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Ubiquitin is a protein, or rather, a polypeptide, that occurs in most eukaryotes. Its main function is to mark other proteins for proteolysis. It can also mark transmembrane proteins (for example, receptors) for removal from the membrane. The marking of the protein is done by the ubiquitin binding to a lysine residue in the target protein.

The process of marking a protein with ubiquitin consists of a series of steps:

  1. Activation of ubiquitin -- the carboxyl group of the terminal glycine of ubiquitin binds to the SH group of an ubiquitin-activating enzyme. This step requires ATP as an energy source and results in a thioester bond between ubiquitin and the enzyme E1.
  2. Transfer of ubiquitin from E1 to the ubiquitin-conjugating enzyme E2 via transacylation.
  3. Then, the final transfer of ubiquitin to the target protein can occur either:
directly from E2. This is primarily used when ubiquitin is transferred to another ubiquitin already in place, creating a branched ubiquitin chain.
via an E3 enzyme, which binds specifically to both E2 and the target protein. This is the usual way to mark specific proteins for proteolysis.

Finally, the marked protein is digested in the 26S-proteasome into small peptides, amino acids, and ubiquitin (which can be reused).

The gene whose omission causes Angelman syndrome has something to do with this process.