E3 ubiquitin-protein ligase RNF19A (RNF19A)

E3 ubiquitin-protein ligase RNF19A is an RBR (Ring-between-Ring) family E3 ligase, containing two RING-finger motifs and an in-between-RING (IBR) domain. It facilitates the transfer of ubiquitin from E2 conjugating enzymes (such as UBE2L3 and UBE2L6) to substrate proteins, thereby targeting them for proteasomal degradation or regulating their function. In neuronal tissues, RNF19A ubiquitylates synphilin-1 and pathogenic SOD1 variants, localizing to Lewy bodies and playing a role in neuroprotection and protein quality control, relevant to Parkinson's disease and ALS. In cancer, RNF19A suppresses homologous recombination repair by ubiquitinating BARD1 and modulating its interaction with BRCA1, thereby increasing cancer cell susceptibility to PARP inhibitors. This dual involvement in neurodegenerative disorders and DNA repair makes RNF19A a critical protein at the intersection of protein degradation and genome maintenance pathways[1][2][3][5][6].

Other names

Double ring-finger proteinRING finger protein 19Ap38DorfinRing finger protein 19DKFZp566B1346Protein p38 interacting with transcription factor Sp1ring-IBR-ring domain containing protein Dorfin

For drugs modulating this pathway: RNF19A enhances cancer cell sensitivity to PARP inhibitors by inhibiting homologous recombination repair, likely via the ubiquitination and nuclear export of BARD1, which impairs BRCA1-BARD1 complex function[1]. It mediates protein ubiquitination, leading to proteasomal degradation of pathogenic substrate proteins such as SOD1[3][5].