E3 ubiquitin-protein ligase RNF26 (RNF26)

E3 ubiquitin-protein ligase RNF26 is a transmembrane enzyme of the endoplasmic reticulum (ER), characterized by a C3HC5-type RING finger domain and an N-terminal leucine zipper[3][4]. It plays a critical role in the spatial organization of endosomes and perinuclear ER integrity by retaining vesicles in the perinuclear “cloud,” and it mediates ubiquitination of substrates such as SQSTM1/p62 and MITA/STING[1][4][5]. RNF26 acts as a platform for positioning the endosomal system and is involved in antiviral innate immune responses by regulating type I interferon signaling through targeted polyubiquitination of MITA/STING and autophagic degradation of IRF3[5]. It also interacts with cytoskeletal protein vimentin to regulate organelle localization and ER morphology, especially under stress conditions[1]. RNF26 expression is upregulated in various human cancers, suggesting it may contribute to carcinogenesis through dysregulation of its ubiquitination targets[3][4].

Other names

RNF26Ring finger protein 26MGC2642Ring finger protein with leucine zipperE3 ubiquitin-protein ligase RNF26

Drugs or molecules targeting RNF26 would most likely act by inhibiting or modifying its E3 ligase activity, affecting the ubiquitination of substrates such as SQSTM1/p62 or MITA/STING[5][4].