RNF19A
Domain
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.
Function
E3 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.
Pathway
Protein modification; protein ubiquitination.
Sequence Similarities
Belongs to the RBR family. RNF19 subfamily.
Tissue Specificity
Widely expressed, with highest levels in heart. Ubiquitously expressed in the central nervous system.
Cellular localization
- Membrane
- Multi-pass membrane protein
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- 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.
Alternative names
RNF19, RNF19A, E3 ubiquitin-protein ligase RNF19A, Double ring-finger protein, RING finger protein 19A, p38, Dorfin