RNF146 E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys- 48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor- mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation. Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N- nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair. Defects in RNF146 are a cause of susceptibility to breast cancer. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; EC 6.3.2.19; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 10|10 A4
Cellular Component:  cytoplasm; cytosol; nucleoplasm; nucleus; plasma membrane
Molecular Function:  metal ion binding; poly-ADP-D-ribose binding; protein binding; transferase activity; ubiquitin-protein transferase activity; zinc ion binding
Biological Process:  positive regulation of canonical Wnt signaling pathway; protein autoubiquitination; protein K48-linked ubiquitination; ubiquitin-dependent protein catabolic process; Wnt signaling pathway
Reference #:  Q9CZW6 (UniProtKB)
Alt. Names/Synonyms: 2610509H23Rik; E3 ubiquitin-protein ligase RNF146; RING finger protein 146; RN146; Rnf146
Gene Symbols: Rnf146
Molecular weight: 38,934 Da
Basal Isoelectric point: 5.05  Predict pI for various phosphorylation states
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RNF146

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene