UBR4

E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm. Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation. Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively. Does not ubiquitinate proteins that are acetylated at the N-terminus. Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified. Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy. Catalytic component of the silencing factor of the integrated stress response (SIFI) complex, a multiprotein complex that turns off the mitochondrial stress response after a specific stress event has been resolved. The SIFI complex ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors such as ABHD10. Within the SIFI complex, UBR4 initiates ubiquitin chains that are further elongated or branched by KCMF1. Mediates ubiquitination of ACLY, leading to its subsequent degradation. Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization..

Function from UniProtKB (Q5T4S7), read 2026-09-23. CC BY 4.0.