UBE1L2, like E1, also activates ubiquitin in the pathway.

Universitat Konstanz scientists discovered a second enzyme involved in initiating the degradation of proteins inside cells. “We essentially found that cleanup in the cell is not supervised by one, but by two proteins,” says Marcus Groettrup, Ph.D., lead author and chair of the immunology department. “This is important because everything we know about this cleanup process assumes that only one enzyme initiates it. The second protein we discovered may either share some functions with the first one or do totally different things.”

Before being degraded, proteins are tagged with a ubiquitin. Three types of enzymes are involved in the tagging process. An enzyme called activating enzyme (E1) first activates ubiquitin and binds to it. Then the ubiquitin is transferred to a second enzyme called ubiquitin-conjugating enzyme (E2). Finally, a third enzyme, ubiquitin ligase (E3), binds to both E2 and the protein to be degraded, so that E2 can transfer the ubiquitin to the protein.

Until now, only one type of E1 enzyme for ubiquitin has been known to exist in the human genome, while (34) E2 enzymes and (531) E3 enzymes have been discovered.

The scientists were searching for an enzyme similar to E1 that activates a protein that looks like ubiquitin called FAT10. However, the enzyme they found could not activate FAT10 but instead activated ubiquitin itself. The researchers also confirmed that this enzyme, which they called UBE1L2, also helped degrade proteins by working with E2 and E3 enzymes.

The team also tested whether UBE1L2 was, like the original E1, expressed in all organs and tissues. They measured the expression levels of UBE1L2 in mice and found that the protein was expressed about five times more in the testis than other organs. They believe this could provide a new understanding of male fertility.

The study is published in the August 3 issue of the Journal of Biological Chemistry.

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