KCMF1

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and then transfers it to targeted substrates, promoting their degradation by the proteasome. Together with UBR4, 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. Does not ubiquitinate proteins that are acetylated at the N-terminus. Together with UBR4, 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 chain that are further elongated or branched by KCMF1..

Function from UniProtKB (Q9P0J7), read 2026-09-23. CC BY 4.0.