E3 ubiquitin-protein ligase RNF5 (RNF5)

E3 ubiquitin-protein ligase RNF5 is a membrane-bound E3 ubiquitin ligase characterized by a RING finger domain, encoded by the *RNF5* gene in humans[4][6]. It localizes primarily to the endoplasmic reticulum and facilitates the transfer of ubiquitin to substrate proteins, primarily catalyzing K48-linked polyubiquitin chains that target these substrates for proteasomal degradation[1][7]. RNF5 regulates a variety of cellular processes, including cell motility (e.g., via paxillin ubiquitination and redistribution), ER-associated degradation (ERAD), muscle development, autophagy, and innate immune signaling[6][7]. It serves as a negative regulator of antiviral responses by promoting the degradation of STING and MAVS, thus limiting type I interferon production and the duration of innate immune responses[1][5][7]. Dysregulation or overexpression of RNF5 has been implicated in several diseases, notably cancer (e.g., breast cancer, melanoma, acute myeloid leukemia), cardiovascular disorders, and infection susceptibility, making it a therapeutically relevant target[3][5][7]. RNF5's functions in ER stress regulation, inflammation, and protein homeostasis underscore its biological significance in health and disease.

Other names

Ring finger protein 5G16RMA1HsRma1NG2RING5Ram1 homologRING-type E3 ubiquitin transferase RNF5protein G16

Promotion of K48-linked polyubiquitination, targeting proteins for proteasomal degradation (e.g., STING, MAVS, viral proteins, glutamine transporter proteins); Modulation of immune responses via degradation of key signaling molecules