Entrez Summary: This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-associated factor 1 (TRAF1), TNFR-associated factor 2 (TRAF2), and cylindromatosis. The interaction with TRAF2 inhibits TRAF2-mediated nuclear factor kappa-B, subunit 1 activation that is required for cell activation and protection against apoptosis. [provided by RefSeq, Jul 2008].
UniProt Summary: E3 ubiquitin ligase acting as a negative regulator of innate immune signaling. Inhibits activation of NF-kappa-B mediated by TNF. Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation (By similarity) (PubMed:22945920). Involved in response to genotoxic lesions during genome replication. Promotes H2AX and RPA2 phosphorylation after replication-associated DNA damage and assists fork progression at UV-induced replication-blocking lesions during S phase (PubMed:26595769). Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys- 63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity (PubMed:24553286). The function in translesion synthesis is controversial (PubMed:26595769). {ECO:0000250|UniProtKB:Q8VIG6, ECO:0000269|PubMed:22945920, ECO:0000269|PubMed:24553286, ECO:0000269|PubMed:26595769, ECO:0000303|PubMed:26595769}.
Pfam DomainsGO Terms
Pfam Domains
No Pfam Domain information is available for this gene.
GO Terms
negative regulation of interferon-beta production
negative regulation of tumor necrosis factor-mediated signaling pathway
negative regulation of type I interferon production
regulation of interferon-beta production
regulation of tumor necrosis factor-mediated signaling pathway
negative regulation of cytokine-mediated signaling pathway
negative regulation of response to cytokine stimulus
negative regulation of NF-kappaB transcription factor activity
regulation of type I interferon production
negative regulation of DNA-binding transcription factor activity
regulation of cytokine-mediated signaling pathway
regulation of response to cytokine stimulus
ubiquitin protein ligase activity
negative regulation of cytokine production
regulation of DNA-binding transcription factor activity
protein ubiquitination
regulation of cytokine production
perinuclear region of cytoplasm
protein modification by small protein conjugation
nucleolus
apoptotic process
protein modification by small protein conjugation or removal
programmed cell death
cell death
negative regulation of molecular function
negative regulation of multicellular organismal process
negative regulation of signal transduction
negative regulation of cell communication
negative regulation of signaling
negative regulation of response to stimulus
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)