ID:RN146_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase RNF146; EC=6.3.2.-; AltName: Full=Dactylidin; AltName: Full=Iduna; AltName: Full=RING finger protein 146; FUNCTION: 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 (By similarity). 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Can form homooligomers. Interacts with PARsylated AXIN1, AXIN2, BLZF1, CASC3, HIST1H1C, IPO7, LIG3, NCL, PARP1, XRCC1, XRCC5 and XRCC6. Interacts with DDB1, DHX15, IQGAP1, LRPPRC, PARP2, PRKDC, RUVBL2, TNKS1 and TNKS2. Binding often leads to interactor ubiquitination, in the presence of the appropriate E1 and E2 enzymes, and proteasomal degradation. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus. Note=Translocates to the nucleus after DNA damage, such as laser- induced DNA breaks, and concentrates at DNA breaks. This translocation requires PARP1 activation and PAR-binding. TISSUE SPECIFICITY: Ubiquitously expressed. Up-regulated in brains from patients with Alzheimer disease. DOMAIN: The WWE domain mediates non-covalent PAR-binding. PTM: Ubiquitinated; autoubiquitinated. Polyubiquitinated in the presence of UBE2D1, UBE2D2 and UBE2D3. Multimonoubiquitinated in the presence of UBE2E1. Not ubiquinated in the presence of UBE2H, CDC34, UBE2L3, UBE2L6, nor UBE2C. In the absence of PAR, autoubiquitination occurs on Lys-85, Lys-95 and Lys-176 via 'Lys- 11' and 'Lys-48' ubiquitin linkages. In the presence of PAR, Lys- 131 and Lys-176 are ubiquitinated via 'Lys-6', 'Lys-33' and 'Lys- 48' ubiquitin linkages. Autoubiquitination is enhanced upon PAR- binding. DISEASE: Note=Defects in RNF146 are a cause of susceptibility to breast cancer. MISCELLANEOUS: Was named dactylidin after the Greek term 'daktylidi' for ring, 'the thing around the finger' (PubMed:15813938). Was named Iduna after the Norse goddess of protection and eternal youth (PubMed:21602803). SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 1 WWE domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NTX7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006511 ubiquitin-dependent protein catabolic process GO:0016055 Wnt signaling pathway GO:0016567 protein ubiquitination GO:0051865 protein autoubiquitination GO:0070936 protein K48-linked ubiquitination GO:0090263 positive regulation of canonical Wnt signaling pathway
US Server
