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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 proinflammatory 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:20813919, PubMed:18804029). In addition to its proinflammatory 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

  • Cytoplasm

Alternative names

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

Target type

Proteins

Molecular weight

69285Da