Ubiquitin-conjugating Enzyme E2K (UBE2K), also known as E2-25K, HIP2, and LIG, is a 200 amino acid (aa) protein with a predicted molecular weight of 25 kDa. Human and mouse UBE2K share 100% aa sequence identity. Similar to other Ubiquitin-conjugating (E2) enzymes, UBE2K/E2-25K contains a conserved Ubiquitin-conjugating domain but is unique in that it also has a C-terminal, non-covalent Ubiquitin binding surface termed the Ubiquitin-associated domain between aa residues 160 and 200. UBE2K/E2-25K mediates the elongation of Lys48-linked poly-Ubiquitin chains. UBE2K/E2-25K catalytic activity can be modulated by the post-translational addition of SUMO at Lys14. Substrates include the Huntingtin protein and the tumor suppressor RB1. UBE2K/E2-25K is widely expressed, with highest levels found in the brain cortex and striatum, and dysregulated UBE2K/E2-25K is implicated in polyglutamine diseases and Alzheimer's disease.