Ubiquitin-conjugating enzyme E2 N (UBE2N)

Ubiquitin-conjugating enzyme E2 N (UBE2N), also known as UBC13, is a member of the E2 ubiquitin-conjugating enzyme family involved in posttranslational modification of proteins via ubiquitination[2][3]. Uniquely, UBE2N, in partnership with cofactors (UBE2V1/UBE2V2), mediates synthesis of Lysine-63 (K63)-linked polyubiquitin chains, a signal involved in non-proteolytic processes such as DNA damage repair, immune signaling (NF-κB, MAPK), and regulation of oncoprotein stability in cancer[1][2][3]. In acute myeloid leukemia (AML) and other malignancies, UBE2N supports proteostasis by preventing degradation of certain oncoproteins. Targeted inhibition of UBE2N has been shown to induce degradation of these proteins via the immunoproteasome, offering a potential therapeutic angle in AML and immune diseases, but safety concerns remain due to its pleiotropic cellular functions[1][2][3].

Other names

UBC13UbcH13UbcH-benBLUMGC8489Bendless-like ubiquitin-conjugating enzymeE2 ubiquitin-conjugating enzyme NUbiquitin carrier protein NUbiquitin-protein ligase NHEL-S-71UBE2NUBCHBENepididymis secretory protein Li 71UBE2N (UBC13 homolog, yeast)Yeast UBC13 homolog

Inhibitors (e.g., UBE2Ni) block UBE2N activity by covalently binding to its active catalytic cysteine, preventing ubiquitin transfer and sequence-specific ubiquitin chain extension[1]. Inhibition leads to degradation of UBE2N-dependent stabilized proteins via altered ubiquitination balance (favoring K48 over K63 linkages)[1].