InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RNF146

Summary

InnateDB Protein

IDBP-96181.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RNF146

Protein Name

ring finger protein 146

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000357297

InnateDB Gene

IDBG-96179 (RNF146)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000250, ECO:0000269PubMed:21478859, ECO:0000269PubMed:21602803, ECO:0000269PubMed:21799911, ECO:0000269PubMed:21825151, ECO:0000269PubMed:22267412}.

Subcellular Localization

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.

Disease Associations

Note=Defects in RNF146 are a cause of susceptibility to breast cancer.

Tissue Specificity

Ubiquitously expressed. Up-regulated in brains from patients with Alzheimer disease.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.

Experimentally validated
Total	29 [view]
Protein-Protein	29 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0072572	poly-ADP-D-ribose binding

Biological Process

GO:0016055	Wnt signaling pathway
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0051865	protein autoubiquitination
GO:0070936	protein K48-linked ubiquitination
GO:0090263	positive regulation of canonical Wnt signaling pathway