NEDD8-conjugating enzyme Ubc12 (UBE2M)

NEDD8-conjugating enzyme Ubc12 (UBE2M) is an E2 enzyme essential for the neddylation process, a ubiquitin-like protein modification where NEDD8 is covalently attached to target proteins—primarily cullins, the scaffold components of cullin-RING ligases (CRLs), which are major E3 ubiquitin ligase complexes[1][3][4][5][7]. UBE2M accepts activated NEDD8 from the E1 enzyme complex (UBA3-NAE1) and, in conjunction with specific E3 ligases (notably RBX1), transfers NEDD8 to specific cullin family members, enabling the assembly and activation of CRLs that drive ubiquitin-mediated proteasomal degradation of key cellular regulators[1][5][6][7]. UBE2M activity is crucial for proper cell cycle progression, DNA repair, and apoptosis. Dysregulation or overexpression of UBE2M correlates with cancer progression in multiple malignancies and poor clinical outcomes[2][4][5]. Targeting UBE2M or its neddylation partners represents a promising therapeutic strategy in cancer, with several small-molecule inhibitors in development[5].

Other names

NEDD8-conjugating enzyme Ubc12UBE2MUBC12hUbc12NEDD8 carrier proteinUbiquitin-conjugating enzyme E2 MUBC-RS2NEDD8 protein ligaseUbiquitin carrier protein MUbiquitin conjugating enzyme E2MUbiquitin-conjugating enzyme E2M (UBC12 homolog, yeast)Ubiquitin-protein ligase MEpididymis secretory sperm binding proteinYeast UBC12 homolog

Inhibition of neddylation (by blocking the E1 enzyme NAEs upstream or the interface with E3 ligases and co-E3s such as DCN1) Induction of cell cycle arrest and apoptosis through impaired cullin neddylation and accumulation of CRL substrates