Characterization and cellular localization of human 5-lipoxygenase and its protein isoforms 5-LOΔ13, 5-LOΔ4 and 5-LOp12

Biochim Biophys Acta Mol Cell Biol Lipids. 2017 May;1862(5):561-571. doi: 10.1016/j.bbalip.2017.02.015. Epub 2017 Feb 28.


Human 5-lipoxygenase (5-LO-WT) initiates the leukotriene (LT) biosynthesis. LTs play an important role in diseases like asthma, atherosclerosis and in many types of cancer. In this study, we investigated the 5-LO isoforms 5-LO∆13, 5-LO∆4 and 5-LOp12, lacking the exons 13, 4 or a part of exon 12, respectively. We were able to detect the mRNA of the isoforms 5-LO∆13 and 5-LOp12 in B and T cell lines as well as in primary B and T cells and monocytes. Furthermore, we found that expression of 5-LO and particularly of the 5-LO∆13 and 5-LOp12 isoforms is increased in monocytes from patients with rheumatoid arthritis and sepsis. Confocal microscopy of HEK293T cells stably transfected with tagged 5-LO-WT and/or the isoforms revealed that 5-LO-WT is localized in the nucleus whereas all isoforms are located in the cytosol. Additionally, all isoforms are catalytically inactive and do not seem to influence the specific activity of 5-LO-WT. S271A mutation in 5-LO-WT and treatment of the cells with sorbitol or KN-93/SB203580 changes the localization of the WT enzyme to the cytosol. Despite colocalization with the S271A mutant, the isoforms did not affect LT biosynthesis. Analysis of the phosphorylation pattern of 5-LO-WT and all the isoforms revealed that 5-LOp12 and 5-LO∆13 are highly phosphorylated at Ser271 and 5-LOp12 at Ser523. Furthermore, coexpression of the isoforms inhibited or stimulated 5-LO-WT expression in transiently and stably transfected HEK293T cells suggesting that the isoforms have other functions than canonical LT biosynthesis.

Keywords: 5-Lipoxygenase; Alternative splicing; Confocal microscopy; Inflammation; Protein isoforms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / chemistry
  • Arachidonate 5-Lipoxygenase / isolation & purification
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure*
  • Cytosol / metabolism
  • Cytosol / ultrastructure*
  • Gene Expression Regulation, Enzymologic
  • HEK293 Cells
  • Humans
  • Leukotrienes / biosynthesis
  • Neutrophils / metabolism
  • Neutrophils / ultrastructure
  • Phosphorylation
  • Protein Isoforms / chemistry
  • Protein Isoforms / isolation & purification
  • Protein Isoforms / metabolism*


  • Leukotrienes
  • Protein Isoforms
  • Arachidonate 5-Lipoxygenase