Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

[9] They all contain a conserved catalytic core domain that interacts with E1 and E3 and many E2s possess additional N- and/or C-terminal protein sequences.

Specifically, UBE2L3 manages cell cycle regulatory protein levels via the ubiquitin proteolytic pathway (UPP) during the G1/S transition and during the actual S phase.

[13] UBE2L3 has been linked to natural killer cell cytotoxic function, and high UBE2L3 levels had contributed to clearing chronic HBV infection.

Loss of UBE2L3 stabilizes 53BP1 and force cells to choose NHEJ to repair DNA double-strand break.