Ubiquitin-conjugating enzyme E2 N (UBE2N) (UBE2N)

Ubiquitin-conjugating enzyme E2 N (UBE2N), commonly known as Ubc13, is a key enzyme in the ubiquitination cascade that specifically catalyzes the formation of Lys63-linked polyubiquitin chains [1, 10]. Unlike the canonical Lys48-linked chains that target proteins for degradation, Lys63-linked chains function as non-proteolytic scaffolds for signal transduction, particularly in the NF-kappaB, JNK, and p38 MAPK pathways [1, 9]. Ubc13 operates as a heterodimer with E2 variants such as Mms2 or Uev1A to regulate critical cellular processes, including DNA damage repair (post-replication repair) and innate immune responses [1, 15, 18]. In many cancers, Ubc13 is overexpressed and contributes to tumor progression, metastasis, and resistance to chemotherapy [1, 13, 21]. Small molecule inhibitors like NSC697923 have been developed to covalently target the active site cysteine of Ubc13, thereby blocking its catalytic activity and downstream oncogenic signaling [5, 7, 12]. However, the essential nature of Ubc13 in maintaining genomic stability and immune function presents significant therapeutic challenges regarding potential systemic toxicity [9, 18, 19].

Other names

Ubc13UBE2NBLUUBC13UbcH-benUbcH13Bendless-like ubiquitin conjugating enzyme

Covalent inhibition of the active site cysteine (Cys87), preventing the formation of the E2-ubiquitin thioester bond and disrupting Lys63-linked polyubiquitin chain synthesis.