Ring finger protein 149 (RNF149)

Ring finger protein 149 (RNF149) is an E3 ubiquitin-protein ligase that participates in the post-translational modification of proteins through ubiquitination, leading to their degradation via the proteasome. It is a type I transmembrane protein, possessing an N-terminal signal peptide, a protease-associated (PA) domain, and a cytosolic RING finger domain required for its ligase activity. RNF149 regulates protein quality control, particularly by targeting misfolded or mislocalized proteins for ER-associated degradation. In innate immunity, RNF149 is induced by viral infection and type I interferon responses, and negatively regulates interferon-beta production by promoting ubiquitination and degradation of IRF3, facilitating increased viral replication. RNF149 also ubiquitinates other substrates, such as BRAF and EPHA2, thereby influencing signaling pathways related to cancer progression and cell differentiation. Knockdown or inhibition of RNF149 has been shown to suppress the proliferation of cancer cells and modulate outcomes in neurodegenerative and myeloproliferative diseases. RNF149’s overexpression plays a pro-tumorigenic and immune-suppressive role, making it a relevant therapeutic target in both oncology and antiviral drug development.

Other names

RNF149E3 ubiquitin-protein ligase RNF149Q8NC42 (UniProt ID)HGNC:23137NCBI Gene:284996ENSG00000163162

Drugs (or interventions) that inhibit RNF149 would potentially restore interferon-beta production, enhance antiviral immunity, decrease viral replication, and limit cancer cell proliferation by blocking ubiquitination and degradation of key substrates like IRF3, BRAF, EPHA2, DNAJC25.