D2H0Y8 · RN146_AILME
- ProteinE3 ubiquitin-protein ligase RNF146
- GeneRNF146
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids359 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
Function
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).
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).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 107 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 110 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 114 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 144 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 153 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 163 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 175 | poly[(1''->2')-ADP-alpha-D-ribose] group (UniProtKB | ChEBI) of a glycoprotein (UniProtKB | ChEBI) | ||||
Sequence: K |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Molecular Function | poly-ADP-D-ribose binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | positive regulation of canonical Wnt signaling pathway | |
Biological Process | protein autoubiquitination | |
Biological Process | protein K48-linked ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process | |
Biological Process | Wnt signaling pathway |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase RNF146
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Ursidae > Ailuropoda
Accessions
- Primary accessionD2H0Y8
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
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.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000409501 | 1-359 | E3 ubiquitin-protein ligase RNF146 | |||
Sequence: MAGCGEIDHSVNMLPTNRKANESCANPAPSLTVPECAICLQTCVHPVSLPCKHVFCYLCVKGASWLGKRCALCRQEIPEDFLDKPTLLSPEELKAASRGNGEYAWYYEGRNGWWQYDERTSRELEDAFSKGKKSTEMLIAGFLYVADLENMVQYRRNEHGRRRKIKRDIIDIPKKGVAGLRLDCEANTVNLARESSADGADSVSAQSGASSVQPLVSSLRPLTSVDGQLTSPATPSPDASTSLEDSFAHLQLSGDSIAERSHRGEGEEDHESPSSGRVPAPDTSVEETESDASSDSEDVSALVAQHSLTQQRLLVPNANQTVSDRSDRSGIDRSVAGGGTVNAGVRSRRPDGQCTVTEV | ||||||
Cross-link | 84 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 94 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 130 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 175 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 290 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 294 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated; autoubiquitinated. Autoubiquitination is enhanced upon poly(ADP-ribose)-binding.
Keywords
- PTM
Interaction
Subunit
Can form homooligomers. Interacts with PARsylated AXIN1, AXIN2, BLZF1, CASC3, H1-2, 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.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for zinc finger, domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 36-74 | RING-type | ||||
Sequence: CAICLQTCVHPVSLPCKHVFCYLCVKGASWLGKRCALCR | ||||||
Domain | 91-167 | WWE | ||||
Sequence: EELKAASRGNGEYAWYYEGRNGWWQYDERTSRELEDAFSKGKKSTEMLIAGFLYVADLENMVQYRRNEHGRRRKIKR | ||||||
Compositional bias | 259-275 | Basic and acidic residues | ||||
Sequence: ERSHRGEGEEDHESPSS | ||||||
Region | 259-359 | Disordered | ||||
Sequence: ERSHRGEGEEDHESPSSGRVPAPDTSVEETESDASSDSEDVSALVAQHSLTQQRLLVPNANQTVSDRSDRSGIDRSVAGGGTVNAGVRSRRPDGQCTVTEV | ||||||
Compositional bias | 295-325 | Polar residues | ||||
Sequence: DSEDVSALVAQHSLTQQRLLVPNANQTVSDR |
Domain
The WWE domain mediates non-covalent poly(ADP-ribose)-binding.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length359
- Mass (Da)38,839
- Last updated2010-02-09 v1
- ChecksumDFE28DC43E92D4CD
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 259-275 | Basic and acidic residues | ||||
Sequence: ERSHRGEGEEDHESPSS | ||||||
Compositional bias | 295-325 | Polar residues | ||||
Sequence: DSEDVSALVAQHSLTQQRLLVPNANQTVSDR |
Keywords
- Technical term