Ubiquitin-conjugating enzyme E2 D3 (UBE2D3)

Ubiquitin-conjugating enzyme E2 D3 (UBE2D3) is an E2 family enzyme that accepts ubiquitin from the E1 activating enzyme and, in conjunction with various E3 ligases, catalyzes the covalent attachment of ubiquitin to target proteins[1][2][3][4]. UBE2D3 is notable for its broad substrate range, playing a central role in the ubiquitin-proteasome pathway by promoting polyubiquitination via Lys-11 and Lys-48 linkages, which target proteins for degradation[1][2][4]. It is involved in the regulation of numerous critical cellular processes, including degradation of the tumor suppressor p53, polyubiquitination of NFKBIA to modulate NF-κB signaling, modulation of receptor tyrosine kinase trafficking (e.g., EGFR), regulation of DNA repair mechanisms, cell cycle control, and histone ubiquitination to repress gene transcription[1][2][4][5]. Disruption or aberrant regulation of UBE2D3 has been linked to cancer progression, developmental defects, and other diseases, highlighting its potential as a therapeutic target; however, no approved drugs currently act specifically on UBE2D3[4][2]. Its high degree of homology with other E2 enzymes and the potential for widespread effects on cell signaling present significant challenges for therapeutic targeting[2].

Other names

UBC5CUBCH5CUbcH5CUbiquitin carrier protein D3Ubiquitin-conjugating enzyme E2(17)KB 3Ubiquitin-conjugating enzyme E2-17 kDa 3Ubiquitin-protein ligase D3E2(17)KB3UBC4/5(E3-independent) E2 ubiquitin-conjugating enzyme D3Ubiquitin-conjugating enzyme E2D 3Ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast)Ubiquitin-conjugating enzyme E2D 3 (homologous to yeast UBC4/5)