e,10e,14z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoic acid
  • 5,12-DiHETE
  • 5,12-Dihydroxy-6,10-trans -8,14-cis -eicosatetraenoate
  • 5,12-Dihydroxy-6,10-trans -8,14-cis -eicosatetraenoic acid
71160-24-2
12-Keto-tetrahydro-leukotriene B4
  • 12-Keto-10,11,14,15-tetrahydro-LTB4
  • 5S-Hydroxy-12-keto-6Z,8E-eicosadienoate
  • 5S-Hydroxy-12-keto-6Z,8E-eicosadienoic acid
Leukotriene A4
  • (5S,6S,7E,9E,11Z,14Z)-5,6-Epoxyicosa-7,9,11,14-tetraenoate
  • (5S,6S,7E,9E,11Z,14Z)-5,6-Epoxyicosa-7,9,11,14-tetraenoic acid
  • (7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyeicosa-7,9,11,14-tetraenoate
  • (7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyeicosa-7,9,11,14-tetraenoic acid
  • (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa- 7,9,11,14-tetraenoate
72059-45-1
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
12-hydroxyeicosatetraenoic acid
genes like me logo Genes that share compounds with LTA4H: view

Drug Products

Transcripts for LTA4H Gene

Unigene Clusters for LTA4H Gene

Leukotriene A4 hydrolase:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for LTA4H

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for LTA4H Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23a ·
SP1: - - - -
SP2: -
SP3: - - - -
SP4: - - -
SP5:
SP6:
SP7:

ExUns: 23b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:

Relevant External Links for LTA4H Gene

GeneLoc Exon Structure for
LTA4H
ECgene alternative splicing isoforms for
LTA4H

Expression for LTA4H Gene

mRNA expression in normal human tissues for LTA4H Gene

mRNA differential expression in normal tissues according to GTEx for LTA4H Gene

This gene is overexpressed in Whole Blood (x8.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for LTA4H Gene



SOURCE GeneReport for Unigene cluster for LTA4H Gene Hs.524648

mRNA Expression by UniProt/SwissProt for LTA4H Gene

P09960-LKHA4_HUMAN
Tissue specificity: Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts
genes like me logo Genes that share expression patterns with LTA4H: view

Protein tissue co-expression partners for LTA4H Gene

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein differential expression in normal tissues for LTA4H Gene

Orthologs for LTA4H Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for LTA4H Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia LTA4H 35
  • 90.45 (n)
  • 93.78 (a)
LTA4H 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LTA4H 35
  • 90.78 (n)
  • 94.76 (a)
LTA4H 36
  • 83 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Lta4h 35
  • 87.23 (n)
  • 92.8 (a)
Lta4h 16
Lta4h 36
  • 93 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia LTA4H 35
  • 99.84 (n)
  • 100 (a)
LTA4H 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Lta4h 35
  • 86.25 (n)
  • 93.29 (a)
oppossum
(Monodelphis domestica)
Mammalia LTA4H 36
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LTA4H 36
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves LTA4H 35
  • 74.74 (n)
  • 76.94 (a)
LTA4H 36
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LTA4H 36
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia lta4h 35
  • 68.37 (n)
  • 68.65 (a)
zebrafish
(Danio rerio)
Actinopterygii lta4h 35
  • 64.92 (n)
  • 63.93 (a)
lta4h 36
  • 64 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG10602 37
  • 44 (a)
CG10602 35
  • 51.29 (n)
  • 46.13 (a)
CG10602 36
  • 45 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009907 35
  • 54.17 (n)
  • 49.91 (a)
worm
(Caenorhabditis elegans)
Secernentea ZC416.6 37
  • 47 (a)
ZC416.6 35
  • 53.14 (n)
  • 48.25 (a)
C42C1.11 36
  • 45 (a)
OneToMany
ZC416.6 36
  • 46 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F03883g 35
  • 48.53 (n)
  • 43.5 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes LAP2 35
  • 49.48 (n)
  • 43.36 (a)
LAP2 36
  • 37 (a)
OneToMany
LAP2 38
thale cress
(Arabidopsis thaliana)
eudicotyledons AT5G13520 35
  • 46.71 (n)
  • 37.66 (a)
rice
(Oryza sativa)
Liliopsida Os03g0819100 35
  • 46.1 (n)
  • 36.66 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.27066 35
bread mold
(Neurospora crassa)
Ascomycetes NCU06732 35
  • 48.17 (n)
  • 40.72 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPCC1322.05c 35
  • 49.1 (n)
  • 42.43 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 50 (a)
OneToOne
Species with no ortholog for LTA4H:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for LTA4H Gene

ENSEMBL:
Gene Tree for LTA4H (if available)
TreeFam:
Gene Tree for LTA4H (if available)

Paralogs for LTA4H Gene

Paralogs for LTA4H Gene

(2) SIMAP similar genes for LTA4H Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with LTA4H: view

Variants for LTA4H Gene

Sequence variations from dbSNP and Humsavar for LTA4H Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs763874 -- 96,026,435(-) GATTT(A/G)TGAGT intron-variant
rs763875 -- 96,026,163(-) ATGGT(C/T)TTGGA intron-variant
rs763876 -- 96,026,256(-) CCTGG(A/G)TTTGG intron-variant
rs1978331 -- 96,015,423(-) CACAC(C/T)GTTCA intron-variant
rs1990611 -- 96,020,206(-) TCTTA(C/T)AGGCT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for LTA4H Gene

Variant ID Type Subtype PubMed ID
nsv7234 OTHER Inversion 18451855
nsv523292 CNV Gain 19592680

Variation tolerance for LTA4H Gene

Residual Variation Intolerance Score: 9.05% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.44; 42.92% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for LTA4H Gene

HapMap Linkage Disequilibrium report
LTA4H

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LTA4H Gene

Disorders for LTA4H Gene

Relevant External Links for LTA4H

Genetic Association Database (GAD)
LTA4H
Human Genome Epidemiology (HuGE) Navigator
LTA4H
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
LTA4H
genes like me logo Genes that share disorders with LTA4H: view

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for LTA4H Gene

Publications for LTA4H Gene

  1. Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors. (PMID: 12207002) Thunnissen M.M. … Haeggstrom J.Z. (FASEB J. 2002) 23 25 67
  2. Cloning and characterization of the human leukotriene A4 hydrolase gene. (PMID: 7628486) Mancini J.A. … Evans J.F. (Eur. J. Biochem. 1995) 2 23 67
  3. The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos. (PMID: 20067482) Via M. … GonzA!lez Burchard E. (Clin. Exp. Allergy 2010) 23 67
  4. Modulating the substrate specificity of LTA4H aminopeptidase by using chemical compounds and small-molecule-guided mutagenesis. (PMID: 20432426) Jiang X. … Lai L. (Chembiochem 2010) 23 67
  5. Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors. (PMID: 19042128) Enomoto H. … Ban M. (Bioorg. Med. Chem. Lett. 2009) 23 67

Products for LTA4H Gene

Sources for LTA4H Gene

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