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 pulmon... See more...

Aliases for LTA4H Gene

Aliases for LTA4H Gene

  • Leukotriene A4 Hydrolase 2 3 5
  • Leukotriene A-4 Hydrolase 3 4
  • LTA-4 Hydrolase 3 4
  • Testicular Secretory Protein Li 27 3
  • Leukotriene A(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. Diseases associated with LTA4H include Tuberculous Meningitis and Intestinal Tuberculosis. Among its related pathways are Innate Immune System and Eicosanoid Synthesis. Gene Ontology (GO) annotations related to this gene include peptidase activity. An important paralog of this gene is RNPEP.

UniProtKB/Swiss-Prot Summary 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.

Additional gene information for LTA4H Gene

No data available for CIViC Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LTA4H Gene

Genomics for LTA4H Gene

GeneHancer (GH) Regulatory Elements for LTA4H Gene

Promoters and enhancers for LTA4H Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LTA4H on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LTA4H

Top Transcription factor binding sites by QIAGEN in the LTA4H gene promoter:
  • AML1a
  • COUP
  • COUP-TF
  • HFH-1
  • HOXA3
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4

Genomic Locations for LTA4H Gene

Genomic Locations for LTA4H Gene
chr12:96,000,753-96,043,520
(GRCh38/hg38)
Size:
42,768 bases
Orientation:
Minus strand
chr12:96,394,606-96,437,298
(GRCh37/hg19)
Size:
42,693 bases
Orientation:
Minus strand

Genomic View for LTA4H Gene

Genes around LTA4H on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LTA4H Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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;
    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

Post-translational modifications for LTA4H Gene

  • Phosphorylation at Ser-416 inhibits enzymatic activity.
  • Ubiquitination at Lys20, Lys64, Lys73, Lys58, Lys83, Lys127, Lys225, Lys355, Lys414, Lys418, Lys480, Lys493, Lys557, Lys573, Lys580, and Lys593
  • Modification sites at PhosphoSitePlus

Other Protein References for LTA4H Gene

No data available for DME Specific Peptides for LTA4H Gene

Domains & Families for LTA4H Gene

Gene Families for LTA4H Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for LTA4H Gene

Suggested Antigen Peptide Sequences for LTA4H Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ51712, moderately similar to Leukotriene A-4 hydrolase (EC 3.3.2.6) (B4DEH5_HUMAN)
  • Leukotriene A(4) hydrolase (LKHA4_HUMAN)
  • LTA4H protein (Q49AK0_HUMAN)

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

UniProtKB/Swiss-Prot Function:
Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + leukotriene A4 = leukotriene B4; Xref=Rhea:RHEA:22324, ChEBI:CHEBI:15377, ChEBI:CHEBI:57461, ChEBI:CHEBI:57463; EC=3.3.2.6; Evidence={ECO:0000269 PubMed:11917124, ECO:0000269 PubMed:12207002, ECO:0000269 PubMed:15078870, ECO:0000269 PubMed:18804029, ECO:0000269 PubMed:1897988, ECO:0000269 PubMed:7667299};.
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.
GENATLAS Biochemistry:
leukotriene A4 hydrolase,highly expressed in spleen,lung,small intestine

Enzyme Numbers (IUBMB) for LTA4H Gene

Phenotypes From GWAS Catalog for LTA4H Gene

Gene Ontology (GO) - Molecular Function for LTA4H Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22658674
GO:0004177 aminopeptidase activity IDA 9774412
GO:0004301 epoxide hydrolase activity TAS,IBA 11154734
GO:0004463 leukotriene-A4 hydrolase activity IBA,IDA 9774412
GO:0005515 protein binding IPI 21044950
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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LTA4H

No data available for Human Phenotype Ontology , 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LTA4H gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 4
plasma membrane 2
cytoskeleton 2
mitochondrion 2
lysosome 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for LTA4H Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
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

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 IEA --
GO:0006691 leukotriene metabolic process TAS --
GO:0019370 leukotriene biosynthetic process IMP,IBA 11675384
GO:0042759 long-chain fatty acid biosynthetic process TAS --
GO:0043171 peptide catabolic process IDA 9774412
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

(52) Drugs for LTA4H Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Captopril Approved Pharma Inhibition, Inhibitor, Target, inhibitor ACE inhibitor, ACE inhibitor; also inhibits LTA4 hydrolase 43
Dexamethasone Approved, Investigational, Vet_approved Pharma Agonist Anti-inflammatory glucocorticoid 2756
Montelukast Approved Pharma Antagonist 291
Dexamethasone acetate Approved, Investigational, Vet_approved Pharma 2756
Water Approved Pharma 0

(13) Additional Compounds for LTA4H Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
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
  • (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
  • 5(S)-5,6-oxido-7,9-trans-11,14-cis-Eicosatetraenoic acid
72059-45-1

(1) Tocris Compounds for LTA4H Gene

Compound Action Cas Number
SC 57461A Selective inhibitor of LTA4 hydrolase 423169-68-0

(2) ApexBio Compounds for LTA4H Gene

Compound Action Cas Number
Bestatin Aminopeptidase inhibitor 58970-76-6
SC 57461A LTA4 hydrolase inhibitor,potent and selective 423169-68-0
genes like me logo Genes that share compounds with LTA4H: view

Transcripts for LTA4H Gene

mRNA/cDNA for LTA4H Gene

3 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LTA4H

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

Expression for LTA4H Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE 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, MaxQB, and MOPED for LTA4H Gene



Protein tissue co-expression partners for LTA4H Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LTA4H

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.

Evidence on tissue expression from TISSUES for LTA4H Gene

  • Lung(4.8)
  • Nervous system(4.7)
  • Eye(4.4)
  • Liver(4.4)
  • Kidney(3.6)
  • Intestine(3.2)
  • Blood(3.1)
  • Heart(2.3)
  • Muscle(2.1)
  • Spleen(2)
genes like me logo Genes that share expression patterns with LTA4H: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
chimpanzee
(Pan troglodytes)
Mammalia LTA4H 31 30
  • 99.84 (n)
OneToOne
dog
(Canis familiaris)
Mammalia LTA4H 31 30
  • 90.78 (n)
OneToOne
cow
(Bos Taurus)
Mammalia LTA4H 31 30
  • 90.45 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Lta4h 17 31 30
  • 87.23 (n)
rat
(Rattus norvegicus)
Mammalia Lta4h 30
  • 86.25 (n)
oppossum
(Monodelphis domestica)
Mammalia LTA4H 31
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LTA4H 31
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves LTA4H 31 30
  • 74.74 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LTA4H 31
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia lta4h 30
  • 68.37 (n)
zebrafish
(Danio rerio)
Actinopterygii lta4h 31 30
  • 64.92 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009907 30
  • 54.17 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG10602 31 32 30
  • 51.29 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea ZC416.6 31 32 30
  • 53.14 (n)
OneToMany
C42C1.11 31
  • 45 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes LAP2 33 31 30
  • 49.48 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F03883g 30
  • 48.53 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT5G13520 30
  • 46.71 (n)
rice
(Oryza sativa)
Liliopsida Os03g0819100 30
  • 46.1 (n)
wheat
(Triticum aestivum)
Liliopsida Ta.27066 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 50 (a)
OneToOne
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPCC1322.05c 30
  • 49.1 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU06732 30
  • 48.17 (n)
Species where no ortholog for LTA4H was found in the sources mined by GeneCards:
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for LTA4H: view image

Paralogs for LTA4H Gene

Paralogs for LTA4H Gene

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

  • LKHA4_HUMAN
  • B4DEH5_HUMAN
  • Q49AK0_HUMAN
genes like me logo Genes that share paralogs with LTA4H: view

Variants for LTA4H Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LTA4H Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
718032 Likely Benign: not provided 96,029,065(-) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
718094 Benign: not provided 96,006,401(-) T/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
718095 Benign: not provided 96,029,046(-) C/G INTRON_VARIANT
786610 Benign: not provided 96,013,217(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
786932 Benign: not provided 96,014,985(-) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for LTA4H Gene

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

Variant ID Type Subtype PubMed ID
esv3630445 CNV gain 21293372
esv3630446 CNV loss 21293372
nsv523292 CNV gain 19592680
nsv7234 OTHER inversion 18451855

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)

Additional Variant Information for LTA4H Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
LTA4H

SNP Genotyping and Copy Number Assay Products

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

Disorders for LTA4H Gene

MalaCards: The human disease database

(10) MalaCards diseases for LTA4H Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
tuberculous meningitis
  • tbm
intestinal tuberculosis
  • tuberculosis of intestine
intracranial chondrosarcoma
meningitis
central nervous system tuberculosis
  • intracranial tuberculoma
- elite association - COSMIC cancer census association via MalaCards
Search LTA4H in MalaCards View complete list of genes associated with diseases

Additional Disease Information for LTA4H

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

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

Publications for LTA4H Gene

  1. Cloning and characterization of the human leukotriene A4 hydrolase gene. (PMID: 7628486) Mancini JA … Evans JF (European journal of biochemistry 1995) 2 3 4 23 54
  2. The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos. (PMID: 20067482) Via M … Genetics of Asthma in Latino Americans (GALA) Study (Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2010) 3 23 41 54
  3. 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. (PMID: 19214143) Tantisira KG … Weiss ST (Pharmacogenetics and genomics 2009) 3 23 41 54
  4. Genetic effects in the leukotriene biosynthesis pathway and association with atherosclerosis. (PMID: 19130089) Crosslin DR … Hauser ER (Human genetics 2009) 3 23 41 54
  5. Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene. (PMID: 19622707) Zhao J … Vaccarino V (Psychosomatic medicine 2009) 3 23 41 54

Products for LTA4H Gene

Sources for LTA4H Gene