Ubiquitin-conjugating enzyme E2 D1 (UBE2D1)

Ubiquitin-conjugating enzyme E2 D1 (UBE2D1) is a member of the UbcH5 family of E2 enzymes that mediates the transfer of ubiquitin from ubiquitin-activating enzymes (E1s) to substrate proteins, in cooperation with various E3 ubiquitin-protein ligases. It is central to the polyubiquitination process, which tags proteins for degradation by the proteasome, and helps regulate cellular processes such as the cell cycle, DNA damage repair, immune signaling, and iron metabolism. UBE2D1’s specificity and enzymatic activity are modulated by interactions with other proteins and post-translational modifications. Dysregulation of its expression or activity is linked to several disease states, especially cancer, where it can promote degradation of tumor suppressors like p53 and influence outcomes. UBE2D1 thus represents an important point of regulation in protein homeostasis and cellular signaling.

Other names

SFTUBC5AUBCH5UBCH5AUbcH5AUBC4/5E2(17)KB1Ubiquitin carrier protein D1UBC4/5 homologStimulator of Fe transportUbiquitin-protein ligase D1Ubiquitin-conjugating enzyme E2-17 kDa 1Ubiquitin-conjugating enzyme E2(17)KB 1E2 ubiquitin-conjugating enzyme D1

Experimental UbVs (ubiquitin variants) bind the backside of UBE2D1, inhibiting its interaction with E1 and E3, attenuating ubiquitin chain formation on substrates. Polyubiquitination by UBE2D1 targets proteins for degradation via the proteasome, regulating the levels of numerous signaling proteins and cell cycle regulators. UBE2D1 partners with RING-type E3 ligases to catalyze ubiquitin transfer, and its conformation can influence the specificity and length of ubiquitin chains (K11, K48, K63 linkages).