UBE4B

Acts as an E3 ubiquitin ligase and E4 ubiquitin chain elongation enzyme specifically involved in polyubiquitin chain assembly. Plays an essential role in cardiac development and in the protection of neurons from degeneration evoked by ER stress (By similarity). Is recruited to early endosomes via interaction with the ESCRT-0 component HGS, where it ubiquitinates membrane protein cargo such as EGFR and APP to promote their sorting into multivesicular bodies and subsequent lysosomal degradation. Promotes MDM2-mediated polyubiquitination and subsequent degradation of the tumor suppressor TP53. May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation. Mediates the formation of 'Lys-11'- or 'Lys-48'-linked polyubiquitin chains on TRA2A and PYCR2 and induces their degradation by the proteasome. Thereby regulates the alternative splicing function of TRA2A. Also regulates the mTOR signaling pathway by polyubiquitinating KLHL22, an E3 ligase that degrades the GATOR1 complex protein DEPDC5 (By similarity). Under mitochondrial depolarization, mediates the ubiquitination of NIPSNAP1, thereby promoting its interaction with autophagy receptors NDP52 and p62/SQSTM1 and its subsequent degradation via the lysosome-dependent pathway..

Function from UniProtKB (O95155), read 2026-09-23. CC BY 4.0.