Ubiquitin-conjugating enzyme E2 D4 (UBE2D4)

Ubiquitin-conjugating enzyme E2 D4 (UBE2D4) is an E2 family enzyme that functions as a central mediator in the ubiquitin-proteasome system, accepting ubiquitin from an E1 enzyme and catalyzing its attachment to target proteins, often as part of protein polyubiquitination and subsequent degradation by the 26S proteasome[3][1]. UBE2D4 is highly homologous to other UBE2D family members and acts in concert with E3 ligases, such as CHIP, to regulate the fate of diverse cellular proteins including receptor tyrosine kinases, tumor suppressors like p53, and components of key signaling pathways (Hedgehog, TGFβ, NFκB)[1][2]. Dysregulation of UBE2D4 activity has been implicated in cancer, where it may contribute to aberrant cell cycle progression and reduced apoptotic control[2]. Structurally, UBE2D4 is characterized by a central UBC domain that mediates both ubiquitin and E3 ligase binding, and its activity may be controlled by post-translational modifications and protein-protein interactions[1][3]. Research has identified novel small molecules that inhibit UBE2D4 with potential therapeutic value in oncology[2].

Other names

UBE2D4UBCH5DHBUCE1E2 ubiquitin-conjugating enzyme D4ubiquitin carrier protein D4ubiquitin-protein ligase D4

Inhibition of UBE2D4 causes impaired polyubiquitination, which may block targeted protein degradation and disrupt proliferation in cancer cells[2]