Lta4h leukotriene A4 hydrolase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Lta4hprovided by MGI
Official Full Name: leukotriene A4 hydrolaseprovided by MGI
Primary source: MGI:MGI:96836
See related: Ensembl:ENSMUSG00000015889 AllianceGenome:MGI:96836
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
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). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
Expression: Ubiquitous expression in large intestine adult (RPKM 63.2), duodenum adult (RPKM 45.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C2; 10 48.42 cM

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (93289258..93320758)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (93453396..93484896)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Leukotriene A4 hydrolase inhibition improves age-related cognitive decline via modulation of synaptic function.
Title: Leukotriene A4 hydrolase inhibition improves age-related cognitive decline via modulation of synaptic function.
Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.
Title: Leukotriene A(4) hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.
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.
LTA4H is the major Pro-Gly-Pro degrading enzyme.
Title: Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors.
These findings indicate that LTA4H is critical for skin carcinogenesis and is an important mediator of cell cycle and the data begin to clarify the mechanisms of LTA4H's role in cancer development.
Title: LTA4H regulates cell cycle and skin carcinogenesis.
There is a critical role for the secondary anti-inflammatory activity of LTA4H in acute pulmonary infection.
Title: Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection.
CS exposure promotes the development of CS-induced emphysema by suppressing the enzymatic activities of the LTA4H aminopeptidase in lung tissues and accumulating PGP and neutrophils in the airspaces.
Title: Role of leukotriene A4 hydrolase aminopeptidase in the pathogenesis of emphysema.
in acute neutrophil-driven lung inflammation, PGP was degraded by LTA(4)H which facilitated resolution of inflammation; cigarette smoke, a major risk factor for COPD,inhibited LTA(4)H aminopeptidase activity leading to accumulation of PGP and neutrophils
Title: A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation.
In the mouse nervous system ,Immunoreactivity for leukotriene A4 hydrolase showed widespread distribution with preference to the sensory-associated structures.
Title: Sensory system-predominant distribution of leukotriene A4 hydrolase and its colocalization with calretinin in the mouse nervous system.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (8) 1 citation
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

48.MMHAP76FLH6.seq (e-PCR)
- UniSTS:124700

RH141007 (e-PCR)
- UniSTS:223007

Lta4h (e-PCR), detects polymorphism
- UniSTS:507037

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables aminopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables aminopeptidase activity	ISO Inferred from Sequence Orthology more info
enables aminopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables epoxide hydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables epoxide hydrolase activity	ISO Inferred from Sequence Orthology more info
enables epoxide hydrolase activity	ISS Inferred from Sequence or Structural Similarity more info
enables leukotriene-A4 hydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables leukotriene-A4 hydrolase activity	ISO Inferred from Sequence Orthology more info
enables leukotriene-A4 hydrolase activity	ISS Inferred from Sequence or Structural Similarity more info
enables metalloaminopeptidase activity	IEA Inferred from Electronic Annotation more info
enables metalloaminopeptidase activity	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in leukotriene biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in leukotriene biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in leukotriene biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in leukotriene metabolic process	ISO Inferred from Sequence Orthology more info
involved_in peptide catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptide catabolic process	ISO Inferred from Sequence Orthology more info
involved_in peptide catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein metabolic process	ISO Inferred from Sequence Orthology more info
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	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: leukotriene A-4 hydrolase

Names: LTA-4 hydrolase; LTA4 hydrodase; tripeptide aminopeptidase LTA4H

NP_001300826.1

EC 3.3.2.6

EC 3.4.11.4

NP_032543.2

EC 3.3.2.6

EC 3.4.11.4

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)

NM_001313897.1 → NP_001300826.1 leukotriene A-4 hydrolase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate coding exon in the 3' end compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AK134931, BF018223, BG807829, BY793553

UniProtKB/Swiss-Prot

P24527

Conserved Domains (3) summary

cd09599
Location:6 → 450

M1_LTA4H; Peptidase M1 family contains leukotriene A4 hydrolase

pfam01433
Location:21 → 387

Peptidase_M1; Peptidase family M1

pfam09127
Location:468 → 521

Leuk-A4-hydro_C; Leukotriene A4 hydrolase, C-terminal
NM_008517.2 → NP_032543.2 leukotriene A-4 hydrolase isoform 1

See identical proteins and their annotated locations for NP_032543.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK134931, AW121450, BY458968, BY793553

Consensus CDS

CCDS24125.1

UniProtKB/Swiss-Prot

P24527, Q3UY71, Q8VDR8

Related

ENSMUSP00000016033.8, ENSMUST00000016033.9

Conserved Domains (3) summary

cd09599
Location:6 → 450

M1_LTA4H; Peptidase M1 family contains leukotriene A4 hydrolase

TIGR02411
Location:6 → 608

leuko_A4_hydro; leukotriene A-4 hydrolase/aminopeptidase

pfam09127
Location:468 → 607

Leuk-A4-hydro_C; Leukotriene A4 hydrolase, C-terminal