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LTA4H leukotriene A4 hydrolase [ Homo sapiens (human) ]

Gene ID: 4048, updated on 3-Nov-2024

Summary

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Official Symbol
LTA4Hprovided by HGNC
Official Full Name
leukotriene A4 hydrolaseprovided by HGNC
Primary source
HGNC:HGNC:6710
See related
Ensembl:ENSG00000111144 MIM:151570; AllianceGenome:HGNC:6710
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
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]
Expression
Ubiquitous expression in lung (RPKM 63.8), bone marrow (RPKM 53.7) and 25 other tissues See more
Orthologs
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Genomic context

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See LTA4H in Genome Data Viewer
Location:
12q23.1
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (96000753..96043520, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (95974750..96017515, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (96394531..96437298, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene amidohydrolase domain containing 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:96350128-96350641 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:96350642-96351154 Neighboring gene AMDHD1 eExon liver enhancer Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:96363883-96364528 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:96364529-96365174 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31139 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 12:96379806 Neighboring gene histidine ammonia-lyase Neighboring gene uncharacterized LOC102723340 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31163 Neighboring gene Sharpr-MPRA regulatory region 10760 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6820 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31173 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31174 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31179 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31194 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6821 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4740 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6824 Neighboring gene tRNA-Asp (anticodon GTC) 2-8 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:96440866-96442065 Neighboring gene uncharacterized LOC124902990 Neighboring gene YPEL5 pseudogene 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. PENG: a neural gas-based approach for pharmacophore elucidation. method design, validation, and virtual screening for novel ligands of LTA4H. Moser D, et al. J Chem Inf Model, 2015 Feb 23. PMID 25625859
  2. Cold adaptation of enzymes: structural, kinetic and microcalorimetric characterizations of an aminopeptidase from the Arctic psychrophile Colwellia psychrerythraea and of human leukotriene A(4) hydrolase. Huston AL, et al. Biochim Biophys Acta, 2008 Nov. PMID 18599387
  3. Modulating the substrate specificity of LTA4H aminopeptidase by using chemical compounds and small-molecule-guided mutagenesis. Jiang X, et al. Chembiochem, 2010 May 17. PMID 20432426
  4. Association analysis of the LTA4H gene polymorphisms and pulmonary tuberculosis in 9115 subjects. Curtis J, et al. Tuberculosis (Edinb), 2011 Jan. PMID 21112816, Free PMC Article
  5. Structural origins for the loss of catalytic activities of bifunctional human LTA4H revealed through molecular dynamics simulations. Thangapandian S, et al. PLoS One, 2012. PMID 22848428, Free PMC Article

See all (135) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin.
    Title: Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin.
  2. Inhibition of Leukotriene A4 Hydrolase Suppressed Cartilage Degradation and Synovial Inflammation in a Mouse Model of Experimental Osteoarthritis.
    Title: Inhibition of Leukotriene A(4) Hydrolase Suppressed Cartilage Degradation and Synovial Inflammation in a Mouse Model of Experimental Osteoarthritis.
  3. LTA4H extensively associates with mRNAs and lncRNAs indicative of its novel regulatory targets.
    Title: LTA4H extensively associates with mRNAs and lncRNAs indicative of its novel regulatory targets.
  4. Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis.
    Title: Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis.
  5. Clinical Implications of LTA4H Genetic Polymorphism in Patients with Chronic Obstructive Pulmonary Disease.
    Title: Clinical Implications of LTA(4)H Genetic Polymorphism in Patients with Chronic Obstructive Pulmonary Disease.
  6. LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.
    Title: LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.
  7. Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.
    Title: Leukotriene A(4) Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.
  8. Identification of Human Leukotriene A4 Hydrolase Inhibitors Using Structure-Based Pharmacophore Modeling and Molecular Docking.
    Title: Identification of Human Leukotriene A4 Hydrolase Inhibitors Using Structure-Based Pharmacophore Modeling and Molecular Docking.
  9. the identification of FSCN1-binding partners enhances understanding of the mechanism of FSCN1-mediated malignant phenotypes, and these findings indicate that FSCN1 binds to AIMP1 and LTA4H might promote the progression of laryngeal squamous cell carcinoma .
    Title: Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1-Binding Proteins in Laryngeal Squamous Cell Carcinoma.
  10. Gliotoxin suppresses the biosynthesis of the potent neutrophil chemoattractant LTB4 by direct interference with LTA4H thereby impairing neutrophil functions in invasive aspergillosis.
    Title: Gliotoxin from Aspergillus fumigatus Abrogates Leukotriene B(4) Formation through Inhibition of Leukotriene A(4) Hydrolase.
Submit: New GeneRIF Correction See all GeneRIFs (43)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ17564

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables aminopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables aminopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables epoxide hydrolase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables epoxide hydrolase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables epoxide hydrolase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables epoxide hydrolase activity TAS
Traceable Author Statement
more info
 PubMed 
enables leukotriene-A4 hydrolase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables leukotriene-A4 hydrolase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metalloaminopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables peptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables tripeptide aminopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables zinc ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables zinc ion binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in leukotriene biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in leukotriene biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in leukotriene biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in lipid metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in peptide catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in peptide catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in response to peptide hormone IEA
Inferred from Electronic Annotation
more info
  
involved_in response to zinc ion IEA
Inferred from Electronic Annotation
more info
  
involved_in type I pneumocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in ficolin-1-rich granule lumen TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in tertiary granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
leukotriene A-4 hydrolase
Names
LTA-4 hydrolase
testicular secretory protein Li 27
tripeptide aminopeptidase LTA4H
NP_000886.1
NP_001243572.1
NP_001243573.1
NP_001401192.1
NP_001401193.1
NP_001401194.1
NP_001401195.1
XP_011536651.1
XP_047284803.1
XP_054228027.1
XP_054228028.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_000895.3 → NP_000886.1  leukotriene A-4 hydrolase isoform 1

    See identical proteins and their annotated locations for NP_000886.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    J03459, R41544
    Consensus CDS
    CCDS9059.1
    UniProtKB/Swiss-Prot
    B4DNQ9, F8VV40, P09960, Q6IAT6, Q9UCT7
    UniProtKB/TrEMBL
    A0A140VK27, B4DVZ8
    Related
    ENSP00000228740.2, ENST00000228740.7
    Conserved Domains (1) summary
    TIGR02411
    Location:6 → 608
    leuko_A4_hydro; leukotriene A-4 hydrolase/aminopeptidase

  2. NM_001256643.1 → NP_001243572.1  leukotriene A-4 hydrolase isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    BC032528, BX647158, DC358373, R41544
    Consensus CDS
    CCDS58267.1
    UniProtKB/TrEMBL
    B4DVZ8
    Related
    ENSP00000449958.1, ENST00000552789.5
    Conserved Domains (3) summary
    cd09599
    Location:30 → 426
    M1_LTA4H; Peptidase M1 family contains leukotriene A4 hydrolase
    TIGR02411
    Location:30 → 584
    leuko_A4_hydro; leukotriene A-4 hydrolase/aminopeptidase
    pfam09127
    Location:444 → 583
    Leuk-A4-hydro_C; Leukotriene A4 hydrolase, C-terminal

  3. NM_001256644.1 → NP_001243573.1  leukotriene A-4 hydrolase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, initiates translation at an alternate start codon and lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (3) is shorter and has distinct N- and C-termini, compared to isoform 1.
    Source sequence(s)
    AK298017, AK308184, R41544
    Consensus CDS
    CCDS58266.1
    UniProtKB/TrEMBL
    B4DVZ8
    Related
    ENSP00000395051.2, ENST00000413268.6
    Conserved Domains (2) summary
    cd09599
    Location:30 → 426
    M1_LTA4H; Peptidase M1 family contains leukotriene A4 hydrolase
    pfam09127
    Location:444 → 492
    Leuk-A4-hydro_C; Leukotriene A4 hydrolase, C-terminal

  4. NM_001414263.1 → NP_001401192.1  leukotriene A-4 hydrolase isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC007298

  5. NM_001414264.1 → NP_001401193.1  leukotriene A-4 hydrolase isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC007298

  6. NM_001414265.1 → NP_001401194.1  leukotriene A-4 hydrolase isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC007298

  7. NM_001414266.1 → NP_001401195.1  leukotriene A-4 hydrolase isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC007298

RNA

  1. NR_132659.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses two alternate splice junctions compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC007298, AI582379, AK293630, AK298017, R41544
    Related
    ENST00000548852.5

  2. NR_182265.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC007298

  3. NR_182266.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC007298

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    96000753..96043520 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047428847.1 → XP_047284803.1  leukotriene A-4 hydrolase isoform X1

  2. XM_011538349.4 → XP_011536651.1  leukotriene A-4 hydrolase isoform X2

    Conserved Domains (2) summary
    cd09599
    Location:6 → 450
    M1_LTA4H; Peptidase M1 family contains leukotriene A4 hydrolase
    pfam01433
    Location:21 → 387
    Peptidase_M1; Peptidase family M1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    95974750..96017515 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372052.1 → XP_054228027.1  leukotriene A-4 hydrolase isoform X1

  2. XM_054372053.1 → XP_054228028.1  leukotriene A-4 hydrolase isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P09960.2 GenPept UniProtKB/Swiss-Prot:P09960

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