The TMEM189 gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens

• DOI: 10.1073/pnas.1917461117
• Publication Date: 2020-03-24T22:49:24Z
• Authors: Ernst R. Werner; Markus A. Keller; Sabrina Sailer; Katharina Lackner; Jakob Koch; Martin Hermann; Stefan Coassin; Georg Golderer; Gabriele Werner-F...; Raphael A. Zoeller; Nicolas Hulo; Johannes Berger; Katrin Watschinger
• Keywords: 0303 health sciences; Vinyl Compounds; Plasmalogens; Biological Sciences; Lipids; 3. Good health; Cell Line; Mice; 03 medical and health sciences; Phenotype; Alzheimer Disease; Ubiquitin-Conjugating Enzymes; Animals; Humans; Oxidoreductases; Oxidation-Reduction

Significance

Although sequencing of the human genome was completed years ago, we still do not know about the physiological significance of thousands of predicted proteins, particularly of predicted membrane proteins. On the other hand, for approximately 100 human enzymes, no coding gene is known even though their enzymatic reaction has been well characterized. In this work, we assign one of those predicted membrane proteins (transmembrane protein 189; TMEM189) to one of the enzymatic reactions with an uncharacterized gene (plasmanylethanolamine desaturase). This enzyme catalyzes the final step in the biosynthesis of plasmalogens, an abundant class of glycerophospholipids that is depleted in such diseases as Alzheimer’s. Our findings enable interpretation of the previously characterized impaired growth phenotype of Tmem189 -deficient mice.