FunctionE3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR. Specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation and to neuronal protection.
Tissue specificityWidely expressed, with highest levels in heart. Ubiquitously expressed in the central nervous system.
PathwayProtein modification; protein ubiquitination.
Sequence similaritiesBelongs to the RBR family. RNF19 subfamily. Contains 1 IBR-type zinc finger. Contains 2 RING-type zinc fingers.
Post-translational modificationsPhosphorylated upon DNA damage, probably by ATM or ATR.
Cellular localizationMembrane. Cytoplasm > cytoskeleton > centrosome. Present in the hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients. Present in the Lewy bodies specifically found in neurons from Parkinson disease patients.