E3 ubiquitin-protein ligase RNF4 (RNF4)

E3 ubiquitin-protein ligase which contrasts polysumoylated chains covalently attached to proteins and mediates'Lys-6'-,'Lys-11'-,'Lys-48'- and'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins such as PML and the transcriptional activator PEA3.

Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complicated by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1.