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    LTA4H leukotriene A4 hydrolase [ Homo sapiens (human) ]

    Gene ID: 4048, updated on 27-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
    mouse all
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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
    • 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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    NEW Try the new Transcript table

    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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