Ubiquitin-conjugating enzyme E2 Z (UBE2Z)

Ubiquitin-conjugating enzyme E2 Z (UBE2Z) is a member of the E2 family of enzymes involved in the ubiquitin-proteasome system, catalyzing the transfer of ubiquitin or the ubiquitin-like modifier FAT10 to substrate proteins during post-translational modification and protein degradation. UBE2Z is unique in its specificity for the activating enzyme UBA6, and it exclusively accepts ubiquitin and FAT10 from UBA6, distinguishing it from other E2 enzymes. The enzyme comprises a conserved N-terminal UBC domain and a C-terminal extension for substrate interaction, with the active site cysteine residue necessary for ubiquitin transfer. UBE2Z is expressed in most human tissues, with increased expression reported in cancer cells. Genetic variants in UBE2Z are associated with chronic kidney disease, coronary artery disease, and abnormal lipid metabolism, and it has been identified as a biomarker in risk stratification for these conditions. Structural characterization has clarified the selectivity mechanisms for ubiquitin and FAT10 conjugation, underscoring its functional importance in cellular homeostasis and disease.

Other names

UBE2ZUSE1HOYS7UBA6-specific E2 conjugating enzyme 1Ubiquitin carrier protein ZUbiquitin-protein ligase ZFLJ13855E2 ubiquitin-conjugating enzyme ZUba6-specific enzyme E2

No direct drugs known. By inference, drugs targeting UBE2Z would likely act as enzyme inhibitors, interfering with its role in protein ubiquitination and downstream degradation. Statins are not direct inhibitors, but clinical benefit is greater in carriers of risk-associated UBE2Z variations, possibly via indirect disease pathway modulation