Ring finger protein 167 (RNF167)

Ring finger protein 167 (RNF167) is a type I transmembrane E3 ubiquitin ligase characterized by a RING-H2 finger domain critical for its ubiquitin transferase activity. RNF167 is localized mainly to endosomes and lysosomes, where it regulates protein ubiquitination, trafficking, and degradation. It participates in metabolic signaling (modulating the mTORC1 pathway by controlling the ubiquitination and degradation of regulators such as CASTOR1 and Sestrin2), adjusts neuronal synaptic transmission by mediating AMPAR GluA2 subunit degradation, and controls endolysosomal sorting and lysosome positioning by targeting additional substrates. Recent research demonstrates a role for RNF167 in innate immune signaling: it negatively regulates type I interferon responses by promoting atypical K6- and K11-linked polyubiquitination and degradation of the antiviral sensors RIG-I and MDA5, thus suppressing host antiviral immune responses. RNF167 is implicated in neurodevelopmental disorders, cancer (via mTOR pathway), and has been proposed as a potential negative regulator of antiviral immunity. No drugs currently target RNF167 in clinical use, and the broad range of substrates suggests careful consideration of safety and specificity in future therapeutic modulation.

Other names

E3 ubiquitin-protein ligase RNF167RING105LP2254DKFZP566H073RING-type E3 ubiquitin transferase RNF1675730408C10Rik

Not drug-targeted clinically; for hypothetical drug development: inhibition or modulation of its E3 ligase activity would alter substrate degradation, affecting mTOR signaling, synaptic transmission, or innate immune responses