RNF146
entrez
81847
canonical
uniprot
Q9NTX7
canonical
ensembl
ENSG00000118518
resolver
ensp
ENSP00000357297
resolver
ensp
ENSP00000476814
resolver
ensp
ENSP00000477168
resolver
ensp
ENSP00000587506
resolver
genesymbol
RNF146
resolver
hgnc
HGNC:21336
resolver
uniprot
E1P572
resolver
uniprot
Q6FIB2
resolver
uniprot
Q7L8H4
resolver
uniprot
Q96K03
resolver
uniprot
Q96T06
resolver
uniprot
Q9NTX6
resolver
uniprot_entry
RN146_HUMAN
resolver
uniprot_sec
E1P572
resolver
uniprot_sec
Q6FIB2
resolver
uniprot_sec
Q7L8H4
resolver
uniprot_sec
Q96K03
resolver
uniprot_sec
Q96T06
resolver
uniprot_sec
Q9NTX6
resolver
amino_acid_sequence
MMAGCGEIDHSINMLPTNRKANESCSNTAPSLTVPECAICLQTCVHPVSLPCKHVFCYLCVKGASWLGKRCALCRQEIPEDFLDKPTLLSPEELKAASRGNGEYAWYYEGRNGWWQYDERTSRELEDAFSKGKKNTEMLIAGFLYVADLENMVQYRRNEHGRRRKIKRDIIDIPKKGVAGLRLDCDANTVNLARESSADGADSVSAQSGASVQPLVSSVRPLTSVDGQLTSPATPSPDASTSLEDSFAHLQLSGDNTAERSHRGEGEEDHESPSSGRVPAPDTSIEETESDASSDSEDVSAVVAQHSLTQQRLLVSNANQTVPDRSDRSGTDRSVAGGGTVSVSVRSRRPDGQCTVTEV
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in RNF146 are a cause of susceptibility to breast cancer.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation (PubMed:21478859, PubMed:21799911, PubMed:22267412). May regulate many important biological processes, such as cell survival and DNA damage response (PubMed:21825151, PubMed:22267412). 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 (PubMed:21478859, PubMed:21799911). Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2 (PubMed:21799911). Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation (PubMed:21799911). Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48' (PubMed:21799911). May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location (PubMed:21799911). Neuroprotective protein (PubMed:21602803). 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 (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 (By similarity). Promotes cell survival after gamma-irradiation (PubMed:21825151). Facilitates DNA repair (PubMed:21825151). {ECO:0000250|UniProtKB:Q9CZW6, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21602803, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151, ECO:0000269|PubMed:22267412}.
uniprot
proteins
mass_dalton
38950
uniprot
proteins
mutagenesis
MUTAGEN 54; /note="H->A: Partially suppression of WNT3A signaling and stabilization of AXIN1, TNKS and TNKS2 with or without WNT3A induction. No effect on TNKS1-binding."; /evidence="ECO:0000269|PubMed:21799911"; MUTAGEN 106; /note="W->A: No effect on Wnt signaling pathway."; /evidence="ECO:0000269|PubMed:21799911"; MUTAGEN 108; /note="Y->A: Loss of iso-ADP-ribose-binding."; /evidence="ECO:0000269|PubMed:22267412"; MUTAGEN 111; /note="R->A: Minor effect on iso-ADP-ribose-binding."; /evidence="ECO:0000269|PubMed:22267412"; MUTAGEN 115; /note="W->A: Strong decrease in iso-ADP-ribose-binding affinity."; /evidence="ECO:0000269|PubMed:22267412"; MUTAGEN 145; /note="Y->A: Loss of iso-ADP-ribose-binding."; /evidence="ECO:0000269|PubMed:22267412"; MUTAGEN 154; /note="Q->A: Loss of iso-ADP-ribose-binding affinity."; /evidence="ECO:0000269|PubMed:22267412"; MUTAGEN 163; /note="R->A: Abolishes the ability to recognize and bind PARsylated proteins."; /evidence="ECO:0000269|PubMed:21478859"; MUTAGEN 164; /note="R->A: Loss of iso-ADP-ribose-binding."; /evidence="ECO:0000269|PubMed:22267412"; MUTAGEN 176; /note="K->A: Minor effect on iso-ADP-ribose-binding."; /evidence="ECO:0000269|PubMed:22267412
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:21478859}.
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; autoubiquitinated. Polyubiquitinated in the presence of UBE2D1, UBE2D2 and UBE2D3. Multimonoubiquitinated in the presence of UBE2E1. Not ubiquitinated 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. {ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151}.
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15813938
uniprot
proteins
pubmed
18326623
uniprot
proteins
pubmed
19517271
uniprot
proteins
pubmed
19690183
uniprot
proteins
pubmed
21445572
uniprot
proteins
pubmed
21478859
uniprot
proteins
pubmed
21602803
uniprot
proteins
pubmed
21799911
uniprot
proteins
pubmed
21825151
uniprot
proteins
pubmed
22267412
uniprot
proteins
sequence_length
359
uniprot
proteins
subcellular_location
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.
uniprot
proteins