E3 ubiquitin-protein ligase RNF19A is an enzyme that in humans is encoded by the RNF19Agene.[1][2][3]
The protein encoded by this gene contains two RING-finger motifs and an IBR (in between RING fingers) motif. This protein is an E3 ubiquitin ligase that is localized in Lewy bodies (LBs), neuronal inclusions characteristic of Parkinson's disease (PD). This protein interacts with UBE2L3/UBCH7 and UBE2E2/UBCH8, but not other ubiquitin-conjugating enzymes. This protein is found to bind and ubiquitylate synphilin 1 (SNCAIP), which is an interacting protein of alpha-synuclein in neurons, and a major component of LB. Alternatively-spliced transcript variants encoding the same protein have been reported.[3]
↑Niwa J, Ishigaki S, Doyu M, Suzuki T, Tanaka K, Sobue G (Mar 2001). "A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase activity". Biochem Biophys Res Commun. 281 (3): 706–13. doi:10.1006/bbrc.2001.4414. PMID11237715.
↑Gunther M, Laithier M, Brison O (Dec 2000). "A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening". Mol Cell Biochem. 210 (1–2): 131–42. doi:10.1023/A:1007177623283. PMID10976766.
Ito T, Niwa J, Hishikawa N, et al. (2003). "Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1". J. Biol. Chem. 278 (31): 29106–14. doi:10.1074/jbc.M302763200. PMID12750386.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Takeuchi H, Niwa J, Hishikawa N, et al. (2004). "Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis". J. Neurochem. 89 (1): 64–72. doi:10.1046/j.1471-4159.2003.02289.x. PMID15030390.
Ishigaki S, Hishikawa N, Niwa J, et al. (2005). "Physical and functional interaction between Dorfin and Valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders". J. Biol. Chem. 279 (49): 51376–85. doi:10.1074/jbc.M406683200. PMID15456787.
Huang Y, Niwa J, Sobue G, Breitwieser GE (2006). "Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin". J. Biol. Chem. 281 (17): 11610–7. doi:10.1074/jbc.M513552200. PMID16513638.
Ishigaki S, Niwa J, Yamada S, et al. (2007). "Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity". Neurobiol. Dis. 25 (2): 331–41. doi:10.1016/j.nbd.2006.09.017. PMID17157513.
