Protein: E3 ubiquitin-protein ligase RNF146 (Q5XIK5)
Organism: Rattus norvegicus (Rat)
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 ubiquitination 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 (By similarity). Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos (By similarity). Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner (By similarity). 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 (By similarity). Promotes cell survival after gamma-irradiation. Facilitates DNA repair (By similarity)
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 (By similarity)
Sequence: MAGCGEIDHSLNMLPTNKKASETCSNTAPSLTVPECAICLQTCVHPVSLPCKHVFCYLCVKGASWLGKRCALCRQEIPEDFLDKPTLLSPEELKAASRGNGEYVWYYEGRNGWWQYDERTSRELEDAFSKGKKNTEMLIAGFLYVADLENMVQYRRNEHGRRRKIKRDIIDIPKKGVAGLRLDCDSNTVNLARESSADGADSGSAHTGASVQLPVPSSTRPLTSVDGQLTSPVTPSPDAGASLEDSFAHLQLSGDSIAERSHRGEGEEDHESPSSGRVPDTSTEETESDASSDIEDAPVVVAQHSLTQQRLLVSSANQTVAERSDRPVAGGGTMSVNVRSRRPDGQCTVTEV
InterPro domains: - IPR044110: RNF146, RING finger, HC subclass (domain) [34-83]
- IPR004170: WWE domain (domain) [91-167]
- IPR001841: Zinc finger, RING-type (domain) [36-74]
- IPR017907: Zinc finger, RING-type, conserved site (conserved_site) [51-60]
- IPR037197: WWE domain superfamily (homologous_superfamily) [75-183]
- IPR018123: WWE domain, subgroup (domain) [100-175]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [12-101]
- IPR033509: E3 ubiquitin-protein ligase RNF146 (family) [17-192]
Interaction partners: - Poly [ADP-ribose] polymerase
- Tankyrase 2
- Axin-2
- Poly [ADP-ribose] polymerase 1
- Ubiquitin-conjugating enzyme E2 D1
- Poly (ADP-ribose) polymerase 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0042592 (homeostatic process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048878 (chemical homeostasis), GO:0009628 (response to abiotic stimulus), GO:0019725 (cellular homeostasis), GO:0042221 (response to chemical), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0055082 (intracellular chemical homeostasis), GO:0001666 (response to hypoxia), GO:1902883 (negative regulation of response to oxidative stress), GO:0060548 (negative regulation of cell death), GO:0010941 (regulation of cell death), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0080134 (regulation of response to stress), GO:0070482 (response to oxygen levels), GO:0080135 (regulation of cellular response to stress), GO:0033500 (carbohydrate homeostasis), GO:1901700 (response to oxygen-containing compound), GO:0010033 (response to organic substance), GO:0071456 (cellular response to hypoxia), GO:1900407 (regulation of cellular response to oxidative stress), GO:0009743 (response to carbohydrate), GO:1903201 (regulation of oxidative stress-induced cell death), GO:0071453 (cellular response to oxygen levels), GO:0071310 (cellular response to organic substance), GO:0036293 (response to decreased oxygen levels), GO:1902882 (regulation of response to oxidative stress), GO:0042593 (glucose homeostasis), GO:1901032 (negative regulation of response to reactive oxygen species), GO:1903202 (negative regulation of oxidative stress-induced cell death), GO:0001678 (intracellular glucose homeostasis), GO:1901701 (cellular response to oxygen-containing compound), GO:0036294 (cellular response to decreased oxygen levels), GO:0071322 (cellular response to carbohydrate stimulus), GO:0071333 (cellular response to glucose stimulus), GO:1901031 (regulation of response to reactive oxygen species), GO:1903205 (regulation of hydrogen peroxide-induced cell death), GO:0034284 (response to monosaccharide), GO:1903206 (negative regulation of hydrogen peroxide-induced cell death), GO:0009746 (response to hexose), GO:0071326 (cellular response to monosaccharide stimulus), GO:0071331 (cellular response to hexose stimulus), GO:0009749 (response to glucose)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)