Tbio RNF146 E3 ubiquitin-protein ligase RNF146

Protein Summary

Description

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. 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.

Uniprot Accession IDs

• Q9NTX7
• E1P572
• Q6FIB2
• Q7L8H4
• Q96K03
• Q96T06
• Q9NTX6

Gene Name

• RNF146

Ensembl ID

• ENST00000309649
• ENSP00000309365
• ENSG00000118518
• ENST00000368314
• ENSP00000357297
• ENST00000608991
• ENSP00000477168
• ENST00000610153
• ENSP00000476814
• ENST00000616343
• ENSP00000479890

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.85
cell type or tissue	0.8
tissue sample	0.73
transcription factor binding site profile	0.69
virus perturbation	0.68

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 23.72   (req: < 5)

Gene RIFs: 17   (req: <= 3)

Antibodies: 61   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 23.72   (req: >= 5)

Gene RIFs: 17   (req: > 3)

Antibodies: 61   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0