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LTA4H

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, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:18804029, PubMed:20813919). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090).

Pathway

Lipid metabolism; leukotriene B4 biosynthesis.

Post-translational modifications

Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity.

Sequence Similarities

Belongs to the peptidase M1 family.

Tissue Specificity

Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.

Cellular localization

Alternative names

LTA4, LTA4H, Leukotriene A-4 hydrolase, LTA-4 hydrolase, Leukotriene A(4) hydrolase, Tripeptide aminopeptidase LTA4H

swissprot:P09960 omim:151570 entrezGene:4048