LTA4H (leukotriene A4 hydrolase)

Gene

• Entrez ID: 4048
• Gene name: Leukotriene A4 hydrolase
• Gene symbol: LTA4H
• Synonyms (NCBI Gene): -
• Chromosome: 12
• Chromosome location: 12q23.1
• 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 b

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023123	hsa-miR-124-3p	Microarray	18668037
MIRT030208	hsa-miR-26b-5p	Microarray	19088304
MIRT052512	hsa-let-7a-5p	CLASH	23622248
MIRT052143	hsa-let-7b-5p	CLASH	23622248
MIRT051821	hsa-let-7c-5p	CLASH	23622248
MIRT045983	hsa-miR-125b-5p	CLASH	23622248
MIRT2034493	hsa-miR-4670-3p	CLIP-seq
MIRT2563971	hsa-miR-216b	CLIP-seq
MIRT2563972	hsa-miR-3675-3p	CLIP-seq
MIRT2563973	hsa-miR-4311	CLIP-seq
MIRT2563974	hsa-miR-4668-3p	CLIP-seq
MIRT2563975	hsa-miR-539	CLIP-seq
MIRT2563971	hsa-miR-216b	CLIP-seq
MIRT2563972	hsa-miR-3675-3p	CLIP-seq
MIRT2563973	hsa-miR-4311	CLIP-seq
MIRT2563974	hsa-miR-4668-3p	CLIP-seq
MIRT2563975	hsa-miR-539	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003723	Function	RNA binding	HDA	22658674
GO:0004177	Function	Aminopeptidase activity	IBA
GO:0004177	Function	Aminopeptidase activity	IDA	9774412, 15078870, 18804029
GO:0004177	Function	Aminopeptidase activity	IEA
GO:0004301	Function	Epoxide hydrolase activity	IBA
GO:0004301	Function	Epoxide hydrolase activity	IDA	15078870
GO:0004301	Function	Epoxide hydrolase activity	IMP	11675384
GO:0004301	Function	Epoxide hydrolase activity	TAS	11154734
GO:0004463	Function	Leukotriene-A4 hydrolase activity	IBA
GO:0004463	Function	Leukotriene-A4 hydrolase activity	IDA	9774412, 15078870
GO:0004463	Function	Leukotriene-A4 hydrolase activity	IEA
GO:0004463	Function	Leukotriene-A4 hydrolase activity	TAS	1881903
GO:0005515	Function	Protein binding	IPI	21044950
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IBA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006508	Process	Proteolysis	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006691	Process	Leukotriene metabolic process	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0008233	Function	Peptidase activity	TAS	1881903
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0008270	Function	Zinc ion binding	IDA	15078870, 18804029
GO:0008270	Function	Zinc ion binding	IEA
GO:0008270	Function	Zinc ion binding	IMP	11675384
GO:0008270	Function	Zinc ion binding	TAS	1881903
GO:0010043	Process	Response to zinc ion	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0019370	Process	Leukotriene biosynthetic process	IBA
GO:0019370	Process	Leukotriene biosynthetic process	IDA	9774412, 15078870
GO:0019370	Process	Leukotriene biosynthetic process	IEA
GO:0019370	Process	Leukotriene biosynthetic process	IMP	11675384
GO:0019370	Process	Leukotriene biosynthetic process	TAS	1881903
GO:0019538	Process	Protein metabolic process	IMP	11675384
GO:0043171	Process	Peptide catabolic process	IBA
GO:0043171	Process	Peptide catabolic process	IDA	9774412, 15078870, 18804029
GO:0043434	Process	Response to peptide hormone	IEA
GO:0045148	Function	Tripeptide aminopeptidase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060509	Process	Type I pneumocyte differentiation	IEA
GO:0070006	Function	Metalloaminopeptidase activity	IMP	11675384
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:1904724	Component	Tertiary granule lumen	TAS
GO:1904813	Component	Ficolin-1-rich granule lumen	TAS

Other IDs

• MIM: 151570
• HGNC: 6710
• e!Ensembl: ENSG00000111144

Protein

• UniProt ID: P09960
• Protein name: Leukotriene A-4 hydrolase (LTA-4 hydrolase) (EC 3.3.2.6) (Leukotriene A(4) hydrolase) (Tripeptide aminopeptidase LTA4H) (EC 3.4.11.4)
• Protein function: Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, Pu
• PDB: 1GW6, 1H19, 1HS6, 1SQM, 2R59, 2VJ8, 3B7R, 3B7S, 3B7T, 3B7U, 3CHO, 3CHP, 3CHQ, 3CHR, 3CHS, 3FH5, 3FH7, 3FH8, 3FHE, 3FTS, 3FTU, 3FTV, 3FTW, 3FTX, 3FTY, 3FTZ, 3FU0, 3FU3, 3FU5, 3FU6, 3FUD, 3FUE, 3FUF, 3FUH, 3FUI, 3FUJ, 3FUK, 3FUL, 3FUM, 3FUN, 3U9W, 4DPR, 4L2L, 4MKT, 4MS6, 4R7L, 4RSY, 4RVB, 5AEN, 5BPP, 5FWQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17900	Peptidase_M1_N	18 → 202		Domain
  PF01433	Peptidase_M1	233 → 448	Peptidase family M1 domain	Domain
  PF09127	Leuk-A4-hydro_C	495 → 608	Leukotriene A4 hydrolase, C-terminal	Family

• Tissue specificity: TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.
• Sequence:

  MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDL
  TIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLT
  PEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETP
  DPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETES
  MLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISH
  SWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGET
  HPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSI
  TTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAK
  EDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWL
  RLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVT
  AMLVGKDLKVD

• Sequence length: 611

Pathways

KEGG:

Arachidonic acid metabolism
Metabolic pathways

Reactome:

Synthesis of Leukotrienes (LT) and Eoxins (EX)
Neutrophil degranulation
Biosynthesis of D-series resolvins
Biosynthesis of protectins
Biosynthesis of E-series 18(S)-resolvins
Biosynthesis of aspirin-triggered D-series resolvins
Biosynthesis of E-series 18(R)-resolvins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATHEROSCLEROSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL DEPRESSION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aortic Aneurysm, Abdominal	Aortic Aneurysm	BEFREE	21078989		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	19130089, 25721704, 29413439		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	11069563, 18547289, 20067482, 22206291, 23167751, 23573270, 25634111, 30352167		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	LHGDN	18547289		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	20067482, 22206291, 23167751, 23573270, 34550981	Associate	★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	CTD_human_DG	16698924		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	BEFREE	19130089, 25721704, 29413439		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	Pubtator	19130089, 21293878, 23153620	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	18323512, 19130089		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	19130089, 24366255	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	18318662, 23324273		★☆☆☆☆ Found in Text Mining only
Childhood asthma	Asthma	BEFREE	23573270		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31085102		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	19130089, 21293878, 24366255, 29067980	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	21293878, 29067980		★☆☆☆☆ Found in Text Mining only
Coronary Disease	Coronary artery disease	Pubtator	19130089	Associate	★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	31093505		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn disease	Pubtator	31093505	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	19622707		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	PSYGENET_DG	19622707		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	19622707	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Down Syndrome	Down Syndrome	BEFREE	27293319		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	27293319	Associate	★☆☆☆☆ Found in Text Mining only
Emphysema	Emphysema	Pubtator	34694182	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	19919819	Associate	★☆☆☆☆ Found in Text Mining only
Glomerulonephritis Membranous	Membranous glomerulonephritis	Pubtator	10337029	Associate	★☆☆☆☆ Found in Text Mining only
Glomerulosclerosis Focal Segmental	Focal segmental glomerulosclerosis	Pubtator	10337029	Associate	★☆☆☆☆ Found in Text Mining only
Graft vs Host Disease	Graft-versus-host disease	Pubtator	15054046	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	28218840		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	29531307		★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	18323512, 23079278		★☆☆☆☆ Found in Text Mining only
Laryngeal Squamous Cell Carcinoma	Laryngeal Carcinoma	BEFREE	31287215		★☆☆☆☆ Found in Text Mining only
Liposarcoma	Liposarcoma	Pubtator	21038090	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	20952510		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	21308720		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of skin	Skin cancer	BEFREE	28575166		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28575166, 30058075		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	24580015		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	19622707		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Depression	Mental Depression	PSYGENET_DG	19622707		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Metabolic Syndrome	Metabolic syndrome	Pubtator	29067980	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	29067980		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	10666225		★☆☆☆☆ Found in Text Mining only
MYELOPROLIFERATIVE DISORDER, CHRONIC, WITH EOSINOPHILIA	Myeloproliferative Disorder with Eosinophilia	BEFREE	30791695		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	16282974, 16987874, 18318662, 18547289, 27893808, 30678701		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial infarction	Pubtator	30678701	Associate	★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic Syndrome	BEFREE	10337029		★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic syndrome	Pubtator	10337029	Associate	★☆☆☆☆ Found in Text Mining only
Neutrophilia (disorder)	Neutrophilia	BEFREE	29202450		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	38238671	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	20952510		★☆☆☆☆ Found in Text Mining only
Precursor B-cell lymphoblastic leukemia	Lymphoblastic Leukemia	BEFREE	7646998		★☆☆☆☆ Found in Text Mining only
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	7646998		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	21308720		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	21308720	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	34694182	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	36923505	Associate	★☆☆☆☆ Found in Text Mining only